Desenvolvimento de Um Sistema Integrado para Avaliação Inicial Dos Doentes Oncológicos Admitidos em Cuidados Paliativos

Desenvolvimento de um Sistema Integrado para Avaliao Inicial dos Doentes Oncolgicos admitidos em Cuidados Paliativos | 1
desenvolvimento de um sistema integrado para avaliao inicial dos doentes oncolgicos admitidos em cuidados paliativos
jos antnio saraiva ferraz gonalves
Orientador: Professor Doutor Rui Nunes Co-orientador: Dr. Nigel Sykes
porto
2011
2 | Desenvolvimento de um Sistema Integrado para Avaliao Inicial dos Doentes Oncolgicos admitidos em Cuidados Paliativos
ttulo Desenvolvimento de um Sistema Integrado para a Avaliao Inicial dos Doentes Oncolgicos admitidos em Cuidados Paliativos. autor Jos Antnio Saraiva Ferraz Gonalves edio do autor isbn 978-989-xxxxxxxxxxxxx ano 2012 edio do texto Ana Meireles acabamento A Medisa
Tese de candidatura ao grau de doutor apresentada Faculdade de Medicina da Universidade do Porto
Artigo 48, pargrafo 3 A Faculdade no responde pelas doutrinas expedidas na dissertao

Regulamento da Faculdade de Medicina da Universidade do Porto Decreto Lei n 19337, de 29 de Janeiro de 1931
Jri da Prova de Doutoramento Presidente Vogais Reitor da Universidade do Porto Doutor Jos Eduardo Torres Eckenroth Guimares Pofessor Catedrtico da Faculdade de Medicina da Universidade do Porto Doutora Maria Amlia Duarte Ferreira Pofessora Catedrtica da Faculdade de Medicina da Universidade do Porto Doutor Rui Manuel Lopes Nunes Pofessor Catedrtico da Faculdade de Medicina da Universidade do Porto Orientador da tese Doutora Guilermina Maria da Silva Rego Pofessora Auxiliar da Faculdade de Medicina da Universidade do Porto Doutora Marlia Assuno Rodrigues Ferreira Dourado Pofessora Auxiliar da Faculdade de Medicina da Universidade de Coimbra Doutor Antnio Jos Feliciano Barbosa Pofessor Auxiliar Convidado da Faculdade de Medicina da Universidade de Lisboa
corpo catedrtico da faculdade de medicina da universidade do porto
Professores Catedrticos Efectivos Alberto Manuel Barros da Silva Altamiro Manuel Rodrigues Costa Pereira Antnio Albino Coelho Marques Abrantes Teixeira Antnio Carlos Freitas Ribeiro Saraiva Daniel Filipe Lima Moura Deolinda Maria Valente Alves Lima Teixeira Francisco Fernando Rocha Gonalves Isabel Maria Amorim Pereira Ramos Joo Francisco Montenegro Andrade Lima Bernardes Jorge Manuel Mergulho Castro Tavares Jos Agostinho Marques Lopes Jos Carlos Neves da Cunha Areias Jos Eduardo Torres Eckenroth Guimares Jos Henrique Dias Pinto de Barros Jos Manuel Lopes Teixeira Amarante Jos Manuel Pereira Dias de Castro Lopes Manuel Alberto Coimbra Sobrinho Simes Manuel Antnio Caldeira Pais Clemente Manuel Jesus Falco Pestana Vasconcelos Maria Amlia Duarte Ferreira Maria Dulce Cordeiro Madeira Maria Ftima Machado Henriques Carneiro Maria Leonor Martins Soares David Patrcio Manuel Vieira Arajo Soares Silva Rui Manuel Almeida Mota Cardoso Rui Manuel Lopes Nunes
Professores Catedrticos Jubilados e Aposentados Abel Jos Sampaio da Costa Tavares Abel Vitorino Trigo Cabral Alexandre Alberto Guerra Sousa Pinto Amndio Gomes Sampaio Tavares Antnio Augusto Lopes Vaz Antnio Carvalho Almeida Coimbra Antnio Fernandes da Fonseca Antnio Fernandes Oliveira Barbosa Ribeiro Braga Antnio Germano Pina Silva Leal Antnio Jos Pacheco Palha Antnio Lus Tom da Rocha Ribeiro Antnio Manuel Sampaio de Arajo Teixeira Belmiro dos Santos Patrcio Cndido Alves Hiplito Reis Carlos Rodrigo Magalhes Ramalho Cassiano Pena de Abreu e Lima Daniel Santos Pinto Serro Eduardo Jorge Cunha Rodrigues Pereira Fernando de Carvalho Cerqueira Magro Ferreira Fernando Tavarela Veloso Francisco de Sousa L Henrique Jos Ferreira Gonalves Lecour de Menezes Jos Augusto Fleming Torrinha Jos Carvalho de Oliveira Jos Fernando Barros Castro Correia Jos Lus Medina Vieira Jos Manuel Costa Mesquita Guimares Levi Eugnio Ribeiro Guerra Lus Alberto Martins Gomes de Almeida Manuel Augusto Cardoso de Oliveira Manuel Machado Rodrigues Gomes Manuel Maria Paula Barbosa Maria da Conceio Fernandes Marques Magalhes Maria Isabel Amorim de Azevedo Mrio Jos Cerqueira Gomes Braga Serafim Correia Pinto Guimares Valdemar Miguel Botelho dos Santos Cardoso Walter Friedrich Alfred Osswald
11 Desenvolvimento de um Sistema Integrado para Avaliao Inicial dos Doentes Oncolgicos admitidos em Cuidados Paliativos |
Para a ngela, o Daniel e o Ricardo.
You may say Im a dreamer But Im not the only one John Lennon
agradecimentos
Num trabalho que representa um corte num processo de investigao que comeou h vrios anos, a par de outros projectos que se vm a realizar, h muitas pessoas que contribuiram e cujo trabalho merece reconhecimento. Desde logo aos investigadores que participaram em todos os projectos que o compem. Tenho de agradecer ao meu orientador o Professor Doutor Rui Nunes pelo seu encorajamento, pelas suas sugestes e pela leitura crtica deste trabalho. Agradeo tambm ao Dr. Nigel Sykes, meu coorientador, as sugestes, sobretudo no que respeita investigao que consta dos captulos 4 e 5. Agradeo ainda Professora Doutora Guilhermina Rego pelo seu apoio e leitura crtica da tese. No posso esquecer a minha equipa na Unidade de Cuidados Paliativos da Rede do IPO - Porto sem a qual este trabalho no teria sido possvel. Tambm a colaborao dos doentes e das suas famlias foi indispensvel. E por ltimo, mas sem dvida mais importante, minha famlia que tornou possvel o atingir deste e doutros objectivos.
ndice
Introduo Introduo A Portuguese Palliative care unit Objectivos do desenvolvimento do sistema integrado para a avaliao inicial dos doentes oncolgicos admitidos em cuidados paliativos
21 23 29 35 39 41 43 53 61 63 65 67 75
Comunicao Comunicao/Informao Diagnosis disclosure in a portuguese oncological centre Breaking bad news: experiences and preferences of advanced cancer patients at a portuguese oncology centre Sntese
Avaliao da Conscincia Avaliao da conscincia Validation of a conscienciousness levels scale for paliative care Avaliao da funo cognitiva
Avaliao dos doentes sem alteraes cognitivas Avaliao dos doentes sem alteraes cognitivas O mtodo de Delfos Discusso
79 81 83 91 97 99 101 107 109 113 115 119 121 125 127 131 157
Avaliao dos doentes com alteraes cognitivas Avaliao dos doentes com alteraes cognitivos Estudo 1 Estudo 2 Discusso
Concluso Concluso
Resumo Resumo
Abstract Abstract
Anexos
10 Artigos publicados 11 Artigos publicados como membro do Research Steering Committee da Associao Europeia de Cuidados Paliativos
273
ndice de quadros
Quadro 1 Quadro 2 Quadro 3 Quadro 4 Quadro 5 Quadro 6 Quadro 7 Quadro 8 Quadro 9
Distribuio das doenas no oncolgicas. Mtodo de avaliao da confuso. Lista inicial de sintomas/problemas. Lista final. Forma final do instrumento. Formulrio de avaliao. Regras para aplicao do mtodo de avaliao do sofrimento. Dados demogrficos. Propores de concordncia.
Quadro 10 Dados demogrficos.
1
INTRODUO
introduo
Em Portugal morrem cerca de 100 000 pessoas em cada ano, das quais cerca de 20% de cancro [1]. Uma percentagem ainda maior morre de doenas cardiovasculares, mas tambm morrem muitos doentes de doenas pulmonares, renais, hepticas, neurolgicas, SIDA, etc. A maioria destas so hoje doenas crnicas, com um perodo mais ou menos longo em que os tratamentos destinados a alterar o seu desenvolvimento natural no so eficazes. Nesta fase, frequentemente, os doentes continuam a ser tratados da mesma maneira como se a sua situao fosse ainda reversvel ou so afastados com a justificao de que no h nada a fazer, mesmo que o doente continue a ser seguido ou esteja mesmo internado. Esta situao deve-se ao modelo de medicina que se estabeleceu devido ao seu prprio desenvolvimento. De facto, o grande desenvolvimento que a medicina conheceu no sculo XX, sobretudo na segunda metade, permitiu que finalmente se pudesse modificar eficazmente o desenvolvimento natural de muitas doenas, curar algumas e evitar o aparecimento de doenas infecciosas que no passado constituram flagelos da humanidade. A varola foi mesmo erradicada. No entanto, este desenvolvimento levou situao actual em que o treino dos mdicos se focou exclusivamente na cura ou no prolongamento da vida, pelo que quando tal no possvel ficam desarmados e tm dificuldade em responder aos problemas dos doentes. O reconhecimento da situao atrs descrita deu origem ao chamado movimento dos hospcios - Cicely Saunders fundou o St. Christophers Hospice em Londres em 1967. Esta a data geralmente reconhecida como a que marca o incio dos cuidados paliativos.
No entanto, Geoffrey Hanks revelou recentemente que j existia um servio no Royal Marsden, o Continuity Care Service fundado em 1964, com a finalidade de tratar os doentes oncolgicos com doena avanada incurvel [2]. Considerava-se que, apesar de no haver possibilidade de deter a doena, a medicina possua recursos que, se usados adequadamente, podiam responder aos problemas destes doentes. Balfour Mount abriu o seu Servio de Cuidados Paliativos em 1975 no Royal Victoria Hospital de Montreal, empregando pela primeira vez a designao cuidados paliativos, que a partir da se generalizou [3]. Mais tarde, em 1990, a Organizao Mundial de Sade (OMS) num documento intitulado Cancer Pain Relief and Palliative Care reconheceu a importncia dos cuidados paliativos e considerou o tratamento da dor e de outros sintomas como uma das suas prioridades na luta contra o cancro, a par da preveno primria, do diagnstico precoce e do tratamento curativo [4]. Nesse importante documento, a OMS afirmava que durante muito tempo ainda os cuidados paliativos sero a nica soluo, ao mesmo tempo humana e realista, para numerosos doentes, e nada mais importante, para a qualidade de vida desses doentes, que a difuso e a aplicao dos conhecimentos j disponveis sobre o tratamento da dor e dos outros sintomas. Os cuidados paliativos so considerados ao mesmo nvel dos outros meios de interveno e no inferiores ou secundrios. Em 2002 a OMS referiu-se aos cuidados paliativos do seguinte modo [5]: Os cuidados paliativos melhoram a qualidade de vida dos doentes e das suas famlias que encaram uma doena ameaadora da vida, proporcionando alvio da dor e de outros sintomas, suporte espiritual e psicossocial desde o diagnstico at ao fim da vida e no luto. Os cuidados paliativos: Proporcionam o alvio da dor e de outros sintomas perturbadores; Afirmam a vida e vem a morte como um processo normal; No pretendem apressar ou adiar a morte; Integram os aspectos psicolgicos e espirituais nos cuidados aos doentes; Oferecem um sistema de suporte para ajudar os doentes a viver to activamente quanto possvel at morte; Oferecem um sistema de suporte para ajudar as famlias a lidar com a doena e o luto;
Usam uma estratgia de equipa para abordar as necessidades dos doentes e das suas famlias, incluindo aconselhamento no luto, se indicado; Melhoram a qualidade de vida e possivelmente tambm influenciam positivamente o curso das doenas; So aplicveis cedo no decurso das doenas, em conjuno com outras teraputicas que pretendem prolongar a vida, tais como a quimioterapia ou a radioterapia, e incluem as investigaes necessrias para melhor compreender e tratar complicaes clnicas perturbadoras.
Assim a OMS considera que os cuidados paliativos no se devem limitar ao fim da vida, mas considera que deveriam estar disponveis desde o diagnstico. A ideia fundamental a de que os cuidados paliativos ajudem as pessoas a viver o mais activamente possvel e no que se concentrem apenas no que rodeia a morte. A ideia proporcionar uma vida digna e no apenas uma morte digna, aspecto em que outros movimentos se concentram, como os que defendem as formas de morte assistida, as quais, como afirma a OMS no se incluem na prtica dos cuidados paliativos. A realidade , porm, bem diferente porque o que se verifica na prtica que os doentes so muitas vezes referenciados muito tarde para cuidados paliativos [6]. H mesmo uma tendncia, pelo menos em alguns pases, para tratar cada vez mais agressivamente os doentes oncolgicos [7]. No entanto, um artigo recente que comparou o tratamento padro do cancro do pulmo de no-pequenas clulas com o tratamento padro mais a interveno precoce dos cuidados paliativos revelou que os doentes em quem houve interveno precoce dos cuidados paliativos tiveram uma melhor qualidade de vida, viveram mais tempo e foram submetidos a tratamentos menos agressivos [8]. Os cuidados paliativos comearam por causa dos doentes oncolgicos, mas hoje considera-se que devem ser prestados independentemente da doena crnica subjacente. A realidade mostra, no entanto, que os doentes oncolgicos continuam a ser os mais referenciados para cuidados paliativos, como acontece no nosso servio em que mais de 95% dos doentes so oncolgicos. Estes dados so semelhantes aos referentes a outros pases. Por exemplo, num estudo realizado na Alemanha verificou-se que 96,5% dos 4182 doentes admitidos em unidades de cuidados paliativos eram doentes oncolgicos [9]. Os no oncolgicos eram 147 (3,5%) e a sua distribuio por doena pode ver-se
no quadro 1. Isto acontece por uma variedade de razes das quais se destacam a maior facilidade em estabelecer o prognstico nos doentes oncolgicos e a conotao negativa que o cancro tem relativamente a outras doenas igualmente, ou mais, letais.
Quadro 1 | Distribuio das doenas no oncolgicas [9]. Doena Sistema Nervoso Doena do neurnio motor Acidente vascular cerebral Demncia Esclerose mltipla Outras Doenas Cardiovasculares Insuficincia cardaca crnica Doena arterial oclusiva Enfarte do miocrdio Outras Doenas Pulmonares Pneumonia Doena pulmonar obstrutiva crnica Outras Sistema Musculoesqueltico Osteoporose Espinal Outras Sistema Urogenital Insuficincia renal Outras Sistema Hematopoitico Doenas Hepticas Sistema Digestivo Outras n
44 12 10 6 4 10 30 12 10 4 4 13 5 4 4 12 12 3 4 10 8 2 9 6 6 17 6,1% 4,1% 4,1% 11,6% 6,8% 8,2% 8,8% 20,4%
%
29,9%
Em Portugal os cuidados paliativos comearam quase 30 anos mais tarde, em 1994, no Centro do Porto do Instituto Portugus de Oncologia (IPO - Porto) por iniciativa da Liga Portuguesa contra o Cancro. Tivemos a honra de ser o responsvel pela direco desse servio. Desde ento apareceram outros servios de cuidados paliativos em Portugal mas o seu nmero ainda muito insuficiente para as necessidades do pas. A recentemente criada Rede Nacional de Cuidados Continuados Integrados prev o desenvolvimento dos cuidados paliativos em todo o pas. Neste captulo, descreve-se seguidamente o desenvolvimento da primeira unidade de cuidados paliativos portuguesa atravs de um artigo intitulado A Portuguese Palliative Care Unit. Na ltima parte deste captulo referir-nos-emos aos objectivos desta tese e ao modo como esta se vai desenvolver.
a portuguese palliative care unit

jos antnio s. ferraz gonalves
Support Care Cancer (2000); 9:4-7
Support Care Cancer (2000) 9 : 47 DOI 10.1007/s005200000211
SUPPORTIVE CARE INTERNATIONAL
Jos Antnio S. Ferraz Gonalves
A Portuguese palliative care unit

Abstract The background to the advanced chronic diseases in an development of the first Portuenvironment where palliative care guese palliative care unit is is not yet well developed. described. The activities of this J.A.S. Ferraz Gonalves (Y) pioneer unit in Porto, which Keywords Palliative care 7 Instituto Portugues de Oncologia, include patient assistance, teaching Portugal Unidade de Cuidados Continuados, R. Dr. Antnio Bernardino de Almeida, and research, are reported, and the 4200-072 Porto, Portugal paper closes with some general E-mail: ferrazg6ipoporto.min-saude.pt or thoughts on the possible ways of ferrazg6mail.telepac.pt providing a more rapid response to Phone: c351-2-5073940 the suffering of patients with far Fax: c351-2-5506833 Abstract The background to the advanced chronic diseases in an Published online: 28 October 2000 development of the first Portuenvironment where palliative care Q Springer-Verlag 2000 guese palliative care unit is not yet well developed. recognized. In thisisdocument, the WHO stated that Introduction described. The activities of this palliative care was a priority in the fight against cancer, J.A.S. Ferraz Gonalves (Y) pioneer unit in Porto, which Keywords Palliative care 7 curative Instituto Portugues de Oncologia, Palliative care has its source in the recognition of a on the same level as prevention, screening and include patient assistance, teaching Unidade de the Cuidados Continuados, problem: inadequate treatment of patients with treatment, and the Portugal only solution that was both humane R. Dr. Antnio Bernardino de Almeida, and can research, are reported, and for the many cancer patients. Palliative mediadvanced chronic diseases. This treatment be inadand realistic 4200-072 Porto, Portugal paper closes with some general equateferrazg by excess or default, that is, E-mail: 6ipoporto.min-saude.pt or failure to recognize cine is now a recognized specialty and is a subject in thoughts the possible ways medical of ferrazg 6mail.telepac.pt the situation and consequent continuation with on aggresuniversity school curricula in the United a more response Phone: c351-2-5073940 sive treatments as if the problem were providing a reversible one, rapid Kingdom and to a few other countries. the suffering of patients with far Fax: c351-2-5506833 or abandonment of the patient without support. Such Since its beginnings, palliative care has spread
Published online: 28 October 2000 Q Springer-Verlag 2000
abandonment occurs not only when patients are sent quickly through the world, mainly, like everything else, home, but often in the hospital too. In this situation the in the more highly developed countries. In Portugal, In isthis the steps. WHO that patients can be labelled as terminal and not followed recognized. palliative care still document, taking its first It stated is the very Introduction care wasis a described priority inhere. the fight against cancer, up with the same interest as others: their needs may not palliative first of these that Palliative care has its source in the recognition of a on the same level as prevention, screening and curative be really considered, and the medications and care they problem: the treatment with treatment, and the only solution that was both humane do receive areinadequate often quite irrelevantoftopatients their condiadvanced chronic diseases. This treatment can be inad- and realistic for many cancer patients. Palliative medition. The beginning equate by excess or default, that is, failure to recognize The start of palliative care is usually dated from the cine is now a recognized specialty and is a subject in the situationof and continuation aggresschool curricula League in the Against United The North medical Section of the Portuguese foundation St.consequent Christophers Hospice with in 1967 by university sive treatments as ifthis the way problem were a movement reversible one, and a few other Cancer recognized the countries. cancer patients situation Cecily Saunders. In the hospice was Kingdom or abandonment of palliative the patient without support. Such described Since its beginnings, palliative care has spread above and decided to build a palliative care initiated. The term care was used officially abandonment occurs not when only when patients sent quickly the world, mainly, like everything else, unit to through be called Unidade de Cuidados Continuados, for the first time in 1975, Balfour Mountare opened home, but oftenCare in theService hospital in too. In this situation the in the would more work highly developed countries. In Portugal, which closely with the Porto Section of the the Palliative the Royal Victoria patients be labelled asIn terminal andWorld not followed care is still of taking its first steps. It is the very Portuguese Institute Oncology. At a certain point in Hospital can in Montreal [1]. 1990, the Health palliative up with the same interest one as others: needs may not first of these is described here. to be the medical the course of that the project I was invited Organization published of itstheir best-known docube really considered, and the medications and care they ments Treatment of cancer pain and palliative care director of the unit. I was a specialist in internal medido arethe often quite irrelevant to their condi[2], receive in which importance of palliative care was cine and oncology and I accepted the position on one tion. The beginning The start of palliative care is usually dated from the foundation of St. Christophers Hospice in 1967 by The North Section of the Portuguese League Against Cecily Saunders. In this way the hospice movement was Cancer recognized the cancer patients situation initiated. The term palliative care was used officially described above and decided to build a palliative care for the first time in 1975, when Balfour Mount opened unit to be called Unidade de Cuidados Continuados, the Palliative Care Service in the Royal Victoria which would work closely with the Porto Section of the Hospital in Montreal [1]. In 1990, the World Health Portuguese Institute of Oncology. At a certain point in Organization published one of its best-known docu- the course of the project I was invited to be the medical ments Treatment of cancer pain and palliative care director of the unit. I was a specialist in internal medicine and oncology and I accepted the position on one [2], in which the importance of palliative care was 10
condition: that I should be allowed to take training in palliative care, which at that time was only possible in units outside Portugal. Over the course of 7 months I visited several European units: St. Christophers Hospice and St. Helena Hospice in England; Intituto Nazionale dei Tumori in Milan; La Foundation Rive-Neuve and the Aubonne Hospital in Switzerland; and Gregorio Maran n Hospital in Madrid. I believe this was very useful and, in my case, the best approach, because the diversity I saw showed me different realities, different experiences, and different styles of palliative care. I concluded that palliative care can be applied in many different conditions, always with the same philosophy and the same principles behind it while the practice is adapted to the local circumstances, and that what is observed in any palliative care service should be taken as an example of what can be done, rather than a model to be copied.
I The opportunity of spreading the principles of palliative care more easily, because there was more direct contact with doctors in the other service I Training the team in more specific work with only a few patients I Possibility of contact with the reality of palliative care, thus allowing selection (self-selection, at that time) of people who really wanted to go on working in palliative care I Economy because the unit was so small it was cheaper to work together with the other service, which made it possible to maintain adequate continuous staffing levels of professionals who needed to be represented at all times, mainly nurses, without having too many professionals relative to the number of patients We can conclude that this experience was useful, and perhaps it could be viewed as an example for other centres where only a small unit can be implemented.
The first unit

Because I finished my training period before the unit was ready, we were allowed to start working with 5 beds belonging to the Radiotherapy Service, which had a total of 25 beds. The staff in that service included the nurses who were keen to work in the future palliative unit, some of whom had had some experience of palliative care in units abroad. Our first patient was admitted on 17 October 1994. This, then, was the day when palliative care started in Portugal. All the personnel, except the chief nurse and myself, were shared between the two services. We started doing inpatient care, outpatient care, and consultation in other services within the hospital. There were various difficulties with this experience: I Problems arising from the physical/architectural setup, which did not make it easy for family members to stay with patients, especially at night I Too few beds for hospital needs I Different treatment of patients in the same service I Difficulty in the implementation of specific routines Other types of problems experienced at this stage were: I Problems relating to misunderstanding of the purpose of the new service I Referral mainly of patients expected to survive for only a few days I Frequent use of the unit as a kind of wastebasket, that is, not with the idea of sending patients to a place where they could be more adequately treated but to get a bed free These early days did also have positive aspects: I The possibility of offering palliative care at all for the first time
The new unit

Finally, the new unit opened on 25 May 1996. We grew step by step as more people were involved in the team (Table 1). Initially, we maintained the same activities, adding to them as circumstances allowed (Table 2). Now we have 20 beds, all in single rooms, which allows a member of any patients family or a friend to stay at any time. The unit has had a day centre since 1997: about 20 patients can attend for up to 3 days each week, and they can enjoy many activities.
Table 1 Staff of unit Doctors Nurses Nursing auxiliaries Social worker Psychologist Nutritionist Chaplain Driver Porters Volunteers 4 with 1 assigned exclusively to home care 24 16 1 1 1 1 1 7 15
Table 2 Evolution of the assistance to patients activity 1995 Inpatient admissions 68 Outpatient clinic observations Internal consultation visits Telephone consultation Home care visits 1996 100 1997 221 549 361 1998 359 1124 596 449 1999 388 1302 910 813 212
11
hold update courses to maintain interest in palliative care and ensure that the knowledge applied is current. Since the beginning of our activities, members of the units staff have participated in many courses, congresses, and other scientific meetings organized by others. And, finally, I teach the palliative care portion of the course for the masters degree in bioethics at the Medical School of Oporto University. Apart from the courses, many doctors, nurses, social workers, psychologists, and priests spend various periods of time in the unit. Research Again, the position this unit occupies in palliative care in Portugal should make research one of its most important activities, on a level with patient assistance and teaching. These two activities should support and be supported continuously by research. However, research takes time to produce results, so that we are not in a hurry to publish research papers, though we are publishing some review papers in Portuguese. However, we have presented some work at congresses of the European Association for Palliative Care and at other congresses, and we intend to start publishing our results soon. The future The unit is still evolving: in the future there will be more than 20 beds, and the home care service will be developed and will reach more patients. Teaching of palliative care will remain important, and it is probable that this unit will continue as the main palliative care teaching centre in Portugal. Faculty members of the Oporto Medical Schools have been contacted about the idea of introducing undergraduate palliative care teaching into their curricula, but I have not yet received any answers this would be a very important step. Research will take up the desired place. The immediate problem is finding people interested in working exclusively in palliative care. Unlike other European countries, Portugal does not have an excess of doctors and nurses, so that recruitment of professionals to the unit will not be easy.
Since 1998 we have offered telephone consultations for the patients being followed by the unit. The patients, their families, or their friends may contact the unit when a problem or a doubt arises, to discuss an adjustment to a medication, or to inform the doctor of the effect of a prescription, for example, 24 hours a day. It is usually possible for them to talk with the physician between 09*E00 and 16*E00 oclock, and with a nurse at other times. In 1999 we started home care. We intend to make this service one of the most important elements of the unit, so that patients can stay at home where their families and their own belongings are, that is to say where their lives are centred. However, the traditional extended family with three generations under one roof providing support for all members of the family in difficult times is changing. Families are becoming smaller and smaller; most people work outside the home, mainly in the bigger cities, and there will therefore probably be more and more difficulties in keeping patients at home, as has already happened in other European countries. Teaching As this is a pioneer unit in Portugal and in view of its size, it was planned that it should be a teaching centre. As professionals working exclusively in palliative care, we have an obligation to contribute to the spread of knowledge in this field. However, the best thing we can do is to go beyond teaching what can be read in books and reviews and also, most importantly, share our experience. This is why we did not start the multidisciplinary courses until we had completed 3 years of work as a palliative care team. Our first multidisciplinary course was in October 1997. Since then, we have held four each year. Each course is held for 12 professionals: 6 doctors and 6 nurses. This small number allows contact with the everyday life of the unit and with the patients. Each course involves 35 hours from Monday to Friday in 1 week. Up to August 2000, 144 professionals from all over the country, even from the islands of Madeira and the Azores, had undergone training in 12 courses. We always have many more candidates than we can admit to the courses, which shows the interest people have in palliative care and how much they feel the need of training in this special field. To help staff who work in our oncological centre but had not been able to get a place on any of the multidisciplinary courses we held a theoretical course in 2000, which was attended by 35 professionals. In 2000 we held the first continuing education course for doctors and nurses who had already completed the multidisciplinary course. And in the future we intend to
Other remarks
Since the opening of the unit, almost 6 years ago, palliative care has not evolved much further in Portugal. There are a few other experiences, but the overall picture is very poor. The implementation of palliative care has been difficult in most countries, and in
12
Portugal it will not be any different. Many still see palliative care not as a resource with its own knowledge and skills, but as what is offered in places where nursing and psychological and religious support are the most important aspects whilst the medical input has a secondary, and not especially skilled, role. Some medical oncologists, for example, claim that they should take care of their patients until their death, forgetting that the reality is different in most cases and that the care patients need when curative treatment is no longer useful must be learned, and is often not what they are providing. However, not all patients need to be treated by palliative care specialists. As in other specialties, many patients can be treated by their own physicians with some training, but there are difficult situations that require specialized resources of different types. In addition, research and teaching should be carried out, and usually only specialists have the knowledge, the experience, the readiness, and a sufficiently large number of patients for this. Palliative care is now needed in Portugal and must be developed. However, I suspect, unfortunately, that it
will be a long time before a serious effort is made to do this. Nonetheless, something must be done quickly. Palliative care can be provided in many different circumstances. Palliative care units are indispensable, in my view, but home care and inpatient support teams are examples of other options that would be easier to implement. In my opinion, it is more important to do something useful immediately for patients with advanced chronic diseases who are suffering unnecessarily than to wait for conditions that anyone might imagine to be ideal. When we started, for example, conditions were not ideal, because the unit was not yet ready. So, professionals and hospital staff members with an interest in this field should start however local conditions allow and then improve their situation at the rate that is possible, but without ever forgetting the training needed. I also believe that doctors have a special responsibility, because if they know and apply the principles and skills of palliative care, even alone, they can have a very important impact on the wellbeing of their patients with chronic advanced diseases.
References
1. Saunders C (1998) Foreword. In: Doyle D, Hanks GWC, MacDonald N (eds) Oxford Medical Publications, Oxford, pp vix 2. World Health Organization (1990) Traitement de la douleur cancreuse et soins palliatifs. (Srie de rapports techniques 804) WHO, Geneva
13
objectivos do desenvolvimento do sistema integrado para a avaliao inicial dos doentes oncolgicos admitidos em cuidados paliativos
A maioria dos doentes com doenas crnicas avanadas tem mltiplos problemas resultantes da sua doena e por vezes tambm dos tratamentos anteriormente efectuados. Acresce que os doentes admitidos em cuidados paliativos apresentam-se em situaes muito diversas a nvel do estado de conscincia, da funo cognitiva, do estado emocional, da funcionalidade, etc. Os doentes podem estar muito dbeis, receosos ou ansiosos. H tambm o problema do trabalho que uma equipa muito ocupada tem de fazer e do tempo que tem disponvel para cada doente. Por isso, uma avaliao extensa pode ser impossvel e pode constituir um fardo para os doentes. Contudo, para ajudar convenientemente os doentes, necessrio identificar e avaliar rigorosamente os seus problemas principais. Mais tarde, outros problemas de mais baixa prioridade podero ser abordados se for apropriado. Para resolver os problemas dos doentes necessrio, em primeiro lugar, reconhec-los. Existem vrias escalas para avaliao de mltiplos sintomas e outras desenhadas para avaliar um sintoma isolado como a dor [10] e a fadiga [11], por exemplo. A extenso e os problemas englobados nessas escalas varivel, embora inevitavelmente tenham pontos comuns, nomeadamente no que se refere aos sintomas fsicos mais comuns como dor, dispneia, nuseas, etc. Outro tipo de escalas tambm com pontos comuns com as anteriores so as que se destinam a avaliar a qualidade de vida, como a EORTC QLQ-C15-PAL [12]. O objectivo desta tese no acrescentar uma nova escala s j existentes, embora tambm seja necessrio desenvolver mtodos de avaliao que estejam de acordo com
o objectivo do trabalho. Este consiste no desenvolvimento de um sistema para avaliao dos principais problemas dos doentes, nas suas vrias dimenses que se adapte s circunstncias dos doentes. O sistema deve conter instrumentos que possam avaliar os problemas mais importantes dos doentes com descritores verbais fceis de compreender por todos os doentes sem alteraes da funo cognitiva. Por exemplo, o termo dispneia, incompreensvel para a maioria das pessoas, deve ser substitudo por falta de ar. A extenso tambm importante porque pode tornar a avaliao difcil ou cansativa para os doentes mais debilitados ou fastidioso para os que no tenham na altura muitos problemas. A limitao da extenso um dos objectivos que justifica o desenvolvimento deste sistema. H ainda o problema da avaliao dos doentes com alteraes cognitivas que impeam a comunicao eficaz. Este aspecto particularmente difcil, devido natureza subjectiva dos sintomas/problemas. No entanto, tambm estes doentes tm de ser avaliados rigorosamente embora de modo diferente. Para isso necessrio desenvolver mtodos de avaliao especficos, adaptados sua situao. Esta uma rea de interveno particularmente difcil. Para avaliar o estado cognitivo h que desenvolver ou utilizar instrumentos j validados que se adeqem aos objectivos do sistema. Esse estado pode ser bvio, mas por vezes no , pelo que as alteraes cognitivas podem passar despercebidas ou consideradas erradamente. Nos doentes com um estado de conscincia obviamente normal no necessrio rastrear o seu nvel de conscincia, mas quando no assim necessrio avaliar esse nvel. Tambm nos doentes que tm alteraes cognitivas bvias, com agitao ou desorientao manifesta, no necessrio fazer qualquer rastreio, mas quando no assim h que faz-lo. A comunicao um aspecto fundamental nos cuidados de sade e em cuidados paliativos este aspecto particularmente valorizado. A comunicao um processo contnuo, mas sobretudo nas fases de transio como a da admisso em cuidados paliativos, tem uma importncia particular porque a informao que os doentes e os familiares receberam anteriormente com frequncia insuficiente ou mesmo errada sobre a finalidade desta nova fase do seu tratamento. natural tambm que os doentes e os familiares desejem ser esclarecidos quanto ao que os espera.
Os cuidados paliativos envolvem os familiares que so afectados pelo sofrimento do seu doente, pelo que tambm so objecto de avaliao e ateno. No entanto, esse aspecto no ser integrado neste sistema que incidir exclusivamente sobre a avaliao dos doentes. De acordo com o que anteriormente foi dito, o sistema que nos propomos construir desenvolver-seem 5 captulos, para alm deste captulo introdutrio. No segundo captulo, da comunicao, procuraremos demonstrar a necessidade e o desejo de informao que a maioria dos doentes sentem e a dificuldade com muitas vezes se deparam, atravs de dois estudos levados a cabo no IPO - Porto nos ltimos anos e j publicados. Procura-se mostrar a necessidade de adequar a informao aos desejos dos doentes e no usar princpios rgidos, procurando seguir a vontade e o ritmo destes. Depois, no terceiro captulo descreve-se o processo de avaliao da conscincia tanto ao nvel da viglia como do contedo. Para avaliar o nvel de viglia desenvolveu-se uma escala, entretanto j publicada. Para avaliar a funo cognitiva nos doentes com um nvel de viglia que permita interaco, introduziu-se um instrumento j em uso na Unidade de Cuidados Paliativos do IPO - Porto, que foi recentemente validado em cuidados paliativos e em portugus. Depois de definido se o doente tem capacidade para ser avaliado ser usado o instrumento descrito no captulo 4 que foi desenvolvido segundo o mtodo de Delfos, com o envolvimento de peritos internacionais. Para os doentes que no podem ser avaliados directamente por alteraes cognitivas foram estudados dois mtodos que se descrevem no captulo 5. Finalmente no captulo 6 integram-se as diferentes partes do sistema, procurando dar-se uma viso de conjunto e coerncia interna a esta ferramenta. Procede-se ainda a uma reflexo sobre a importncia que este sistema pode ter na melhoria da qualidade assistencial em cuidados paliativos.
referncias
http://www.ine.pt/xportal/xmain?xpid=INE&xpgid =ine_indicadores&indOcorrCod=0001675&selTab= tab2 (acedido em 08/06/2009). Geoffrey H. Palliative care: careless use of language undermines our identity. Palliat Med 2008; 22:109-110. Ferraz Gonalves. Cuidados Paliativos em Oncologia. Arquivos de Medicina 1998; 12 (3):170-173. WHO expert committee report. Cancer pain relief and palliative care. World Health Organization. Geneva 1990. http://www.who.int/cancer/palliative/en/.(acedido em 28/05/2009). Ferraz Gonalves, Goyanes C. Use of chemotherapy at the end of life in a Portuguese oncology center. Support Care Cancer 2008;16:321327. Earle CC, Neville BA, Landrum MB, Ayanian JZ, Block SD, Weeks JC. Trends in the aggressiveness of cancer care near the end of life. J Clin Oncol 2004;22:315321.
Temel JS, Greer JA, Muzikansky A, et al. Early Palliative Care for Patients with Metastatic NonSmallCell Lung Cancer. N Engl J Med 2010;363:733-742. Ostgathe C, Alt-Epping B, Golla H, et al. Non-cancer patients in specialized palliative care in Germany: what are the problems? Palliat Med 2010;25:148-152.
10 Caraceni A, Cherny N, Fainsinger R, Kaasa S, Poulain P, Radbruch L, De Conno F, and the Steering Committee of the EAPC Research Network. Pain Measurement Tools and Methods in Clinical Research in Palliative Care: Recommendations of an Expert Working Group of the European Association of Palliative Care. J Pain Symptom Manage 2002;23:239255. 11 Radbruch L, Strasser F, Elsner F, Ferraz Gonalves, Lge , Kaasa, Nauck, Stone P, the Research Steering Committee of the European Association for Palliative Care (EAPC). Fatigue in palliative care patients - an EAPC approach. Palliat Med 2008; 22: 1332. 12 Groenvold M, Petersen MA, Agronson NK, et al. The development of the EORTC QLQ-C15-PAL. Eur J Cancer 2006;42:55-64.
2
COMUNICAO
comunicao/informao
A comunicao um aspecto fundamental nas relaes humanas. Na relao dos doentes com os profissionais de sade a comunicao reveste-se de grande importncia e nos cuidados paliativos -lhe dada tradicionalmente uma particular relevncia. Demonstrou-se que a qualidade da comunicao tem um efeito positivo no bem-estar emocional e fsico dos doentes. A boa comunicao associa-se melhoria da satisfao e ao ajustamento psicolgico dos doentes. Para os doentes e suas famlias a comunicao uma componente vital da qualidade dos cuidados de fim de vida [1]. Contudo, as atitudes relacionadas com a informao prestada aos doentes diferem muito de pas para pas e tem variado ao longo do tempo. Por exemplo, nos Estados Unidos da Amrica e nos pases do Norte da Europa a informao sobre vrios aspectos da doena habitual, enquanto nos pases do sul da Europa, nomeadamente em Portugal, a situao parece ser diferente. Invocam-se geralmente questes culturais para explicar essas diferenas e elas existem certamente. Mas h que dizer que a situao no esttica pois tem-se verificado uma evoluo no sentido de dar maior informao aos doentes [3]. O maior acesso informao, a melhoria da literacia e o maior envolvimento em ensaios clnicos faro, certamente, com que os doentes venham a possuir e a exigir maior informao sobre a sua situao. Na fase de transio para cuidados paliativos h certamente muitas dvidas e a consequente ansiedade associada. A transio para cuidados paliativos reveste-se de particular dramatismo pelo seu significado. Porque embora os cuidados paliativos possam e devam ser integrados no tratamento dos doentes juntamente com as tcnicas curativas, na maioria dos casos ainda significam que a possibilidade de modificar a
evoluo da doena est esgotada. Este facto, tem naturalmente um grande impacto psicolgico nos doentes que deve ser explorado. Embora haja a impresso de que em Portugal a informao prestada aos doentes deficiente, necessrio conhecer o que realmente se passa e quais so as preferncias dos doentes quanto a este aspecto. da investigao por ns realizada nesta rea que se d conta neste captulo, introduzindo dois artigos j publicados: Diagnosis disclosure in a Portuguese oncological centre - estudo sobre a prtica dos oncologistas de um centro oncolgico quanto informao que prestam aos doentes sobre o seu diagnstico; e Breaking bad news: experiences and preferences of advanced cancer patients at a Portuguese oncology centre - estudo sobre o ponto de vista dos doentes com cancro avanado sobre a informao que receberam. O captulo termina com uma breve snteses dos 2 artigos.
diagnosis disclosure in a portuguese oncological centre

j. ferraz gonalves, s. castro
Palliative Medicine (2001); 15:35-41
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Palliative Medicine 2001; 15: 3541
Diagnosis disclosure in a Portuguese oncological centre

J Ferraz Gonalves Director and S Castro Psychologist, Unidade de Cuidados Continuados, Instituto Portugus de Oncologia, Porto Abstract: The disclosure of a diagnosis of cancer to patients is a controversial matter. There have been major differences in practice concerning this issue through time and between cultures. A questionnaire was sent to the doctors of the Oporto Centre of the Portuguese Institute of Oncology in order to assess their attitudes. We received 45 responses (40%) from the 113 questionnaires sent. Of these, 32 (71%) said that they disclose the diagnosis as a general policy or at the patients request, and 13 (29%) disclose it rarely or not at all. The most frequent reason indicated by these 13 physicians was that the disclosure might damage the patients psychologically. Forty-four (98%) doctors inform the family of the diagnosis. Thirty-nine (87%) think that patients are satised with the information provided. This study was carried out in one oncological centre only, so it is inappropriate to conclude that this is what happens throughout Portugal. As far as we know, this is the rst study in Portugal addressing this area of practice. This subject is a very important topic of research both in Portugal and in other countries, as many published recommendations are not research based. Key words: breaking bad news; communication; diagnosis disclosure; physicianpatient relation Resumo: A revelao do diagnstico aos doentes com cancro um assunto controverso. Tem havido grandes diferenas na prtica respeitante a esta questo ao longo do tempo e entre as diversas culturas. Envimos um questionrio aos mdicos do Centro do Porto do Instituto Portugus de Oncologia para avaliar as suas atitudes. Recebemos 45 respostas (40%) dos 113 questionrios enviados. Destes, 32 (71%) dizem que revelam o diagnstico por princpio ou quando os doentes o pedem e 13 (29%) revelam-no raramente ou nunca. A razo mais frequentemente indicada por estes 13 mdicos foi a de que a revelao pode causar dano psicolgico aos doentes. Quarenta e quatro (98%) mdicos informam a famlia do diagnstico. Trinta e nove (87%) pensam que os doentes esto satisfeitos com a informao dada. Este estudo foi feito num nico centro oncolgico, por isso no podemos dizer que isto que se passa, de um modo geral, em Portugal. Tanto quanto sabemos, este o primeiro estudo realizado em Portugal sobre este aspecto da prtica mdica. Este um tpico de investigao muito importante tanto em Portugal como noutros pases, porque muitas recomendaes prticas publicadas no se baseiam na investigao. Palavras-chave: dar ms notcias; comunicao; revelao do diagnstico; relao mdicodoente
Address for correspondence: Dr J Ferraz Gonalves, Unidade de Cuidados Continuados, Instituto Portugus de Oncologia, R. Dr. Antnio Bernardino de Almeida, 4200-072 Porto, Portugal. Arnold 2001 02692163(01)PM396OA
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36 J Ferraz Gonalves and S Castro
Introduction
The disclosure of a diagnosis of cancer to patients is a controversial matter. The dominant attitude among physicians has changed over time, and there have always been voices advocating against it.1 We will also nd different attitudes when we compare practice in countries with different cultures. In the United States and northern European countries,24 for example, the usual practice is to disclose the diagnosis. However, in other countries, including those of southern Europe,48 the situation is different: doctors attitudes are more paternalistic, and in many cases they do not disclose the diagnosis. In Portugal, the current practice seems to be one of non-disclosure. However, as far as we know, no research on this subject has been carried out in Portugal.
mittee of the Portuguese Institute of Oncology Oporto Centre.
Results
The questionnaire was sent to 113 doctors, and 45 responses (40%) were obtained. In Table 1 we show the specialities and demographic data of the doctors who returned the questionnaires. There is a similar percentage in all specialities, with the exception of radiotherapy (Table 1). Nineteen (42%) participants added comments, clarifying their views or adding other hypotheses to those included in the questionnaire. The questions most commented on were: the one that asked if doctors disclose the diagnosis of cancer to the patients, and if not, why not; and the questions about the patients and families participation in therapeutic decisions. Among our respondents, 14 (31%) doctors stated that their policy was to disclose the diagnosis, three (7%) do not do it at all, 10 (22%) rarely do it and 18 (40%) disclose it only at the patients request (Table 2). A much higher number, 44 (98%), inform the family about the patients diagnosis; in one case (2%) the answer was omitted. The most frequent reason indicated by the 13 doctors (34%), who rarely or never disclose the diagnosis to patients (Table 3), for so acting was the possibility of damaging the patients psychologically (11, 85%). The comments added to the questions about the disclosure to patients and the reasons for not disclosing the cancer diagnosis, again, show a concern with the eventual psychological damage that the disclosure might produce. Some examples of these comments can be seen in Table 4. To the question do your patients often request more information from you? 29 (64%) answered
Methods
We conducted a survey in the Oporto Centre of the Portuguese Institute of Oncology, which is one of the most important Portuguese oncological centres. It has 350 beds and about 4000 new patients are admitted every year. It has services and equipment equivalent to those of any major European oncological centre, including a palliative care unit. This centre is a public hospital that serves the population from the whole of northern Portugal. The patients belong to all social classes and education levels. A questionnaire (see the Appendix), specically designed for this study but not subjected to a pilot test, was sent to each doctor at the centre who treated adult patients. Those with other functions, such as radiologists and pathologists, were excluded. This study was approved by the Ethics ComTable 1 Doctors speciality and demographic data Speciality Surgery Medical oncology Radiotherapy Other Total No. of questionnaires sent 52 24 24 13 113
No. of questionnaires returned 22 12 5 6 45
Total returned (%) 49 27 11 13 100
Returned per speciality (%) 42 50 21 46
Age: mean 46 years (range: 3165 years); median 45 years. Sex: male 27 (60%); female 17 (38%); not stated 1 (2%).
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Diagnosis disclosure in a Portuguese oncological centre 37

Table 2 Diagnosis disclosure to the patient No. (%) Yes No Rarely At patients request 14 (31) 3 (7) 10 (22) 18 (40)
Table 3 Reasons invoked for rare or non-disclosure (13 doctors) Reason Difculties in discussing the diagnosis Not prepared to deal with the situation Not useful to the patient Psychologically deleterious Not having enough time Others Yes 0 0 3 11 2 4 No 13 13 10 2 11 9
Table 4 Examples of comments to questionnaire questions 1 and 2 The decision to disclose the diagnosis should consider the psychological, intellectual, cultural and social conditions of the patient It is necessary to inform the patients gradually and with sensitivity and gentleness, without coldness After the information has been provided, psychological support is needed Most patients are not prepared to receive the information of a malignant disease The information must be given when it is useful to the patient The information can cause depression Never use the word cancer Patients often ask for information to feel hopeful in their lives (we understand this statement means that the patient does not really want the truth but a negative answer)
yes and 16 (36%) answered no. These 16 doctors presume that their patients are satised with the information they get, or simply do not wish any more information at all (Table 5). This agrees with the answers to question 4, to which 39 (87%) said that they think their patients are satised with the information they give them. Forty-one doctors (91%) think that patients should participate in decisions about treatment and four (9%) think they should not. The reasons for these opinions are shown in Tables 6 and 7. Only 25 (56%) thought that family members should participate in making treatment decisions. The few comments about the patients participation in therapeutic decisions suggest that they should not participate or even inuence them. It was, however, conceded that if offered two equally effective treatments the patient can choose the one that is more bearable for him or her. Similar comments were made about family participation in these decisions. One respondent stated that the decision belongs to doctors, and that family can be involved to encourage the patient to accept the recommended treatment and to endure its toxicity.
Table 6 Reasons why patients should participate in treatment decisions (41 doctors) To preserve patient autonomy To make the adherence to treatment easier To protect the doctor from legal problems To allow the patient to prepare himself for adverse effects To allow the patient to refuse the treatment eventually Other 25 35 19 30 23 4
Table 5 Reasons to explain why patients often do not request more information from their doctors (16 doctors) They are satised with the information they have been given They are not at ease to ask questions They do not wish for more information They feel you do not have enough time to talk to them They think they will not understand the information you can give 7 1 5 2 0
Table 7 Reasons why patients should not participate in treatment decisions (four doctors) It is difcult for you to discuss treatment with patients You think it is not useful to patients You do not have enough time to discuss treatment with the patients The discussion might damage the patients psychologically Other 1 2 4 1 1
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38
J Ferraz Gonalves and S Castro admitted to an oncological service and a palliative care unit who had not been informed of their diagnosis, 42% did not want to receive more information. An alternative explanation of our results is, perhaps an element of denial, because breaking bad news is recognized by most experts as being difcult and causing some degree of discomfort, even for experienced professionals;9 in Portugal this problem is not addressed in any way, except in some limited educational activity. It is possible that doctors are hiding their own difculties in dealing with these aspects of communication behind a paternalistic attitude. Communication with patients can be learned, but denial can delay or prevent the decision to act accordingly. However, we must be very careful with the interpretation of the results obtained and avoid preconceptions. It seems to be a contradiction that 91% of the doctors think that patients should participate in treatment decisions, because this percentage is higher than those who inform patients, and without information about their disease it is not possible for patients to decide rationally about the treatment. On the other hand, doctors think that family members, who are almost always informed, should participate in treatment decisions in a much smaller proportion of cases (56%). The comments about the decisions also have a paternalistic character when they state that patients should not decide about treatment. However, these comments represent a minority because 91% think that patients should participate in those decisions. The family is seen as a possible doctor ally, facilitating the adherence to treatment and helping the patient to endure the treatment decided on by the doctor. The available data show that Portuguese doctors, who work in this oncological centre, disclose the diagnosis to patients less frequently than doctors from other countries, including those of the southern Europe, such as Greece. This study was carried out in one centre only so it is inappropriate to generalize, but the result obtained agrees with, or is even higher than, what we expected was happening in Portugal. This study reects the way in which doctors see themselves, not necessarily what happens, and is more important, in our point of view, if the information is tailored to the desire of the individual
Discussion
This study was carried out in an oncological centre, where informing patients about their diagnoses is an everyday matter. We only had a 40% response rate, which is rather low although similar to that obtained in at least one very important paper.2 This must be borne in mind when considering our ndings. The reason why radiotherapists participated less than other specialists is not clear. The percentage of doctors (71%) who disclose the diagnosis of cancer as their general policy or when requested by patients is smaller than that found in other studies in which questionnaires were addressed to doctors,24 even some of those carried out in southern European countries.4 But the practice of informing the family almost always (98%) is the same as what usually happens in those countries.5 Doctors most frequently indicated the reason for rarely or never disclosing the diagnosis was that it might damage the patients psychologically. It seems that those doctors prefer to protect the patients from possible psychological damage rather than to respect their autonomy. A lack of training in dealing with requests for information was not suggested as a reason for these responses. Doctors whose experience is not to have frequent requests for information feel that this happens because the patients are satised with the information they get or because they just do not want more information at all. Indeed, 87% think that patients are satised with the information provided and this percentage is higher than those who inform their patients as a general policy or when requested. The comments also show a concern for the patients protection: inform with sensitivity and gentleness; without coldness; inform those we think have sufcient psychological and intellectual resources; the need for psychological support; the information can cause depression; never use the word cancer. Again, a decision not to inform seems to be due not to a lack of training or difculty in dealing with the situation but to have its roots in a protective attitude to the patients, in order not to affect them psychologically and may be understood as what they really want. In fact, in a study conducted in Spain,6 with a culture similar to that of Portugal, of the 68% of 97 patients
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Diagnosis disclosure in a Portuguese oncological centre patient. So, it is also very important to know what Portuguese patients think about medical information issues, not only disclosure of the diagnosis but also about the prognosis and their participation in therapeutic decisions. The research on these topics is very important and is not extensive. Most of the medical literature providing practical advice is not research based.10 To explain the differences in attitude between the countries in what concerns cancer diagnosis disclosure, cultural causes have been indicated. However, perhaps these cannot explain, at least completely, those differences, because if we go back to the 1950s and 1960s we nd that in the USA most doctors used not to disclose a cancer diagnosis to their patients, but nowadays almost all do so.2 The reasons for this change are certainly many: the spread of information in the media about cancer treatment advances (real or not) and the treatment options available in some cases, where the choice only depends on patients wish (for example, conservative breast surgery); the spread of information on patients rights and the growing demand for quality of medical services; the patients enrolment in research protocols demanding informed consent; and legal matters that involve the medical profession. These matters are progressively arising in Portugal and other countries, and we believe that, as time goes by, the picture concerning cancer diagnosis disclosure will be similar to that already present in the USA and northern European countries.
39
References
1 Reiser SJ. Words as scalpels: transmitting evidence in the clinical dialogue. Ann Intern Med 1980; 92: 83742. 2 Novack DH, Plumer R, Smith RL, Ochitill H, Morrow GR, Bennett JM. Changes in physicians attitudes toward telling the cancer patient. J Am Med Assoc 1979; 241: 897900. 3 Loge JH, Kaasa S, Ekeberg , Falkum E, Hytten K. Attitudes toward informing the cancer patient a survey of Norwegian physicians. Eur J Cancer 1996; 32A: 134448. 4 Thomsen O, Wulff HR, Martin A, Singer PA. What do gastroenterologists in Europe tell cancer patients? Lancet 1993; 341: 47376. 5 Mystakidou K, Liossi C, Viachos L, Papadimitrou J. Disclosure of diagnostic information to cancer patients in Greece. Palliat Med 1996; 10: 195200. 6 Corts CC, Olarte JMN. Questioning diagnosis disclosure in terminal cancer patients: a prospective study evaluating patients responses. Palliat Med 1994; 8: 3944. 7 Estap J, Palombo H, Hernndez E et al. Cancer diagnosis disclosure in a Spanish hospital. Ann Oncol 1992; 3: 45154. 8 Surbone A. Truth telling to the patient. J Am Med Assoc 1992; 268: 166162. 9 Buckman R. Communication in palliative care: a practical guide. In: Doyle D, Hanks GWC, MacDonald N eds. Oxford textbook of palliative medicine, 2nd edn. Oxford: Oxford University Press, 1998: 4761. 10 Ptacek JT, Eberhardt RL. Breaking bad news. J Am Med Assoc 1996; 276: 496502.
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J Ferraz Gonalves and S Castro
Appendix
Diagnosis disclosure survey Age: ............................................................................ Gender: ...................................................................... 1. Do you disclose the diagnosis to cancer patients? Yes Rarely No At the patients request Speciality: .................................................................... Service: ........................................................................
2. If the answer was No or Rarely, indicate the reasons: You nd difcult to disclose the diagnosis You were not prepared to deal with this information You do not nd useful to the patient to know that information The disclosure might damage the patient psychologically You do not have time enough Other Specify: 3. Do you disclose the diagnosis to the family of cancer patients? Yes No
4. Do you think that your patients are satised with the information you give them? Yes No 5. Do your patients often request more information from you? Yes No
(if you answered Yes, go to question 7) 6. You think your patients do not request more information from you often, because: They are satised with the information they have been given They are not at ease to ask questions They do not wish more information They feel you do not have enough time to talk to them They think they will not understand the information you can give Other Specify:
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Diagnosis disclosure in a Portuguese oncological centre 7. Do you think patients should participate in treatment decisions? Yes No If your answer is Yes, indicate the alternative(s): To preserve the patients autonomy To make easier the adherence to treatment To protect the doctor from legal problems To allow the patient to prepare himself to adverse effects To allow the patient to refuse the treatment eventually Other Specify: If you answered No, indicate the alternative(s): It is difcult for you to discuss treatment with patients You think it is not useful to patients You do not have enough time to discuss treatment with the patients The discussion might damage the patients psychologically Other Specify: 8. Do you think that the family should participate in the decisions concerning treatment? Yes No 41
27
breaking bad news: experiences and preferences of advanced cancer patients at a portuguese oncology centre
ferraz gonalves, gata marques, snia rocha, pedro leito, teresa mesquita, susana moutinho
Palliative Medicine (2005); 19:526-531
Palliative Medicine 2005; 19: 526 /531
Breaking bad news: experiences and preferences of advanced cancer patients at a Portuguese oncology centre
gata Marques, So Ferraz Gonc nia Rocha, Pedro Leita o, Teresa Mesquita and Susana Moutinho alves, A Palliative Care Unit, Portuguese Institute of Oncology, Oporto The disclosure of information to patients about diagnosis and prognosis and other aspects of care is still a matter of debate. We have conducted a study in advanced cancer patients about their experiences and preferences concerning this issue. A questionnaire was developed and completed during the first appointment in the outpatient clinic of an oncology centres palliative care unit, before the patient had any contact with the staff of the unit. The study was conducted on a convenience sample of 47 patients. We found that 34 (72%) of those patients thought they had been informed of their diagnosis, most of them by the hospital doctor. However, not all stated the diagnosis in a manner clearly showing that they were aware of the nature of their disease. Most patients were with a family member when the diagnosis was disclosed, which is what the majority had preferred. Of the 13 uninformed patients, only one preferred to remain uninformed. Most patients (89%) participated in decisions concerning treatment, although only 68% thought they should have participated. Some 39 patients (83%) were informed that they were being referred to the palliative care unit, but surprisingly only eight had received an explanation of the units function. We concluded that, although most patients had been informed of their disease, there remains many problems, the most important of which, in our view, is the difference between the information provided and the patients needs. stico o progno stico e outros aspectos dos A revelac a o da informac a o sobre o diagno ainda um assunto em debate. Realiza mos um estudo em doentes com cancro cuidados e ncias e prefere ncias no que diz respeito a este tema. Foi avanc ado sobre as suas experie rio que foi aplicado na primeira consulta externa de uma unidade desenvolvido um questiona gico, antes de terem contacto com o pessoal da de cuidados paliativos de um centro oncolo ncia de 47 doentes. unidade. O estudo foi realizado numa amostra de convenie mos que 34 (72%) desses doentes pensavam que tinham sido informados do Constata stico, a maioria pelo me dico do hospital. Contudo, nem todos nomearam o seu diagno stico de um modo que mostrasse claramente que tinham noc diagno a o da natureza da stico foi sua doenc a. A maioria dos doentes estava com um familiar quando o diagno um revelado e era assim que a maior parte preferia. Dos 13 doentes na o informados so preferia manter-se sem informac a o. A maior parte dos doentes (89%) participou nas uticas, embora so 68% pensasse que devia ter participado. Trinta e nove deciso es terape doentes (83%) foram informados de que tinham sido referenciados para a unidade de oito tinham tido uma explicac cuidados paliativos, mas surpreendentemente so a o sobre a func mos que embora a maioria dos doentes tenha sido informada da a o da unidade. Conclu ainda muitos problemas, sendo o mais importante, do nosso ponto de vista, sua doenc a ha a diferenc a entre a informac a o prestada e as necessidades dos doentes. Palliative Medicine 2005; 19: 526 /531
Key words: breaking bad news; cancer patients; cultural issues; information disclosure; palliative care patients
Address for correspondence: Dr Ferraz Gonc alves, Unidade de Cuidados Continuados, Instituto Portugue s de Oncologia, Rua Dr Anto nio Bernardino de Almeida, 4200-072 Porto, Portugal. E-mail: ferrazg@netcabo.pt
# 2005 Edward Arnold (Publishers) Ltd 10.1191/0269216305pm1070oa
Breaking bad news 527
Introduction
The information delivered to cancer patients is still a matter of controversy, with wide cultural differences. In northern European countries,1,2 and the US,3 most doctors disclose the diagnosis as standard practice, but in southern and eastern European countries,2,4,5 the attitude is more paternalistic and patients are often protected from such information. However, even in those countries where the usual practice is now to disclose the diagnosis, a few decades ago the attitude was the opposite.3 This shows that the problem of information can change with time. There are also differences between countries relative to patients and families preferences for the type of information they require. A study in a palliative care setting comparing attitudes in Spain and Canada,6 concluded that the majority of Canadian patients preferred to be clearly informed, while the Spanish patients placed less value on full disclosure. In the same study, family members in Canada agreed with the detailed information to patients, while in Spain 89% of family members indicated that full disclosure was not important to the patient. A few years ago, we conducted a survey of doctors at the Oporto Centre of the Portuguese Institute of Oncology concerning the disclosure of diagnoses to patients.7 In that study, 71% of doctors stated that they always, or at the patients request, disclosed a cancer diagnosis and most doctors who rarely or never disclosed did not do so because they thought that the information could be psychologically deleterious. However, uncertainty can be worse than bad news,8 and some patients assume that a non-threatening diagnosis would be disclosed to them and the absence of such a disclosure is taken to indicate that their condition must be serious.9 Non-disclosure isolates patients as it excludes them from the discussion of problems that probably concern them most. On the other hand, there is a minority of patients who prefer to remain uninformed, and that must be respected as that is the strategy they have evolved to maintain hope. For those who lose hope of a cure or longer life due to the disclosure, hope can be kept alive through other aspects, such as their physician not abandoning them, their remaining free from significant suffering, being with their family and close friends and having time to settle matters important to them. That survey reflected the view of doctors, which can be very different to patients views. Therefore, the obvious next step was to ask patients for their opinion concerning the quantity and quality of information they receive from health professionals and their preferences. Cultural issues are relevant factors in the attitudes of doctors, patients and their families in relation to the disclosure of information. That is why it is important to add data
from different countries, and that is the reason providing justification for this study.
Methods
A survey was conducted between January 2002 and June 2003 on a convenience sample of patients referred to the outpatient clinic of our palliative care unit.10 This is a palliative care unit included in an oncology centre; therefore all patients had cancer as their primary diagnosis. All patients were aged 15 or over, as younger patients are treated in the paediatric service. A questionnaire was specifically designed for this study to acquire the information considered relevant in an exploratory survey. The aim of the survey was to obtain patient preference regarding information and to compare this with what actually occurs. The broad topics of the questionnaire included: who should be informed first when a life threatening disease like cancer is diagnosed; who should and who actually did convey the information; where the information was and where it should have been conveyed; who was and who should have been with the patient; participation in the treatment decision-making process; information provided on palliative care; and a request to name the diagnosed disease. Patients were addressed when they arrived for the first time at the outpatient clinic, before they had any contact with the health professionals of the unit. Psychology students undergoing long-term training in the unit presented the questionnaire to the patients. Patients that were very frail, bedridden or suffering cognitive failure, as assessed by the shortened version of the Confusion Assessment Method,11 were excluded. A descriptive study of all variables included in the study was performed. Chi-square and Fishers exact test were used to compare categorical variables with the status of informed or not informed patients. Age and follow-up time at the oncology centre, before admission to the palliative care unit, were compared between informed and uninformed patients using the Mann / Whitney U -test. The ethics committee of the hospital approved this study.
Results
The survey included 47 patients, 21 males (45%) and 26 females (55%); their median age was 66 years (range: 21 /86 years); 39 were married (83%), six single (13%) and two widowed (4%). The median follow-up time at the oncology centre before admission to the palliative care unit was 16 months (range: 2 /195).
F Gonc alves et al.
Table 2 Actual experience and preferred option of the 34 informed patients on who should be with them when the diagnosis is disclosed
Actual experience n (%)* Family member Friend Alone Other professionals Other patients Indifferent 22 2 8 8 0 / (65) (6) (24) (24) (0) Preferred option n (%) 19 0 3 1 1 7 (61) (0) (10) (3) (3) (23)
528
All patients preferred the questions to be read aloud by the psychology students instead of filling the questionnaires in themselves. Thirty-four patients (72%) stated that they had been informed and 13 (28%) that they had not been informed of their diagnosis. Disclosure of the diagnosis Twenty-six (55%) stated that patients should be the first person to be informed, whereas 21 (45%) preferred a family member or a friend. Most patients (41 /87%) thought that the information should be disclosed by a doctor and no one chose a nurse or a social worker. Details regarding what actually occurred and the preferred options for diagnosis disclosure can be seen in Table 1. Nineteen patients (56%) stated that they were surprised with the information, while 15 (44%) suspected the diagnosis. Most patients (68%) received the information at the outpatient clinic, only two received it in an inpatient setting, three at home and one in another place; the three patients who received the information at home were among those informed by a family member, as expected. Most patients preferred to be with a family member when the diagnosis was disclosed and this was what actually occurred, but there were differences between the preferred option and the actual experience (Table 2). We did not find any correlation between information and sex, marital status, age or the follow-up time at the oncology centre before admission to the palliative care unit. Information and participation in treatment decisionmaking process Forty-two patients (89%) were always informed about treatment and two sometimes; therefore only three (6%) were never informed. Twenty-nine patients (62%) always participated in decisions regarding treatment and two participated sometimes; 15 (32%) never participated in decisions regarding treatment (one piece of data missing). Only 32 (68%) thought they should participate in those decisions, 23 (49%) thought that close family members should participate, and 10 (21%) that only doctors should
Table 1 Who should communicate information about diagnosis? Actual experience and preferred options of the 34 informed patients
Actual experience n (%) Family doctor Hospital doctor Any doctor Psychologist Nurse Social worker Family member Other 8 19 / 0 2 0 4 1 (24) (56) (0) (6) (0) (12) (3) Preferred option n (%) 17 10 3 1 0 0 0 3 (50) (29) (9) (3) (0) (0) (0) (9)
*The sum of the actual experience items does not total 34 (or 100%) because some patients were with more than one person.
take the decisions. Seven patients (15%) refused proposed treatments. Effectiveness of the information For 19 patients (56%), the information was disclosed in an acceptable manner, clearly and sensitively, whereas 15 (44%) found the disclosure poorly carried out. However, none of the latter commented further on why they deemed it incorrect. Only one of 13 uninformed patients preferred to remain so. This group of patients was not informed because they were not at ease to ask, the information was refused, they felt they were tricked, the professionals tried not to answer the questions or the information was unclear. On the other hand, five of the 34 informed patients preferred that they had not been informed. Therefore, only six of the 47 patients did not want to know (Table 3). The 34 informed patients stated they had one of the following: cancer / 15 (44%); a tumour / 10 (29%); a bad disease / one (3%); other / seven (21%); do not know / one (3%). The 13 uninformed patients stated they had one of the following: cancer / two (15%); tumour / 0; other / four (31%); do not know / seven (54%). If we consider all patients stating cancer, tumour and bad disease to be informed and all patients stating they do not know or other to be uninformed then the results for informed patients are as follows: 26 (76%) are really informed and eight (24%) are not informed, and for uninformed patients: two (15%) are informed and 11 (85%) are not informed; the
Table 3 Information obtained and patients preferences
Patients preferences To be informed Not to be informed n (%) n (%) Informed patients (n 0/34) Uninformed patients (n 0/13) Total (n 0/47) 29 (85) 12 (92) 41 (87) 5 (15) 1 (8) 6 (13)
Breaking bad news 529 difference between the two groups was significant (P B/0.001) (Table 3). Regarding the referral to palliative care, 39 patients (83%) were informed of the referral, but only eight (17%) had received an explanation regarding the palliative care unit. this preference was limited to older patients. The encouragement to participate in treatment decisionmaking can be associated with higher levels of anxiety, which can persist for at least two weeks.19 In the previous study of doctors at our hospital,7 91% thought that patients should participate in the decisions regarding treatment, which was a higher percentage than that recorded for doctors who always, or on request, informed patients (70%); this seems a contradictory fact given that patients need information to decide rationally; it appears to be the contrary to the patients wishes as observed herein. Sometimes doctors are not very effective in informing patients, as shown by the difference recorded between the information delivered and the patients needs, i.e., there were patients informed that did not want to be informed and patients not informed that had wanted to be informed. These observations are very important because the issue is not the disclosure of information but matching it to the will of patients. Also, the surprise that the diagnosis caused in many patients suggests a lack of appropriate patient preparation concerning the possibility of a diagnosis of cancer during the period of diagnostic tests.18 Furthermore, many patients thought they were poorly informed, without commenting further on why they thought so. This is an important issue because a poor or insensitive disclosure of information may have a negative emotional impact. Patients satisfied with diagnosis communication reported less emotional distress than patients who would have preferred different.18 There are, however, other aspects, besides the way the information was disclosed, which are considered of greater importance, such as emotional support and a shorter period of time between seeking medical assistance and the confirmation of cancer.13,17,18 Also important for patient emotional support is the certainty that the physician will not abandon the patient and will be available to answer all questions.13 The communication of a poor prognosis is an even more difficult task that doctors often avoid. That is probably the explanation why only a few patients were aware of why they had been referred to the palliative care unit, even when they knew their diagnosis and participated in the treatment decisions. This is not exclusive to our hospital.19,20 For example, Cassileth et al . found that more patients receiving curative radiotherapy tended to provide a correct diagnosis than patients receiving palliative radiotherapy,20 which was also interpreted by the authors as being due to the difficulties that doctors have communicating an adverse prognosis. Although physicians often state that non-disclosure is a means of protecting patients, in fact there is a reluctance to give bad news, especially in the transition from curative or life prolonging therapy to symptomatic treatment.21 An
Discussion
The percentage of patients considering themselves to be informed (72%) is similar to the percentage of doctors (71%) that always, or at the patients request, disclosed the diagnosis in a former study carried out at our hospital.7 This number is higher than that observed in a Spanish study about ten years ago, where only 32% of the patients with advanced cancer had been informed of the nature of their disease.12 This is surprising because Spanish culture is deemed to be similar in many aspects to Portuguese culture. It seems unlikely that the ten years separating these two studies can explain the difference. Moreover, 42% of the uninformed patients did not want to receive more information,12 which again contrasts with our observation that only one of the 13 uninformed patients (8%) clearly preferred to remain uninformed. The reasons why those patients were not informed were related to the doctors attitude and a lack of proactive effort to find out the patients information needs, which can be inferred from the manner in which the patients answered this question. On the other hand, five of the informed patients preferred that the information had not been disclosed. Therefore, only a minority of the patients did not want to be informed. Usually patients prefer to be informed by a doctor, and most prefer the family doctor, probably because they are more familiar with them, as patients do not like to be informed by unknown doctors.13 However, most are informed by a hospital doctor, as demonstrated in this and other studies.14 16 Doctors are, in fact, the preferred person to convey the information.17,18 The study of Yun et al .,17 which explores the reasons for this preference, showed that the most important factor is the doctors understanding of the disease and capacity to explain the entire situation; other reasons included trust placed in the doctor, the doctors awareness of the patients emotional, psychological, social and physical situation, and the duty of doctors to provide information. Most patients were informed about treatments and only a minority did not participate in decisions concerning those treatments. But many patients think that they should not participate in those decisions and that only doctors should make such decisions, as observed in other studies;8,11 although in one study,8
F Gonc alves et al. Acknowledgements This study was supported in part by the North Section of the Portuguese League Against the Cancer.
530
alternative or complementary explanation for these observations is denial amongst patients.22
Conclusion References
One important limitation of this study is the small number of patients, which raises questions about the external validity of the data and whether the findings can be extrapolated to Portuguese cancer patients as a whole. This said, we tentatively conclude that most Portuguese cancer patients want to be informed of their diagnosis and want to participate in decisions regarding treatment. However, there are also some patients who do not want that, mainly in relation to treatment decision-making. Most patients wish to be with a family member, but not with other health professionals. Some patients stated they had been informed but gave ambiguous answers when asked to name their disease, which does not necessarily mean that they were wrong but casts doubt on the correct nature of their information. Communicating with cancer patients and, in particular, breaking bad news is a very important aspect of the patient /doctor relationship. However, it is often neglected in the training of doctors. Many people, including health professionals, think that the art of communication is a natural skill, ignoring the fact that, just as with other aspects of patient care, it can be learned. There are many general guidelines published on how to break bad news,23 28 which provide general basic knowledge on how to communicate properly, but it is also necessary to learn via practice, through basic programmes,29,30 with follow-up and consolidation.31 Perhaps the most important findings of this study, also verified in all other studies on the problem of information disclosure, are the large differences observed in patients preferences. Even when there is a clear preference on a particular aspect, there is never unanimity. Therefore, the data provided by studies of information preferred by patients in different populations should be seen only as marking out trends or general indications, because in the presence of a particular patient we do not know what he or she wants before we try to find out. Patient preference should not be assumed based on these general data. These studies, important as they are, show population data, which do not necessarily encompass individual needs. The findings of this work can be relevant to anyone working with cancer patients. It adds data relative to patients of a southern European environment, which does not seem to match, at least in those aspects statistically handled, other cultures deemed to be similar, such as that of neighbouring Spain.
/, Falkum E, Hytten K. 1 Loge JH, Kaasa S, Ekeberg Attitudes toward informing the cancer patient / a survey of Norwegian physicians. Eur J Cancer 1996; 32A: 1344 /48. 2 Thomsen O, Wulff HR, Martin A, Singer P. What do gastroenterologists in Europe tell cancer patients? Lancet 1993; 341: 473 /76. 3 Novack DH, Plumer R, Smith RL, Ochitill H, Morrow GR, Bennet JM. Changes in physicians attitudes toward telling the cancer patient. JAMA 1979; 241: 897 /900. 4 Estape J, Palombo H, Herna ndez E et al . Cancer diagnosis disclosure in a Spanish hospital. Ann Oncol 1992; 3: 451 /54. 5 Mystakidou K, Liossi C, Viachos L, Papadimitriou J. Disclosure of diagnostic information to cancer patients in Greece. Palliat Med 1996; 10: 195 /200. 6 Fainsinger RL, Nu n ez-Olarte JM, Demoissac DM. The cultural differences in perceived value of disclosure and cognition: Spain and Canada. J Palliat Med 2003; 19: 43 /48. 7 Ferraz Gonc alves J, Castro S. Diagnosis disclosure in a Portuguese oncological centre. Palliat Med 2001; 15: 35 / 41. 8 Cassileth BR, ZurpKis RV, Sutton-Smith K, March V. Information and participation preferences among cancer patients. Ann Intern Med 1980; 92: 832 /36. 9 McIntosh J. Patients awareness and desire for information about diagnosed but undisclosed malignant disease. Lancet 1976; ii: 300 /303. 10 Ferraz Gonc alves JA. A Portuguese palliative care unit. Support Care Cancer 2001; 9: 4 /7. 11 Inouye SK, van Dick CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. Ann Intern Med 1990; 113: 941 /48. 12 Centeno-Corte s C, Nu n ez-Olarte JM. Questioning diagnosis disclosure in terminal cancer patients. Palliat Med 1994; 8: 39 /44. 13 Sardell AN, Trierweiler SJ. Disclosing the cancer diagnosis: procedures that inuence patient hopefulness. Cancer 1993; 72: 3355 /65. 14 Chan A, Wooddruff RK. Communicating with patients with advanced cancer. J Palliat Care 1997; 13: 29 /33. 15 Lind SE, Good MJD, Seidel S, Csordas T, Good BJ. Telling the diagnosis of cancer. J Clin Oncol 1989; 7: 583 /89. 16 Barnett MM. Effect of breaking bad news on patients perceptions of doctors. J R Soc Med 2002; 95: 343 /47. 17 Yun YH, Lee CG, Kim S, et al . The attitudes of cancer patients and their families toward the disclosure of terminal illness. J Clin Oncol 2004; 22: 307 /14.

18 Butow PN, Kazemi JN, Beeney LJ, Grifn AM, Dunn SM, Tattersall MHN. When the diagnosis is cancer: patient communication experiences and preferences. Cancer 1996; 77: 2630 /37. 19 Gattellari M, Voigt KJ, Butow PN, Tattersall MHN. When the treatment goal is not cure: are cancer patients equipped to make informed decisions? J Clin Oncol 2002; 20: 503 /13. 20 Cassileth BR, Volckmar D, Goodman RL. The effect of experience on radiation therapy patients desire for information. Int J Radiat Oncol Biol Phys 1980; 6: 493 /96. 21 Falloweld LJ, Jenkins VA, Beveridge HA. Truth may hurt but deceit hurts more: communication in palliative care. Palliat Med 2002; 16: 297 /303. 22 Jones JS. Telling the right patient. Br Med J 1981; 283: 291 /92. 23 Faulkner A, Maguire P, Regnard C. Breaking bad news / a ow diagram. Palliat Med 1994; 8: 145 /51. 24 Richards MA, Ramirez AJ, Degner LF, Falloweld LJ, Maher EJ, Neuberger J. Offering choice of treatment to patients with cancer. A review based on a symposium held at the 10th Annual Conference of the British Psychosocial Oncology Group, December 1993. Eur J Cancer 1995; 31A: 112 /16. Girgis A, Sanson-Fisher RW. Breaking bad news: consensus guidelines for medical practitioners. J Clin Oncol 1995; 13: 2449 /56. Falloweld L. Giving sad and bad news. Lancet 1993; 341: 476 /78. Creagan ET. How to break bad news / and not devastate the patient. Mayo Clin Proc 1994; 69: 1015 /17. Buckman R. How to break bad news . London: Pan Books, 1992. Falloweld L, Jenkins V, Farewell V, Saul J, Duffy A, Eves R. Efcacy of a cancer research UK communication skills training model for oncologists: a randomised controlled trial. Lancet 2002; 359: 650 /56. Jenkins V, Falloweld L. Can communication skills training alter physicians beliefs and behaviour in clinics? J Clin Oncol 2002; 20: 765 /69. Razavi D, Merckaert I, Marchal S, et al . How to optimize physicians communication skills in cancer care: results of a randomized study assessing the usefulness of post-training consolidation workshops. J Clin Oncol 2003; 21: 3141 /49.
25
26 27 28 29
30
31
sntese
Tomando estes dois estudos em conjunto pode concluir-se que a informao prestada aos doentes no est muitas vezes de acordo com os seus desejos. No primeiro estudo, uma razo frequentemente invocada pelos mdicos para no dar a informao aos doentes a possibilidade de lhes causar dano psicolgico o que est em contradio com os dados da investigao como referido anteriormente. No esclarecer os doentes quando esse o seu desejo pode ter boas intenses e frequentemente apoiado pelos familiares. Pode, porm, representar uma defesa dos prprios mdicos porque a comunicao reveste-se de aspectos muitos difceis, sobretudo dar ms notcias. A investigao, no entanto, sugere que o facto de os doentes no terem uma ideia, pelo menos em termos gerais, da sua situao acarreta muitas consequncias. Entre essas consequncias esto internamentos desnecessrios, aumento da proporo de mortes hospitalares e referenciaes tardias para cuidados paliativos ou mesmo a sua ausncia [6]. Pode haver tambm consequncias psicolgicas, como desconfiana a sentimentos de abandono [6]. No segundo estudo verificou-se que 87% dos doentes desejavam ser informados, enquanto s 72% tinham sido informados. Os que no tinham sido informados referiram que no estavam vontade para perguntar, a informao foi recusada, foi pouco clara ou porque se sentiram enganados. Verificou-se tambm que alguns dos doentes que foram informados teriam preferido no o ter sido e vice-versa. Este ponto muito importante porque o principal no ser ou no ser informado mas ver satisfeitas as
suas necessidades informativas para melhor lidar com a situao. Essas necessidades so variveis e alguns doentes lidam melhor com a situao sem informao. H ainda a acrescentar que a informao no pode ser vista como pontual, mas sim como progressiva e contnua, podendo os desejos do doente mudar com o tempo. A constatao de que muitos doentes so referenciados para cuidados paliativos sem que lhes seja dada uma explicao da razo e do significado desse facto refora a necessidade de que no primeiro encontro se explore essa questo. Verificou-se tambm que h doentes que no tm informao, mas que por vrias razes, que no tm a ver com o seu desejo, no questionam os profissionais. Por isso, os profissionais devem ter uma atitude proactiva. O facto de no se prestarem as informaes que os doentes desejem de forma a poderem tomar decises informadas lesivo dos seus interesses e dos seus direitos. Na realidade, sem essa informao no h consentimento informado, condio indispensvel para se cumprir o princpio da tica biomdica do respeito pela autonomia. Alm da questo tica de no informar, h tambm violao da legislao, quer do cdigo penal quer do cdigo deontolgico dos mdicos. Muito do que hoje recomendado sobre o processo da comunicao e da informao baseia-se na experincia e no bom senso e no predominantemente na investigao, mas certamente que em primeiro lugar h que saber que informao o doente j tem [5]. O processo de comunicao eficaz requer que no haja alteraes cognitivas significativas. O processo de avaliao da conscincia o objecto do captulo seguinte.
referncias
1 Grunfeld E, Folkes A, Urquhart R. Do available 4 questionnaires measure the communication factors that patients and families consider important at end of life? J Clin Oncol 2008;26:3874-3878. Ferraz Gonalves, Castro S. Diagnosis disclosure in a Portuguese oncological centre. Palliative Medicine 5 2001;15: 3541. Novack DH, Plumer R, Smith RL, Ochitill H, Morrow GR, 6 Bennett JM. Changes in physicians attitudes toward telling the cancer patient. J Am Med Assoc 1979; 241: 897900. Ferraz Gonalves, Marques A, Rocha S, Leito P, Mesquita T, Moutinho S. Breaking bad news: experiences and preferences of advanced cancer patients at a Portuguese oncology centre. Palliative Medicine 2005; 19: 526-/531. Buckman R. How to break bad news: a guide to health-care professionals. Pan Books 1994. Innes S, Payne S. Advanced cancer patients prognostic information preferences: a review. Palliat Med 2009; 23:29-39.
3
AVALIAO DA CONSCINCIA
avaliao da conscincia
O termo conscincia tem sido tomado ao longo do tempo em sentidos diversos. Tem sido objecto de reflexo por diversos filsofos [1] e de estudo cientfico. Tem sido considerada do ponto de vista moral, a chamada conscincia moral. Mais recentemente, tm sido as neurocincias a dominar este campo. J muito antigo o conceito de que a conscincia depende de uma funo cerebral intacta. De facto, j Hipcrates o considerava [2]. A conscincia foi definida por William James em 1890 como o estado de conhecimento de si prprio e do ambiente [3]. A conscincia tem dois componentes: a viglia e o contedo. A viglia o estar acordado. aquilo a que normalmente se chama estar consciente. No entanto, esse aspecto apenas no nos diz nada sobre a capacidade cognitiva. H estados em que os indivduos esto acordados, mas tm um capacidade cognitiva reduzida ou nula, como acontece nos doentes com delirium, demncias ou no estado vegetativo persistente. Nestas situaes o estado de viglia pode estar normal ou quase normal mas o contedo est mais ou menos afectado. Para se poder avaliar o contedo da conscincia necessrio, porm, um certo grau de viglia. Foram desenvolvidos vrios mtodos de avaliao destas duas dimenses da conscincia. No havia, porm, nenhum instrumento desenvolvido especificamente para a populao em cuidados paliativos para avaliar o estado de viglia. Os intrumentos usados foram desenvolvidos para outras situaes referidas no artigo inserido neste captulo, alguns
dos quais no foram validados. Por isso se validou o presente instrumento que simples, intuitivo, de fcil apredizagem e que demora apenas alguns segundos a aplicar. Alm disso, no carece de qualquer esforo da parte dos doentes. Estas caractersticas tornam este instrumento adequado para ser usado em cuidados paliativos e para ser integrado no sistema que nos propusemos desenvolver. A avaliao da conscincia indispensvel no contacto com os doentes, nomeadamente no primeiro encontro. Sem essa avaliao no possvel estar-se seguro da fiabiliadade da avaliao subsequente. Assim, se o estado de viglia no for obviamente normal necessrio determinar o seu nvel pelo mtodo validado apresentado a seguir. Se o nvel de viglia for suficiente para se fazer a avaliao do contedo da conscincia e se este no for obviamente anormal deve avaliar-se a funo cognitiva. Neste captulo apresenta-se a seguir o mtodo de avaliao do estado de viglia, apresentando um artigo j publicado Validation of a Consciousness Level Scale for Palliative Care em que descreve uma escala e o processo da sua validao desenvolvida por ns especificamente para cuidados paliativos. Segue-se a descrio do mtodo escolhido para avaliao da funo cognitiva e a justificao para a sua escolha.
validation of a consciousness level scale for palliative care

f. gonalves, mj bento, m. alvarenga, i. costa and l. costa
Palliative Medicine (2008); 22:724
Validation of a Consciousness Level Scale for Palliative Care

F Gonalves Palliative Care Unit Network, Portuguese Institute of Oncology, Porto, MJ Bento Epidemiology Service, Portuguese Institute of Oncology, Porto, M Alvarenga, I Costa and L Costa Palliative Care Service, Portuguese Institute of Oncology, Porto The main objective of this study is to validate a Consciousness Scale for palliative care. The scale was named Consciousness Scale for palliative care (CSPC). The validation had two phases: 1) face validity the scale was assessed by seven healthcare professionals, both doctors and nurses, experienced in palliative care; 2) reliability and construct validity performed by four investigators, two nurses and two doctors. The construct validation was performed by comparing the CSPC with a Visual Analogue Scale (VAS) of 100 mm, anchored in the terms awake and unarousable, and then with the Glasgow Coma Scale (GCS). In this study, all four observers completed 44 periods of observation relative to 38 patients resulting in a total of 176 observations. In the phase of face validation, there were no discrepancies in relation to the issue: the scale provides measures for measurement; the scale can be useful to clinical practice; the scale can improve communication among professionals and the scale is easy to use. As a measure of internal consistency, Cronbachs was found to be very high (0.99). The inter-rater reliability was also very high with an intraclass correlation coefficient of 0.99 (P < 0.001). The correlation of the CSPC to the VAS was 0.94 (P < 0.001) and the CSPC to the GCS was 0.82 (P < 0.001). The CSPC can be a very useful tool for assessing consciousness in palliative care patients. It is very ease to use, not time consuming and can be used with minimal training. Communication between professionals can be improved in the clinical setting and in the research environment. Palliative Medicine (2008); 22: 724729
Key words: consciousness; consciousness level scale; palliative care; sedation
Introduction
A large percentage of palliative care patients undergo temporary or definitive changes in their consciousness level. This can be due to the involvement of the central nervous system brought on by cancer, metabolic alterations, infections, medication or a combination of these factors. When it is caused by medication, the level of consciousness can be intentionally affected or not. When intentional, with the aim of controlling suffering, the action is called palliative sedation. Sedation in palliative care is a very important task. It has been under discussion for more than a decade. Chater et al.1 defined sedation as the intention to deliberately induce and maintain deep sleep, but not deliberately causing death, in very specific circumstances. However, the objective is to control suffering (physical or psychological
Correspondence to: Dr Ferraz Gonalves, Instituto Portugus de Oncologia, UCP-R, Rua Dr. Antnio Bernardino de Almeida, 4200-072 Porto, Portugal. Email: ferrazg@ipoporto.min-saude.pt or ferrazg@netcabo.pt
symptoms, existential distress, etc.) and not the level of sedation. Hence, the deepness of sedation should be, such as to acceptably control, the cause of suffering, which cannot be controlled by any other means. No validated palliative care scale to measure the level of consciousness exists. The absence of such a scale is one of the reasons why data from studies, such as those dealing with sedation, are difficult to compare. Therefore, a reliable consciousness level scale could improve communication between professionals, making the comparison of data of different studies easier, and it would be useful to clinical practice and research in general. The purpose of this study is to develop and validate such a scale for palliative care. The scale developed herein is called the Consciousness Scale for Palliative Care (CSPC). Consciousness has two dimensions: wakefulness and awareness.2 There are other scales that measure cognitive function, and therefore awareness, for example, the minimental state examination,3 and others. The intention of that scale is to primarily measure wakefulness and not the content of consciousness.
2008 SAGE Publications, Los Angeles, London, New Delhi and Singapore
Downloaded from http://pmj.sagepub.com by Jos Antnio Ferraz Gonalves on October 7, 2008
10.1177/0269216308094104
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Consciousness Level Scale for Palliative Care
725
Methods
This study was conducted at the Palliative Care Service of the Porto Section of the Portuguese Institute of Oncology. The study was approved by the ethics committee of the institution. As this study was non-interventional and there was no added risk to patients, a written informed consent was waived. The design of the scale To identify other existing level of consciousness scales, a MEDLINE search was done for the period January 1970 to September 2003, using the following keywords: coma scale, coma assessment, sedation scale and sedation assessment. Reference lists of the resulting articles were reviewed. Although there are many scales used in different environments, only a small number were assessed for reliability and validity, which was also observed by others.4,5 Most of them were designed for use in intensive care units (ICU) or on neurological patients. None have been designed for or studied in a palliative care setting. None of the identified scales are suited to use in a palliative care setting for a large number of reasons, the most relevant being:

nosis, metastases, sedative medication and if the patient was intentionally sedated or not. The study had two phases. In phase 1, face/content validity was carried out. Seven healthcare professionals experienced in palliative care, three doctors and four nurses, not involved in the design of the scale, applied the scale to about 20 patients each in order to familiarise themselves with it. They then answered the following questions using a five-point scale ranging from strongly agree to strongly disagree:

Does the scale measure what it is intended to measure? Can the scale be useful to clinical practice? Can the scale improve communication among healthcare professionals with regard to consciousness level? Is the scale easy to use?

Most of the scales used in ICU include the assessment of items such as anxiety or agitation.611 Other scales used in ICU have items related to compliance with mechanical ventilation.6,1113 Some scales were designed for neurological conditions; therefore, they contain items that are irrelevant to our purpose.1417 Some scales were designed to focus on particular conditions and therefore contain items that are only of relevance to such conditions.1822 Some were designed for children.23,24 Many do not have the levels of the scale clearly defined, or these are not mutually exclusive.25,26
Although the existing scales were considered inadequate for use in palliative care, they included the elements that should be used in a new scale. There are, therefore, elements common to all these scales. In fact, following the study of those scales, the CSPC was constructed based on the responses to the stimuli ranked in a logical manner. The chosen responses are mutually exclusive. The stimuli, which are common to many scales, are simple and also performed in a logical progression: first observation then, if required, vocal stimulus and finally painful stimulus. This study included bedridden patients over 18 years of age, on a convenience basis. A patient may be included more than once if observations are carried out at least 48 h apart. The data collected included age, gender, diag-
The investigators were asked to give suggestions that might improve the scale, if they thought the scale could be improved. In phase 2, reliability and construct validation were performed. Because there is not any golden standard to evaluate consciousness level against which the CSPC can be compared, a criterion validation could not be performed. Therefore, we had to perform a construct validation of the scale, comparing it with other tools we think can measure consciousness level, as is usually the case in these types of study. A visual analogue scale (VAS) and the Glasgow Coma Scale (GCS) were used, as was the case in similar studies undertaken in different settings, such as in an ICU environment.4,6,7,13 The VAS was assessed by drawing a perpendicular mark on a 100 mm horizontal line based on the terms awake and unarousable, and then the distance between the left end of the line and the mark was measured in millimetres. The data were collected by four investigators involved in the study: two doctors and two nurses. All four investigators underwent a training period with the VAS for evaluating consciousness level, to familiarise with the scale. Each patient was simultaneously observed by three investigators, one doctor and two nurses. One investigator interacted with the patient, as per the instructions set forth in the appendix, and rated the patient, whereas the other two observed and rated the patient independently: two scored using the CSPC and one using the VAS. In all, 15 min later, the other doctor performed the GCS, recording the score of each item (motor and verbal responses, and eye opening). A rotation system was used so that each healthcare professional performed all the roles a similar number of times, except with regards to the GCS, which was always performed by the doctors and always by the doctor who did not participate in the first part of evaluation.
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726 F Gonalves et al. Statistical analysis

Table 2 Distribution of consciousness scale for palliative care scores between raters
Scores 1 1st rater 1 2 3 4 5 6 9 2 0 0 0 0 2 2 9 0 0 0 0 3 0 0 5 0 0 0 2nd rater 4 0 0 1 3 0 0 5 0 0 0 0 6 0 6 0 0 0 0 0 7
Cronbachs was performed to measure internal consistency.27 The intraclass correlation coefficient was used to measure the degree of concurrence between raters.28 The association between the CSPC, VAS and GCS was evaluated using Spearmens .29 The non-parametric Wilcoxon rank sum test was used to compare CSPC values with previously identified subgroups (gender, age, use of sedatives).30
Results
In this study, all four observers made 44 periods of observation relative to 38 patients, resulting in 176 observations. None of the patients was subject to more than two periods of observation. The demographic data of those patients are detailed in Table 1. Forty-two patients (96%) were medicated with one or more drugs with sedative effects: 91% opioids, 57% neuroleptics, 43% benzodiazepines and 30% others. Six patients were intentionally sedated: 1 was at level 4, 3 at level 5 and 2 at level 6 of the scale. There was, in those patients, 100% coincidence between the two raters of the scale.
Therefore, the range of responses went from strongly agree to the middle of the scale, without any disagreements. Internal consistency As a measure of internal consistency, the Cronbachs was very high (0.99). Inter-rater reliability The scores recorded by the raters are displayed in Table 2. The same score on the scale was selected in 39 cases (89%). In the five cases where a different score was selected, the difference was always not more than one level of the scale. The degree of agreement between raters with regard to the scale was, therefore, very high, with an intraclass correlation coefficient of 0.99 (P < 0.001). There were no significant within-subject differences in subgroups (age, gender) when analyzed by the Wilcoxon rank sum text. The median age of the patients (68 years) was used to divide this item into two groups. In women and those aged over 68 years, the scores coincided. The analysis of the group that used sedatives was not performed because 96% of the patients were using them. Construct validity The correlation of the CSPC to the VAS and GCS was very high (Table 3). The correlation coefficient of the CSPC to the VAS was 0.94 (P < 0.001) for the first observer and 0.95 (P < 0.001) for the second. The correlation coefficient of the scale to the GCS was 0.82 (P < 0.001) for the first observer and 0.85 (P < 0.001) for the second. Note that the coefficient of the CSPC to
Table 3
Scales CSPC1CSPC2 CSPC1VAS CSPC2VAS CSPC1GCS CSPC2GCS
Face validity The results for face validity were as follows:

The scale measures what it is intended to measure. Mean = 1.7 (range: 1 to 2). The scale can be useful to clinical practice. Mean = 1.6 (range: 1 to 3). The scale can improve communication among healthcare professionals: Mean = 2.0 (range: 1 to 3). The scale is easy to use. Mean = 1.6 (1 to 2).
Table 1 Demographic data

No. (%) Gender Male Female Primary Gynaecologic Colorectal Head and neck Gastric Astrocytoma Lung Melanoma Other 19 (50) 19 (50) 8 6 5 3 3 2 2 9 (21) (16) (13) (8) (8) (5) (5) (24)
Correlation between scales

0.98 0.96 0.96 0.88 0.88 P <0.001 <0.001 <0.001 <0.001 <0.001
Age: median of 68 years (range: 3882).
CSPC1 and CSPC2 are the 1st and 2nd ratings of the scale. CSPC, Consciousness Scale for Palliative Care; VAS, Visual Analogue Scale; GCS, Glasgow Coma Scale.
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Consciousness Level Scale for Palliative Care the GCS was negative due to the scales scoring being inverted in relation to each other; in other words, the best score of the CSPC is the lowest, whereas the best score of the GCS is the highest.
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Discussion
An ideal assessment tool should be inexpensive, easy to learn and easy to use by doctors and nurses at bedsides. This last aspect is particularly important in palliative care because it is practised in many settings and by healthcare professionals from heterogeneous backgrounds. Yet, the assessment tool should undergo rigorous testing to show validity and reliability. Probably, the most used scale is the Ramsay Scale. This scale was developed in an ICU to control the level of sedation with alphaxalone-alphadolone and published in the British Medical Journal in 1974.25 The scale was really a secondary aspect of the article; however, since then, it has been widely used in many settings without undergoing any process of validation. This was carried out recently.31 Although that scale has been extensively used, it has been criticised for many reasons,32 the criticisms most relevant to palliative care being: the six levels of the Ramsay scale are not mutually exclusive; patients may be restless or agitated (level 1), whereas at the same time being responsive only to light physical or loud auditory stimulus (level 4 and 5) and the sedation levels are not clearly defined or fully inclusive. The goal of this study was the development and validation of a scale with the above-described characteristics, in an attempt to avoid the drawbacks of the Ramsay scale and other scales. The structure of the scale is very ease to use and the levels are clearly defined, with a phase of observation and, if required, consecutive phases of verbal interaction and of physical stimulation. The scale can be administered in a few seconds, using common and unambiguous stimuli in a logical sequence. The stimuli are also standardized, which does not happen with most scales. The inter-rater reliability of the scale was very good for all patients, with coincident scores in almost 90% of the cases, and in the few cases without coincidence, the difference was never greater than one level. In women and in patients aged over 68 years, there was complete agreement in the scores, as well as among the six patients who were intentionally sedated. As no gold standard exists for sedation, against which the CSPC could be compared to validate it, the validation of the CSPC was performed by correlating it to a VAS based on the terms awake and unarousable and the GCS, which is a scale that was designed to assess the prognosis of coma after head injury33 but which is widely used in many settings to assess the consciousness level. The correlation of the CSPC to the VAS and the GCS was very high.
There are potential limitations to the use of the CSPC. As it relies on the patients auditory and visual acuity, it is not suitable for use on patients with major impairment of these senses. The intensity of the stimuli can vary with the observer; in other words, louder voices or more firm pinching of the trapezius might eventually result in different scores. Patients can have a not normal score simply because they were normally sleeping, but this is common to all scales. Nevertheless, the CSPC can be a very useful tool for assessing consciousness in palliative care patients. It is very ease to use, not time consuming and can be performed with minimal training. Communication between healthcare professionals can be improved in the clinical setting and in a research environment by the lack of ambiguity of the levels and of the method of interaction with the patient. However, the scale should be evaluated in other locations in a palliative care setting to confirm the results achieved by this study.
References
1 Chater, S, Viola, R, Paterson, J, Jarvis, V. Sedation for intractable distress in the dying a survey of experts. Palliat Med 1998; 12: 255269. 2 Laureys, S. The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci 2005; 19: 556559. 3 Folstein, MF, Folstein, SE, McHugh, PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 188189. 4 Ely, EW, Truman, B, Shintani, A, Thomason, JW, Wheeler, AP, Gordon, S, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA 2003; 289: 29832991. 5 Jacobi, J, Fraser, G, Coursin, DB, Riker, RR, Fontaine, D, Wittbrodt, ET, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adults. Crit Care Med 2002; 30: 119141. 6 Sessler, CN, Gosnell, MS, Grap, MJ, Brophy, GM, ONeal, PV, Keane, KA, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166: 13381344. 7 Devlin, JW, Boleski, G, Mlynarek, M, Nerenz, DR, Peterson, E, Jankowski, M, et al. Motor Activity Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care. Crit Care Med 1999; 27: 12711275. 8 Riker, RR, Picard, JT, Fraser, GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999; 27: 13251329. 9 Detriche, O, Berr, J, Massaut, J, Vincent, JL. The Brussels Sedation Scale: use of a simple clinical sedation scale
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can avoid excessive sedation in patients undergoing mechanical ventilation in the intensive care unit. Br J Anaesth 1999; 83: 698701. Chaudhri, S, Kenny, GNC. Sedation after cardiac bypass surgery: comparison of propofol and midazolam in the presence of a computerized closed loop arterial pressure controller. Br J Anaesth 1992; 68: 9899. Riker, RR, Fraser, GL, Cox, PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med 1994; 22: 433440. Mallick, A, Smith, SN, Bodenham, AR. Local anaesthesia to the airway reduces sedation requirements in patients undergoing artificial ventilation. Br J Anaesth 1996; 77: 731734. Riker, RR, Fraser, GL, Simmons, LE, Wilkins, ML. Validating the Sedation-Agitation Scale with the bispectral index and Visual Analog Scale in adult ICU after cardiac surgery. Intensive Care Med 2001; 27: 853858. Wijdicks, EFM, Kokmen, E, OBrien, PC. Measurement of impaired consciousness in the neurological intensive care unit: a new test. J Neurol Neurosurg Psychiatry 1998; 64: 117119. Stanczak, DE, White, JG, Gouview, WD, Moehle, KA, Daniel, M, Novack, T, et al. Assessment of level of consciousness following severe neurological insult: a comparison of the psychometric qualities of the Glasgow Coma Scale and the Comprehensive Level of Consciousness Scale. J Neurosurg 1984; 60: 955960. Sugiura, K, Muraoka, K, Chishiki, T, Baba, M. The Edinburg-2 Coma Scale : a CSPC for assessing impaired consciousness. Neurosurgery 1983; 12: 411415. Benzer, A, Mitterschiffthaler, G, Marosi, M, Luef, G, Phringer, F, De La Renotiere, K, et al. Prediction of non-survival after trauma: Innsbruck Coma Scale. Lancet 1991; 338: 977978. Miller, DR, Martineau, RJ, Hull, KA, Vall, F, LeBel, M. Optimizing sedation following major vascular surgery: a double-blind study of midazolam administered by continuous infusion. Can J Anaesth 1994; 41: 782793. Sanchez-Izquierdo-Riera, JA, Caballero-Cubedo, RE, Perez-Vela, JL, Ambros-Checa, A, CantalapiedraSantiago, JA, Alted-Lopez, E. Propofol versus midazolam: safety and efficacy for sedating the severe trauma patient. Anesth Analg 1998; 86: 12191224. Eddleston, JM, Pollard, BJ, Blades, JF, Doram, B. The use of propofol for sedation of critically ill patients undergoing haemodiafiltration. Intensive Care Med 1995; 21: 342347. Checketts, MR, Gilhooly, CJ, Kenny, GNC. Patientmaintained analgesia with target-controlled alfentanil infusion after cardiac surgery: a comparison with morphine PCA. Br J Anaesth 1998; 80: 748751. Irwin, MG, Thompson, N, Kenny, GNC. Patientmaintained propofol sedation. Anaesthesia 1997; 52: 525530. Malviya, S, Voepel-Lewis, T, Huntington, J, Siewert, M, Green, W. Effects of anesthetic technique on side effects associated with fentanyl oralet premedication. J Clin Anesth 1997; 9: 374378. Ambuel, B, Hamlett, KW, Marx, CM, Blumer, JL. Assessing distress in pediatric intensive care environments: the COMFORT scale. J Pediatric Psychol 1992; 17: 95109. Ramsay, MAE, Savege, TM, Simpson, BRJ, Goodwin, R. Controlled sedation with alphaxalone-alphadolone. BMJ 1974; 2: 656659. De Jonghe, B, Cook, D, Appere-De-Vecchi, C, Guyatt, G, Meade, M, Outin, H. Using and understanding sedation scoring systems: a systematic review. Intensive Care Med 2002; 26: 275285. Bland, JM, Altman, DG. Cronbachs alpha. BMJ 1997; 314: 572. Anlisis de la concordancia. In: Palls, JMA, Villa, JJ, (Eds), Mtodos de investigacin: clnica e epidemiolgica, segunda edicin. Madrid: Ediciones Harcourt S.A., 2000; p. 321325. Relation between two continuous variables. In: Altman, DG, (Ed), Practical statistics for medical research. 1st ed. London: Chapman and Hall, 1991; p. 277324. Comparing groups continuous data. In: Altman, DG, (Ed), Practical statistics for medical research, 1st ed. London: Chapman and Hall, 1991; p. 179228. Yate, PM, Thomas, D, Short, SM, Sebel, PS, Morton, J. Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients of the ITU. Br J Anaesth 1986; 58: 10911099. Hansen-Flaschen, J, Cowen, J, Polomano, RC. Beyond the Ramsay Scale: need for a validated measure of sedating drug efficacy in the intensive care unit. Crit Care Med 1994; 22: 732733. Teasdale, G, Jennett, B. Assessment of coma and impaired consciousness. Lancet 1974; 13: 8184.
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Consciousness Level Scale for Palliative Care Appendix

Nvel 1 2 3 4 5 6 Level 1 2 3 4 5 6 Portuguese version Acordado/a Acorda quando chamado/a pelo seu nome e permanece acordado durante a conversao Acorda quando chamado/a pelo seu nome mas adormece durante a conversao Reage com movimentos ou abrindo brevemente os olhos, mas sem contacto visual, quando chamado/a pelo seu nome Reage a belisco no trapzio No reage English translation
729
Awake Awakens when called by his/her name and stays awake during conversation Awakens when called by his/her name but falls asleep during conversation Reacts with movement or brief eye opening, but without eye contact, when called by his/her name Reacts to trapezius muscle pinching Does not react
Procedures for assessment:

Stimulation Patient is awakened, calm or agitated, without the need for any external stimulus Patient is not spontaneously alert. Patient is called loudly by name Patient is not spontaneously alert and does not react to voice. A firm pinching of the trapezius muscle is applied Score Level 1 Levels 2, 3 and 4, according to the reaction observed Level 5 and 6, according to the reaction observed
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avaliao da funo cognitiva
A insuficincia cognitiva muito frequente nos doentes com doenas avanadas. H vrios distrbios associados insuficincia cognitiva, sendo o delirium o mais frequente na fase final da vida. Para se poder avaliar o estado cognitivo, o contedo da conscincia, necessrio que haja uma certa capacidade de estar vgil. O delirium ocorre em 28% a 83% dos doentes quando prximos do fim da vida [4]. O delirium pode ser bvio, sobretudo a sua variante hiperactiva em que h agitao psicomotora, mas numa percentagem que pode atingir os 50% pode no ser detectado. Isto deve- se a diversos motivos dos quais se destacam: a flutuao do comportamento dos doentes ao longo do dia, com este a aproximar-se do normal, em geral mais frequentemente de manh, agravando-se medida que o dia avana, tornando-se pior ao fim da tarde e noite; e a variante hipoactiva em que a agitao geralmente associada ao delirium no est presente ou ocorre episodicamente. O problema de no se detectar uma percentagem significativa dos casos de delirium no se limita aos cuidados paliativos, verificando-se frequentemente nos doentes internados em geral, sobretudo nos idosos, no ps-operatrio e nos cuidados intensivos. Por isso, foram desenvolvidos inmeros instrumentos com o fim de melhorar o rastreio e/ou o diagnstico do delirium [5]. O interesse de se fazer o rastreio do delirium reside no facto de ser reversvel em muitos casos e em poder ser indicativo, por vezes o nico sinal em doentes debilitados, de uma ocorrncia que complique o estado dos doentes, como uma infeco ou hipercalcemia, por exemplo.
O mtodo de rastreio mais conhecido e usado sem dvida o Mini Exame do Estado Mental (Mini-Mental-Status Examination) [6]. Este instrumento tem uma validade excelente para detectar alteraes cognitivas e para avaliar a sua gravidade, podendo assim servir para avaliar a sua evoluo, mas no permite o diagnstico de delirium. O problema principal quanto a ns o de exigir uma participao importante dos doentes, nomeadamente a realizao de um desenho. Num estudo recente, Fayers et al. concluram que possvel reduzir o nmero de perguntas mantendo uma boa acurcia para o rastreio de alteraes cognitivas [7]. Outro instrumento muito usado pela sua simplicidade, sobretudo na sua verso curta tambm designada algoritmo, o Mtodo de Avaliao da Confuso (MAC) [8]. composto apenas por quatro itens e no exige qualquer esforo do doente, j que pela observao do comportamento e das respostas do doente durante a consulta que o profissional de sade diagnosticar ou no delirium. Este mtodo permite o diagnstico de delirium ao contrrio do Mini-Exame do Estado Mental (MEEM), mas por outro lado no quantitativo, pelo que no permite medir a gravidade nem a evoluo da situao. Este mtodo foi recentemente validado em cuidados paliativos [9]. No entanto, o MAC foi desenhado para ser aplicado baseado em observaes realizadas durante uma avaliao cognitiva formal com instrumentos como o MEEM [8,10]. O MAC quando aplicado por enfermeiros sem uma avaliao cognitiva formal revelou uma sensibilidade baixa, embora mantendo uma especificidade alta [11]. O MAC foi recentemente validado em portugus, embora no Brasil [12]. A verso validada foi a verso completa e no o algoritmo, mas este apenas uma forma resumida da verso completa. Por outro lado, tem sido usado por ns desde h cerca de 15 anos. Por todas estas razes, ser um mtodo simples, validado em portugus e praticado por ns desde h muito tempo ser o mtodo adoptado neste sistema (quadro 2), reconhecendo que no est isento de problemas. A avaliao destes 2 aspectos da conscincia apresentados neste captulo que permitiro decidir a forma de avaliao a efectuar, cujas variantes se apresentam nos 2 captulos seguintes.
Quadro 2 | Mtodo de avaliao da confuso. 1 Incio agudo e curso flutuante H evidncia de uma alterao aguda do estado mental do doente; O comportamento anormal flutua ao longo do dia; (estas informaes obtem-se geralmente de um membro da famlia ou de outra pessoa). 2 Inateno O doente tem dificuldade em manter a ateno. 3 Pensamento desorganizado O doente tem pensamento desorganizado ou incoerente, tal como conversao irrelevante ou desconexa, fluxo de ideias pouco claro ou ilgico ou muda imprevisivelmente de assunto para assunto. 4 Alterao do nvel de conscincia Globalmente o nvel de conscincia poderia classificar-se como: alerta (normal), vigilante (hiperalerta), letrgico (sonolento, acorda facilmente), estupor (acorda dificilmente), coma (no acorda).
O diagnstico de delirium requer a presena de 1 e 2 e de 3 ou 4.
referncias
Van Gulick R. Consciousness. Em Stanford Encyclope- 7 dia of philosophy. http://plato.stanford.edu/entries/ consciousness/ (acedido em 30/06/2011). Plum F, Posner JB. The pathologic physiology of signs and symptoms of coma. Em The diagnosis of stupor and 8 coma 3 ed. Philadelphia, F. A. Davis Company. 1982. The Multi-Society Task Force on PVS. Medical aspects of the persistent vegetative state. N Engl J Med 1994; 9 330:1499.1508.
Fayers PM, Hjermstad MJ, Ranhoff AH, Kaasa S, Skogstad L, Klepstad P, Loge JH. Which mini-mental state exam items can be used to screen for delirium and cognitive impairment? J Pain Symptom Manage. 2005;30:41-50. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: The Confusion Assessment Method. Ann Intern Med 1990;113:941-948. Ryan K, Leonard M, Guerin S, Donnelly S, Conroy M, Meagher D. Validation of the confusion assessment method in the palliative care setting. Palliat Med 2009;23:40-45.
Casarett DJ, Inouye SK. Diagnosis and management of delirium near the end of life. Ann Intern Med 2001; 10 Wong CL, Holroyd-Ledue J, Simel DL, Straus SE. Does 135:32-40. this patient have delirium? Value of bedside instruments. JAMA 2010;304:779-786. Smith MJ, Breitbart WS, Platt MM. A critique of instruments and methods to detect, diagnose, and 11 Inouye SK, Foreman MD, Mion LC, Katz KH, Cooney LM. rate delirium. J Pain Symptom Manage 1995; Nurses recognition of delirium and its symptoms: comparison 10:35-77. of nurse and researcher ratings. Arch Intern Med 2001; 161:2467-2473. Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method of grading the cognitive state of patients 12 Fabbri RMA, Moreira MA, Garrido R, Almeida OP. Validity for the clinician. J Psychiatric Res 1975;12:189-198. and reliability of the Portuguese version of the Confusion Assessment Method (CAM) for the detection of delirium in the elderly. Arq Neuropsiquiatr 2001;59:175-179.
4
AVALIAO DOS DOENTES SEM ALTERAES COGNITIVAS
avaliao dos doentes sem alteraes cognitivas
Os doentes em cuidados paliativos tm uma grande variedade de sintomas/problemas. Verificou-se que h uma diferena significativa entre o nmero de sintomas referido espontaneamente e o nmero detectado quando os doentes so sistematicamente interrogados, sendo maior este ltimo [1]. A diferena no foi igual para todos os tipos de sintomas. Assim, sintomas como dor, alteraes intestinais, nuseas e vmitos e problemas de mobilidade foram mais frequentemente referidos espontaneamente, enquanto sintomas como fadiga, perda de apetite, perda de peso e edemas foram mais frequentemente detectados quando interrogados. Pode haver vrias razes para isso, sendo uma forte hiptese o facto de os doentes atriburem mais importncia a uns sintomas do que a outros, quer porque uns tm uma maior influncia no seu bem-estar do que outros quer porque no atribuem importncia a outros por os considerarem inevitveis na sua situao ou porque os atribuem a outros factores, como a idade, por exemplo. Desta observao se pode concluir que, por um lado, importante fazer uma avaliao sistemtica de sintomas e outros problemas e, por outro lado, no necessrio fazer uma avaliao abrangente na fase inicial porque os doentes no atribuem a mesma importncia a todos os sintomas/problemas. Acresce a circunstncia de na avaliao inicial poder no haver possibilidade ou convenincia de se fazer essa avaliao abrangente pelas razes j aduzidas na introduo. Na literatura de cuidados paliativos encontram-se, como j foi referido, muitos instrumentos de avaliao que, embora naturalmente incluam problemas comuns, como a dor, incluem uma variedade grande de sintomas/problemas e so assim muito diferentes em termos de contedo e extenso. Para exemplificar essa variedade mostram-se no anexo 1 os sintomas/problemas fsicos includos em 10 instrumentos. Em face desta diversidade considerou-se que havia espao para evoluir.
Para cumprir a finalidade deste sistema, expressa na introduo, h que reduzir o nmero de sintomas/problemas a avaliar ao essencial para a primeira avaliao, independentemente de avaliaes subsequentes. O mtodo escolhido para a seleco dos sintomas/problemas foi o mtodo de Delfos.
o mtodo de delfos
O mtodo de Delfos foi desenvolvido nos anos 50 do sculo XX pela Companhia Rand de Santa Monica, California, com fins militares [2]. O nome deriva do Orculo de Delfos da Grcia antiga onde as sacerdotisas de Apolo, as Pitonisas, faziam profecias. As profecias do orculo so predies no refutveis, porque no tm a propriedade de serem verdadeiras ou falsas[2]. O mtodo de Delfos uma forma de estudo de assuntos controversos. uma forma de obter consensos atravs da opinio de peritos que individual e anonimamente respondem s questes colocadas em duas ou mais voltas [3]. Ao fim de cada volta os peritos envolvidos recebem um sumrio das respostas de todos os outros e tm a oportunidade de reconsiderar as suas respostas e eventualmente de as modificar na volta seguinte. As vantagens do mtodo de Delfos na obteno de consensos residem: No facto de os peritos poderem exprimir as suas opinies sem contrangimentos, isto , anonimamente e sem discusso directa com outros peritos, no conduzindo a um eventual predomnio das opinies de quem tem uma personalidade dominante ou de quem se expresse com mais facilidade; Em poder-se fazer por correio electrnico, no havendo, portanto, limitaes geogrficas; Por ser mais barato j que no necessrio fazer reunies num determinado local, com os custos inerentes, por se fazer por correio electrnico.
O mtodo de Delfos uma tcnica de investigao flexvel que tem sido aplicado de formas variadas de acordo com os objectivos do projecto de investigao [4]. Por todas estas razes, o uso do mtodo de Delfos tem vindo a expandir-se na medicina em geral e em particular em cuidados paliativos [5,6]. A primeira fase O primeiro passo foi uma reviso extensa da literatura de cuidados paliativos relevante para a finalidade do estudo. Foi construda uma lista dos problemas/sintomas a partir de instrumentos conhecidos e validados como: Rotterdam Symptom Checklist [7], The Memorial Symptom Assessment Scale Short Form [8], Problems and Needs in Palliative Care Questionnaire - short form [9], Edmonton Symptom Assessment Scale (ESAS) [10], The European Organization for Research and Treatment of Cancer QLQ-30 [11], the Needs Near the End-of-Life Care Screening Tool [12], o M. D. Anderson Symptom Inventory [13], o Cancer Rehabilitation Evaluation System - Short Form (CARES-SF) [14] entre outros [15-17]. Foram consideradas escalas desenvolvidas para a avaliao da qualidade de vida, como a EORTC QLQ-C15-PAL [18] e a Hospice Quality of Life Index [19] desenvolvidas especificamente para cuidados paliativos. Foram tambm considerados estudos sobre a prevalncia de sintomas/problemas no cancro avanado a vrios nveis [20-23]. Foram ainda analisados instrumentos especficos de algumas dimenses. Por exemplo, relativamente espiritualidade foi analisada a Spiritual Transformation Scale [24]. Foram estudados outros instrumentos, mas verificou-se que no acrescentavam nova informao, visto que os mesmos itens se repetiam, embora com composies diversas. Foi feita uma lista abrangente com base nos problemas contidos nesses instrumentos, excluindo alguns que eram evidentemente menos relevantes de modo a manter a lista num tamanho manejvel e, nos casos em que havia termos equivalentes escolheram-se os que aparentemente seriam de mais fcil compreenso. A lista continha uma pergunta aberta geral o que que o incomoda mais? Esta pergunta era j utilizada h vrios anos na avaliao inicial na nossa unidade de cuidados paliativos como forma de hierarquizar as prioridades do ponto de vista do doente, mas suportada tambm pelo estudo de Shah et al. [25]. De forma semelhante o estudo de Hoekstra et al. tambm mostra que determinar qual o sintoma mais perturbador tem um valor adicional relativamente determinao apenas da presena e intensidade dos sintomas [26].
Os domnios que a lista inicial continha eram os seguintes: Sintomas fsicos, com 61 problemas/sintomas; Sntomas psicolgicos, com 13 problemas/sintomas; Capacidade funcional, com 10 itens; Problemas sociais, com 11 problemas; Aspectos espirituais/existenciais, com 6 itens; Problemas financeiros, com 3 itens.
A ltima pergunta refere-se ao bem-estar. uma pergunta que envolve uma avaliao global do estado do doente do seu ponto de vista. Por isso, foi colocada no fim, ao contrrio do que se passa na ESAS [10], e de acordo com a sugesto de alguns dos doentes que participaram num estudo que visava examinar os processos cognitivos dos doentes enquanto completavam aquele instrumento [27]. A lista de problemas sintomas continha, portanto, inicialmente 106 itens (quadro 3).
Quadro 3 | Lista inicial de sintomas/problemas. General question What bothers you the most? Physical symptoms
Pain Weight loss Lack of appetite Tiredness/fatigue Lack of energy Nausea Vomiting Difficulty sleeping Daytime sleepiness Dizziness Decreased sexual interest Sexual difficulties Constipation Diarrhoea Heartburn Tremor Tingling of hands or feet Swelling of arms or legs Abdominal distension Numbness Difficulty concentrating Sore mouth/pain when swallowing Loc. weakness (paralysis/paresis) Difficulty swallowing Hair loss Burning/sore eyes Cough Shortness of breath Dry mouth Taste changes Leakage of urine Problems with urination Sweating Itching Feeling full after eating Changes in skin Wounds Pressure ulcers Altered vision Light hypersensitivity (eyes) Altered audition Sound hypersensitivity Bleeding Hiccups Dyspepsia (indigestion) Tracheostomy Colostomy Nephrostomy Altered body image Altered speech Hallucinations Nightmares Faecal incontinence Expectoration Salivation Fainting Cramps Fever Problems remembering Thirst Early satiety
(continua)
Physicological symptoms/problems
Irritability Worrying Depression Nervousness Despairing about the future Tension Anxiety Sadness Fear of future Fear of suffering Loss of autonomy Distress Worrying about work
Activity level
Care for yourself (dress, wash, etc) Walk at home Light housework Climb stairs Heavy housework Walk out of doors Shopping Go to work Hobbies Not being able to do the things you used to do
Spiritual issues
Belief/faith (Do you have religious belief/faith?) Importance of the belief/faith Importance of addressing this issues Difficulties in accepting the disease Feelings of guilt Feelings of shame
Social issues
Problems in the relationship with companion Difficulties in talking about the disease with the companion Difficulties of communication with the companion Difficult interaction with the companion Neglected by the companion Support from family/friends Difficulties in talking about the disease Difficulties in finding someone to talk Difficulties in the contact with family and friends Loneliness Housing problems
Finantial problems
Extra expenses because of the disease Loss of income because of the disease Financial difficulties
Overall quality of life

Well-being
A aplicao do mtodo de Delfos Esta longa lista inicial, incomportvel para uma avaliao til e eficaz foi ento submetida a um processo de seleco utilizando a tcnica de Delfos. Os critrios de seleco dos peritos a convidar para participar no processo foi serem mdicos envolvidos em cuidados paliativos e serem bem conhecidos internacionalmente por terem publicado vrios estudos no mbito dos cuidados paliativos. Segundo estes critrios foram abordados 20 mdicos por correio electrnico convidando-os a participar. O texto enviado foi o seguinte:
Dear Colleague, There are many tools to assess the problems and symptoms of patients in palliative care. As you know, they are very different and to illustrate this point I am sending attached a table which includes only the physical symptoms of a few of those tools. Therefore, we feel that there is room to improvement. In my unit we have a particular research question which is: what should be assessed in the first contact with a palliative care patient? Why this question? Patients contact palliative care in very different conditions at the consciousness, cognitive, emotional, performance status and symptom burden levels. The patient can be insecure or anxious, particularly in this situation of change from a curative paradigm to a palliative one. Therefore, a comprehensive assessment can be a burden to the patient. There is also the problem of all the work that must be done in a busy unit. However, the main problems should not be missed. For now, our focus is cancer patients without cognitive failure. The objective is to develop a screening tool that must be short, not time consuming, but able to detect the main problems of those patients in the first encounter, despite the assessment of other problems/symptoms in a later moment. With this aim we have made an extensive review of the literature. From this review a long list of problems/symptoms resulted. To shorten it to the essential ones we believe that a good way would be a consensus and among the different methods to reach a consensus the Delphi method would be the most reasonable. Probably two rounds will be needed to reach the consensus. As you are a recognized expert in the field of palliative care I am kindly asking for your help in our project. I hope you accept. In that case, I will send you the list of the problems/symptoms. Warmest regards. Desses 20 mdicos, 13 aceitaram participar. As suas nacionalidades so as seguintes: alem: 1; canadiana: 1; espanhola: 3; francesa: 1; inglesa: 1; italiana: 2; norueguesa: 2; sueca: 1; sua:1. A lista de sintomas/problemas foi enviada pedindo a cada mdico que pontuasse numa escala de 0 a 10 cada sintoma/problema quanto sua relevncia para a avaliao dos doentes em cuidados paliativos (anexo 2).
Considerou-se que foi atingido o consenso nos casos em que a mdia das pontuaes foi 8 ou <5, sendo que os primeiros foram includos e os segundos excludos. Nos casos que se situaram entre os dois valores considerou-se que no havia consenso, tendo a lista dos sintomas/problemas sem consenso sido enviada para uma segunda ronda. Nesta ronda foi enviada tambm a informao sobre a mdia das pontuaes do prprio mdico e as respostas dos outros membros do painel. Um exemplo desse processo pode ver-se no anexo 3. Com as respostas da segunda ronda no foi includo nenhum sintoma/problema, mas foram excludos muitos, usando os mesmos critrios da primeira ronda. Para no perpetuar o processo, na terceira ronda foi pedido que a resposta fosse de sim ou no, com a concordncia de todos os peritos. Os sintomas/problemas cujo nmero de sins foi maioritrio, isto 7 foram includos e os outros excludos. Foi feita uma lista final com os sintomas/problemas includos nas trs rondas (quadro 4).
Quadro 4 | Lista final. General question What brothers you the most? Physical symptoms
Pain Lack of appetite Vomiting Tiredness/fatigue Nausea Constipation Shortness of breath
Psychological symptoms/problems
Depression Anxiety Difficulty sleeping
Activity level Care for yourself (dress, wash, etc) Social issues Support from family/friends Overall quality of life Well-being
A lista foi construda em ingls para permitir a interveno dos mdicos estrangeiros. Foi depois submetida a uma traduo para portugus por uma pessoa cuja lngua me o portugus e de novo retrovertida para ingls por uma pessoa cuja lngua me o ingls, sendo que ambos tm conhecimentos extensos da outra lngua. A traduo e a retroverso no produziram resultados controversos que necessitassem de outras intervenes. Aos itens deste instrumento possvel adicionar um ou mais sintomas/problemas que os doentes considerem importantes no seu caso particular. A aplicao prtica dos itens seleccionados ser feita numa escala tipo Likert de cinco pontos. Decidiu-se avaliar os sintomas do ponto de vista da influncia que tm no bem-estar e no na sua intensidade, porque na realidade isso que mais interessa (quadro 5). Os termos usados na escala foram submetidos apreciao de mdicos e enfermeiros do servio, que sugeriram algumas alteraes. Foram aceites as que pareceram melhorar a escala.
Quadro 5 | Forma final do instrumento. Avaliao inicial de sintomas/problemas Durante a ltima semana quais foram os sintomas ou problemas que o incomodaram? O que o incomoda mais? Dor Falta de apetite Vmitos Cansao/Fadiga Nuseas/Enjoos Obstipao/Priso de ventre Falta de ar Depresso/Tristeza Ansiedade/Nervosismo Dificuldade em dormir Outro: Cuidar de s (vestir-se, lavar-se, etc) Independente Total Bem-estar Excelente Bom Razovel Mau Muito mau Com dificuldade Bastante S com ajuda Quando peo Muito pouco Pouco Incapaz Nenhum Apoio da famlia/amigos Nada Nada Nada Nada Nada Nada Nada Nada Nada Nada Nada Nada Um pouco Um pouco Um pouco Um pouco Um pouco Um pouco Um pouco Um pouco Um pouco Um pouco Um pouco Um pouco Bastante Bastante Bastante Bastante Bastante Bastante Bastante Bastante Bastante Bastante Bastante Bastante Muito Muito Muito Muito Muito Muito Muito Muito Muito Muito Muito Muito Muitssimo Muitssimo Muitssimo Muitssimo Muitssimo Muitssimo Muitssimo Muitssimo Muitssimo Muitssimo Muitssimo Muitssimo
H ainda a decidir se esta parte do sistema ser feita por autoavaliao ou com assistncia de profissionais como sugerido por doentes includos num estudo do ESAS [27]. tambm da experincia de outros estudos realizados por ns em Portugal que os doentes preferem que sejam os profissionais a fazer as perguntas e a preencher os formulrios [28].
discusso
Neste estudo foram includos 13 mdicos peritos em cuidados paliativos. O nmero apropriado de peritos a envolver num estudo de Delfos no obtem consenso na literatura [29]. De facto, h grandes diferenas entre os estudos. Um nmero de 10 a 15 peritos pode ser adequado se tiverem uma experincia homognea no assunto em causa [29]. No caso presente isso mesmo que se passa, pelo que o nmero de peritos pode considerar-se suficiente. Este processo produziu um instrumento de avaliao inicial dos doentes admitidos em cuidados palitivos sem alteraes cognitivas que inclui os sintomas/problemas incluidos na maioria dos instrumentos semelhantes, excluindo muitos outros cuja relevncia no foi considerada suficiente para a finaliadade em vista. No entanto, a possibilidade de incluir outros itens que pertubem um ou outro doente resolve a questo da grande diversidade de problemas que podem afectar os doentes. Um instrumento semelhante a ESAS [10] que tem 10 itens. A ESAS provavelmente o instrumento mais usado em cuidados paliativos. Embora haja semelhanas entre os dois instrumentos eles no so idnticos. A ESAS no inclui sintomas como vmitos, fadiga, obstipao e dificuldade em dormir. Por outro lado, o presente instrumento no inclui os itens sonolncia e distress. A ESAS tambm no inclui a dimenso social e trata de modo diferente a actividade. de notar que estes dois instrumentos tm finalidades diferentes. A ESAS um instrumento que foi desenvolvido para ser aplicado diariamente (na realidade em Edmonton onde foi desenvolvida aplicada duas vezes por dia), para a avaliao dos sintomas fsicos e psicolgicos, embora j tenha sido usado com outras finalidades, por exemplo, como um instrumento de auditoria [30]. O presente instrumento,
porm, foi construdo para a avaliao inicial dos doentes admitidos em cuidados paliativos, o que pode explicar algumas das diferenas. Os sintomas fsicos e psicolgicos seleccionados so naturalmente dos mais frequentes como mostram vrios estudos de prevalncia de sintomas no cancro avanado [20-23]. Duas dimenses foram completamente excludas: a espiritual e a financeira. No claro porque o foram, mas certo que no foram consideradas suficientemente relevantes para avaliao no primeiro encontro. No que fossem consideradas dimenses menores na avaliao dos doentes. Talvez se tenha considerado que no primeiro encontro no h intimidade suficiente para se abordarem essas questes, sobretudo no que diz respeito s questes espirituais, podendo ser abordadas mais tarde. O caso particular dos problemas psicolgicos A National Comprehensive Cancer Network define distress como uma experincia emocional desagradvel que se estende ao longo de uma continuidade que vai de sentimentos normais comuns de vulnerabilidade, tristeza e receios, a problemas que se podem tornar incapacitantes, como depresso, ansiedade, pnico, isolamento social e crises existenciais e espirituais [31]. Ora so estes que interessa detectar e, de facto, o foco de ateno tem sido nos diagnsticos psiquitricos convencionais como a depresso. A prevalncia da depresso nos doentes com cancro avanado, segundo a literatura, varia entre 3,7% e 58% [32]. Esta disparidade de nmeros reflecte bem o problema da deteco da depresso nestes doentes. De facto, os critrios de diagnstico de depresso incluem sintomas fsicos, como alteraes do apetite, astenia e alteraes do sono so comuns nestes doentes devido prpria doena. Por outro lado, a tristeza um sintoma comum nos doentes com cancro avanado, sendo uma manifestao normal dada a situao difcil com que os doentes se confrontam. No entanto, a tristeza por si s no significa depresso, embora comummente se associem os termos. Sabe-se tambm que mais de 50% dos problemas psicolgicos no so detectados por rotina em contextos mdicos [33]. A importncia da deteco da depresso reside na possibilidade de a tratar e no impacto negativo que tem na qualidade de vida dos doentes e das suas famlias quando presente.
Existem vrios questionrios de extenso varivel para o rastreio da depresso, mas poucos foram validados em cuidados paliativos. Numa reviso feita por um grupo de trabalho de peritos para a Associao Europeia de Cuidados Paliativos concluiu-se que a evidncia actual no permite recomendar nenhum mtodo de rastreio da depresso para cuidados paliativos [32]. A validao destes questionrios dever ser feita por comparao com um gold standard. No caso da depresso o mtodo que mais se aproxima de um gold standard a entrevista psiquitrica [32]. No entanto, este um recurso moroso, que poucos dominam e, portanto, pouco adequado como mtodo de rastreio. De acordo com o objectivo do instrumento aqui desenvolvido, o mtodo de rastreio deve basear-se num nmero de perguntas o mais pequeno possvel. O resultado obtido resultou numa s pergunta, como no estudo de Chochinov et al [34]. Neste estudo, a pergunta: Est deprimido(a)? atingiu uma sensibilidade e especificidade de 100%. No entanto, estes resultados no foram replicados noutros estudos, o que pode ter sido influenciado por razes culturais [35]. A definio de depresso no estudo de Chochinov et al. inclua a depresso minor. Portanto, o que se determinou foi a capacidade de detectar humor deprimido e no apenas casos de depresso major [36]. Payne et al. estudaram a sensibilidade e a especificidade de duas perguntas: Est deprimido(a)? e Perdeu interesse em coisas ou actividades de que normalmente gostava? [37]. Neste estudo a combinao das duas perguntas mostrou uma sensibilidade de 90,7% e uma especificidade de 72,6%. Por se tratar de um mtodo de rastreio, a sensibilidade deve ser privilegiada em relao especificidade pelo que aquela especificidade pode ser aceitvel. A incluso de um item que aborde a questo do humor deprimido importante. A pergunta usada como rastreio e no para diagnstico. O humor deprimido um elemento essencial no diagnstico de depresso segundo, por exemplo, o Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) [38]. No h depresso sem humor deprimido, portanto, a pergunta sobre o humor fundamental num instrumento de rastreio da depresso.
referncias
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Delphi method. http://www.u ido.org/fileadmin/import 13 Cleeland CS, Mendonza TR, Wang XS, Chou C, Harle /16959_DelphiMethod.pdf (acedido em 02/06/11). MT, Morrisey M, Engstrom MC. Assessing symptom distress in cancer patients. Cancer 2000;89:1634-1646. 3 Fink A, Kosecoff J, Chassin M, Brook RH. Consensus methods: characteristics and guidelines for use. Am J 14 Schag CAC, Ganz PA, Heinrich RL. Cancer Rehabilitation Public Health 1984;74:979-983. Evaluation System - Short Form (CARES-SF): a cancer specific rehabilitation and quality of life instrument. Cancer 1991;68:1406-1413. 4 Skulmoski GJ, Hartman FT, Krahn J. The Delphi method for graduate research. J Inform Technol Ed 2007;6:1-21. 15 Barresi MJ, Shadbolt Byrne D, Stuart-Harris R. The development of the Canberra symptom scorecard: a 5 Pigni A, Brunelli C, Gibbins J, Hanks G, DeConno F, Kaasa S, Klepstad P, Radbruch L, Caraceni A. Content tool to monitor the physical symptoms of patients with development for European guidelines on the use of advanced tumours. BMC Cancer 2003;3:32. opioids for cancer pain: a systematic review and expert consensus study. Minerva Anestisiol 2010;76:833-843. 16 Hoekstra J, Bindels PJE, van Duijn NP, Shad E. The symptom monitor. A diary for monitoring physical symptoms for cancer patients in palliative care: feasibility, reliability and 6 Biondo PD, Nekolaichuk CL, Stiles C, Fainsinger R, Hagen NA. Applying the Delphi process to palliative care tool compliance. J Pain Symptom Manage 2004:27:24-35. development: lessons learned. Support Care Cancer 2008;16:935-942. 17 Berry DL, TRigg LJ, Lober WB, Karras TB, Galligan ML, Austin-Seymour M, Martin S. Computerized symptom and quality-of-life assessment for patients with cancer 7 de Haes JCJM, Olschewski, Fayers P, Visser MRM, Cull A, Hopwood Sanderman R. The Rotterdam Symptom part 1: development and pilot testing. Oncol Nurs Forum Checklist (RSCL): a manual. Northern Centre for 2004;31:E75-E83. Healthcare Research. University of Groningen, The Netherlands; 1966. 18 Groenvold M, Petersen MA, Agronson NK, et al. The development of the EORTC QLQ-C15-PAL. Eur J Cancer 2006;42:55-64. 8 Chang VT, Hwang SS, Feuerman M, Kasimis BS, Thaler HT. The Memorial Symptom Assessment Scale Short Form (MSAS-SF) Cancer 2000;89:1162-1171. 19 McMillan SC, Mahon M. Measuring quality of life in hospice patients using a newly developed Hospice Quality of Life Index. Qual Life Res 1994;3:437-447. 9 Osse BHP, Vernooij-Dassen MJFJ, Schad E, Grol RPTM. A practical instrument to explore patients needs in palliative care: the Problems and Needs in Palliative 20 Teunissen SCCM, Wesker W, Kruitwagen C, de Haes HCJM, Care questionnaire - short version. Palliat Med 2007; Voest EE, Graeff A. Symptom prevalence in patients with 21:391-399. incurable cancer: a systematic review. J Pain Symptom Manage 2007;34:94-104. 10 Chang VT, Hwang SS, Feuerman M. Validation of the Edmonton Symptom Assessment Scale. Cancer 21 Strmgren AS, Groenvold M, Pedersen L, Olsen AK, 2000;88:2164-2171. Sjogren P. Symptomatology of cancer patients in palliative care: content validation of self-assessment questionnaires against medical records. Eur J Cancer 2002;38:788-794. 11 Aaronson NK, Ahmedzai S, Bergman B, et al. The European Organization for Research and Treatment of Cancer QLQ-30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-376. 2
22 Jimnez-Gordo AM, Feliu J, Martnez B, et al. Descriptive analysis of clinical factors affecting terminally ill cancer patients. Support Care Cancer 2009;17:261-269. 23 Lidstone V, Butters E, Seed PT, Sinnot C, Beynon T, Richards M. Symptoms and concerns amongst cancer outpatients: identifying the need for specialist palliative care. Palliat Med 2003;17:588-595. 24 Cole BS, Hopkins CM, Tisak J, Steel JL, Carr BI. Assessing spiritual growth and spiritual decline following a diagnosis of cancer: reliability and validity of the spiritual transformation scale. Psycho-Oncology 2008; 17:112-121. 25 Shah M, Quill T, Norton S, Sada Y, Buckley M, Fridd C. What bothers you most? Initial responses from patients receiving palliative care consultation.Am J Hosp Palliat Care 2008;25:88-92. 26 Hoekstra J, Vernooij MJFJ, de Vos R, Bindels PJE. The added value of assessing the most troublesome symptom among patients with cancer in the palliative phase. Patient Educ Counsel 2007;65:223-229. 27 Watanabe S, Nekolaichuk C, Beaumont C, Mawani A. The Edmonton symptom assessment system - what do patients think? Support Care Cancer 2009;17:675-683. 28 Ferraz Gonalves, Marques A, Rocha S, Leito P, Mesquita T, Moutinho S. Breaking bad news: experiences and preferences of advanced cancer patients at a Portuguese oncology centre. Palliative Medicine 2005; 19: 526-/531. 29 Hsu CC, Sandford BA. The Delphi technique: making sense of consensus. Practical Assessment, Research and Evaluation 2007;12:10. 30 Dudgeon DJ, Harlos M, Clinch JJ. The Edmonton Assessmente Scale (ESAS) as an audit tool. J Palliat Care 1999;15:14-19. 31 National Comprehensive Cancer Network. Clinical practice guidelines in oncology v.1. 2009. http://www. nccn.org/professionals/physician_gls/PDF/distress. pdf. (acedido em 18/05/2009). 32 Stiefel F, Trill Md, Berney A, Olarte JMN, Razavi D. Depression in palliative care: a pragmatic report from the Expert Working Group of the European Association for Palliative Care. Support Care Cancer 2001;9:477-488. 33 Thekkumpurath P, Venkateswaran C, Kumar M, Bennet MI. Screening for psychological distress in palliative care: a systematic review. J Pain Symptom manage 2008;36: 520.528. 34 Chochinov HM, Wilson KG, Enns M, Lander S. Are you depressed? Screening for depression in the terminally ill. Am J Psychiatry. 1997;154:674-676. 35 Lloyd-Williams M, Spiller J, Ward J. Which depression screening tools should be used in palliative care? Palliat Med 2003;17:40-43. 36 Rayner L, Loge JH, Wasteson E, Higginson I. The detection of depression in palliative care. Curr Opin Support Palliat Care 2009;3:55-60. 37 Payne A, Barry S, Creedon B, Stone C, Sweeney C, OBrien T, OSullivan K. Sensitivity and specificity of a two-question screening tool for depression in a specialist palliative care unit. Palliat Med 2007;21:193-198. 38 http://emedicine.medscape.com/article/286759 overview (acedido em 13/05/2010).
5
AVALIAO DOS DOENTES COM ALTERAES COGNITIVAS
avaliao dos doentes com alteraes cognitivas
H pessoas com alteraes cognitivas que ainda assim so capazes de comunicar os seus problemas de modo suficientemente claro. No entanto, muitas dessas pessoas no so capazes de o fazer [1]. A natureza subjectiva dos sintomas torna o relato do doente a melhor forma de avaliar os seus sintomas/problemas. Quando as alteraes cognitivas no o permitem fazer necessrio utilizar outros meios. Uma alternativa a avaliao por um familiar ou outra pessoa prxima. No entanto, parece que esta forma de avaliao s til se houver um contacto regular como o/a doente [2]. Outro problema que este mtodo acarreta a necessidade da presena dessas pessoas na altura da avaliao, o que torna o mtodo problemtico. A alternativa mais usada a avaliao comportamental. Seguindo esta linha, foram desenvolvidos vrios instrumentos para avaliar doentes com alteraes cognitivas. A maioria concentra-se no problema da avaliao da dor [3-9]. H tambm instrumentos desenvolvidos para a avaliao de outros sintomas [10], para avaliar a qualidade de vida [11-14] e para a deteco do sofrimento em geral [15,16]. Muitos dos estudos realizados para avaliao dos sintomas/problemas dos doentes com alteraes cognitivas centraram-se nos doentes com demncias [2,6-17], em doentes com alteraes cognitivas de outra causa [5] e nos doentes em cuidados intensivos [18]. Esses instrumentos avaliam os sintomas/problemas pelas expresses faciais, actividade, humor, interaco social, comportamento vocal, etc. Como foi referido a maioria foi desenvolvida para avaliao da dor. No entanto, h muitos outros sintomas para alm
da dor. Uma dificuldade inerente avaliao destes sintomas em doentes que no podem dizer o que sentem a de saber se as manifestaes de sofrimento inferidas por esses instrumentos se devem a dor ou a qualquer outro tipo de causa fsica ou afectiva ou mesmo s prprias alteraes cognitivas. Depois de se ter considerado o exposto no pargrafo anterior, o primeiro passo dever ser determinar se o doente tem ou no manifestaes de desconforto ou sofrimento. Se as tiver, as possibilidades de inferir a causa sero atravs da histria anterior s alteraes cognitivas colhida atravs dos familiares ou da informao clnica que eventualmente acompanhe o doente e do exame fsico. Haver, certamente, situaes em que no ser possvel chegar a uma concluso sobre a causa do sofrimento manifestado pelo doente. Os instrumentos at agora desenvolvidos revelaram fragilidades de vria ordem, incluindo as suas propriedades psicomtricas e utilidade clnica [3,19]. Por esse motivo tentou-se desenvolver um outro mtodo de avaliao. De acordo com a finalidade geral deste sistema pretendeu-se detectar sinais de sofrimento que necessitassem de uma explorao posterior ou se esses sinais estavam ausentes e nenhuma interveno diferente das que estavam em curso necessitaria de ser executada.
estudo
Mtodos O primeiro passo foi fazer uma reviso extensa da literatura para verificar se existiria algum instrumento que pudesse estar validado e pudesse ser usado na avaliao dos doentes, tendo-se detectado os problemas j referidos. No entanto, esses instrumentos foram usados para seleccionar os elementos que vieram a constituir o presente instrumento. Os elementos escolhidos para a construo do instrumento foram a expresso facial, a vocalizao e as reaces fsicas (quadro 6). Estes elementos pareceram os mais adequados, eliminando-se aspectos sociais que se mostraram pouco consistentes em alguns estudos. Os elementos iniciais foram sujeitos a um teste com os 8 investigadores envolvidos, mdicos e enfermeiros. Nessa avaliao inicial foram reconhecidos alguns problemas, nomeadamente de compreenso dos itens que compunham o instrumento. Foi corrigido o que segundo a avaliao inicial havia a corrigir e foram escritas instrues para a sua aplicao (quadro 7).
Quadro 6 | Formulrio de avaliao. Expresso facial Serena ou sorridente * *se positivo, passar para vocalizao
Inexpressiva Triste Testa franzida Faz caretas Aproximar as sobrancelhas Sobrancelhas elevadas Olhos muito abertos Olhos fechados foradamente Boca em arco convexidade superior
sim
no
Vocalizao Voz calma ou sem queixas * *se positivo, passar para reaces fsicas
Apelativo(a) Gemido Choro Grito Verbalmente abusivo ou insultuoso
Reaces fsicas Relaxado(a) * *se positivo, terminar

Respirao rpida Resiste aos cuidados Inquietao Agitao Agressividade Tenso Vaguear aumentado
Quadro 7 | Regras para a aplicao do mtodo de avaliao do sofrimento. A avaliao feita pela observao simultnea dos doentes por 3 observadores. Na interaco com o doente que eventualmente exista, no deve haver perguntas sobre o seu estado, antes do preenchimento do formulrio. O formulrio ser preenchido por 2 dos observadores e um terceiro, confirmar nos doentes que poderem responder se h ou no sofrimento. Expresso facial O primeiro passo a avaliao global da expresso. Se for serena ou sorridente, a avaliao deste aspecto termina, passando-se de imediato para a vocalizao considerando-se todos os outros itens referentes expresso negativos; As alteraes registam-se segundo os modelos (ver folha prpria); Nesta fase devem registar-se todas as alteraes detectadas, mesmo que sejam parecidas. Caretas quando h mltiplos elementos, distoro da face ou mudanas rpidas de expresso. Vocalizao O doente fala com voz calma ou no produz qualquer som que possa sugerir sofrimento como os itens includos em baixo, passa-se imediatamente para as reaes fsicas. Reaces fsicas Se o doente est relaxado, a observao termina; Resistir aos cuidados significa que o doente tem reaco de defesa ou evita o contacto; Tenso significa tenso muscular (no espasticidade); Vaguear aumentado significa que o doente deambula sem propsito e com mais intensidade do que habitualmente.
O estudo foi realizado numa amostra de convenincia de doentes internados na Unidade de Cuidados Paliativos do IPO - Porto. A avaliao foi feita por oito elementos, 2 mdicos e 6 enfermeiros. A avaliao fez-se pela observao simultnea dos doentes por 3 observadores. Na interaco com o doente que eventualmente existisse, no devia haver perguntas sobre o seu estado, antes do preenchimento do formulrio desenvolvido para este estudo. O formulrio era preenchido independentemente por 2 dos observadores e um terceiro confirmava, nos doentes que podiam responder, se havia ou no naquele momento algum motivo de sofrimento. Os doentes seleccionados tinham alteraes da conscincia, de acordo com a avaliao pelos mtodos includos neste sistema e descritos no captulo respectivo. Como o instrumento se destinava a avaliar manifestaes de desconforto em determinado momento e como a situao dos doentes
dinmica alterando-se por vezes rapidamente com perodos de tranquilidade e outros de algum desconforto, alguns doentes foram avaliados vrias vezes desde que em dias diferentes. Dado no existir nenhum mtodo que se possa considerar um gold standard, a nica possibilidade de confirmar o resultado da avaliao o relato dos doentes. Deste modo, alguns dos doentes com alteraes cognitivas que tinham a possibilidade de responder, pelo menos em termos de sim ou no, eram questionados sobre se havia algum factor de sofrimentos na altura da avaliao. Os mtodos estatsticos utilizados para avaliar a concordncia entre os avaliadores foram o coeficiente kappa de Cohen [20] e as propores de concordncia positiva e negativa [21]. Foi ainda determinada a sensibilidade, a especificidade e os valores preditivos positivo e negativo. O estudo foi aprovado pela Comisso de tica e pelo Conselho de Administrao do IPO - Porto. Sempre que possvel era pedida autorizao aos familiares, por escrito, aps esclarecimento da finalidade do estudo. Porm, dado que no era possvel em muitos casos faz-lo e como o estudo no envolvia nenhuma manobra invasiva nem qualquer esforo e, por outro lado, podia ter vantagem directa e imediata para os doentes, muitos doentes foram envolvidos sem a autorizao da famlia luz da doutrina do consentimento presumido. Resultados O estudo decorreu entre 07/04/2011 e 13/05/2011, tendo sido feitas 75 observaes, numa base de convenincia, em 24 doentes, cujos dados demogrficos se encontram no quadro 8. O nmero de observaes variou entre 1 e 9, mediana 1. Das 75 observaes, em 53 (71%) foi possvel obter uma resposta: positiva em 19 (36%) e negativa em 34 (64). Das 19 respostas positivas, a dor foi a razo em 13 (68%), mal-estar em 4 (21%), dispneia em 1 (11%) e em 3 (16%) no foi possvel obter resposta sobre a razo do desconforto.
Quadro 8 | Dados demogrficos. Tumor primrio Ginecolgico Bexiga Pulmo Cabea/pescoo SNC Prstata Mama Vias biliares Outro Total Gnero: Masculino Feminino Idade: mediana n 4 3 3 2 2 2 2 2 4 24 8 16 76 anos % (17) (13) (13) (8) (8) (8) (8) (8) (8) (100) (33%) (67%) (15-90)
O coeficiente kappa revelou uma concordncia entre os avaliadores boa, (0,61 a 0,80) segundo Altman [22], apenas no item Apelativo(a) da seco Vocalizao. Todos os outros foram inferiores (quadro 9). Nos itens com um coeficiente kappa pelo menos moderado (> 0,40) [22], foram calculadas as propores de concordncia positivas e negativas. Verificou-se que a proporo de concordncia positiva foi relativamente baixa, quer dizer, a concordncia dos avaliadores sobre a positividade de um item foi baixa, enquanto que a proporo de concordncia negativa foi alta e em alguns casos muito alta, atingindo mais de 0,90, muito perto da concordncia total que 1. Quanto ao kappa global, isto , a comparao da concordncia entre todos os itens negativos e a comparao de concordncia de haver pelo menos um item positivo foi de -0,09. A sensibilidade do instrumento foi de 21% (IC 95%: 0,10-0,32) e a especificidade de 97% (IC 95%: 0,92-1,00), com um valor preditivo positivo de 80% (IC 95%: 0,68-0,91) e um valor preditivo negativo de 69% (IC 95%: 0,56-0,81).
Quadro 9 | Propores de concordncia. Expresso facial Serena ou sorridente Inexpressiva Triste Testa franzida Faz caretas Aproximar as sobrancelhas Sobrancelhas elevadas Olhos muito abertos Olhos fechados foradamente Boca em arco convexidade superior Vocalizao Voz calma ou sem queixas Apelativo(a) Gemido Choro Grito Verbalmente abusivo ou insultuoso Reaces fsicas Relaxado(a) Respirao rpida Resiste aos cuidados Inquietao Agitao Agressividade Tenso Vaguear aumentado
K = 0,50; cp = 0,57; cn = 0,93 K = 0,31 * K = 0,28 K = 0,00 * K = 0,28 * K = 0,48; cp = 0,53; cn = 0,95 K = 0,65; cp = 0,67; cn = 0,99 K = 0,47; cp = 0,50; cn = 0,97 * * *
Proporo de concordncia
K = 0,51; cp = 0,73; cn = 0,79 K = 0,02 K = 0,41; cp = 0,40; cn = 0,96 K = 0,48; cp = 0,53; cn =0,95 K = 0,32 K = 0,59; cp= 0,69; cn =0,90 K = 0,22 * K = 0,49; cp = 0,50; cn = 0,99 K = 0,42; cp = 0,53; cn = 0,88
K = coeficiente kappa; cp = concordncia positiva; cn = concordncia negativa * Nestes itens no houve qualquer caso
estudo
Dado a avaliao do instrumento anterior no ter sido satisfatria procurou-se mudar de estratgia realizando outro estudo. Neste estudo procurou-se fazer uma avaliao pelo aspecto global do doente assinalando se apresentava ou no sinais de desconforto. Portanto, h apenas que responder a uma pergunta: o/a doente apresenta sinais de desconforto? Esta avaliao global era j utilizada na Unidade de Cuidados Paliativos do IPO - Porto nos casos de alteraes da conscincia ou grande dificuldade de comunicao. Com este estudo procurava-se evitar focar a ateno em detalhes que, em geral, no se mostraram consistentes no estudo anterior e fazer a avaliao global, evitando olhar para as rvores focando a ateno na floresta. Mtodos A estrutura do estudo foi semelhante do anterior, com 2 investigadores a avaliarem simultaneamente o/a doente, registando de forma independente a sua avaliao. Um terceiro investigador perguntava aos doentes que retinham capacidade de comunicao se na altura se sentiam desconfortveis. Os investigadores so elementos da Unidade de Cuidados Paliativos do IPO - Porto, 2 mdicos e 5 enfermeiros que no tinham participado no estudo 1. Os mtodos estatsticos utilizados foram os mesmos do estudo 1. Resultados O estudo decorreu entre 12/05/2011 e 30/06/2011. Foram avaliados 32 doentes de 1 a 8 vezes, mediana 2 avaliaes, numa base de convenincia, totalizando 64 avaliaes. Os dados demogrficos podem ver-se no quadro 10. Das 64 observaes,
em 50 (78%) foi possvel obter uma resposta: positiva em 15 (30%) e negativa em 35 (70%). Das 15 respostas positivas, a dor a foi razo em 8 (53%), dispneia em 3 (20%) e em 4 (27%) no foi possvel obter resposta sobre a razo do desconforto. A concordncia avaliada pelo coeficiente kappa de 0,612 o que segundo Altman boa (0,61 a 0,80) [22]. A proporo de concordncia global foi de 0,91, sendo a proporo de concordncia positiva 0,67 e a de concordncia negativa 0,95. A sensibilidade foi de 40% (IC 95%: 0,26-0,54) e a especificidade foi de 97% (IC 95%: 0,92-1,00). O valor preditivo positivo foi de 86% (IC 95%: 0,76-0,96) e o valor preditivo negativo de 79% (IC 95%: 0,68-0,91).
Quadro 10 | Dados demogrficos. Diagnstico Oncolgico Estmago Cabea/pescoo Ginecolgico Bexiga Mama Pulmo SNC Esfago Outro No oncolgico Total Gnero: Masculino Feminino Idade: mediana n 4 4 4 3 2 2 2 2 7 2 32 13 19 66 anos % (13) (13) (13) (9) (6) (6) (6) (6) (22) (6) (100) (41%) (59%) (24-87)
discusso
Procurava-se construir um mtodo para avaliao de manifestaes de sofrimento em doente sem capacidade de o comunicarem por si prprios. um assunto que tem sido estudado sobretudo nos doentes com demncias para os quais foram desenvolvidos vrios instrumentos focados essencialmente na avaliao da dor. No h nenhum mtodo desenvolvido especificamente para cuidados pliativos. Os Intrumentos at agora desenvolvidos revelaram vrios problemas, incluindo a suas propriedade psicomtricas e utilidade clnica [3,19]. Numa reviso sistemtica das escalas de avaliao da dor em idosos com demncia grave concluiu-se que actualmente nenhuma dessas escalas de avaliao pode de modo convincente ser indicado como o mais apropriado para avaliar a dor nos idosos com demncia [3]. No referido estudo destacava-se, no entanto, a escala DOLOPLUS-2 [3]. Esta escala foi validada em vrias lnguas, nomeadamente em portugus, validao essa para a qual contribumos [23]. A escala DOLOPLUS [4] foi desenvolvida a partir da escala Douleur Enfant Gustave Roussy para crianas [3]. Esta escala foi tida em conta na construo do instrumento utilizado no Estudo 1, porm exclumos o domnio psicossocial porque se revelou pouco til e de validade duvidosa [24]. A escala DOLOPLUS tem tambm uma finalidade diferente do nosso instrumento. Enquanto que pretendamos avaliar o desconforto num dado momento, porque os sintomas e a sua intensidade variam, por isso que se prescreve sempre medicao de resgate para administrar se houver um aumento pontual da intensidade dos sintomas. A finalidade de ser includa no sistema de avaliao inicial dos doentes implica tambm que a avaliao possa ser feita pelo profissional que estiver presente,
independentemente de conhecer o doente ou no. Este instrumento deveria tambm ser utilizado noutros contextos. Pelo contrrio a escala DOLOPLUS foi construda para uma avaliao colectiva, pela equipa cuidadora, no num dado momento, e que visa essencialmente monitorizar a evoluo individual da dor e do seu controlo ao longo do tempo. Os resultados dos estudos que realizamos demonstram a dificuldade de avaliar os sintomas/problemas nos doentes com alteraes cognitivas. No Estudo 1 verificou-se que a concordncia entre os avaliadores pelo coeficiente kappa era inferior a moderada na maioria dos itens segundo Altman [22], apenas com um item com uma concordncia boa. No entanto, a concordncia negativa foi em muitos casos superior a 90% o que significa que quando esses itens eram classificados como negativos, os avaliadores tendiam a concordar mais vezes do que quando eram cassificados como positivos. A concordncia global foi aproximadamente como se a resposta tivesse sido aleatria. Isto significa que o instrumento na sua presente forma no til. Na tentativa de resolver o problema em causa estudou-se o mtodo em uso no servio que foi adoptado h muito tempo, embora sem qualquer estudo prvio. No foi estudado antes porque na realidade muito diferente dos instrumentos referidos na literatura que tm a mesma finalidade. A concordncia entre os avaliadores segundo o coeficiente kappa foi boa, embora marginalmente. A proporo de concordncia negativa foi mesmo muito alta, quase perfeita. A especificidade foi tambm muito alta, reflectindo-se tambm no alto valor predictivo positivo, significando que quando o teste positivo, isto , quando h sinais de desconforto a probabilidade de haver efectivamente desconforto muito alta. O grande problema o da sensibilidade do mtodo que de apenas 40%, o que significa que s uma minoria de casos de desconforto detectada, o que afecta gravemente o mtodo como mtodo de rastreio. O que poder ter conduzido a estes resultados? O reduzido nmero de doentes envolvidos no Estudo 1 pode ter afectado os resultados, mas a nossa escolha de preferir o nmero de observaes, visto que em momentos diferentes a intensidade dos sintomas varia, tornou o tamanho da amostra razovel. O estudo foi interrompido neste ponto quando a anlise preliminar ento realizada tornou claro que o mtodo de avaliao no se revelava til. O Estudo 2 teve tambm um nmero de avaliaes razovel
atendendo ao reduzido nmero de variveis em estudo. Outra possibilidade poder ser a influncia que as alteraes cognitivas possam ter tido na preciso das respostas de alguns doentes. Finalmente, os itens que constituiram os dois instrumentos pode no ter sido os mais adequados. Os resultados do Estudo 2 podem ter ainda assim alguma utilidade visto que a sua especificidade muito alta. O seu alto valor preditivo positivo assegura que os casos detectados correspondem de facto a desconforto que requer interveno. O problema principal o da baixa sensibilidade que diminui o mtodo como instrumento de rastreio. A sensibilidade referida poucas vezes na validao dos instrumentos de avaliao dos doentes com dificuldades de comunicao, mas j tem sido referida como prxima da verificada neste estudo. No anexo 4 pode ver-se o comentrio do coorientador desta tese. Em concluso, a questo da avaliao do sofrimento em geral ou de sintomas especficos tem-se revelado difcil, no existindo actualmente nenhum mtodo consensual. Os estudos aqui apresentados obtiveram resultados que esto longe dos ideais, pelo que este aspecto necessita de continuara ser investigado no futuro.
referncias
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Lotan M, Ljunggren EA, Johnsen TB, Defrin R, Pick CG, Strand LI. A modified version of the Non-communicating 10 Campbell ML, Templim T, Walch J. A respiratory distress Children Pain Checklist-Revised, adapted to adults with observation scale for patients unable to self-report dyspnea. intellectual and developmental disabilities: sensitivity to J Palliat Med 2010;13:285-290. pain and internal consistency. J Pain 2009;10:398-407.
11 Logsdon RG, Gibbons LE, McCurry SM, Teri L. Quality of life in Alzheimer disease: patient and caregiver reports. J Mental Health Aging 1999;5:21-31. 12 Kasper JD, Black BS, Shore AD, Rabins PV. Evaluation of the validity and reliability of the Alzheimer Disease -related Quality of Life Assessment Instrument. Alzheimer Dis Assoc Disord 2009;0:1-10. 13 Martin-Cook K, Hynan LS, Rice-Koch K, Svetlik DA, Weiner MF. Responsiveness of the Quality of Life in Late-stage Dementia Scale to psychotropic drug treatment in late-stage dementia. Dement Geriatr Cogn Disord 2005;19:82-85. 14 Ettema TP, Dres RM, de Lange J, Mellenberg GJ, Ribbe MW. A review of quality of life instruments used in dementia. Qual Life Res 2005;14:675-686. 15 Aminoff BZ, Purits E, Noy S, Adunsky A. Measuring the suffering of end-stage dementia: reliability and validity of the Mini-Suffering State Examination. Arch Gerontol Geriatr 2004;38:123-130. 16 Kovach CR, Noonan PE, Griffie J, Muchka S, Weissman DE. The Assessment of Discomfort in Dementia Protocol. Pain Manage Nurs 2002;3:16-27. 17 Volicer L, Hurley AC, Blasi ZV. Scales for evaluation of end-of-life care in dementia. Alzheimer Dis Assoc Disord 2001;15:194-200. 18 Glinas C, Harel F, Fillion L, Puntillo KA, Johnston C. Sensitivity and specificity of the Critical-care Pain Observation Tool for the detection of pain in intubated adults after cardiac surgery. J pain Symptom Manage 2009;37:58-67. 19 Hlen JC, Saltvedt, Fayers PM, Hjermstad MJ, Loge JH, Kaasa S. Doloplus-2, a valid tool for behavioural pain assessment? BMC Geriatrics 2007;7:29. 20 Cohen J. A coefficient of agreement for nominal scales. Educational and Psychological Measurement, 1960, 20, 37-46. 21 http://www.john-uebersax.com/stat/raw.htm (acedido em 01/07/2011). 22 Altman DG (1991) Practical statistics for medical research. London: Chapman and Hall. 23 Pickering G, Gibson SJ, Serbouti S, Odetti P, Ferraz Gonalves J, Gambassi G, Guarda H, Hamers JP, Lussier D, Monacelli F, Prez-Castejn Garrote JM, Zwakhalen SM, Barneto D; Collectif Doloplus, Wary B. Reliability study in five languages of the translation of the pain behavioural scale Doloplus. Eur J Pain 2010;14:545.e1-10. 24 Hlen JC, Saltvedt I, Fayers PM, Bjrnnes M, Stenseth G, Hval B, Filbet M, Loge JH, Kaasa S. The Norwegian Doloplus-2, a tool for behavioural pain assessment: translation and pilot-validation in nursing home patients with cognitive impairment. Palliat Med. 2005l;19: 411-417.
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CONCLUSO
concluso
Os cuidados paliativos constituem hoje o padro de interveno para os doentes com doenas avanadas e progressivas quando os tratamentos que visam alterar a sua progresso no so eficazes, mas tambm em fases mais precoces em conjunto com esses tratamento. Desde Cicely Saunders que se tem procurado credibilizar os cuidados paliativos como disciplina cientfica. No entanto, muitas pessoas chegaram aos cuidados paliativos imbudas sobretudo de sentimentos humanitrios, desconhecendo a necessidade de evoluo cientfica desta rea. Esta atitude vai-se progressivamente reduzindo, havendo um crescente esforo de incluir prticas baseadas na evidncia. Este trabalho procura ir no sentido de desenvolver prticas baseadas na investigao. A razo de ser do desenvolvimento deste sistema integrado de avaliao inicial dos doentes oncolgicos admitidos em cuidados paliativos , como foi referido na introduo, a avaliao rigorosa e eficiente dos doentes no primeiro encontro com os cuidados paliativos, seja qual for o seu estado. As vantagens de uma avaliao sistemtica e padronizada so as de permitir a avaliao em menos tempo, sem perder rigor nem a abrangncia necessria para detectar os problemas principais, condies indespensveis para uma interveno rigorosa. Mas este sistema de avaliao deve ser visto como um ponto de partida, um sistema de rastreio. No basta saber se um doente sem alteraes cognitivas que impeam a avaliao directa tem dor ou no. Se tiver necessrio iniciar o processo especfico de avaliao da dor, das suas caractarsticas como a sua intensidade, os factores que a agravam e os que a aliviam, os eventuais tratamentos que fez anteriormente para a controlar e a sua eficcia e efeitos indesejados, outros problemas de sade que possam
contraindicar certos frmacos, pedir exames que eventualmente sejam necessrios para esclarecer um ou outro aspecto, etc. S depois se poder tratar a dor eficazmente. Isto aplica-se a qualquer outro sintoma fsico ou psicolgico, a alteraes da conscincia, seja da capacidade de acordar seja do contedo da conscincia. Nos doentes com alteraes que no permitam uma avaliao directa, a deteco de sinais de sofrimento pe o problema imediato de determinar a sua causa. Resolver este problema pode ser difcil. Nesta situao a histria do doente colhida das informaes de quem o referencia e/ou de quem o acompanha pode ser determinante, assim como o exame fsico ou a atitude do doente. Se o doente imoblizar uma zona do corpo ou gemer quando um determinado segmento mobilizado isso indica que a causa muito provavelmente dor. Se o doente est polipneico com baixa saturao de oxignio e alteraes auscultatrias o problema certamente dispneia. Por vezes os sinais de desconforto ou sofrimentos podem dever-se s alteraes cognitivas. O funcionamento global do sistema ser do modo que a seguir se apresenta: 1 Se o doente estiver em sofrimento evidente (ex. dor no controlada) que no permita prosseguir a avaliao: a. Controlar a sua causa: i. Pode no ser possvel prosseguir nesta altura a avaliao porque o problema de difcil resoluo ou porque o efeito dos meios utilizados o impede (ex. sonolncia provocada por um opiide). 2 Se o problema for controlado ou no havia sofrimento que impedisse a avaliao: a. Determinar o estado de conscincia (viglia), se no obviamente normal: i. Se o doente se apresenta acordado o seu estado de viglia obviamente normal, mas se no se apresenta assim o seu estado deve ser avaliado pelo mtodo indicado no captulo 3. b. Determinar o estado cognitivo, se no obviamente anormal: i. Se o doente se apresenta agitado evidente que o seu contedo da conscincia anormal, mas se no for assim necessria a avaliao pelo mtodo indicado no captulo 3; ii. Esta avaliao faz-se no decorrer da avaliao global observando se ocorrem alteraes includas no mtodo de avaliao da confuso.
c. Determinao das necessidades de informao: i. um aspecto importantssimo que pode ocorrer noutro momento; ii. Nos doentes com alteraes cognitivas pode no ser possvel dependendo da sua gravidade; iii. A comunicao ocorre, porm, durante toda a consulta. d. Avaliao dos problemas principais, se cognio normal: i. Pelo mtodo indicado no captulo 4; e. Avaliao dos problemas principais, se cognio anormal que no permita a avaliao directa; i. Pelo mtodo indicado no captulo 5. Tendo sido desenvolvido com o objectivo da avaliao inicial dos doentes admitidos em cuidados paliativos, a maioria dos elementos pode ser usado como mtodo de rastreio na avaliao por rotina dos doentes. Assim, a Escala do Nvel de Conscincia para Cuidados Paliativos pode ser aplicada em qualquer altura. Tambm o Mtodo de Avaliao da Confuso pode ser aplicado regularmente. A avaliao dos doentes com alteraes cognitivas pode ser usada sempre que ocorram alteraes que impeam a avaliao pelo relato do doente. Esta escala apesar da sua baixa sensibilidade tem uma especificidade muito alta e um valor preditivo positivo alto, pelo que pode ser til, embora a investigao nesta rea tenha de continuar. A investigao um processo contnuo. Mesmo instrumentos validados devem continuar a ser estudados sobre outros aspectos. Alguns dos instrumentos mais usados tm vindo a ser estudados h 15 ou mais anos. Este sistema, fruto do resultado de largos anos de trabalho de equipa e de investigao sistemtica, parece ser til para a finalidade com que foi construdo podendo inclusivamente ser utilizado noutros contextos clnicos devendo, porm, ser alvo de um processo de aperfeioamento contnuo. Esta tese insere-se num processo de procura de solues para questes que se colocam na prtica diria. Foi esse processo que me levou a explorar os problemas ticos do fim de vida que se concretizou na minha tese de mestrado concluda h cerca de 4 anos.
7
RESUMO
resumo
Geralmente reconhece-se a fundao do St. Christophers Hospice em Londres em 1967 por Cicely Saunders como o incio dos cuidados paliativos modernos. Desde ento, tem vindo a expandir-se por todo o mundo. Em Portugal os cuidados paliativos tiveram incio em 1994 com a abertura da Unidade de Cuidados Continuados no IPO - Porto. Hoje, so considerados os cuidados padro para os doentes com doenas crnicas avanadas e progressivas, podendo ser usados em conjunto com os tratamentos curativos. Os cuidados paliativos comearam por causa dos problemas dos doentes com cancro avanado, mas hoje considera-se que devem ser prestados independentemente da doena crnica subjacente. A realidade mostra, no entanto, que os doentes oncolgicos continuam a ser os mais referenciados para cuidados paliativos.
A maioria dos doentes com doenas crnicas avanadas tem mltiplos problemas resultantes da sua doena e por vezes tambm dos tratamentos anteriormente efectuados. Alm disso, os doentes admitidos em cuidados paliativos apresentam-se em situaes muito diversas a nvel do estado de conscincia, da funo cognitiva, do estado emocional, da funcionalidade, dos sintomas etc. Os doentes podem estar muito dbeis, receosos ou ansiosos. H tambm o problema do trabalho que uma equipa muito ocupada tem que fazer e do tempo que tem disponvel para cada doente. Por isso, uma avaliao extensa pode ser impossvel e pode constituir um fardo para os doentes. Contudo, para os ajudar, necessrio identificar e avaliar rigorosamente os seus problemas principais. Mais tarde, outros problemas de mais baixa prioridade podero ser abordados se for apropriado.
Para responder s questes anteriormente colocadas procurou desenvolver-se um sistema integrado para a avaliao inicial dos principais problemas dos doentes oncolgicos admitidos em cuidados paliativos que se adapte s diversas circunstncias em que se podem apresentar. Este sistema deve ser considerado como um sistema de rastreio, pelo que os problemas detectados necessitam de ser explorados sobre as suas caractersticas e causas para poderem ser resolvidos. Os elementos que constituem o sistema so apresentados em quatro captulos: a.
No captulo Comunicao procura-se demonstrar a necessidade e o desejo de informao que a maioria dos doentes sentem e a dificuldade com que muitas vezes se deparam, atravs de dois estudos levados a cabo no IPO - Porto nos ltimos anos e j publicados. Procura-se mostrar a necessidade de adequar a informao aos desejos dos doentes e no usar princpios rgidos, procurando seguir a vontade e o ritmo destes; No terceiro captulo descreve-se o mtodo de avaliao da conscincia tanto ao nvel da viglia como do contedo. Para avaliar o nvel de viglia desenvolveu-se uma escala, entretanto j publicada. Para avaliar a funo cognitiva nos doentes com um nvel de viglia que permita interaco, introduziu-se o Mtodo de Avaliao da Confuso porque j estava em uso na Unidade de Cuidados Paliativos do IPO - Porto e porque foi recentemente validado em cuidados paliativos e em portugus; No quarto captulo apresenta-se um instrumento desenvolvido segundo o mtodo de Delfos, com o envolvimento de peritos internacionais, para a avaliao dos doentes sem alteraes cognitivas. O instrumento inclui 10 sintomas, uma questo sobre a capacidade de os doentes de se autocuidarem, uma questo social e uma questo geral sobre a avaliao que os doentes fazem do seu bem-estar; Para os doentes que no podem ser avaliados directamente por alteraes cognitivas foram estudados dois mtodos que se descrevem no captulo 5. O mtodo que melhores resultados produziu foi a avaliao geral de sinais de desconforto. Mesmo assim, a sensibilidade do mtodo foi relativamente baixa (40%), embora a especificidade tenha sido muito alta (97%) assim como o valor preditivo positivo (86%).
b.
c.
d.
O funcionamento global do sistema ser do modo que a seguir se apresenta: 1 Se o doente estiver em sofrimento evidente (ex. dor no controlada) que no permita prosseguir a avaliao: a. Controlar a sua causa i. Pode no ser possvel prosseguir nesta altura a avaliao porque o problema de difcil resoluo ou porque o efeito dos meios utilizados o impede (ex. sonolncia provocada por um opiide). Se o problema for controlado ou se no havia sofrimento que impedisse a avaliao: a. Avaliao do estado de conscincia (viglia) com o mtodo includo no captulo 3: b. Avaliao do estado cognitivo, se o estado de viglia o permitir, usando o MAC: i. A avaliao faz-se no decorrer da avaliao global observando se ocorrem alteraes includas no MAC. c. Avaliao das necessidades de informao, se for adequado: i. um aspecto importantssimo que pode ocorrer neste ou noutro momento; d. Avaliao dos problemas principais, se a cognio o permitir, usando o mtodo indicado no captulo 4. e. Avaliao dos problemas principais, se a cognio for anormal no permitindo a avaliao directa, usando o mtodo indicado no captulo 5.
Embora este mtodo tenha sido desenvolvido para a avaliao inicial dos doentes oncolgicos admitidos em cuidados paliativos, a maioria dos elementos deste instrumento tambm pode ser usada na rotina diria. Este sistema, fruto do resultado de largos anos de trabalho de equipa e de investigao sistemtica, parece ser til para a finalidade com que foi construdo e pode provavelmente ser utilizado noutros contextos clnicos. Porm, deve ser melhorado continuamente.
8
ABSTRACT
abstract
Usually the foundation of the St. Christophers Hospice in London in 1967 by Cicely Saunders is recognized as the beginning of modern palliative care. Since then, palliative care has spread all over the world. In Portugal palliative care began in 1994 with the opening of the Continuing Care Unit at the Portuguese Institute of Oncology (IPO) - Porto. Nowadays, palliative care is the standard of treatment for patients with advanced and progressive chronic diseases and can also be used alongside curative treatments. Palliative care began because of the problems of patients with advanced cancer; but today there is a consensus about its potential usefulness independently of the type of underlying chronic disease. However, it remains the case that oncological patients continue to make up the greatest number of people referred to palliative care. Most patients with chronic diseases have multiple problems due to their disease and sometimes also to the treatment they underwent previously. Furthermore, patients admitted to palliative care arrive with very different conditions in aspects such as consciousness, cognitive function, emotional state, performance, symptoms, etc. Patients may be very frail, frightened or anxious. There is also the problem of the work that a busy team has and the time available to each patient. Therefore, an extensive evaluation might be impossible and can be also a burden for the patient. However, to help the patients the main problems should be identified rigorously. Other problems can be addressed later if appropriate.
To respond to the variety of situations explained above an integrated system for the initial evaluation of the main problems of oncological patients was developed which can adapt to those diverse circumstances. The system should be seen as a screening method, as the problems detected need to be assessed further in their characteristics and causes if they are to be solved. The elements of the system are presented in four of the chapters of this thesis: a. In the chapter Communication we try to demonstrate the need and the wish for information that most patients feel and the difficulties they often have to obtain it with two studies concluded some years ago in the IPO - Porto which have already been published. We try to show the need to match the information disclosed to patients wishes without following rigid principles, but following the patients will and rhythm; In the third chapter the method to assess consciousness is described at the wakefulness and the content levels. To assess wakefulness a scale was developed, which has been published. To assess the cognitive function in those patients with a wakefulness level allowing interaction, the Confusion Assessment Method was included because it was already in use in the Palliative Care Unit of the IPO - Porto and because it was recently validated in palliative care and in Portuguese; In the fourth chapter a tool developed with the Delphi method, involving international experts, for the assessment of patients without cognitive failure is presented. The tool includes 10 symptoms, a question about the patients capacity for self care, a question about social issues and a general question about the evaluation that patients do about their own well-being; For those patients who cannot be assessed directly because of cognitive failure two methods were studied that are described in chapter 5. The method with the better results was the general evaluation of signs of discomfort. Even so, its sensitivity was relatively low (40%); although its specificity was very high (97%) as was the positive predictive value (86%).
b.
c.
d.
The general mode of functioning of the system is the following: 1 If the patient were obviously suffering (eg. uncontrolled pain) making it inappropriate to pursue the assessment: a. Control its cause: i. The assessment may not be pursued at that time because the problem is difficult to solve or the side effects of the treatment do not allow it (eg. somnolence caused by an opioid). 2 If the problem can be controlled without problems at that moment or if there was no suffering which precluded the assessment: a. Assess the wakefulness using the method included in chapter 3; b. Assess cognition, if the wakefulness state allows it, using the CAM: i. The assessment should be done while the patient is globally evaluated, looking for the problems included in the CAM. c. Assessment of information needs if cognition is adequate: i. This is a very important issue, but the delivery of information can occur at this or at another moment; d. Assessment of the main problems if cognition allows it using the method indicated in chapter 4. e. Assessment of the main problems, if cognition is abnormal not allowing the direct assessment, using the method indicated in chapter 5. Although this method of screening has been developed for the initial assessment the problems of oncological patients admitted in palliative care, most elements of the tool can also be used in the everyday work routine. This system results from many years of team work and systematic clinical research. It seems to meet its aim and probably can be used in other clinical settings. However, it should be continuously improved.
9
ANEXOS
1
ferramentas de avaliao
- domnio dos sintomas fsicos
ANEXO 1 Ferramentas de avaliao Domnio dos sintomas fsicos

PNPC[3] Lack appetite ()Fatigue ()Fatigue ()Fatigue Tiredness ()Fatigue Tiredness Lack appetite Lack appetite Lack appetite Lack appetite Lack appetite ESAS[4] SDS[5] EORTC QLQ-30 [6] NACPRD [7] MDASI [8] BHI [9] EORTC QLQ-C15PAL [10] Lack appetite Tiredness
RSCL[1]
MSAS-SF[2]
Lack appetite
Lack appetite
Tiredness
Sore muscles Lack of energy Lack of energy
Lack energy
Lack of energy
Low back pain Nausea Dificult Sleeping Headaches Vomiting Dizziness Vomiting Vomiting Dificult Sleeping Dificult Sleeping Dificult Sleeping Nausea Nausea Nausea Nausea Nausea Nausea Dificult Sleeping
Nausea
Nausea
Dificult Sleeping
Dificult Sleeping
Headaches
Vomiting
Vomiting
Dizziness
Dizziness
Dec. sexual interest
Abdominal aches Constipation Diarrhoea Diarrhoea Diarrhoea Constipation Constipation
Constipation
Constipation
Diarrhoea
Diarrhoea
Acid indigestion
Shivering Tingling hands/feet Diffic. concentrating Diffic. concentrating Sore mouth
Tingling hands/feet
Tingling hands/feet
Tingling hands/feet
Diffic. concentrating
Diffic. concentrating
Sore mouth
Sore mouth
Loss of air
Loss of air
Burning eyes Shortness of breath Shortness of breath Shortness of breath Shortness of breath Dry mouth Pain Cough Pain Pain Pain Pain Pain Pain Pain Shortness of breath Shortness of breath
Shortness of breath
Shortness of breath
Shortness of breath
Dry mouth
Dry mouth
Pain Cough
Skin changes Feeling drowsy
Feeling drowsy
RSCL[1]
MSAS-SF[2]
PNPC[3]
ESAS[4]
SDS[5]
EORTC QLQ-30 [6]
NACPRD [7]
MDASI [8]
BHI [9]
EORTC QLQ-C15PAL [10]
Feeling bloated Problems urination Sweats Itching
Problems urination
Sweats
Itching
Diffic. swallowing Food taste Weight loss Weight gain Shakiness Pain eating Early satiety Diffic. remembering
Food taste
Weight loss
RSCL - Rotterdam symptom checklist; MSAS-RF Memorial Symptom Assessment Scale Short Form; PNPC - Problems and Needs in Palliative Care questionnaire short version; ESAS - Edmonton Symptom Assessment Scale; SDS symptom distress scale; EORTC QLQ-C30 - The European Organization for Research and Treatment of Cancer QLQ-30; NACPRD - A needs assessment of cancer patients with recurrent disease; MDASI M.D. Anderson Symptom Inventory; BHI Brief Hospice Inventory; EORTC QLQ-C15-PAL - The European Organization for Research and Treatment of Cancer QLQ-C15-PAL;
2
list of symptoms/problems
Anexo 2
List of symptoms/problems
Please rate how relevant you think the symptoms/problems are to be included in the tool, by using a 0 to 10 scale; 0 indicating no relevance and 10 indicating the highest relevance. Please have always in mind the aim of the tool: the initial evaluation of patients without cognitive failure in a diversity of performance and mind states by a busy team. Therefore, the tool must be short but able to detect the most relevant symptoms/problems. Please rate also the subheadings; for example, the relevance of including a general question, social issues, spiritual issues or financial problems at the first encounter. If you have suggestions of additional items you can use the blank rows. Symptoms/problems 0 1 2 3 4 5 6 7 8 9 10 Comments General question What bothers you the most?
Physical symptoms
Pain
Weight loss
Lack of appetite
Tiredness/fatigue
Lack of energy
Nausea
Vomiting
Difficulty sleeping
Daytime sleepiness
Symptoms/problems Dizziness
0 1 2 3 4 5 6 7 8 9 10
Comments
Decreased sexual interest
Sexual difficulties
Constipation
Diarrhoea
Heartburn
Tremor
Tingling of hands or feet
Swelling of arms or legs
Abdominal distension
Numbness
Difficulty concentrating
Sore mouth/pain when swallowing
Difficulty swallowing
Hair loss
Burning/sore eyes
Cough
Shortness of breath
Dry mouth
Symptoms/problems Taste changes
0 1 2 3 4 5 6 7 8 9 10
Comments
Leakage of urine
Problems with urination
Sweating
Itching
Feeling full after eating
Changes in skin
Wounds
Pressure ulcers
Altered vision
Light hypersensitivity (eyes)
Altered audition
Sound hypersensitivity
Bleeding
Hiccups
Localized weakness (paralysis/paresis)
Dyspepsia (indigestion)
Tracheotomy
Colostomy
Symptoms/problems Nephrostomy
0 1 2 3 4 5 6 7 8 9 10
Comments
Altered body image
Altered speech
Hallucinations
Nightmares
Faecal incontinence
Expectoration
Salivation
Fainting
Cramps
Fever
Problems remembering
Thirst
Early satiety
Psychological symptoms/problems
Irritability
Worrying
Symptoms/problems Depression
0 1 2 3 4 5 6 7 8 9 10
Comments
Nervousness
Despairing about the future
Tension
Anxiety
Sadness
Fear of future
Fear of suffering
Loss of autonomy
Distress
Worrying about work
Activity level
Care for yourself (dress, wash, etc)
Walk at home
Light housework
Climb stairs
Heavy housework
Symptoms/problems Walk out of doors
0 1 2 3 4 5 6 7 8 9 10
Comments
Shopping
Go to work
Hobbies
Not being able to do the things you used to
do
Social issues with
Problems
in
the
relationship
companion
Difficulties in talking about the disease with
the companion
Difficulties of communication with the
companion
Difficult interaction with the companion
Neglected by the companion
Support from family/friends
Difficulties in talking about the disease
Symptoms/problems Difficulties in finding someone to talk
0 1 2 3 4 5 6 7 8 9 10
Comments
Difficulties in the contact with family and
friends
Loneliness
Housing problems
Spiritual issues religious
Belief/faith
(Do
you
have
belief/faith?)
Importance of the belief/faith
Importance of addressing this issues
Difficulties in accepting the disease
Feelings of guilt
Feelings of shame
Financial problems
Extra expenses because of the disease
Symptoms/problems Loss of income because of the disease
0 1 2 3 4 5 6 7 8 9 10
Comments
Financial difficulties
Overall quality of life
Well-being
3
delphi
- round 2
Anexo 3
Delphi - round 2
0 1 2 3 4 5 6 7 8 9 10
Expert's name
Comments
3 2
2 1
1 1 2 4
1 1 1
2 1 2
3 1 1 2 1
1 1
3 1
1 2
1 3 1 1 1 2
3 1 1 2 1
1 1
1 1 1 3 2 2 1 1
2 1 3 2 2
Symptoms/problems Physical symptoms Weight loss Your previous score = 7; mean = 6,8 Lack of energy Your previous score = 8; mean = 5,7 Vomiting Your previous score = 9; mean = 7,7 Difficulty sleeping Your previous score = 8; mean = 7,8 Daytime sleepiness Your previous score = 8; mean = 6,0 Difficulty concentrating Your previous score = 9; mean = 5,1 Sore mouth/pain when swallowing Your previous score = 9; mean = 5,1 Difficulty swallowing Your previous score = 9; mean = 5,6 Cough Your previous score = 9; mean = 5,5 Dry mouth Your previous score = 9; mean = 6,5 Problems with urination Your previous score = 8; mean = 5,4
1 1 3 1 1 1 2 1 3 1 1 1 5 1 1
0 1 2 3 4 5 6 7 8 9
10
Comments
2 5 2
2 1
1 2 1 2 2 1
1 1 1
1 3 2 2 1
2 1 4 1
2 1 2
1 3 1
1 2 1
1 1 1 1 4 1
1 2 1
2 4 1
1 2 1
3 3 1
2 4 4
1 1 1 2 4
2 1 1
Hallucinations Your previous score = 9; mean = 6,2 Psychological symptoms/problems Worrying Your previous score = 9; mean = 5,2 Nervousness Your previous score = 6; mean = 5,4 Anxiety (screening tool?) Your previous score = 10; mean = 7,5 Sadness Your previous score = 8; mean = 5,0 Fear of suffering Your previous score = 8; mean = 5,2 Loss of autonomy Your previous score = 8; mean = 5,3 Distress Your previous score = 7; mean = 5,3 Activity level Care for yourself (dress, wash, etc) Your previous score = 8; mean = 7,7 Walk at home Your previous score = 7; mean = 5,0 Not being able to do the things you used to do Your previous score = 8; mean = 5,4 Social issues Problems in the relationship with companion Your previous score = 9; mean = 5,4
1 1 1 2 2 1 4 1 1 1 1 1 2 1 3 2
0 1 2 3 4 5 6 7 8 9
10
Comments
1 1
1 3 1 1 2 1
1 1
1 1 3 1 3
3 2 1
Difficulties of communication with the companion Your previous score = 8; mean = 5,3 Support from family/friends Your previous score = 8; mean = 6,0 Difficulties in talking about the disease Your previous score = 7; mean = 5,8 Spiritual issues Belief/faith (Do you have religious belief/faith?) Your previous score = 8; mean = 5,0 Overall quality of life Well-being Your previous score = 8; mean = 7,8
1 1 1 1 1 2 2 1 1 2 1 2 1 3 1 4
4
parecer do co-orientador, dr. nigel sykes
Anexo 4
Dear Jose Antonio, This is very interesting and I think shows what a difficult area this is to tackle. Negative results are still important and it is rather fascinating that observers are so disagreed on what constitute signs of discomfort. I wonder if there is any way of exploring why there was so little agreement? Perhaps at this distance from the original assessments there isn't, as I guess you would have to do two (or more) assessments straight after each other and then get the raters together in front of the patient to explain their thought processes to each other. Again, it is interesting that while it is fairly easy to be sure when a patient is distressed it is much harder to say when they are not. Given the range of types of distress and the range of degrees of stoicism this might, perhaps, be expected. It seems to me that what you propose by way of including this measure, set appropriately against the background of the existing literature on the assessment of non-communicating patients, is reasonable. But your negative results, with accompanying discussion of why they might have arisen, are also an important part of the results. Best wishes, Nigel Dr Nigel Sykes Medical Director Consultant in Palliative Medicine St Christopher's Hospice Lawrie Park Road London SE26 6DZ Tel: 020 8768 4551 Fax: 020 8659 8680
10
ARTIGOS PUBLICADOS

Abstract The background to the advanced chronic diseases in an development of the first Portuenvironment where palliative care guese palliative care unit is is not yet well developed. described. The activities of this J.A.S. Ferraz Gonalves (Y) pioneer unit in Porto, which Keywords Palliative care 7 Instituto Portugues de Oncologia, include patient assistance, teaching Portugal Unidade de Cuidados Continuados, R. Dr. Antnio Bernardino de Almeida, and research, are reported, and the 4200-072 Porto, Portugal paper closes with some general E-mail: ferrazg6ipoporto.min-saude.pt or thoughts on the possible ways of ferrazg6mail.telepac.pt providing a more rapid response to Phone: c351-2-5073940 the suffering of patients with far Fax: c351-2-5506833 Abstract The background to the advanced chronic diseases in an Published online: 28 October 2000 development of the first Portuenvironment where palliative care Q Springer-Verlag 2000 guese palliative care unit is not yet well developed. recognized. In thisisdocument, the WHO stated that Introduction described. The activities of this palliative care was a priority in the fight against cancer, J.A.S. Ferraz Gonalves (Y) pioneer unit in Porto, which Keywords Palliative care 7 curative Instituto Portugues de Oncologia, Palliative care has its source in the recognition of a on the same level as prevention, screening and include patient assistance, teaching Unidade de the Cuidados Continuados, problem: inadequate treatment of patients with treatment, and the Portugal only solution that was both humane R. Dr. Antnio Bernardino de Almeida, and can research, are reported, and for the many cancer patients. Palliative mediadvanced chronic diseases. This treatment be inadand realistic 4200-072 Porto, Portugal paper closes with some general equateferrazg by excess or default, that is, E-mail: 6ipoporto.min-saude.pt or failure to recognize cine is now a recognized specialty and is a subject in thoughts the possible ways medical of ferrazg 6mail.telepac.pt the situation and consequent continuation with on aggresuniversity school curricula in the United a more response Phone: c351-2-5073940 sive treatments as if the problem were providing a reversible one, rapid Kingdom and to a few other countries. the suffering of patients with far Fax: c351-2-5506833 or abandonment of the patient without support. Such Since its beginnings, palliative care has spread
Published online: 28 October 2000 Q Springer-Verlag 2000
abandonment occurs not only when patients are sent quickly through the world, mainly, like everything else, home, but often in the hospital too. In this situation the in the more highly developed countries. In Portugal, In isthis the steps. WHO that patients can be labelled as terminal and not followed recognized. palliative care still document, taking its first It stated is the very Introduction care wasis a described priority inhere. the fight against cancer, up with the same interest as others: their needs may not palliative first of these that Palliative care has its source in the recognition of a on the same level as prevention, screening and curative be really considered, and the medications and care they problem: the treatment with treatment, and the only solution that was both humane do receive areinadequate often quite irrelevantoftopatients their condiadvanced chronic diseases. This treatment can be inad- and realistic for many cancer patients. Palliative medition. The beginning equate by excess or default, that is, failure to recognize The start of palliative care is usually dated from the cine is now a recognized specialty and is a subject in the situationof and continuation aggresschool curricula League in the Against United The North medical Section of the Portuguese foundation St.consequent Christophers Hospice with in 1967 by university sive treatments as ifthis the way problem were a movement reversible one, and a few other Cancer recognized the countries. cancer patients situation Cecily Saunders. In the hospice was Kingdom or abandonment of palliative the patient without support. Such described Since its beginnings, palliative care has spread above and decided to build a palliative care initiated. The term care was used officially abandonment occurs not when only when patients sent quickly the world, mainly, like everything else, unit to through be called Unidade de Cuidados Continuados, for the first time in 1975, Balfour Mountare opened home, but oftenCare in theService hospital in too. In this situation the in the would more work highly developed countries. In Portugal, which closely with the Porto Section of the the Palliative the Royal Victoria patients be labelled asIn terminal andWorld not followed care is still of taking its first steps. It is the very Portuguese Institute Oncology. At a certain point in Hospital can in Montreal [1]. 1990, the Health palliative up with the same interest one as others: needs may not first of these is described here. to be the medical the course of that the project I was invited Organization published of itstheir best-known docube really considered, and the medications and care they ments Treatment of cancer pain and palliative care director of the unit. I was a specialist in internal medido arethe often quite irrelevant to their condi[2], receive in which importance of palliative care was cine and oncology and I accepted the position on one tion. The beginning The start of palliative care is usually dated from the foundation of St. Christophers Hospice in 1967 by The North Section of the Portuguese League Against Cecily Saunders. In this way the hospice movement was Cancer recognized the cancer patients situation initiated. The term palliative care was used officially described above and decided to build a palliative care for the first time in 1975, when Balfour Mount opened unit to be called Unidade de Cuidados Continuados, the Palliative Care Service in the Royal Victoria which would work closely with the Porto Section of the Hospital in Montreal [1]. In 1990, the World Health Portuguese Institute of Oncology. At a certain point in Organization published one of its best-known docu- the course of the project I was invited to be the medical ments Treatment of cancer pain and palliative care director of the unit. I was a specialist in internal medicine and oncology and I accepted the position on one [2], in which the importance of palliative care was 10
condition: that I should be allowed to take training in palliative care, which at that time was only possible in units outside Portugal. Over the course of 7 months I visited several European units: St. Christophers Hospice and St. Helena Hospice in England; Intituto Nazionale dei Tumori in Milan; La Foundation Rive-Neuve and the Aubonne Hospital in Switzerland; and Gregorio Maran n Hospital in Madrid. I believe this was very useful and, in my case, the best approach, because the diversity I saw showed me different realities, different experiences, and different styles of palliative care. I concluded that palliative care can be applied in many different conditions, always with the same philosophy and the same principles behind it while the practice is adapted to the local circumstances, and that what is observed in any palliative care service should be taken as an example of what can be done, rather than a model to be copied.
I The opportunity of spreading the principles of palliative care more easily, because there was more direct contact with doctors in the other service I Training the team in more specific work with only a few patients I Possibility of contact with the reality of palliative care, thus allowing selection (self-selection, at that time) of people who really wanted to go on working in palliative care I Economy because the unit was so small it was cheaper to work together with the other service, which made it possible to maintain adequate continuous staffing levels of professionals who needed to be represented at all times, mainly nurses, without having too many professionals relative to the number of patients We can conclude that this experience was useful, and perhaps it could be viewed as an example for other centres where only a small unit can be implemented.
The first unit

Because I finished my training period before the unit was ready, we were allowed to start working with 5 beds belonging to the Radiotherapy Service, which had a total of 25 beds. The staff in that service included the nurses who were keen to work in the future palliative unit, some of whom had had some experience of palliative care in units abroad. Our first patient was admitted on 17 October 1994. This, then, was the day when palliative care started in Portugal. All the personnel, except the chief nurse and myself, were shared between the two services. We started doing inpatient care, outpatient care, and consultation in other services within the hospital. There were various difficulties with this experience: I Problems arising from the physical/architectural setup, which did not make it easy for family members to stay with patients, especially at night I Too few beds for hospital needs I Different treatment of patients in the same service I Difficulty in the implementation of specific routines Other types of problems experienced at this stage were: I Problems relating to misunderstanding of the purpose of the new service I Referral mainly of patients expected to survive for only a few days I Frequent use of the unit as a kind of wastebasket, that is, not with the idea of sending patients to a place where they could be more adequately treated but to get a bed free These early days did also have positive aspects: I The possibility of offering palliative care at all for the first time
The new unit

Finally, the new unit opened on 25 May 1996. We grew step by step as more people were involved in the team (Table 1). Initially, we maintained the same activities, adding to them as circumstances allowed (Table 2). Now we have 20 beds, all in single rooms, which allows a member of any patients family or a friend to stay at any time. The unit has had a day centre since 1997: about 20 patients can attend for up to 3 days each week, and they can enjoy many activities.
Table 1 Staff of unit Doctors Nurses Nursing auxiliaries Social worker Psychologist Nutritionist Chaplain Driver Porters Volunteers 4 with 1 assigned exclusively to home care 24 16 1 1 1 1 1 7 15
Table 2 Evolution of the assistance to patients activity 1995 Inpatient admissions 68 Outpatient clinic observations Internal consultation visits Telephone consultation Home care visits 1996 100 1997 221 549 361 1998 359 1124 596 449 1999 388 1302 910 813 212
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hold update courses to maintain interest in palliative care and ensure that the knowledge applied is current. Since the beginning of our activities, members of the units staff have participated in many courses, congresses, and other scientific meetings organized by others. And, finally, I teach the palliative care portion of the course for the masters degree in bioethics at the Medical School of Oporto University. Apart from the courses, many doctors, nurses, social workers, psychologists, and priests spend various periods of time in the unit. Research Again, the position this unit occupies in palliative care in Portugal should make research one of its most important activities, on a level with patient assistance and teaching. These two activities should support and be supported continuously by research. However, research takes time to produce results, so that we are not in a hurry to publish research papers, though we are publishing some review papers in Portuguese. However, we have presented some work at congresses of the European Association for Palliative Care and at other congresses, and we intend to start publishing our results soon. The future The unit is still evolving: in the future there will be more than 20 beds, and the home care service will be developed and will reach more patients. Teaching of palliative care will remain important, and it is probable that this unit will continue as the main palliative care teaching centre in Portugal. Faculty members of the Oporto Medical Schools have been contacted about the idea of introducing undergraduate palliative care teaching into their curricula, but I have not yet received any answers this would be a very important step. Research will take up the desired place. The immediate problem is finding people interested in working exclusively in palliative care. Unlike other European countries, Portugal does not have an excess of doctors and nurses, so that recruitment of professionals to the unit will not be easy.
Since 1998 we have offered telephone consultations for the patients being followed by the unit. The patients, their families, or their friends may contact the unit when a problem or a doubt arises, to discuss an adjustment to a medication, or to inform the doctor of the effect of a prescription, for example, 24 hours a day. It is usually possible for them to talk with the physician between 09*E00 and 16*E00 oclock, and with a nurse at other times. In 1999 we started home care. We intend to make this service one of the most important elements of the unit, so that patients can stay at home where their families and their own belongings are, that is to say where their lives are centred. However, the traditional extended family with three generations under one roof providing support for all members of the family in difficult times is changing. Families are becoming smaller and smaller; most people work outside the home, mainly in the bigger cities, and there will therefore probably be more and more difficulties in keeping patients at home, as has already happened in other European countries. Teaching As this is a pioneer unit in Portugal and in view of its size, it was planned that it should be a teaching centre. As professionals working exclusively in palliative care, we have an obligation to contribute to the spread of knowledge in this field. However, the best thing we can do is to go beyond teaching what can be read in books and reviews and also, most importantly, share our experience. This is why we did not start the multidisciplinary courses until we had completed 3 years of work as a palliative care team. Our first multidisciplinary course was in October 1997. Since then, we have held four each year. Each course is held for 12 professionals: 6 doctors and 6 nurses. This small number allows contact with the everyday life of the unit and with the patients. Each course involves 35 hours from Monday to Friday in 1 week. Up to August 2000, 144 professionals from all over the country, even from the islands of Madeira and the Azores, had undergone training in 12 courses. We always have many more candidates than we can admit to the courses, which shows the interest people have in palliative care and how much they feel the need of training in this special field. To help staff who work in our oncological centre but had not been able to get a place on any of the multidisciplinary courses we held a theoretical course in 2000, which was attended by 35 professionals. In 2000 we held the first continuing education course for doctors and nurses who had already completed the multidisciplinary course. And in the future we intend to
Other remarks
Since the opening of the unit, almost 6 years ago, palliative care has not evolved much further in Portugal. There are a few other experiences, but the overall picture is very poor. The implementation of palliative care has been difficult in most countries, and in
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Portugal it will not be any different. Many still see palliative care not as a resource with its own knowledge and skills, but as what is offered in places where nursing and psychological and religious support are the most important aspects whilst the medical input has a secondary, and not especially skilled, role. Some medical oncologists, for example, claim that they should take care of their patients until their death, forgetting that the reality is different in most cases and that the care patients need when curative treatment is no longer useful must be learned, and is often not what they are providing. However, not all patients need to be treated by palliative care specialists. As in other specialties, many patients can be treated by their own physicians with some training, but there are difficult situations that require specialized resources of different types. In addition, research and teaching should be carried out, and usually only specialists have the knowledge, the experience, the readiness, and a sufficiently large number of patients for this. Palliative care is now needed in Portugal and must be developed. However, I suspect, unfortunately, that it
will be a long time before a serious effort is made to do this. Nonetheless, something must be done quickly. Palliative care can be provided in many different circumstances. Palliative care units are indispensable, in my view, but home care and inpatient support teams are examples of other options that would be easier to implement. In my opinion, it is more important to do something useful immediately for patients with advanced chronic diseases who are suffering unnecessarily than to wait for conditions that anyone might imagine to be ideal. When we started, for example, conditions were not ideal, because the unit was not yet ready. So, professionals and hospital staff members with an interest in this field should start however local conditions allow and then improve their situation at the rate that is possible, but without ever forgetting the training needed. I also believe that doctors have a special responsibility, because if they know and apply the principles and skills of palliative care, even alone, they can have a very important impact on the wellbeing of their patients with chronic advanced diseases.
References
1. Saunders C (1998) Foreword. In: Doyle D, Hanks GWC, MacDonald N (eds) Oxford Medical Publications, Oxford, pp vix 2. World Health Organization (1990) Traitement de la douleur cancreuse et soins palliatifs. (Srie de rapports techniques 804) WHO, Geneva
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Diagnosis disclosure in a Portuguese oncological centre

J Ferraz Gonalves Director and S Castro Psychologist, Unidade de Cuidados Continuados, Instituto Portugus de Oncologia, Porto Abstract: The disclosure of a diagnosis of cancer to patients is a controversial matter. There have been major differences in practice concerning this issue through time and between cultures. A questionnaire was sent to the doctors of the Oporto Centre of the Portuguese Institute of Oncology in order to assess their attitudes. We received 45 responses (40%) from the 113 questionnaires sent. Of these, 32 (71%) said that they disclose the diagnosis as a general policy or at the patients request, and 13 (29%) disclose it rarely or not at all. The most frequent reason indicated by these 13 physicians was that the disclosure might damage the patients psychologically. Forty-four (98%) doctors inform the family of the diagnosis. Thirty-nine (87%) think that patients are satised with the information provided. This study was carried out in one oncological centre only, so it is inappropriate to conclude that this is what happens throughout Portugal. As far as we know, this is the rst study in Portugal addressing this area of practice. This subject is a very important topic of research both in Portugal and in other countries, as many published recommendations are not research based. Key words: breaking bad news; communication; diagnosis disclosure; physicianpatient relation Resumo: A revelao do diagnstico aos doentes com cancro um assunto controverso. Tem havido grandes diferenas na prtica respeitante a esta questo ao longo do tempo e entre as diversas culturas. Envimos um questionrio aos mdicos do Centro do Porto do Instituto Portugus de Oncologia para avaliar as suas atitudes. Recebemos 45 respostas (40%) dos 113 questionrios enviados. Destes, 32 (71%) dizem que revelam o diagnstico por princpio ou quando os doentes o pedem e 13 (29%) revelam-no raramente ou nunca. A razo mais frequentemente indicada por estes 13 mdicos foi a de que a revelao pode causar dano psicolgico aos doentes. Quarenta e quatro (98%) mdicos informam a famlia do diagnstico. Trinta e nove (87%) pensam que os doentes esto satisfeitos com a informao dada. Este estudo foi feito num nico centro oncolgico, por isso no podemos dizer que isto que se passa, de um modo geral, em Portugal. Tanto quanto sabemos, este o primeiro estudo realizado em Portugal sobre este aspecto da prtica mdica. Este um tpico de investigao muito importante tanto em Portugal como noutros pases, porque muitas recomendaes prticas publicadas no se baseiam na investigao. Palavras-chave: dar ms notcias; comunicao; revelao do diagnstico; relao mdicodoente
Address for correspondence: Dr J Ferraz Gonalves, Unidade de Cuidados Continuados, Instituto Portugus de Oncologia, R. Dr. Antnio Bernardino de Almeida, 4200-072 Porto, Portugal. Arnold 2001 02692163(01)PM396OA
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36 J Ferraz Gonalves and S Castro
Introduction
The disclosure of a diagnosis of cancer to patients is a controversial matter. The dominant attitude among physicians has changed over time, and there have always been voices advocating against it.1 We will also nd different attitudes when we compare practice in countries with different cultures. In the United States and northern European countries,24 for example, the usual practice is to disclose the diagnosis. However, in other countries, including those of southern Europe,48 the situation is different: doctors attitudes are more paternalistic, and in many cases they do not disclose the diagnosis. In Portugal, the current practice seems to be one of non-disclosure. However, as far as we know, no research on this subject has been carried out in Portugal.
mittee of the Portuguese Institute of Oncology Oporto Centre.
Results
The questionnaire was sent to 113 doctors, and 45 responses (40%) were obtained. In Table 1 we show the specialities and demographic data of the doctors who returned the questionnaires. There is a similar percentage in all specialities, with the exception of radiotherapy (Table 1). Nineteen (42%) participants added comments, clarifying their views or adding other hypotheses to those included in the questionnaire. The questions most commented on were: the one that asked if doctors disclose the diagnosis of cancer to the patients, and if not, why not; and the questions about the patients and families participation in therapeutic decisions. Among our respondents, 14 (31%) doctors stated that their policy was to disclose the diagnosis, three (7%) do not do it at all, 10 (22%) rarely do it and 18 (40%) disclose it only at the patients request (Table 2). A much higher number, 44 (98%), inform the family about the patients diagnosis; in one case (2%) the answer was omitted. The most frequent reason indicated by the 13 doctors (34%), who rarely or never disclose the diagnosis to patients (Table 3), for so acting was the possibility of damaging the patients psychologically (11, 85%). The comments added to the questions about the disclosure to patients and the reasons for not disclosing the cancer diagnosis, again, show a concern with the eventual psychological damage that the disclosure might produce. Some examples of these comments can be seen in Table 4. To the question do your patients often request more information from you? 29 (64%) answered
Methods
We conducted a survey in the Oporto Centre of the Portuguese Institute of Oncology, which is one of the most important Portuguese oncological centres. It has 350 beds and about 4000 new patients are admitted every year. It has services and equipment equivalent to those of any major European oncological centre, including a palliative care unit. This centre is a public hospital that serves the population from the whole of northern Portugal. The patients belong to all social classes and education levels. A questionnaire (see the Appendix), specically designed for this study but not subjected to a pilot test, was sent to each doctor at the centre who treated adult patients. Those with other functions, such as radiologists and pathologists, were excluded. This study was approved by the Ethics ComTable 1 Doctors speciality and demographic data Speciality Surgery Medical oncology Radiotherapy Other Total No. of questionnaires sent 52 24 24 13 113
No. of questionnaires returned 22 12 5 6 45
Total returned (%) 49 27 11 13 100
Returned per speciality (%) 42 50 21 46
Age: mean 46 years (range: 3165 years); median 45 years. Sex: male 27 (60%); female 17 (38%); not stated 1 (2%).
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Diagnosis disclosure in a Portuguese oncological centre 37

Table 2 Diagnosis disclosure to the patient No. (%) Yes No Rarely At patients request 14 (31) 3 (7) 10 (22) 18 (40)
Table 3 Reasons invoked for rare or non-disclosure (13 doctors) Reason Difculties in discussing the diagnosis Not prepared to deal with the situation Not useful to the patient Psychologically deleterious Not having enough time Others Yes 0 0 3 11 2 4 No 13 13 10 2 11 9
Table 4 Examples of comments to questionnaire questions 1 and 2 The decision to disclose the diagnosis should consider the psychological, intellectual, cultural and social conditions of the patient It is necessary to inform the patients gradually and with sensitivity and gentleness, without coldness After the information has been provided, psychological support is needed Most patients are not prepared to receive the information of a malignant disease The information must be given when it is useful to the patient The information can cause depression Never use the word cancer Patients often ask for information to feel hopeful in their lives (we understand this statement means that the patient does not really want the truth but a negative answer)
yes and 16 (36%) answered no. These 16 doctors presume that their patients are satised with the information they get, or simply do not wish any more information at all (Table 5). This agrees with the answers to question 4, to which 39 (87%) said that they think their patients are satised with the information they give them. Forty-one doctors (91%) think that patients should participate in decisions about treatment and four (9%) think they should not. The reasons for these opinions are shown in Tables 6 and 7. Only 25 (56%) thought that family members should participate in making treatment decisions. The few comments about the patients participation in therapeutic decisions suggest that they should not participate or even inuence them. It was, however, conceded that if offered two equally effective treatments the patient can choose the one that is more bearable for him or her. Similar comments were made about family participation in these decisions. One respondent stated that the decision belongs to doctors, and that family can be involved to encourage the patient to accept the recommended treatment and to endure its toxicity.
Table 6 Reasons why patients should participate in treatment decisions (41 doctors) To preserve patient autonomy To make the adherence to treatment easier To protect the doctor from legal problems To allow the patient to prepare himself for adverse effects To allow the patient to refuse the treatment eventually Other 25 35 19 30 23 4
Table 5 Reasons to explain why patients often do not request more information from their doctors (16 doctors) They are satised with the information they have been given They are not at ease to ask questions They do not wish for more information They feel you do not have enough time to talk to them They think they will not understand the information you can give 7 1 5 2 0
Table 7 Reasons why patients should not participate in treatment decisions (four doctors) It is difcult for you to discuss treatment with patients You think it is not useful to patients You do not have enough time to discuss treatment with the patients The discussion might damage the patients psychologically Other 1 2 4 1 1
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J Ferraz Gonalves and S Castro admitted to an oncological service and a palliative care unit who had not been informed of their diagnosis, 42% did not want to receive more information. An alternative explanation of our results is, perhaps an element of denial, because breaking bad news is recognized by most experts as being difcult and causing some degree of discomfort, even for experienced professionals;9 in Portugal this problem is not addressed in any way, except in some limited educational activity. It is possible that doctors are hiding their own difculties in dealing with these aspects of communication behind a paternalistic attitude. Communication with patients can be learned, but denial can delay or prevent the decision to act accordingly. However, we must be very careful with the interpretation of the results obtained and avoid preconceptions. It seems to be a contradiction that 91% of the doctors think that patients should participate in treatment decisions, because this percentage is higher than those who inform patients, and without information about their disease it is not possible for patients to decide rationally about the treatment. On the other hand, doctors think that family members, who are almost always informed, should participate in treatment decisions in a much smaller proportion of cases (56%). The comments about the decisions also have a paternalistic character when they state that patients should not decide about treatment. However, these comments represent a minority because 91% think that patients should participate in those decisions. The family is seen as a possible doctor ally, facilitating the adherence to treatment and helping the patient to endure the treatment decided on by the doctor. The available data show that Portuguese doctors, who work in this oncological centre, disclose the diagnosis to patients less frequently than doctors from other countries, including those of the southern Europe, such as Greece. This study was carried out in one centre only so it is inappropriate to generalize, but the result obtained agrees with, or is even higher than, what we expected was happening in Portugal. This study reects the way in which doctors see themselves, not necessarily what happens, and is more important, in our point of view, if the information is tailored to the desire of the individual
Discussion
This study was carried out in an oncological centre, where informing patients about their diagnoses is an everyday matter. We only had a 40% response rate, which is rather low although similar to that obtained in at least one very important paper.2 This must be borne in mind when considering our ndings. The reason why radiotherapists participated less than other specialists is not clear. The percentage of doctors (71%) who disclose the diagnosis of cancer as their general policy or when requested by patients is smaller than that found in other studies in which questionnaires were addressed to doctors,24 even some of those carried out in southern European countries.4 But the practice of informing the family almost always (98%) is the same as what usually happens in those countries.5 Doctors most frequently indicated the reason for rarely or never disclosing the diagnosis was that it might damage the patients psychologically. It seems that those doctors prefer to protect the patients from possible psychological damage rather than to respect their autonomy. A lack of training in dealing with requests for information was not suggested as a reason for these responses. Doctors whose experience is not to have frequent requests for information feel that this happens because the patients are satised with the information they get or because they just do not want more information at all. Indeed, 87% think that patients are satised with the information provided and this percentage is higher than those who inform their patients as a general policy or when requested. The comments also show a concern for the patients protection: inform with sensitivity and gentleness; without coldness; inform those we think have sufcient psychological and intellectual resources; the need for psychological support; the information can cause depression; never use the word cancer. Again, a decision not to inform seems to be due not to a lack of training or difculty in dealing with the situation but to have its roots in a protective attitude to the patients, in order not to affect them psychologically and may be understood as what they really want. In fact, in a study conducted in Spain,6 with a culture similar to that of Portugal, of the 68% of 97 patients
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Diagnosis disclosure in a Portuguese oncological centre patient. So, it is also very important to know what Portuguese patients think about medical information issues, not only disclosure of the diagnosis but also about the prognosis and their participation in therapeutic decisions. The research on these topics is very important and is not extensive. Most of the medical literature providing practical advice is not research based.10 To explain the differences in attitude between the countries in what concerns cancer diagnosis disclosure, cultural causes have been indicated. However, perhaps these cannot explain, at least completely, those differences, because if we go back to the 1950s and 1960s we nd that in the USA most doctors used not to disclose a cancer diagnosis to their patients, but nowadays almost all do so.2 The reasons for this change are certainly many: the spread of information in the media about cancer treatment advances (real or not) and the treatment options available in some cases, where the choice only depends on patients wish (for example, conservative breast surgery); the spread of information on patients rights and the growing demand for quality of medical services; the patients enrolment in research protocols demanding informed consent; and legal matters that involve the medical profession. These matters are progressively arising in Portugal and other countries, and we believe that, as time goes by, the picture concerning cancer diagnosis disclosure will be similar to that already present in the USA and northern European countries.
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References
1 Reiser SJ. Words as scalpels: transmitting evidence in the clinical dialogue. Ann Intern Med 1980; 92: 83742. 2 Novack DH, Plumer R, Smith RL, Ochitill H, Morrow GR, Bennett JM. Changes in physicians attitudes toward telling the cancer patient. J Am Med Assoc 1979; 241: 897900. 3 Loge JH, Kaasa S, Ekeberg , Falkum E, Hytten K. Attitudes toward informing the cancer patient a survey of Norwegian physicians. Eur J Cancer 1996; 32A: 134448. 4 Thomsen O, Wulff HR, Martin A, Singer PA. What do gastroenterologists in Europe tell cancer patients? Lancet 1993; 341: 47376. 5 Mystakidou K, Liossi C, Viachos L, Papadimitrou J. Disclosure of diagnostic information to cancer patients in Greece. Palliat Med 1996; 10: 195200. 6 Corts CC, Olarte JMN. Questioning diagnosis disclosure in terminal cancer patients: a prospective study evaluating patients responses. Palliat Med 1994; 8: 3944. 7 Estap J, Palombo H, Hernndez E et al. Cancer diagnosis disclosure in a Spanish hospital. Ann Oncol 1992; 3: 45154. 8 Surbone A. Truth telling to the patient. J Am Med Assoc 1992; 268: 166162. 9 Buckman R. Communication in palliative care: a practical guide. In: Doyle D, Hanks GWC, MacDonald N eds. Oxford textbook of palliative medicine, 2nd edn. Oxford: Oxford University Press, 1998: 4761. 10 Ptacek JT, Eberhardt RL. Breaking bad news. J Am Med Assoc 1996; 276: 496502.
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J Ferraz Gonalves and S Castro
Appendix
Diagnosis disclosure survey Age: ............................................................................ Gender: ...................................................................... 1. Do you disclose the diagnosis to cancer patients? Yes Rarely No At the patients request Speciality: .................................................................... Service: ........................................................................
2. If the answer was No or Rarely, indicate the reasons: You nd difcult to disclose the diagnosis You were not prepared to deal with this information You do not nd useful to the patient to know that information The disclosure might damage the patient psychologically You do not have time enough Other Specify: 3. Do you disclose the diagnosis to the family of cancer patients? Yes No
4. Do you think that your patients are satised with the information you give them? Yes No 5. Do your patients often request more information from you? Yes No
(if you answered Yes, go to question 7) 6. You think your patients do not request more information from you often, because: They are satised with the information they have been given They are not at ease to ask questions They do not wish more information They feel you do not have enough time to talk to them They think they will not understand the information you can give Other Specify:
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Diagnosis disclosure in a Portuguese oncological centre 7. Do you think patients should participate in treatment decisions? Yes No If your answer is Yes, indicate the alternative(s): To preserve the patients autonomy To make easier the adherence to treatment To protect the doctor from legal problems To allow the patient to prepare himself to adverse effects To allow the patient to refuse the treatment eventually Other Specify: If you answered No, indicate the alternative(s): It is difcult for you to discuss treatment with patients You think it is not useful to patients You do not have enough time to discuss treatment with the patients The discussion might damage the patients psychologically Other Specify: 8. Do you think that the family should participate in the decisions concerning treatment? Yes No 41
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JOURNAL OF PALLIATIVE MEDICINE Volume 6, Number 6, 2003 Mary Ann Liebert, Inc.
The Last Forty-Eight Hours of Life in a Portuguese Palliative Care Unit: Does it Differ from Elsewhere?
J. FERRAZ GONALVES, M.D.,1 MARGARIDA ALVARENGA, R.N.,1 and ALEXANDRA SILVA, R.N.2
ABSTRACT The last few days of life have received significant attention in the literature. Reports have shown similarities and differences between programs. As a palliative care service in a cultural context that has not been reported on, we thought that an audit of our own experience in the care of patients in the last 48 hours of life and a comparison with other programs would be important. A prospective audit was designed to record data for four general domains: general demographic information, symptom prevalence, patient performance status, and perceived level of comfort. The inclusion criteria of patients were: older than 15 years of age (an admission criterion for patients of the unit), diagnosis of cancer, no active cancer-direct treatments, and patients who were on the unit for longer than 48 hours. The audit was completed when the 300th eligible patient died in the unit. Twenty-nine of 300 patients (9.6%) required sedation and the most common cause was delirium. Morphine was the most widely prescribed medication (85% of patients). The subcutaneous route was utilized extensively. Only 12% of the patients received parenteral fluids, usually via hypodermoclisis. Death was considered by staff to have been peaceful in 86% of cases. Our practice appears to mirror that of other palliative care groups.
INTRODUCTION
that palliative care provides, the last few days of life have received significant attention in the literature. 15 Issues such as frequency of various symptoms, symptom management, and palliative sedation are among the subjects that have been reported on. These reports, from various centers and care settings, have indicated similarities and differences between programs and have prompted discussion and reflection. Being a relatively new palliative care service6 in
ITHIN THE CONTINUUM OF CARE
a cultural context that has not previously been reported on, we felt that it would be important to document our own experiences in caring for patients in the last 48 hours of life and compare these with experiences of other programs for the purpose of clinical audit and improvement of care. The audit focused on the frequency of use of palliative sedation, the indications for palliative sedation, the presence of various symptoms and problems, and whether or not the interdisciplinary team felt that the patients appeared comfortable or not, recognizing the limitations of viewing this parameter from a health care professionals perspective.
1 Unidade 2 Servio
de Cuidados Continuados, Instituto Portugus de Oncologia, Porto, Portugal. de Medicina A, Hospital de S. Pedro-Vila Real, Vila Real, Portugal.
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METHODS
A prospective audit was designed to record various facets of care during the last 48 hours of life prior to the death of patients admitted to the palliative care unit of the Portuguese Institute of Oncology of Porto, Portugal. Data were collected on four general domains: general demographic information, symptom prevalence, patient performance status, and perceived level of comfort (the latter perceived by the attending physician and/or nurse present at the time of death). A data recording sheet was utilized to document the data. The inclusion criteria of patients were: older than 15 years of age (an admission criterion for patients of the unit), diagnosis of cancer, no active cancer-direct treatments, and patients who were on the unit for longer than 48 hours. Patients who were on the unit for less than 48 were excluded from this audit. All consecutive admissions to the unit were reviewed and the audit was completed once 300 consecutive patients who met the inclusion criteria had been admitted. The audit was begun in January 1995 and completed in July 1998, when the 300th eligible patient died in the unit. For the purposes of this audit, the presence or absence of a symptom or problem was documented. Many patients in their last 48 hours of life are unable to report the intensity of their symptoms for reasons of frailty or confusion. As part of the normal practice of the unit, the presence or absence of various symptoms and problems are recorded on a daily basis using a standardized checklist. In addition to more common symptoms such as pain, dyspnea, and nausea, other problems such coughing, fever, sweating, myoclonus, hemorrhaging, upper airway rattling from secretions, urinary retention, catheterization, and ostomy tubes are routinely documented. These data were analyzed for the purpose of this audit. The symptoms are routinely measured in the unit using a 0 to 4 scale, where 0 indicates the absence of symptoms and 4 indicates an unbearably high intensity of that symptom. The range of symptoms is similar to those used in the Memorial Symptom Assessment Scale. 7 A verbal scale (none, light, moderate, severe, unbearable) is utilized when patients are unable to use the numeric scale. When this happens, the data are transformed to a numeric scale so as to facilitate data entry and analyses. For those patients who are unable to report their own
symptom distress and intensity, a nurse or a physician does a proxy assessment. However, it is recognized that proxy assessments by both health care providers and families are often unreliable. 8 It is also customary on the unit to exclude certain symptoms such as fatigue and anorexia from the list of symptoms when patients were frail and obviously in their last days of life, to minimize patient burden, and because their assessment is unlikely to modify management. In addition to the scales, the presence or absence of certain problems such as hemorrhaging, fever, urinary incontinence and retention, and myoclonus is recorded using a checklist. The short version of the Confusion Assessment Method (CAM)9 is used to screen for delirium. The CAM is applied once a week and whenever there is any mental alteration detected by a member of the staff or family. For the purposes of this audit, communication was broadly defined as the ability to understand at least simple questions (example: Do you have pain?) and make oneself understood, even if intermittently. The definition by Chater et al.10 of palliative sedation was used: The intention of deliberately inducing and maintaining deep sleep, but not deliberately causing death . . . for the relief of one or more intractable symptoms when all other possible interventions have failed and the patient is perceived to be close to death . . . At the start of this audit, this definition had not been published and a broader definition was being used. When this definition was published, we felt that it constituted a more reliable definition and therefore conducted a retrospective review of the charts, applying the definition suggested by Chater and colleagues. The policy on the unit is to include patients, if they are competent, in the decision-making process when palliative sedation is considered. If incompetent, family members or guardians are approached. Exceptions to this are when patients are incompetent and family members absent when unexpected crises that require prompt sedation occur. The physicians of the unit also indicated whether or not the patients death was expected and if they felt the patient was comfortable and peaceful in the last 48 hours. For the purpose of this study, peacefulness was defined as a good level of comfort from the perspective of the physician and/or nurse present at the time of death. The medications administered were also audited.
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TABLE 1. Tumor Head and neck Stomach Breast Colorectal Lung Cervix Gastrointestinal others Genito-urinary male Ovary Multiple Other DEMOGRAPHICS
AND
897
PRIMARY TUMORS No. 44 42 39 29 25 21 14 12 9 9 56 (%) 15 14 13 10 8 7 5 4 3 3 19
Gender: male, 148 (49%); female, 152 (51%). Age: median, 61 years; range, 1795. Length of stay: median, 14 days; range, 2121.
The attending physician, with the nurse and/or the physician present at the time of death, was required to review the patient chart and record the data within 48 hours of the patients death on the data form. The palliative care unit is a freestanding unit within an oncology center complex in Porto, Portugal. It started with 5 beds and now has 20 beds6 and shares resources with the oncology center. The unit receives its referrals from the cancer center. Physicians, nurses, a psychologist, a social worker, and a nutritionist make up the units interdisciplinary team. The investigators did not seek approval from the institutions ethics research board on the basis that the data collected were derived from normal daily screening and evaluation practices. Moreover, the study did not evaluate any direct intervention on patients. However, the investigators acknowledge that current standards would likely require approval from an ethics board.
The demographic profiles of the 300 eligible patients are listed in Table 1. Table 2 lists the prevalence of symptoms and problems experienced by the 300 eligible patients in the last 48 hour of their lives. Twenty-nine of 300 patients (9.6%) required palliative sedation. The indications for these are listed in Table 3. Delirium was the most common indication for palliative sedation. Palliative sedation was initiated in one patient after the patient requested to be sedated. This patient had broncheoloalveolar carcinoma of the lung with dyspnea and anxiety that worsened and became untreatable a few hours before death. Palliative sedation was implemented in two patients for a combination of intractable symptoms: the first for pain and dyspnea and the second for agitation and dyspnea. Midazolam was the most frequently used drug to achieve palliative sedation26 patients requiring sedation received this medication. The time from starting the palliative sedation and death was 20.5 hours (mean) and 9.0 hours (median), with a range of 5 minutes to 72.5 hours. One hundred forty-six of the 300 patients (49%) patients entered the last 48 hours of their life with a normal consciousness level. Of these patients, only 26 (9%) maintained a full level of consciousness up until the time of the death. One hundred sixty-nine (56%) were communicative. This decreased to 42 (14%) patients on the date of death. Thirty-one (10%) were walking with the assistance of others 2 days before dying and only 10 patients (3%) were walking without assistance. Nine (3%) were mobile up to the time of death.
TABLE 2.
THE
SYMPTO M PREVALENCE 300 ELIGIBLE PATIENTS No. 146 141 139 118 105 93 51 48 45 26 18 6 66 24
IN
RESULTS
From January 1995 to the closure of the audit in July 1998 a total of 597 patients were admitted to the unit. Of these, 354 died (59%) and 243 (41%) were discharged back home or to other hospitals. Fifty-four patients died within 48 hours of admission to the unit and were therefore not included in the analysis. Three hundred patients met the inclusion and exclusion criteria. These numbers represent patients not admissions, although some patients had more than one admission.
Symptom Delirium Incident pain Death rattle Fever Dyspnea Sweating Nausea/vomiting Cough Hemorrhage Background pain Myoclonus Seizures Incontinence urinary Retention urinary
(%) 49 47 46 39 36 31 17 16 15 9 6 2 22 8
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TABLE 3. REASONS
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SEDATION (%) 51.7 20.7 17.2 3.4 3.4 3.4 100
No. Delirium Hemorrhage Dyspnea Patient wish Pain/dyspnea Agitation/dyspnea Total 15 6 5 1 1 1 29
for delirium, and 1 patient for a combination of dyspnea and pain.
DISCUSSION
Delirium was the most frequent symptom, affecting almost half of the patients. This and the frequency of other symptoms such as pain and dyspnea are consistent with previous reports.1113 The relatively high frequency of incident pain reported here can be somewhat misleading because in cognitively impaired patients the painrelated behavior can be difficult to distinguish from delirium-related behavior. Therefore, some cases ascribed by the staff as pain with passive turning of patients in bed were likely manifestations of delirium. Respiratory tract rattling occurred frequently and was in most cases managed by reassuring families. When severe, it was treated pharmacologically with hyoscine hydrobromide (scopolamine), although the impact of this on patient comfort is uncertain. Fever and sweating are rarely mentioned in other studies, but in this audit they occurred in a high percentage. Future studies should assess the impact of these problems on patient comfort and quality of life. A relatively small number of patients (10%) required palliative sedation. This number is lower than the rates reported in other acute and tertiary units.1,2,5,14,15 However, this may be difficult to
LAST 48 HOURS IV % 71 19 31 25 0 23 23 0 17 0 0 8 0 3 0 No. 2 5 1 0 0 2 0 0 2 0 0 14 14 0 0 % 1 2 1 0 0 1 0 0 1 0 0 5 5 0 0 Other No. 21 11 10 10 10 0 0 31 2 30 36 0 4 2 2 % 7 4 3 3 3 0 0 10 1 10 12 0 1 1 1
Table 4 lists the medications used in the last 48 hours. Morphine was the most widely prescribed medication and 255 patients (85%) were on this opioid in the last 48 hours of life. Dexamethasone, haloperidol, and midazolam were used relatively frequently in contrast to drugs such as antibiotics, nonsteroidal anti-inflammatory drugs, and diuretics, which were used less frequently. The subcutaneous route of administration was utilized extensively. Only a small number of patients (12%) were receiving parenteral fluid in the last 48 hours and when administered was usually via subcutaneous hypodermoclysis. In most cases, a combination of different routes was used in patients. The attending physicians recorded that 16 (5%) deaths were unexpected. The physicians and/or nurses felt that the last 48 hours were peaceful in 258 patients (86%). Of the 42 patients (14%) that they thought were uncomfortable, 8 required sedation4 patients for hemorrhaging, 3 patients
TABLE 4. FREQUENCY
OF
USE
OF
DIFFERENT MEDICATIONS Oral
IN THE
Total Drug Morphine Dexamethasone Midazolam Haloperidol Laxatives Scopolamine butylbromide Scopolamine hydrobromide Lorazepam Metoclopramide Paracetamol Salbutamol Parenteral fluids Antibiotics NSAIDs Diuretic No. 255 111 100 100 79 70 68 68 66 53 36 35 26 24 18 % 85 37 33 33 26 23 23 23 22 18 12 12 9 8 6 No. 42 44 0 21 73 0 0 37 16 23 0 0 12 13 20
SC % 14 15 0 7 24 0 0 12 5 8 0 0 4 4 7 No. 212 56 94 74 0 68 68 0 51 0 0 25 0 9 0
No. means the number of patients who use the drug; total or by the indicated route. SC, subcutaneous; IV, intravenous; NSAIDS, nonsteroidal anti-inflammatory drugs.
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compare because of inconsistencies in defining palliative sedation. Midazolam was the most frequently used drug for sedation. However, there were differences in the method depending on the symptom. In agitated delirium, haloperidol was often used firstline. In dyspnea, midazolam was used first-line if sedation was required. In hemorrhage a standardized protocol was used with morphine 10 mg and midazolam 10 mg intramuscularly as recommended in the Oxford Textbook of Palliative Medicine 16; more recently we changed the protocol to midazolam 15 mg intramuscularly. This route is used because significant vasoconstriction limits the subcutaneous route. Otherwise, the intramuscular route is rarely used to administer drugs. The most frequent indications for palliative sedation in our audit were delirium and dyspnea. Intractable pain was an uncommon reason for initiating palliative sedation. These findings are consistent with the results of studies in other centers.5,14,15 The relatively high frequency of palliative sedation for hemorrhaging probably reflects the large numbers of patients admitted with head and neck tumors, many of them with large, ulcerating lesions. Unlike North America, advanced directives, including do-not-resuscitate orders, are generally not discussed with patients. Furthermore, there is no legislation that mandates these discussions. This may reflect the same paternalistic approach, fears, and discomforts of health care professionals to discuss this issues with terminally ill observed in North America a few decades ago. Our decision to assess the perception of death from a health care professionals perspective was based on the impact that dying has on staff. While much time is justifiably dedicated to evaluating the last stages of dying (last 48 hours) from a patients and familys perspective, reviewing the perception of staff merits attention. The staff in our audit considered death nonpeaceful in 14% of patients. The impact of this on staff needs to be explored, along with ways to better improve care in the last days of life, to prepare for difficult cases and become aware of personal responses and team responses to difficult deaths. Interestingly, eight of the patients whom staff felt experienced a nonpeaceful death were sedated. This perception need to be further explored because it may reflect the staffs own discomfort, rather than that of the patients. Although there
are limitations to defining and standardizing peacefulness as perceived by the health care professionals, this problem has an important impact on the staff. Opportunities for debriefing are required. Morphine was the most used drug more often by the subcutaneous route. It was used in the treatment of pain and dyspnea. The subcutaneous route was the most used in this phase because it is the most convenient alternative to the oral route. However most patients had more than one route used. The intravenous route was also used in a few cases. We use the intravenous route mainly when patients already have peripheral or central access at the time of admission. Parenteral hydration is administered infrequently. When indicated, we generally administer via hypodermoclysis. Apart from standardizing the definition of peacefulness, this study has several other limitations. The retrospective assessment of sedation, introduced towards the end of the study, may have provided less accurate information than if it were done prospectively. In future studies sedation should be graduated in several levels, and not just seen on a yes or no basis, because the goal is symptom control and the deepness of sedation to reach it is not necessarily always the same. Assessing the symptom intensity is challenging. Self-reporting of symptoms, while a gold standard, is often not possible in the last 48 hours. Proxy-graded observations, made by professional or by a family member have been shown to be largely unreliable. 8 The results of this audit will be discussed among the staff in order to identify areas for improvement of care. What can be done about patients whose deaths are not peaceful? Could something else be done at least in some cases? Should some of those patients have been sedated? Are our feelings interfering with our practice?
CONCLUSIONS
We recognize the need for regularly ongoing clinical audit for improvement of care. It is important that those involved in palliative care audit their practice in order to compare them with the results of others and so evaluate the quality of their work and eventually change their practice. While in many ways our patterns of practice appear to be similar to other groups, several areas
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8. Nekolaichuk CL, Bruera E, Spachynski K, MacEachern T, Hanson J, Maguire TO: A comparison of patient and proxy symptom assessments in advanced cancer patients. Palliat Med 1999;13:311323. 9. Inouye SK, van Dyck CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI: Clarifying confusion: The confusion assessment method: A new method for detection of delirium. Ann Intern Med 1990:113:941948. 10. Chater S, Viola R, Paterson J, Jarvis V: Sedation for intractable distress in the dyingA survey of experts. Palliat Med 1998;12:255269. 11. Fainsinger RL, Tapper M, Bruera E: A perspective on the management of delirium in terminally ill patients on a palliative care unit. J Palliat Care 1993;9:48. 12. Higginson I, McCarthy M: Measuring symptoms in terminal cancer: Are pain and dyspnoea controlled? J R Soc Med 1989;82:264267. 13. Reuben DB, Mor V: Dyspnea in terminally ill cancer patients. Chest 1986;89:234236. 14. Fainsinger RL, Landman W, Hoskings M, Bruera E: Sedation for uncontrolled symptoms in a south african hospice. J Pain Symptom Manage 1998;16: 145152. 15. Fainsinger RL, Waller A, Bercovici M, Bengtson K, Landman W, Hosking M, Nunez-Olarte JM, de Moissac D: A multicentre international study of sedation for uncontrolled symptoms in terminally ill patients. Palliat Med 2000;14:257265. 16. Twycross RG, Lichter I: The terminal phase. In: Doyle D, Hanks GWC, MacDonald N (eds): Oxford Textbook of Palliative Medicine. Oxford: Oxford University Press, 1993, pp. 651661.
for improvement and reflection have been identified.
ACKNOWLEDGMENT
The authors are grateful to Dr. Jos Pereira, from the Division of Palliative Medicine, University of Calgary, Calgary, Canada, for his invaluable help and advise in the preparation of the manuscript.
REFERENCES
1. Ventafrida V, Ripamonti C, De Conno F, Tamburini M, Cassileth BR: Symptom prevalence and control during cancer patients last days of life. J Palliat Care 1990;6:711. 2. Peruselli C, Di Giulio P, Toscani F, Gallucci M, Brunelli C, Costantini M, Tamburini M, Paci E, Miccinesi G, Addington-Hall JM, Higginson IJ: Home palliative care for terminal cancer patients: a survey on the final week of life. Palliat Med 1999;13:233241. 3. Turner K, Chye R, Aggarwal G, Philip J, Skeels A, Luckiss N: Dignity in dying: A preliminary study of patients in the last three days of life. J Palliat Care 1996;12:713. 4. Lichter I, Hunt E: The last 48 hours of life. J Palliat Care 1990;6:715. 5. Fainsinger R, Miller MJ, Bruera E, Maceachern T: Symptom control during the last week of life on a palliative care unit. J Palliat Care 1991;7:511. 6. Ferraz Gonalves JA: A Portuguese palliative care unit. Support Care Cancer 2001;9:47. 7. Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Kiyasu E, Sobel K, Coyle N, Kemeny N, Norton L, et al: The Memorial symptom assessment scale: an instrument for the evaluation of symptom prevalence, characteristics and distress. Eur J Cancer 1994;30A:13261336.
Address reprint requests to: Dr. J. Ferraz Gonalves Unidade de Cuidados Continuados Instituto Portugus de Oncologia R. Dr. Antnio Bernardino de Almeida 4200-072 Porto Portugal E-mail: ferrazg@ipoporto.min-saude.pt
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Temporal Distribution of Deaths in Cancer Patients During the Day in Different Settings
JOS FERRAZ GONALVES,1 EUGNIA FONSECA,1 MARGARIDA ALVARENGA,1 and MARIA ROSA MORAIS2 ABSTRACT Background: All living organisms perform their functions normally according to circadian rhythms. Certain diseases, such as ischemic heart disease and asthma, produce symptoms that are distributed during the day in a nonrandom fashion. Chronomodulated therapy with some regimens of chemotherapy and other drugs produce better results than traditional schedules. Even death is not evenly distributed during the day. Significant differences in the time of death through the day could influence the work planning and care activities. Objective: To determine whether timing of death from a population of cancer patients admitted at our Oncology Institute varied during the day and according to different settings: at home (H), at the palliative care unit (PCU), and at other services (OS) of the hospital. Comparing the timing of deaths from different settings can give some clues about the possible existence of a circadian rhythm and the influence of external circumstances in the time of death of cancer patients. Design: We conducted a retrospective study of the records of time of death at the different settings. Results: The study involved 772 patients from the PCU and 997 from OS who died between May 25, 1996, and May 24, 2000, and 347 patients who died at H between April 1, 1999, and December 31, 2001. A statistically significant difference was found in the distribution of time of death in patients at the PCU (p .001), but not at OS or at H. There were two peaks between 08:00 and 10:00 and between 00:00 and 02:00, and one trough between 04:00 and 08:00. This suggests that a temporal variation occurs in the time of death of cancer patients dying in the PCU, but not in other settings. Conclusions: The clinical relevance of the results obtained in this study would depend on the amplitude of the eventual variation detected in the number of deaths during the day. Therefore, although there was a statistically significant variation at the time of death during the day, its amplitude is not high enough to make it clinically significant. The differences observed among the various settings suggest that, even if circadian rhythms exist at the time of death in cancer patients, external factors can overcome these rhythms.
INTRODUCTION
OTATION OF EARTH ABOUT ITS AXIS and its revolution about the sun produce rhythmic events. These events influence the functioning of all living organisms. The rotation about its axis
creates the succession of days and nights. The biologic events connected with this succession repeated with a period of about 24 hours are referred to as circadian (circa, about; dies, day). These events result from the biological adaptation to the natural 24-hour cycle of light and dark-
1Palliative
Care Unit and 2Statistics Service, Portguese Institute of OncologyPorto Center.
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ness. A biologic clock controls circadian rhythms, which is located in mammals in the suprachiasmatic nuclei of the hypothalamus.1 At the subcellular level, circadian rhythms are generated by transcriptional positive and negative feedback loops involving multiple clock genes.1,2 The internal clock has a free-running period of about 25 hours that does not exactly match the 24-hour day.2 Therefore, the internal clock must be reset every day to stay synchronized with the solar time. The main synchronizer in most species is light, but in humans, who use artificial light, the synchronization is made by the sleepwake cycle and, perhaps, social interactions.3 Traditionally, the internal milieu of the organism is seen as constant (the homeostatic theory).4 However, the functional integrity of an organism depends mainly on the maintenance of synchronized temporal relationships between oscillating variables.3 In human beings, body temperature, sleep, hormonal levels, cognitive and motor efficiency, urinary volume, and the like, vary, following a daily rhythm. Circadian rhythms also influence the activity and metabolism of some medications, such as chemotherapy, which when chronomodulated can result in less side effects, better objective response, and longer patient survival5,6; other examples are theophylline, nonsteroidal antiinflammatory drugs, and corticosteroids.4 There are also variations in the survival of elderly patients associated with the time of day they undergo hemodialysis,7 the frequency of asthma attacks,8 myocardial infarction,9 and death itself. Many studies indicate that the distribution of sudden deaths of cardiac cause is not uniform during the day.914 Only two reports exist15,16 in the literature concerning the timing of death in cancer patients, and both were conducted in palliative care units. Our study differs from these because, besides including patients who died at our palliative care unit, patients who died at home and at other services in the hospital were also included to see if the same pattern occurred in those settings and whether clues on the existence of a circadian rhythm at the time of death or external circumstances were more important. The potential relevance of this study to clinical practice depends on the existence of a variation in the number of deaths during the day and on the amplitude of this variation. If the differences are high enough, the reflection about the possible causes can lead to changes in work planning and care activities.
METHODS
The Porto Center of the Portuguese Institute of Oncology has 400 beds and admits about 4000 new patients every year. The hospital has services equivalent to any advanced oncology center in Europe, as well as a palliative care unit (PCU). This center is a public hospital that serves the population from the northern part of the country. Patients belong to all social classes and educational levels. In the PCU, beyond the inpatient service with 20 single rooms, patients are followed in an ambulatory regimen, home care regimen, and at the day center.17 All patients admitted to the PCU had cancer, were not undergoing any antineoplastic treatment, and were older than 15 years, since younger patients are treated in the pediatrics service. One hospital policy is to officially record patients time of death, independently of which service this occurs. We retrospectively reviewed these documents from patients who: 1. Died at the PCU from May 25, 1996 (the opening date of the PCU), until May 24, 2000. 2. Died during the same period of time at other services (OS), including Medical Oncology, Surgery, and Radiotherapy, with the exclusion of special services as the Bone Marrow Transplantation Unit, Intensive Care Unit, and Pediatrics. 3. Were followed by the PCU and died at home (H). The decision to include these patients was taken later, and therefore the time of death recordings in this group began on April 1, 1999. Also, due to the small number of patients in this group, recordings were prolonged until December 31, 2001. The homogeneity of the distribution of deaths during the day was analyzed in periods of 1 hour using the Pearson chi-square test for nonparametric variables; that is, the actual hourly distribution of the number of deaths was compared with the number of deaths that would occur if the number of deaths were evenly distributed during the day. Significance was accepted at the 95% confidence level.
RESULTS
Seven hundred and seventy two deaths occurred at the PCU and 997 deaths occurred at OS.
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FIG. 1.
Frequency of deaths by time of day at the PCU.
Of the 347 deaths that occurred at H, time of death was obtained from 251 (72%). Figure 1 shows the frequency of death by time at the PCU. The difference between the number of deaths observed and the number of deaths expected, if the distribution throughout the hours of the day was uniform, was statistically significant: 2 54.438 (p .001). The period with the greatest number of deaths occurred between the time interval of 08:00 and 16:00, followed by 00:00 and 08:00. The lowest number of deaths occurred between 16:00 and 24:00 (Table 1), the most stable 8-hour period, with very small hourly variations. We can observe a trough between 04:00 and 08:00 and peaks between 00:00 and 02:00 and 08:00 and 10:00. Figure 2 shows the distribution of deaths at OS. No significant variation in the distribution of deaths was observed: 2 30.024 (p 0.1). Although no significant differences were observed at OS, the period with the highest number of deaths was observed between 08:00 and 16:00, followed by 16:00 and 24:00 and between 00:00 and 08:00. The distribution of deaths during the day at H is shown in Fig. 3. No significant variation was observed in this setting: 2 24.815 (p 0.2).
number of deaths at the OS of the institute or with patients dying at H. The data obtained from studies of cancer patients dying at palliative care units show: In the study of Davies, a trough was observed between 02:00 and 05:00, without any peak.16 The study of Neumann et al. shows a peak between 08:00 and 10:00 and between 18:00 and 20:0015 and, although not mentioned in the text, a trough could be observed in one graphic presented, between 00:00 and 04:00. Our study shows a prolonged trough between 04:00 and 08:00, preceded by a peak between 00:00 and 02:00, and followed by another peak between 08:00 and 10:00. These three studies show in common a consistent trough in the number of deaths existing during the night, although the exact time varies somewhat among the studies, in patients dying in palliative care units. Also, in two of these three studies, a peak was observed between 08:00 and 10:00. The analysis of our data in the present study raises some questions. One is whether the differTABLE 1. FREQUENCY
OF
DEATHS
IN
DIFFERENT SETTINGS OS (%) H (%) 35.1 32.2 32.7
DISCUSSION
The results of our study show a statistically significant temporal variation in the number of deaths during the day at the PCU, but not in the
Hours 07 815 1623
PCU (%) 31.9 39.2 28.9
32.7 33.9 33.4
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FIG. 2.
Frequency of deaths by time of day at OS.
ences observed in the distribution of time of death are real. Recordings obtained from the H setting may be inaccurate since patients death is not recorded by a professional, whereas in the hospital setting (PCU and OS) this is unlikely. The officially recorded time of death does not exclude some small deviations relative to the real time. However, some inaccuracy of the records cannot be completely excluded. Accepting the differences as real, a possible explanation for the pattern observed in the PCU may be the influence of factors related to routine practices in the unit, such as medication schedules, and different levels of activity and care during the 24 hours and not to a natural occurrence resulting from circadian rhythms. This can also
explain the differences in the exact time of the variations observed among the studies of time of death of cancer patients. Can we establish an analogy or even a relationship between cardiovascular events and the pattern of deaths of cancer patients in this study? That is, is there a circadian rhythm at the time of death that is modified by certain circumstances as it occurs in events and deaths due to cardiovascular causes? If there is an association, it could explain the differences observed among settings. For example: Can the peak seen at the PCU between 08:00 and 10:00 be related to the wake-up period and the peak of activity in the service? Events of cardio-
FIG. 3.
Frequency of deaths by time of day at H.
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vascular cause, among them sudden death, predominate between 07:00 and 11:00, with a secondary peak in the late afternoon and early evening, and a trough between 24:00 and 06:00.18 Willich et al. showed that the highest risk of cardiovascular events occurred in the first 3 hours after wake-up10; therefore, it seems that the risk of sudden death is more related with wake-up than with the time of day. One possible explanation given for the wake-up morning peak was the assumption of the upright posture associating with the rising of catecholamines, which increases vascular reactivity, heart rate, blood pressure, ventricular ectopy, platelet adhesiveness and aggregability, and other interrelated processes. However, the peak at the end of the day is more difficult to explain.18 At the PCU, the explanation cannot be for most patients the assumption of the upright posture, but this period of the morning is certainly the peak of activity related with nursing care, such as baths and dressing changes. These can induce stress affecting the cardiovascular system, which can precipitate death, such as occurs in cardiac patients. At the PCU the peak at the early night is also difficult to explain, as is the peak observed at evening in cardiovascular deaths. Can the absence of significant variation in OS result from factors interfering with sleep and so affecting patients biologic clocks? Cardiac deaths in hospitalized patients seem to be randomly distributed in the 24 hours, contrary to patients not hospitalized. This has been explained by the fact that these patients are submitted to a variety of stimuli during the night and are in bed during a large part of the day, which can affect their biologic clock.18 At the PCU, where all patients are in single rooms and a good nights sleep is a goal of care, a lower level of stimulation occurs than for OS, and so the biologic clock is probably less affected. Therefore, there is an analogy between cancer patients and cardiac patients in this situation when there is an activity in services, which interferes with circadian rhythms. Can the absence of significant variation at H be due to probably less rigid schedules and routines that could attenuate the circadian rhythm? Another factor could be a less rigorous recording of the time of death. Another question, perhaps the most important, is the meaning of the variation at the time of death
at the PCU. The statistical significance observed does not necessarily imply it is clinically significant. The clinical significance depends, in first place, on the magnitude of the difference. However, the difference seen in this study does not indicate any significant clinical meaning, perhaps with the exception of the morning peak. The increase in the number of deaths in the morning, observed in our study and in the study of Neumann et al.,15 but not observed in other settings in our study, should be further explored in other studies to find out if there are any external factors that can influence it. In conclusion, studies reporting time of death produce many questions regarding death and its nearest causes. The differences related to the time of day at our PCU and among the settings allow an analogy with cardiac patient deaths and speculation on possible reasons to explain them. The differences seen among the various settings suggest that, even if circadian rhythms exist at the time of death in cancer patients, external factors can overcome them. This is the first study exploring the differences at the time of death of cancer patients among different settings, so these differences may be confirmed in other studies.
REFERENCES
1. Sassone-Corsi P. Molecular clocks: mastering time by gene regulation. Nature 1998;392:871874. 2. Rajaratnam SMW, Arent J. Health in a 24-h society. Lancet 2001;358:9991005. 3. McFadden ER. Circadian rhythms. Am J Med 1988; 85(suppl 1B):25. 4. Smolensky MH, DAlonzo GE. Biologic rhythms and medicine. Am J Med 1988;85(suppl 1B):3446. 5. Bjarnason GA. Chronobiology: implications for cancer chemotherapy. Acta Oncolog 1995;34:615624. 6. Lvi F, Zidani R, Brienza S, Dogliotti L, Perpoint B, Rotarski M, Letoumeau Y, Llory JF, Chollet P, Le Roi A, Focan C. A multicenter evaluation of intensified, ambulatory, chronomodulated chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin as initial treatment of patients with metastatic colorectal carcinoma. Cancer 1999;85:25322540. 7. Bliwise DL, Kutner NG, Zhang R, Parker KP. Survival by time of day of hemodialysis in an elderly cohort. JAMA 2001;286:26902694. 8. Pincus DJ, Beam WR, Martin RJ. Chronobiology and chronotherapy of asthma. Clin Chest Med 1995;16: 699713. 9. Cohen MC, Rohtla KM, Lavery CE, Muller JE, Mittleman MA. Meta-analysis of the morning excess of acute myocardial infarction and sudden cardiac death. Am J Cardiol 1997;79:15121516.
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10. Willich SN, Goldberg RJ, Maclure M, Perriello L, Muller JE. Increased onset of sudden cardiac death in the first three hours after awakening. Am J Cardiol 1992;70:6568. 11. Behrens S, Fisher SG, Fletcher RD, Franz MR, Singh SN. Effects of amiodarone on the circadian pattern of sudden cardiac death. Am J Cardiol 1997;80:4548. 12. Thakur RK, Hoffmann RG, Olson DW, Joshi R, Tresch DD, Aufderheide TP, Ip JH. Circadian variation in sudden cardiac death: effects of age, sex, and initial cardiac rhythm. Ann Emerg Med 1996;27:2934. 13. Hayashi S, Toyoshima H, Miyanishi K, Tanabe N, Funazaki T, Obata A, Kamimura K. Circadian variations of sudden death. Nippon Koshu Eisei Zasshi 1992; 39:8389. 14. Hayashi S, Toyoshima H, Tanabe N, Miyanishi K. Daily peaks in the incidence of sudden cardiac death and fatal stroke in Niigata Prefecture. Jpn Circ J 1996;60:193200. 15. Neumann CM, Hanson J, Kuehn N, Bruera E. Temporal distribution of deaths in cancer patients admit-
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ted to a palliative care unit. J Palliat Care 1999; 15:1013. 16. Davies AN. Circadian variation in time of death in patients with cancer. Palliat Med 1998;12:483. 17. Ferraz Gonalves JA. A Portuguese palliative care unit. Support Care Cancer 2001;9:47. 18. Peters RW. Circadian patterns and triggers of sudden cardiac death. Cardiol Clin 1996;14:185194.
Address reprint requests to: Dr. Ferraz Gonalves Unidade de Cuidados Continuados Instituto Portugus de Oncologia Rua Dr Antnio Bernardino de Almeida 4200-072 Porto Portugal E-mail: ferrazg@ipoporto.min-saude.pt or ferrazg@netcabo.pt
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Support Care Cancer (2005) 13: 752756 DOI 10.1007/s00520-005-0800-0
SHORT COMMUNI CATIO N
Jos Ferraz Gonalves Isabel Costa Carolina Monteiro
Development of a prognostic index in cancer patients with low performance status
Received: 30 August 2004 Accepted: 23 February 2005 Published online: 31 March 2005 # Springer-Verlag 2005
J. F. Gonalves (*) . I. Costa . C. Monteiro Unidade de Cuidados Continuados, Instituto Portugus de Oncologia, Rua Dr Antnio Bernardino de Almeida, 4200-072 Porto, Portugal e-mail: ferrazg@ipoporto.min-saude.pt Tel.: +351-22-5073940 Fax: +351-22-5506833
Abstract Background: Prognosis is a very important medical function. In advanced cancer it is also important to help planning the care to deliver to individual patients with more accuracy, in the process of decision about the opportunity for some interventions and in the selection of patients for clinical trials. Although the performance status indexes are by themselves prognostic factors, among patients in all stages there are wide variations in survival. In what concerns bedridden patients, survival varies between hours and months. Therefore it would be useful to develop a method which could allow a more precise estimation of the length of survival in these patients. Patients and methods: We have studied prospectively 110 bedridden patients exploring six variables: consciousness level, recognition of familiar people, continence and capacity to communicate, to eat and to swallow. Each factor was scored on a scale of 0 to 2. Our aim was to
construct a classification system with the sum of the scores of the variables significantly correlated with survival. The cut-off-points were calculated using the percentiles 25, 50 and 75 according to the method of Altman et al. (J Natl Cancer Inst 86:829835. 1994). Results: Four of the variables were significantly associated with survival, and an index with three stages was constructed with the sum of these four variables: I0 to 3; II4 to 6; III7 to 8. The differences in survival among the stages are statistically significant and the probability of survival at the 7th, 30th, 60th, and 90th days is also different. Conclusion: The differences in survival observed among the stages can be clinically relevant to the establishment of a prognostic to individual patients. Keywords Advanced cancer . Prognosis . Bedridden patients . Palliative care
When the goal of the treatment of patients with cancer is no longer to cure or prolong survival, the strategy must be changed and the interventions to be implemented must be directed to the well-being of the patients and their families. This is the aim of palliative care.
In palliative care, one of the concerns expressed by the patients and/or their families is life expectancy. Accurate prediction of patients survival is important to facilitate better planning of care of individual patients and to help in the process of decision making about opportunities for
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some interventions and in the selection of patients for clinical trials. Therefore, the study of factors and the construction of prognostic scores that can help in estimating the life span of patients with end-stage cancer is an important objective for research. Several studies have addressed the problem of prognosis in advanced cancer. The studies completed so far included the evaluation of performance status index [15], the clinical estimation of survival [2, 69], evaluation of symptoms [1019], and study of biochemical and hematological variables [15, 18, 2022]. Some of these studies used a combination of these different types of factors. The performance status index proved to be an important prognostic factor [15, 10, 23]. However, there are wide variations in survival in all stages of a disease. In the case of bedridden patients, those with the lowest performance status, therefore having the worst prognosis, duration of survival varies between hours and months. We tried to develop a prognostic index to predict more accurately the length of survival of these patients based on observed variables that do not need the active participation of patients or require invasive procedures (e.g., venous punctures) and are therefore applicable to all patients, independently of their condition.
Table 1 Variables and definition of the scores
Consciousness level Normal Sleepiness, wakens easily Wakens with difficulty or not at all Communication Normal Difficult Not at all Recognize familiar people Always Irregularly Never Feeding capacity Independent With help Not at all Swallowing capacity Normal Difficult Not at all Continence, feces and urine Always Occasional leaks Not at all
2 1 0
2 1 0 2 1 0 2 1 0 2 1 0 2 1 0
Patients and methods

This study was carried out in a palliative care unit in an oncological center described elsewhere [24]. The performance status index used at the unit is the Eastern Cooperative Oncology Group (ECOG) scale. We studied 110 bedridden patients due to advanced cancer, classified as ECOG stage 4, and some that could be classified as ECOG 3 who were successively admitted to the palliative care unit between March 2000 and April 2001. Because the performance status is a continuous variable that is classified in stages that creates a twilight zone between them wherein the classification of patients may not be easy, we decided to study bedridden patients without other considerations. Six variables were explored prospectively: consciousness level, capacity to communicate, recognition of familiar people, capacity to eat, capacity to swallow, and continence. These factors were chosen for three main reasons: they make clinical sense, that is, they are associated with the functional status and so possibly with survival; some of them proved to be relevant to prognosis in other studies; and the data result from observation and, therefore, do not need any participation from the patients or any invasive intervention. Each factor was scored on a scale of 0 to 2, as indicated in Table 1. Our aim was to construct a classification system with the sum of the scores of the variables significantly correlated with survival. The index was constructed with three stages whose cutoff points were determined using the percentiles 25, 50, and 75 according to the method of Altman et al. [25]. The cutoff points of 7, 30, 60, and 90 days to evaluate the probability of survival were chosen on the basis of clinical utility in order to classify patient survival into short term, intermediate term, and longer term. Survival was defined as the number of days between the evaluation and death. The three physicians of the palliative care unit rated patients only once, at the first contact with them or when they became bedridden. The analysis of data used methods of descriptive statistics. Adjustment of data to simple linear regressions was done by the least squares method with survival time as a dependent variable. The Student t test was used to assess the significance of the coefficients of regression and correlation. The KaplanMeier method was applied to determine the survival curves, and the log-rank or Breslow test to compare studies concerning the length of survival.
Results
The median age was 65 years (range, 2690). Forty-one (37%) patients were men and 69 (63%) were women. The primary tumors are shown in Table 2. The median survival time was 11 days (range, 1201). From the six variables, consciousness level, communication, and the capacity to eat and to swallow were significantly associated with survival (Table 3). Using the percentiles 25, 50 and 75 to determine the cutoff points, the scores of the three stages were as follows: I, 0 to 3; II, 4
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Table 2 Primary tumors and demographic data Tumor Breast Stomach Colorectal Prostate Cervix Gynecologic others Pancreas Lung Bladder Head and neck Melanoma Others Total Number (%) 16 16 9 8 8 8 7 6 6 5 4 17 110 (15) (15) (8) (7) (7) (7) (6) (5) (5) (5) (4) (15) (100)
Cum Survival
1,1 1,0 ,9 ,8 ,7 ,6 ,5 ,4 ,3 ,2 ,1 0,0 0 15
II I
30 45 60 75
I Stage I II Stage II III Stage III
III
90 105 120 135 150 165 180 195 210
Days
Men, n=41(37%); women, n=69 (63%). Age: median, 65; range, 2690
Fig. 1 Overall survival and stage
Table 3 Variables studied and their correlation with survival Variables Consciousness level Feeding capacity Swallow capacity Communication Recognizing people Continence ns non-significant t 3.40 2.54 2.56 2.20 1.74 1.44 r2 0.097 0.057 0.058 0.043 0.043 0.019 r 0.311 0.239 0.241 0.207 0.207 0.138 p <0.0001 <0.001 <0.001 <0.05 ns ns
each stage at 7, 30, 60, and 90 days are shown in Table 5. Survival beyond 60 days was infrequent (Fig. 1).
Discussion
All the studies trying to find out prognostic factors result from the fact that clinical estimation alone is not reliable. Studies of the clinical length of survival produced heterogeneous results [2, 69]. However, a review of the literature shows that clinical estimation is an independent prognostic factor [10], and a more recent systematic review revealed that clinical estimation is highly correlated with survival, although clinicians consistently overestimate survival [26]. However, those clinical estimations should be considered as only one among other prognostic factors and not as an isolated one [9, 10]. Performance status indexes such as Karnofsky or ECOG are prognostic factors that have been used for many years in cancer patients with success. In advanced cancer, the performance status has also proved to be one of the most important prognostic factors [1, 3, 4, 13]. However, as stated before, patients at each level show wide variations in survival. In palliative care, many patients are bedridden and a system to provide a more accurate prediction of their life span would be useful. Because many of these patients are very frail and have cognitive failure it can be ethically problematic to perform invasive procedures such as venous punctures to make blood tests and impracticable to evaluate symptoms. Therefore, in order to include all patients, independently of their condition, we tried to develop a prognostic index only with factors observed without the need of the patients participation. From the initial variables, we chose the four significantly associated to survival. The non-significant variables, continence and capacity to recognize familiar people, had some problems of classification that could have contributed to
Table 4 Comparison of survival between stages I vs II I vs III II vs III
2 9.17 20.05 3.52
p 0.003 <0.0001 0.02
Table 5 Probability of survival by stage
Days 7 30 60 90
I (%) 29 11 4
II (%) 65 31 15 4
III (%) 87 47 13 13
to 6; III, 7 to 8. The number of patients in each stage was I, 28; II, 52; III, 30. The median survival times for stages I, II, and III were 4, 10, and 29 days, respectively. The comparative study of the differences in survival among the three stages is significant, with patients in stage I showing the worst survival (Table 4). The probabilities of survival for
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their non-significance: continence was impossible to classify in patients with indwelling urinary catheters, and the signs of recognition of familiar people were difficult to interpret in the most frail patients who often had a very limited capacity to communicate. The stages constructed showed differences in the probability of the length of survival among them high enough to help the health professionals to plan the decisions concerning care and satisfying the patients and their families information needs. Other studies also concluded that feeding and swallowing problems are factors significantly associated with survival [10, 11, 13, 1518], although there are significant methodological differences relative to our study. In general, these symptoms were reported by patients [11, 13, 1518] instead of being reported by the observer as in our study, excluding the patients unable to do that. Other studies differed in other ways. For example, the study of Reuben et al. [13], with 1,592 patients, differed from our study because it did not include only bedridden patients, the feeding problems were not clearly defined, and there was a large percentage (29%) of patients unable to answer who were substituted in the evaluation by the primary care person, which proved to be largely unreliable [14].
Cognitive failure was an important prognostic factor in some studies [10, 12, 19]. In our study, cognitive failure was also a relevant factor, as evaluated by the consciousness level and the capacity to communicate. The capacity to recognize familiar people, which could be also an indicator of the cognitive status, was not significantly associated with survival probably because of the problems referred to above. Prognostication is an important topic in medicine in general and in palliative care in particular, where time is usually short. The present study intends to be one step further in the construction of a more reliable way to preview survival of patients with advanced cancer, particularly those who, by the criterion of the performance status, already have a bad prognosis. The prognostic index based on observation is a new approach to this problem. Our aim when we planned this study was to construct a quantifiable prognostic index that would allow health professionals to predict more reliably survival of bedridden patients in periods useful for clinical practice. We believe that this index can be a useful tool.
Acknowledgements The authors would like to thank Dr. Maria Jos Bento for her invaluable help in the statistic analysis.
References
1. Evans C, McCarthy M (1985) Prognostic uncertainty in terminal care: can the Karnofsky index help? Lancet 1:12041206 2. Maltoni M, Nanni O, Derni S et al (1994) Clinical prediction of survival is more accurate than the Karnofsky performance status in estimating life span of terminally ill cancer patients. Eur J Cancer 30A:764766 3. Mor V, Laliberte L, Morris JN, Wiemann M (1984) The Karnofsky performance status: an examination of its reliability and validity in a research setting. Cancer 53:20022007 4. Yates JW, Chalmer B, McKegney P (1980) Evaluation of patients with advanced cancer using the Karnofsky performance status. Cancer 45:22202224 5. Maltoni M, Pirovano M, Nanni O, Labianca R, Amadori D (1994) Prognostic factors in terminal cancer patients. Eur J Palliat Care 1:122125 6. Forster LE, Lynn J (1988) Predicting life span for applicants to inpatient hospice. Arch Intern Med 148:25402543 7. Oxenham D, Cornbleet MA (1998) Accuracy of prediction of survival by different professional groups in a hospice. Palliat Med 12:117118 8. Hardy J, Turner R, Edmonds P, AHern R (1997) Prediction of survival in patients referred to a palliative care unit. Palliat Med 11:73 9. Parkes CM (1972) Accuracy of predictions of survival in later stages of cancer. BMJ 2:2931 10. Vigan A, Dorgan M, Buckingham J, Bruera E, Suarez-Almanzor ME (2000) Survival prediction in terminal cancer patients: a systematic review of the medical literature. Palliat Med 14:363374 11. Llobera J, Esteva M, Rif J et al (2000) Terminal cancer: duration and prediction of survival time. Eur J Cancer 36:20362043 12. Bruera E, Miller MJ, Kuehn N, MacEachern T, Hanson J (1992) Estimates of survival of patients admitted to a palliative care unit: a prospective study. J Pain Symptom Manage 7:8286 13. Reuben DB, Mor V, Hiris J (1988) Clinical symptoms and length of survival in patients with terminal care. Arch Intern Med 148:15861591 14. Nekolaichuk CL, Bruera E, Spachynski K, MacEachern T, Hanson J, Maguire TO (1999) A comparison of patient and proxy symptom assessments in advanced cancer patients. Palliat Med 13:311323 15. Glare P, Virik K (2001) Independet prospective validation of the PaP Score in terminally ill patients referred to a hospital-based palliative medicine consultation service. J Pain Symptom Manage 22:891898 16. Walsh D, Rybicki L, Nelson KA, Donnelly S (2002) Symptoms and prognosis in advanced cancer. Support Care Cancer 10:385388 17. Maltoni M, Pirovano M, Scarpi E et al (1995) Prediction of survival of patients terminally ill with cancer. Cancer 75:26132622 18. Maltoni M, Nanni O, Pirovano M et al (1999) Successful validation of the palliative prognostic score in terminally ill cancer patients. J Pain Symptom Manage 17:240247 19. Caraceni A, Nanni O, Maltoni M et al (2000) Impact of delirium on the short term prognosis of advanced cancer patients. Cancer 89:11451149 20. Fainsinger RL, Tapper M, Bruera E (1993) A perspective on the management of delirium in terminally ill patients on a palliative care unit. J Palliat Care 9:48 21. Romagnoli A, Rapin CH (1991) Valeur pronostique de certains paramtres biologiques chez des sujects gs hospitaliss. Age Nutri 2:130136
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22. Flp T, Herrmann F, Rapin CH (1991) Prognostic role of serum prealbumin levels in elderly patients at admission to a geriatric hospital. Arch Gerontol Geriatr 12:3139
23. den Daas N (1995) Estimating length of survival in end-stage cancer: a review of the literature. J Pain Symptom Manage 10:548555 24. Ferraz Gonalves JA (2001) A Portuguese palliative care unit. Support Care Cancer 9:47 25. Altman DG, Lousen B, Sauerbrei W, Schumacher M (1994) Dangers of using optimal cut-off-points in the evaluation of prognostic factors. J Natl Cancer Inst 86:829835
26. Glare P, Virik K, Jones M et al (2003) A systematic review of physicians survival prediction in terminally ill cancer patients. BMJ 327:195200
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Breaking bad news: experiences and preferences of advanced cancer patients at a Portuguese oncology centre
gata Marques, So Ferraz Gonc nia Rocha, Pedro Leita o, Teresa Mesquita and Susana Moutinho alves, A Palliative Care Unit, Portuguese Institute of Oncology, Oporto The disclosure of information to patients about diagnosis and prognosis and other aspects of care is still a matter of debate. We have conducted a study in advanced cancer patients about their experiences and preferences concerning this issue. A questionnaire was developed and completed during the first appointment in the outpatient clinic of an oncology centres palliative care unit, before the patient had any contact with the staff of the unit. The study was conducted on a convenience sample of 47 patients. We found that 34 (72%) of those patients thought they had been informed of their diagnosis, most of them by the hospital doctor. However, not all stated the diagnosis in a manner clearly showing that they were aware of the nature of their disease. Most patients were with a family member when the diagnosis was disclosed, which is what the majority had preferred. Of the 13 uninformed patients, only one preferred to remain uninformed. Most patients (89%) participated in decisions concerning treatment, although only 68% thought they should have participated. Some 39 patients (83%) were informed that they were being referred to the palliative care unit, but surprisingly only eight had received an explanation of the units function. We concluded that, although most patients had been informed of their disease, there remains many problems, the most important of which, in our view, is the difference between the information provided and the patients needs. stico o progno stico e outros aspectos dos A revelac a o da informac a o sobre o diagno ainda um assunto em debate. Realiza mos um estudo em doentes com cancro cuidados e ncias e prefere ncias no que diz respeito a este tema. Foi avanc ado sobre as suas experie rio que foi aplicado na primeira consulta externa de uma unidade desenvolvido um questiona gico, antes de terem contacto com o pessoal da de cuidados paliativos de um centro oncolo ncia de 47 doentes. unidade. O estudo foi realizado numa amostra de convenie mos que 34 (72%) desses doentes pensavam que tinham sido informados do Constata stico, a maioria pelo me dico do hospital. Contudo, nem todos nomearam o seu diagno stico de um modo que mostrasse claramente que tinham noc diagno a o da natureza da stico foi sua doenc a. A maioria dos doentes estava com um familiar quando o diagno um revelado e era assim que a maior parte preferia. Dos 13 doentes na o informados so preferia manter-se sem informac a o. A maior parte dos doentes (89%) participou nas uticas, embora so 68% pensasse que devia ter participado. Trinta e nove deciso es terape doentes (83%) foram informados de que tinham sido referenciados para a unidade de oito tinham tido uma explicac cuidados paliativos, mas surpreendentemente so a o sobre a func mos que embora a maioria dos doentes tenha sido informada da a o da unidade. Conclu ainda muitos problemas, sendo o mais importante, do nosso ponto de vista, sua doenc a ha a diferenc a entre a informac a o prestada e as necessidades dos doentes. Palliative Medicine 2005; 19: 526 /531
Key words: breaking bad news; cancer patients; cultural issues; information disclosure; palliative care patients
Address for correspondence: Dr Ferraz Gonc alves, Unidade de Cuidados Continuados, Instituto Portugue s de Oncologia, Rua Dr Anto nio Bernardino de Almeida, 4200-072 Porto, Portugal. E-mail: ferrazg@netcabo.pt
# 2005 Edward Arnold (Publishers) Ltd 10.1191/0269216305pm1070oa
Breaking bad news
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Introduction
The information delivered to cancer patients is still a matter of controversy, with wide cultural differences. In northern European countries,1,2 and the US,3 most doctors disclose the diagnosis as standard practice, but in southern and eastern European countries,2,4,5 the attitude is more paternalistic and patients are often protected from such information. However, even in those countries where the usual practice is now to disclose the diagnosis, a few decades ago the attitude was the opposite.3 This shows that the problem of information can change with time. There are also differences between countries relative to patients and families preferences for the type of information they require. A study in a palliative care setting comparing attitudes in Spain and Canada,6 concluded that the majority of Canadian patients preferred to be clearly informed, while the Spanish patients placed less value on full disclosure. In the same study, family members in Canada agreed with the detailed information to patients, while in Spain 89% of family members indicated that full disclosure was not important to the patient. A few years ago, we conducted a survey of doctors at the Oporto Centre of the Portuguese Institute of Oncology concerning the disclosure of diagnoses to patients.7 In that study, 71% of doctors stated that they always, or at the patients request, disclosed a cancer diagnosis and most doctors who rarely or never disclosed did not do so because they thought that the information could be psychologically deleterious. However, uncertainty can be worse than bad news,8 and some patients assume that a non-threatening diagnosis would be disclosed to them and the absence of such a disclosure is taken to indicate that their condition must be serious.9 Non-disclosure isolates patients as it excludes them from the discussion of problems that probably concern them most. On the other hand, there is a minority of patients who prefer to remain uninformed, and that must be respected as that is the strategy they have evolved to maintain hope. For those who lose hope of a cure or longer life due to the disclosure, hope can be kept alive through other aspects, such as their physician not abandoning them, their remaining free from significant suffering, being with their family and close friends and having time to settle matters important to them. That survey reflected the view of doctors, which can be very different to patients views. Therefore, the obvious next step was to ask patients for their opinion concerning the quantity and quality of information they receive from health professionals and their preferences. Cultural issues are relevant factors in the attitudes of doctors, patients and their families in relation to the disclosure of information. That is why it is important to add data
from different countries, and that is the reason providing justification for this study.
Methods
A survey was conducted between January 2002 and June 2003 on a convenience sample of patients referred to the outpatient clinic of our palliative care unit.10 This is a palliative care unit included in an oncology centre; therefore all patients had cancer as their primary diagnosis. All patients were aged 15 or over, as younger patients are treated in the paediatric service. A questionnaire was specifically designed for this study to acquire the information considered relevant in an exploratory survey. The aim of the survey was to obtain patient preference regarding information and to compare this with what actually occurs. The broad topics of the questionnaire included: who should be informed first when a life threatening disease like cancer is diagnosed; who should and who actually did convey the information; where the information was and where it should have been conveyed; who was and who should have been with the patient; participation in the treatment decision-making process; information provided on palliative care; and a request to name the diagnosed disease. Patients were addressed when they arrived for the first time at the outpatient clinic, before they had any contact with the health professionals of the unit. Psychology students undergoing long-term training in the unit presented the questionnaire to the patients. Patients that were very frail, bedridden or suffering cognitive failure, as assessed by the shortened version of the Confusion Assessment Method,11 were excluded. A descriptive study of all variables included in the study was performed. Chi-square and Fishers exact test were used to compare categorical variables with the status of informed or not informed patients. Age and follow-up time at the oncology centre, before admission to the palliative care unit, were compared between informed and uninformed patients using the Mann / Whitney U -test. The ethics committee of the hospital approved this study.
Results
The survey included 47 patients, 21 males (45%) and 26 females (55%); their median age was 66 years (range: 21 /86 years); 39 were married (83%), six single (13%) and two widowed (4%). The median follow-up time at the oncology centre before admission to the palliative care unit was 16 months (range: 2 /195).
F Gonc alves et al.
Table 2 Actual experience and preferred option of the 34 informed patients on who should be with them when the diagnosis is disclosed
Actual experience n (%)* Family member Friend Alone Other professionals Other patients Indifferent 22 2 8 8 0 / (65) (6) (24) (24) (0) Preferred option n (%) 19 0 3 1 1 7 (61) (0) (10) (3) (3) (23)
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All patients preferred the questions to be read aloud by the psychology students instead of filling the questionnaires in themselves. Thirty-four patients (72%) stated that they had been informed and 13 (28%) that they had not been informed of their diagnosis. Disclosure of the diagnosis Twenty-six (55%) stated that patients should be the first person to be informed, whereas 21 (45%) preferred a family member or a friend. Most patients (41 /87%) thought that the information should be disclosed by a doctor and no one chose a nurse or a social worker. Details regarding what actually occurred and the preferred options for diagnosis disclosure can be seen in Table 1. Nineteen patients (56%) stated that they were surprised with the information, while 15 (44%) suspected the diagnosis. Most patients (68%) received the information at the outpatient clinic, only two received it in an inpatient setting, three at home and one in another place; the three patients who received the information at home were among those informed by a family member, as expected. Most patients preferred to be with a family member when the diagnosis was disclosed and this was what actually occurred, but there were differences between the preferred option and the actual experience (Table 2). We did not find any correlation between information and sex, marital status, age or the follow-up time at the oncology centre before admission to the palliative care unit. Information and participation in treatment decisionmaking process Forty-two patients (89%) were always informed about treatment and two sometimes; therefore only three (6%) were never informed. Twenty-nine patients (62%) always participated in decisions regarding treatment and two participated sometimes; 15 (32%) never participated in decisions regarding treatment (one piece of data missing). Only 32 (68%) thought they should participate in those decisions, 23 (49%) thought that close family members should participate, and 10 (21%) that only doctors should
Table 1 Who should communicate information about diagnosis? Actual experience and preferred options of the 34 informed patients
Actual experience n (%) Family doctor Hospital doctor Any doctor Psychologist Nurse Social worker Family member Other 8 19 / 0 2 0 4 1 (24) (56) (0) (6) (0) (12) (3) Preferred option n (%) 17 10 3 1 0 0 0 3 (50) (29) (9) (3) (0) (0) (0) (9)
*The sum of the actual experience items does not total 34 (or 100%) because some patients were with more than one person.
take the decisions. Seven patients (15%) refused proposed treatments. Effectiveness of the information For 19 patients (56%), the information was disclosed in an acceptable manner, clearly and sensitively, whereas 15 (44%) found the disclosure poorly carried out. However, none of the latter commented further on why they deemed it incorrect. Only one of 13 uninformed patients preferred to remain so. This group of patients was not informed because they were not at ease to ask, the information was refused, they felt they were tricked, the professionals tried not to answer the questions or the information was unclear. On the other hand, five of the 34 informed patients preferred that they had not been informed. Therefore, only six of the 47 patients did not want to know (Table 3). The 34 informed patients stated they had one of the following: cancer / 15 (44%); a tumour / 10 (29%); a bad disease / one (3%); other / seven (21%); do not know / one (3%). The 13 uninformed patients stated they had one of the following: cancer / two (15%); tumour / 0; other / four (31%); do not know / seven (54%). If we consider all patients stating cancer, tumour and bad disease to be informed and all patients stating they do not know or other to be uninformed then the results for informed patients are as follows: 26 (76%) are really informed and eight (24%) are not informed, and for uninformed patients: two (15%) are informed and 11 (85%) are not informed; the
Table 3 Information obtained and patients preferences
Patients preferences To be informed Not to be informed n (%) n (%) Informed patients (n 0/34) Uninformed patients (n 0/13) Total (n 0/47) 29 (85) 12 (92) 41 (87) 5 (15) 1 (8) 6 (13)
Breaking bad news 529 difference between the two groups was significant (P B/0.001) (Table 3). Regarding the referral to palliative care, 39 patients (83%) were informed of the referral, but only eight (17%) had received an explanation regarding the palliative care unit. this preference was limited to older patients. The encouragement to participate in treatment decisionmaking can be associated with higher levels of anxiety, which can persist for at least two weeks.19 In the previous study of doctors at our hospital,7 91% thought that patients should participate in the decisions regarding treatment, which was a higher percentage than that recorded for doctors who always, or on request, informed patients (70%); this seems a contradictory fact given that patients need information to decide rationally; it appears to be the contrary to the patients wishes as observed herein. Sometimes doctors are not very effective in informing patients, as shown by the difference recorded between the information delivered and the patients needs, i.e., there were patients informed that did not want to be informed and patients not informed that had wanted to be informed. These observations are very important because the issue is not the disclosure of information but matching it to the will of patients. Also, the surprise that the diagnosis caused in many patients suggests a lack of appropriate patient preparation concerning the possibility of a diagnosis of cancer during the period of diagnostic tests.18 Furthermore, many patients thought they were poorly informed, without commenting further on why they thought so. This is an important issue because a poor or insensitive disclosure of information may have a negative emotional impact. Patients satisfied with diagnosis communication reported less emotional distress than patients who would have preferred different.18 There are, however, other aspects, besides the way the information was disclosed, which are considered of greater importance, such as emotional support and a shorter period of time between seeking medical assistance and the confirmation of cancer.13,17,18 Also important for patient emotional support is the certainty that the physician will not abandon the patient and will be available to answer all questions.13 The communication of a poor prognosis is an even more difficult task that doctors often avoid. That is probably the explanation why only a few patients were aware of why they had been referred to the palliative care unit, even when they knew their diagnosis and participated in the treatment decisions. This is not exclusive to our hospital.19,20 For example, Cassileth et al . found that more patients receiving curative radiotherapy tended to provide a correct diagnosis than patients receiving palliative radiotherapy,20 which was also interpreted by the authors as being due to the difficulties that doctors have communicating an adverse prognosis. Although physicians often state that non-disclosure is a means of protecting patients, in fact there is a reluctance to give bad news, especially in the transition from curative or life prolonging therapy to symptomatic treatment.21 An
Discussion
The percentage of patients considering themselves to be informed (72%) is similar to the percentage of doctors (71%) that always, or at the patients request, disclosed the diagnosis in a former study carried out at our hospital.7 This number is higher than that observed in a Spanish study about ten years ago, where only 32% of the patients with advanced cancer had been informed of the nature of their disease.12 This is surprising because Spanish culture is deemed to be similar in many aspects to Portuguese culture. It seems unlikely that the ten years separating these two studies can explain the difference. Moreover, 42% of the uninformed patients did not want to receive more information,12 which again contrasts with our observation that only one of the 13 uninformed patients (8%) clearly preferred to remain uninformed. The reasons why those patients were not informed were related to the doctors attitude and a lack of proactive effort to find out the patients information needs, which can be inferred from the manner in which the patients answered this question. On the other hand, five of the informed patients preferred that the information had not been disclosed. Therefore, only a minority of the patients did not want to be informed. Usually patients prefer to be informed by a doctor, and most prefer the family doctor, probably because they are more familiar with them, as patients do not like to be informed by unknown doctors.13 However, most are informed by a hospital doctor, as demonstrated in this and other studies.14 16 Doctors are, in fact, the preferred person to convey the information.17,18 The study of Yun et al .,17 which explores the reasons for this preference, showed that the most important factor is the doctors understanding of the disease and capacity to explain the entire situation; other reasons included trust placed in the doctor, the doctors awareness of the patients emotional, psychological, social and physical situation, and the duty of doctors to provide information. Most patients were informed about treatments and only a minority did not participate in decisions concerning those treatments. But many patients think that they should not participate in those decisions and that only doctors should make such decisions, as observed in other studies;8,11 although in one study,8
F Gonc alves et al. Acknowledgements This study was supported in part by the North Section of the Portuguese League Against the Cancer.
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alternative or complementary explanation for these observations is denial amongst patients.22
Conclusion References
One important limitation of this study is the small number of patients, which raises questions about the external validity of the data and whether the findings can be extrapolated to Portuguese cancer patients as a whole. This said, we tentatively conclude that most Portuguese cancer patients want to be informed of their diagnosis and want to participate in decisions regarding treatment. However, there are also some patients who do not want that, mainly in relation to treatment decision-making. Most patients wish to be with a family member, but not with other health professionals. Some patients stated they had been informed but gave ambiguous answers when asked to name their disease, which does not necessarily mean that they were wrong but casts doubt on the correct nature of their information. Communicating with cancer patients and, in particular, breaking bad news is a very important aspect of the patient /doctor relationship. However, it is often neglected in the training of doctors. Many people, including health professionals, think that the art of communication is a natural skill, ignoring the fact that, just as with other aspects of patient care, it can be learned. There are many general guidelines published on how to break bad news,23 28 which provide general basic knowledge on how to communicate properly, but it is also necessary to learn via practice, through basic programmes,29,30 with follow-up and consolidation.31 Perhaps the most important findings of this study, also verified in all other studies on the problem of information disclosure, are the large differences observed in patients preferences. Even when there is a clear preference on a particular aspect, there is never unanimity. Therefore, the data provided by studies of information preferred by patients in different populations should be seen only as marking out trends or general indications, because in the presence of a particular patient we do not know what he or she wants before we try to find out. Patient preference should not be assumed based on these general data. These studies, important as they are, show population data, which do not necessarily encompass individual needs. The findings of this work can be relevant to anyone working with cancer patients. It adds data relative to patients of a southern European environment, which does not seem to match, at least in those aspects statistically handled, other cultures deemed to be similar, such as that of neighbouring Spain.
/, Falkum E, Hytten K. 1 Loge JH, Kaasa S, Ekeberg Attitudes toward informing the cancer patient / a survey of Norwegian physicians. Eur J Cancer 1996; 32A: 1344 /48. 2 Thomsen O, Wulff HR, Martin A, Singer P. What do gastroenterologists in Europe tell cancer patients? Lancet 1993; 341: 473 /76. 3 Novack DH, Plumer R, Smith RL, Ochitill H, Morrow GR, Bennet JM. Changes in physicians attitudes toward telling the cancer patient. JAMA 1979; 241: 897 /900. 4 Estape J, Palombo H, Herna ndez E et al . Cancer diagnosis disclosure in a Spanish hospital. Ann Oncol 1992; 3: 451 /54. 5 Mystakidou K, Liossi C, Viachos L, Papadimitriou J. Disclosure of diagnostic information to cancer patients in Greece. Palliat Med 1996; 10: 195 /200. 6 Fainsinger RL, Nu n ez-Olarte JM, Demoissac DM. The cultural differences in perceived value of disclosure and cognition: Spain and Canada. J Palliat Med 2003; 19: 43 /48. 7 Ferraz Gonc alves J, Castro S. Diagnosis disclosure in a Portuguese oncological centre. Palliat Med 2001; 15: 35 / 41. 8 Cassileth BR, ZurpKis RV, Sutton-Smith K, March V. Information and participation preferences among cancer patients. Ann Intern Med 1980; 92: 832 /36. 9 McIntosh J. Patients awareness and desire for information about diagnosed but undisclosed malignant disease. Lancet 1976; ii: 300 /303. 10 Ferraz Gonc alves JA. A Portuguese palliative care unit. Support Care Cancer 2001; 9: 4 /7. 11 Inouye SK, van Dick CH, Alessi CA, Balkin S, Siegal AP, Horwitz RI. Clarifying confusion: the confusion assessment method. Ann Intern Med 1990; 113: 941 /48. 12 Centeno-Corte s C, Nu n ez-Olarte JM. Questioning diagnosis disclosure in terminal cancer patients. Palliat Med 1994; 8: 39 /44. 13 Sardell AN, Trierweiler SJ. Disclosing the cancer diagnosis: procedures that inuence patient hopefulness. Cancer 1993; 72: 3355 /65. 14 Chan A, Wooddruff RK. Communicating with patients with advanced cancer. J Palliat Care 1997; 13: 29 /33. 15 Lind SE, Good MJD, Seidel S, Csordas T, Good BJ. Telling the diagnosis of cancer. J Clin Oncol 1989; 7: 583 /89. 16 Barnett MM. Effect of breaking bad news on patients perceptions of doctors. J R Soc Med 2002; 95: 343 /47. 17 Yun YH, Lee CG, Kim S, et al . The attitudes of cancer patients and their families toward the disclosure of terminal illness. J Clin Oncol 2004; 22: 307 /14.

18 Butow PN, Kazemi JN, Beeney LJ, Grifn AM, Dunn SM, Tattersall MHN. When the diagnosis is cancer: patient communication experiences and preferences. Cancer 1996; 77: 2630 /37. 19 Gattellari M, Voigt KJ, Butow PN, Tattersall MHN. When the treatment goal is not cure: are cancer patients equipped to make informed decisions? J Clin Oncol 2002; 20: 503 /13. 20 Cassileth BR, Volckmar D, Goodman RL. The effect of experience on radiation therapy patients desire for information. Int J Radiat Oncol Biol Phys 1980; 6: 493 /96. 21 Falloweld LJ, Jenkins VA, Beveridge HA. Truth may hurt but deceit hurts more: communication in palliative care. Palliat Med 2002; 16: 297 /303. 22 Jones JS. Telling the right patient. Br Med J 1981; 283: 291 /92. 23 Faulkner A, Maguire P, Regnard C. Breaking bad news / a ow diagram. Palliat Med 1994; 8: 145 /51. 24 Richards MA, Ramirez AJ, Degner LF, Falloweld LJ, Maher EJ, Neuberger J. Offering choice of treatment to patients with cancer. A review based on a symposium held at the 10th Annual Conference of the British Psychosocial Oncology Group, December 1993. Eur J Cancer 1995; 31A: 112 /16. Girgis A, Sanson-Fisher RW. Breaking bad news: consensus guidelines for medical practitioners. J Clin Oncol 1995; 13: 2449 /56. Falloweld L. Giving sad and bad news. Lancet 1993; 341: 476 /78. Creagan ET. How to break bad news / and not devastate the patient. Mayo Clin Proc 1994; 69: 1015 /17. Buckman R. How to break bad news . London: Pan Books, 1992. Falloweld L, Jenkins V, Farewell V, Saul J, Duffy A, Eves R. Efcacy of a cancer research UK communication skills training model for oncologists: a randomised controlled trial. Lancet 2002; 359: 650 /56. Jenkins V, Falloweld L. Can communication skills training alter physicians beliefs and behaviour in clinics? J Clin Oncol 2002; 20: 765 /69. Razavi D, Merckaert I, Marchal S, et al . How to optimize physicians communication skills in cancer care: results of a randomized study assessing the usefulness of post-training consolidation workshops. J Clin Oncol 2003; 21: 3141 /49.
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Support Care Cancer (2006) 14: 11471151 DOI 10.1007/s00520-006-0045-6
SHORT COMMUNI CATION
Ferraz Gonalves Mnica Mozes Isabel Saraiva Cristina Ramos
Gastrostomies in palliative care
Received: 29 September 2005 Accepted: 16 February 2006 Published online: 20 April 2006 # Springer-Verlag 2006
F. Gonalves (*) . M. Mozes . I. Saraiva . C. Ramos Unidade de Cuidados Continuados, Instituto Portugus de Oncologia, Rua Dr. Antnio Bernardino de Almeida, Porto 4200-072, Portugal e-mail: ferrazg@ipoporto.min-saude.pt Tel.: +351-225073940 Fax: +351-225506833
Abstract Objective: In palliative care, gastrostomies are used to provide nutritional support or to decompress the bowel. To evaluate what happened to the patients monitored at our palliative care unit (PCU) who underwent gastrostomy between October 1994 and January 2005, a retrospective audit was made. Method: The charts of 154 patients were reviewed. Results: The most frequent reason why a patient underwent a gastrostomy was dysphagia due to head and neck and/or esophageal cancer. Only one patient underwent a drainage gastrostomy because of intestinal obstruction. Interventional radiology performed 96% of the gastrostomies. Early complications occurred in 53 patients (34%) who underwent the gastrostomy for feeding and the most common was local pain, usually mild. However,
there was one death due to peritonitis, probably related with the procedure. Late complications also occurred in 53 patients and major complications occurred in 22 patients, the most common was extrusion. The median survival after the performance of the gastrostomy was 61 days (range 1 to 551 days). Nineteen patients (12%) survived 1 week or less, 28 (18%) between 8 and 30 days, 51 (33%) from 31 to 90 days, 53 (35%) 91 days or more, and one unknown. The patient who underwent a gastrostomy for bowel obstruction survived for only 7 days. One hundred and twentyfive patients (81%) died at the PCU, 26 (17%) at home, and four (3%) at other places. Keywords Gastrostomies . Palliative care . Nutrition . Dysphagia . Bowel obstruction
Introduction
Gastrostomies are used to provide nutritional support in patients who are unable to ingest food and drinks normally for neurological or mechanical reasons. More rarely, they are performed to decompress the bowel in patients with intestinal obstruction. The procedure involves the placement of a tube into the stomach through the abdominal wall. Egeberg, a Norwegian surgeon, conceived the surgical technique in 1837 and Charles Sedillot of Stasbourg performed the first recorded operation of this type in 1849 [1]. Since then, all the
gastrostomies recorded ended in the patients death, usually from peritonitis, as it was only in 1876 when Verneuil performed the first successful surgical gastrostomy in Paris [1]. It was not before 1979 that a new technique was presented when the Americans Gauderer and Ponsky performed the first percutaneous endoscopic gastrostomy (PEG) [2]. Two years later in 1981, the Canadian Preshaw introduced the percutaneous radiological gastrostomy (PRG) [3]. In palliative care, it is quite common to treat patients with dysphagia or intestinal obstruction. To assess what happened to the patients monitored at our palliative care
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unit (PCU) who underwent a gastrostomy, a retrospective audit was made.
Table 1 Demographic data of the 153 patients who underwent the gastrostomy for feeding Gender Male Female Age (year) Median Minimum Maximum ECOGa 1 2 3 4 Unknown Diagnosis Head & neck Esophagus Head & neck + esophagus Colon Breast Primary unknown Metastasis Locally advanced Lymph nodes
a
Materials and methods

A retrospective review was done on the charts of all patients admitted in the PCU of the Porto section of the Portuguese Institute of Oncology since its foundation until January 2005, who had a gastrostomy and died. The unit was founded in 1994 and is described elsewhere [4]. All patients admitted to the PCU who are candidates to undergo a procedure, such as a gastrostomy, are informed of the method, advantages, and risks involved. They sign a standard informed consent document according to the policy of our hospital. The search was made through the computerized database of the hospital. The patients charts were reviewed by three doctors for demographic data, diagnosis, performance status using the Eastern Cooperative Oncology Group (ECOG) index, reason to undergo the gastrostomy, presence of tracheostomy, metastasis, method, complications, and place of death. To analyze the complications of the gastrostomies, we divided them according to early and late when its occurrence was in the first 5 days after the procedure or after 5 days. The rational to this classification was the distinction between complications related with the performance of the procedure and those related with the use of the tube. The severity of the complications was classified as minor or major according to the following criteria: minor when they are light, transitory, and controllable by simple measures and major when there were severe symptoms, the complication was actually or potentially dangerous, or needed the cooperation of professionals from outside the unit to be solved, such as tube extrusion. The analysis of data used methods of descriptive statistic. The method of Kaplan Meier was applied to determine the survival curves and the Breslow test to do the comparative studies concerning the length of survival after the gastrostomy among the ECOG scores.
123 (80%) 30 (20%) 56 26 85 1 18 34 20 12 124 20 6 1 1 1 (1%) (21%) (40%) (24%) (14%) (81.0%) (13.1%) (3.9%) (0.7%) (0.7%) (0.7%)
145 (95%) 77 (50%)
Total of 85 patients who underwent gastrostomy after the admission into the PCU
Data of the patient with bowel obstruction will be presented separately and only when indicated. The demographic data are shown in Table 1. The most frequent reason why a patient underwent a gastrostomy was dysphagia caused by head and neck cancer and/or esophagus cancer (Table 2).
Table 2 Motives, goals, and methods for gastrostomies in all the 154 patients Number of patients (%) Motive Dysphagia Fistula orocutaneous Fistula tracheoesophageal Bowel obstruction Unknown Goal Feeding Drainage Method Radiological Surgery Endoscopy Unknown 142 8 1 1 2 (92) (5) (1) (1) (1)
Results
From a total of 167 patients admitted to the PCU who had undergone a gastrostomy since its foundation in October 1994 until the end of January 2005, only the charts of 154 (92%) could be reviewed because the other 13 could not be found. From those 154, 69 (45%) underwent the gastrostomy before the admission to the PCU and 86 (56%) after it. Only one patient underwent a gastrostomy for drainage due to intestinal obstruction. In all the others, the gastrostomy was performed for nutrition. Due to this huge disparity, the analysis of the data includes only the 153 patients who underwent a gastrostomy for nutrition.
153 (99) 1 (1) 148 3 1 2 (96) (2) (1) (1)
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Most tumors were local recurrences or were locally advanced at the time of the diagnosis; the most frequent metastases were in the regional lymph nodes. Reflecting the localization of the underlying disease, 79 (52%) patients also had a tracheostomy. Interventional radiology performed almost all the gastrostomies (Table 2), as this was the commonly used method at our hospital. Early complications occurred in 53 (34%) patients. The most common early complication was local pain, which was minor in general (Table 3). Major early complications occurred in five patients with one death at the forth day after the gastrostomy due to peritonitis probably related with the performance of the gastrostomy. Late complications also occurred in 53 patients. Major complications were more frequent in these ones, occurring in 22, and the most common was extrusion, but there was a case of pneumoperitoneum and septic shock, which required a laparotomy and treatment with antibiotics (Table 3). However, the patient recovered dying only 2 months later. The overall median survival after the procedure for feeding was 61 days (range 1 to 551 days). Nineteen patients (12%) survived 1 week or less after performing the gastrostomy, 28 (18%) between 8 and 30 days, 51 (33%) 31 to 90 days, 53 (35%) 91 days or more, and two unknown. In other words, 31% survived for 1 month or less and 69% survived for more than 1 month. Analyzing the survival of only the 73 patients who only underwent the gastrostomy
Table 3 Complications observed in the 153 patients who underwent the gastrostomy for nutrition Early Number of patients (%) Minor Abdominal pain, mild 39 (25) Fullness after feeding 4 (3) Nausea/vomiting 3 (2) Infection, local 2 (1) Tube blockage 4 (3) Stomal leak 2 (1) Total 55 Major Peritonitis 1 (1) Pneumoperitoneum + septic shock Tube extrusion 1 (1) Infection, local severe Abdominal pain, 1 (1) replacement needed Abdominal pain, 2 (1) severe Total 5 Late Number of patients (%) 17 5 1 5 4 2 35 (11) (3) (1) (3) (3) (1)
Table 4 Survival after gastrostomy performance for nutrition of the 73 patients whose ECOG score was known Survival after the gastrostomy (days) 17 ECOG 1 2 3 4 Total 1 2 7 4 14 830 3190 >90
1 10 7 18
7 10 7 24
8 7 2 17
All patients underwent the gastrostomy after admission to the PCU
for nutrition after the admission to the PUC and whose ECOG performance status index was known, we can observe that 14 patients (19%) died in the first week (Table 4). From those patients, 20 were classified as ECOG 4, although nine of them survived for more than 1 month and two for more than 3 months. On the other hand, the only patient in this series with a performance status ECOG 1 survived for only 1 day due to a cause probably unrelated with the gastrostomy and two patients classified as ECOG 2 died in the first week after the gastrostomy (Table 4). In fact, the only statistically significant difference was observed between the survival after the gastrostomy of ECOG 2 and ECOG 4 patients (p<0.05). The patient who underwent a gastrostomy for bowel obstruction was a 52-year-old man with colon cancer with peritoneal carcinomatosis and an ECOG 3 when the gastrostomy was performed. He survived for only 7 days. The only complication observed was mild local pain. One hundred and twenty-five patients (81%) died at the PCU, 26 (17%) at home, and four (3%) at other places.
Discussion
In palliative care, feeding can have different objectives. Eating can be one of the most pleasant activities in life; one of its goals is to maintain nutritional status and functional performance; another goal is to satisfy hunger and thirst. Nutrition prevents cachexia and related symptoms, although not always; feeding has a comfort objective, which in some cases, mainly in the last phase of life, is the only one. Food and meals also have important social and emotional aspects, which in many cases influence the feelings and decisions of patients and their families and they tend to pressure the professionals to do something to keep feeding them in situations when it is biologically futile, even after detailed explanations. The goals of enteral nutrition, in this case via gastrostomy, is more modest, however important. The biologic goals are to restore or maintain the nutritional status and to improve or prevent the symptoms related to malnutrition such as weakness, nausea, depression, irritability, and loss
1 (1) 16 (10) 3 (2)
2 (1) 22
Some patients had more than one complication
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of concentration. There are also emotional effects because the patient is being fed. At our unit, when the situation is stable, usually 30 kcal/kg of body weight per day are given, as calculated by the nutritionist, besides hydration. With the evolution of the disease and the deterioration of the patients condition, the situation is frequently reviewed and in the last days, if it is foreseeable, only hydration is given. When gastrostomies are in place, they can also be very useful for medication, besides nutrition and hydration. Dysphagia is common in head and neck and esophagus cancers. This is a situation very different from the incapacity of swallowing due to frailty when patients are close to death. Frequently, head and neck and esophageal cancers cause dysphagia not necessarily because they are far advanced but due to its strategic position. However, starvation caused by dysphagia can deteriorate patients quality of life quickly. Therefore, bypassing the obstruction can be justified. Besides dysphagia, there are other justifications for bypassing the mouth or the esophagus like fistulas orocutaneous, which can cause leaks of liquids and food from the mouth, or fistulas tracheoesophageal, which allow the passage to the trachea causing cough, infections, and dyspnea. There are various methods to feed patients, either parenteral or enteral. Parenteral nutrition should be reserved for patients who cannot tolerate enteral feeding and have a reasonable prognosis [5]. Enteral feeding is a more physiologic approach, besides a much less expensive one, and should be used when the digestive tract is functional. The gastrointestinal delivery of nutrients is thought to improve the status of the gut immune system and maintain the normal gut architecture and microflora [6]. The nasogastric tube (NG) is an easy and inexpensive method. However, it should be reserved for short-term feeding because it can cause a number of complications such as: migration of the tube (mainly into the esophagus), pulmonary aspiration of infused solutions, lesions of the gastrointestinal tract mucosa by the tip of the tube, ear and nose infections, esophageal strictures, vocal cord and pharyngeal paralysis, and others [6]. Besides these possible complications, there is the problem of the self-image. Studies comparing NG with PRG in advanced head and neck cancer [7] and with PEG in neurological patients [8] showed that gastrostomy is a safe and effective method of providing long-term parenteral nutrition and offers important advantages over NG. Considering all those reasons, gastrostomy is probably the method of choice for long-term enteral feeding. There are other methods that can be used such as jejunostomy, cervical pharyngostomy, and esophagostomy. There are, however, a number of complications related to the procedure, most of them minor. The criteria used in other studies to classify the severity of the complications were usually not stated and sometimes the classification
was contentious such as when aspiration pneumonia was considered a minor problem [8]. Some complications are early, the most frequent is local light pain related with the procedure, which disappears in a few days. Others are late, the most common is tube extrusion, which usually does not result in a bad outcome, although it is inconvenient because it upsets the patients and the family and requires travelling to the place where the situation can be solved, such as when the patient is at home, and sometimes a new gastrostomy must be done. There is rarely a fatal outcome, as described by others [9] due to peritonitis or respiratory problems. In one study of 50 patients with head and neck cancer, there were two respiratory arrests during the PEG performance that recovered uneventfully [10]. Although we have some patients with NGs and jejunostomies, by far the most used method for enteral feeding is percutaneous gastrostomy performed by interventional radiology. However, the Service of Gastroenterology of our hospital has started to perform PEG recently, so probably in the future they will be more used than PRG because they allow the use of tubes with wider calibre. PRG, however, will remain a useful alternative to PEG when they cannot be performed due to an obstruction of the upper digestive tract preventing the introduction of the endoscope. Other useful use of enteric tubes is to decompress the gut when there is intestinal obstruction in selected cases when surgery is not indicated and pharmacological measures fail to acceptably palliate the symptoms. Malone et al. [11] in 1986 were the first to report the use of gastrostomies to decompress the bowel under radiological guidance. This allows patients to ingest at least liquids at ease without vomiting by opening the tube from time to time or when they feel nausea. In our study, only one patient underwent a gastrostomy to drain the bowel content, but in the study of Hull et al. [9], 67% of the gastrostomies were performed in patients with bowel obstruction. There are also studies describing only gastrostomies for drainage [11, 1315] showing satisfactory safety and significant improvement in the patients quality of life. Nineteen patients (12%) lived for 1 week or less. That could be due to the inadequate selection of some of them and/or to the well-known uncertainly in prognostication. Anyway, we should be attentive to this fact and discuss it in the team to try to make a better selection of the patients for gastrostomies. The ECOG performance status index demonstrates in this study that it is not accurate enough to select patients to gastrostomies because there is, in each level of the ECOG, a wide range of survival times. This study has the weaknesses typical to retrospective studies. There is a number of missing data and some difficulty to interpret the records, which usually are not suited to be studied later. It would be important to assess the level of patients satisfaction with the procedure and
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nutritional status before the operation and regularly during the follow-up and to assess its impact in symptoms such as fatigue and the quality of life.
Conclusion
Gastrostomies are a useful method to palliate dysphagia and some cases of bowel obstruction. However, there are a
number of complications, usually minor, but some of them potentially severe and even rarely fatal. Palliative care patients are probably particularly vulnerable to complications because of their weakness and denutrition associated with advanced disease. Therefore, the patients should be carefully selected to undergo gastrostomies. Patients with a very short survival do not benefit from the procedure and so it should not be considered. It would be interesting to know the results of the practice of other PCUs.
References
1. Walker LG (1984) L. L. Straton MD, and the first successful gastrostomy in America. Surg Gynecol Obstet 158:387388 2. Wollman B, DAgostino HB, WalusWigle JR, Easter DW, Beale A (1995) Radiologic, endoscopic, and surgical gastrostomy: an institutional evaluation and meta-analysis of the literature. Radiology 197:699704 3. Preshaw RM (1981) A percutaneous method for inserting a feeding gastrostomy tube. Surg Gynecol Obstet 152:659660 4. Ferraz Gonalves JAS (2001) A Portuguese palliative care unit. Support Care Cancer 9:47 5. Mercadante S (1998) Parenteral versus enteral nutrition in cancer patients: indications and practice. Support Care Cancer 6:8593 6. Waitzberg DL, Plopper C, Terra RM (2000) Access route for nutritional therapy. World J Surg 24:14681476 7. Magn N, Marcy PY, Foa C, Falewee MN, Schneider M, Demard F, Bensadoun RJ (2001) Comparison between nasogastric tube feeding and percutaneous fluoroscopic gastrostomy in advanced head and neck cancer patients. Eur Arch Otorhinolaryngol 258:8992 8. Park RHR, Allison MC, Lang J et al (1992) Randomised comparison of percutaneous endoscopic gastrostomy and nasogastric tube feeding in patients with persisting neurological dysphagia. BMJ 304:14061409 9. Hull MA, Rawlings J, Murray FE et al (1993) Audit of outcome of long-term enteral nutrition by percutaneous endoscopic gastrostomy. Lancet 341:869872 10. Hunter JG, Lauretano L, Shellito PC (1989) Percutaneous endoscopic gastrostomy in head and neck cancer patients. Ann Surg 210:4246 11. Malone JM, Koonce T, Larson DM, Freedman RS, Carrasco CHO, Saul PB (1986) Palliation of small bowel obstruction by percutaneous gastrostomy in patients with progressive ovarian carcinoma. Obstet Gynecol 68:431433 12. OKeeffe F, Carrasco CH, Charnsangajev C, Richli WR, Wallace S, Freedman RS (1989) Percutaneous drainage and feeding gastrostomies in 100 patients. Radiology 172:341343 13. Scheidbach H, Horbach T, Groitl H, Hohenberger W (1999) Percutaneous endoscopic gastrostomy/jejunostomy (PEG/PEJ) for decompression in the upper gastrointestinal tract. Surg Endosc 13:11031005 14. Pothuri B, Montemarano M, Gerardi M et al (2005) Percutaneous endoscopic gastrostomy tube placement in patients with malignant bowel obstruction due to ovarian carcinoma. Gynecol Oncol 96:330334 15. Brooksbank MA, Game PA, Ashby MA (2002) Palliative venting gastrostomy in malignant intestinal obstruction. Palliat Med 16:520526
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VOLUME 24 NUMBER 25 SEPTEMBER 1 2006
JOURNAL OF CLINICAL ONCOLOGY
C O R R E S P O N D E N C E
Sedation and Expertise in Palliative Care

TO THE EDITOR: Sedation intending to control pain related with a procedure is not an ethical problem, is used in many elds of medicine, and is widely accepted. Therefore, I will not address this particular context and I will only focus on sedation used to control the suffering that doctors cannot treat by any other means. Among palliative care professionals there is a consensus that sedation is, in certain conditions, an acceptable method to control symptoms that cannot be controlled without affecting the consciousness level. However, this consensus does not exist among all health professionals, as this practice was thought by some of them to be related with euthanasia,1 and sometimes is called slow euthanasia.2 Palliative care literature has produced important denitions and guidelines regarding this kind of sedation, trying to create an ethical framework and a common language, in order to reach comparability among data from diverse settings. I believe there is now a consensus that the level of sedation to be reached should be the one that relieves the symptom and not necessarily a deep sedation, as the denition of Chater et al implies.3 That is, the goal is symptom control, not a certain level of consciousness. Mild sedation (conscious sedation) if enough to make a patient comfortable is not an ethical problem, but deep sedation can make physicians and ethicists disagree about its legitimacy, namely if nutrition and hydration should be maintained and the implication of withholding or withdrawing them on survival.1,4 I also believe that there is a consensus among palliative care physicians that the decision to initiate sedation is legitimate only if the symptom is refractory. And a refractory symptom, according to Cherny and Portenoy,5 can be dened as one that cannot be adequately controlled despite aggressive efforts to identify a tolerable therapy that does not compromise consciousness and the physician should perceive that other intervention either invasive or noninvasive are: (A) incapable of providing adequate relief, (B) associated with excessive and intolerable acute or chronic morbidity, or (C) unlikely to provide relief within a tolerable time frame.5 A different situation would be a symptom that is difcult to control, but that is potentially controllable within a tolerable time frame, and in this case, sedating the patient is not indicated. Another consensus, implied by the denition of refractory symptom, is the expertise and experience required in palliative care and symptom control in order to ensure that sedation is used as a last resource, when nothing else effectively works. Expertise and experience are, however, a relative concept and heterogeneous in a worldwide context and even within the countries. Although, trying to distinguish difcult from refractory symptoms is an important theoretic effort, the distinction will never be settled in a way that can be universally applied. There are countries where there are only a few palliative care teams, if there are any. The stage of development of the teams can be very different. Probably, in most countries, the majority of the patients with very advanced chronic
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diseases are treated by doctors and teams without any expertise in symptom control. What can we recommend in this situation? Should we say that, as they are not experts in palliative care, perhaps the problem could be controlled by someone else? However, someone else who might know what to do is probably not available. And, certainly, the most important concern is to relieve patients suffering. To let them suffer is not an option. As Robert Twycross wrote about euthanasia a doctor who leaves a patient to suffer intolerably is morally more reprehensible than the doctor who performs euthanasia.6 More reprehensible would be to leave a patient suffer without trying a method which is, in general, believed as morally much less problematic. My point is that the rules that palliative care physicians establish for themselves in order to control the quality of their work and achieve the excellence of care which patients deserve are not universally applicable. Without expertise in palliative care, the priority should continue to be the control of suffering, certainly involving discussion in the team and all the knowledge available of colleagues, pain specialists, psychiatrists, and all others who can help, without forgetting that time can be an important variable. But, if after that, the problem is not satisfactorily solved and many doubts remain, I believe that if the patient agrees (if the patient is incompetent, the team should act according to the patients best intereststhis is another discussion), the sedation needed to control the problem should start. However, in those contexts of much uncertainty, sedation should proceed carefully (well, in all contexts it should) and if deep sedation is required, it should be intermittent with scheduled periods of relief and revaluation. At least hydration should be maintained in order to keep the reversibility of the process, unless the patient was not eating or drinking anymore or is obviously dying in a few hours. Usually, sedation is morally justied by the principle of double effect,7 which distinguishes the intended from the foreseen consequences of an act. However, these intensions may be ambiguous and sometimes even the actor is not sure about their real intensions. It is, perhaps, more realistic to consider that the primary obligation of a doctor to a suffering patient, with an untreatable very advanced chronic disease, is to relieve him or her, and sometimes there is not a solution for it that does not compromise consciousness. The will of the patient, if can be expressed, is essential in the process of decision. I believe that this topic deserves a broad discussion. Therefore, I hope to hear comments on this letter.
Jos Anto nio Ferraz Gonc alves

Instituto Portugue s de Oncologia, Porto, Portugal
REFERENCES
1. Orentlicher D: The Supreme court and physician-assisted suicide: Rejecting assisted suicide but embracing euthanasia. N Engl J Med 337:1236-1239, 1997 2. Billings JA, Block SD: Slow euthanasia. J Palliat Care 12:21-30, 1996 3. Chater S, Viola R, Paterson J, et al: Sedation for intractable distress in the dying: A survey of experts. Palliat Med 12:255-269, 1998 4. Craig GM: On withholding articial hydration and nutrition from terminally ill sedated patients: The debate continues. J Med Ethics 22:147-153, 1996 5. Cherny NI, Portenoy RK: Sedation in the management of refractory symptoms: Guidelines for evaluation and treatment. J Palliat Care 10:31-38, 1994 6. Twycross RG: Euthanasia: Going Dutch? J R Soc Med 89:61-63, 1996
Journal of Clinical Oncology, Vol 24, No 25 (September 1), 2006: pp e44-e45
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Correspondence
7. Rousseau P: The ethical validity and clinical experience of palliative sedation. Mayo Clin Proc 75:1064-1069, 2000
Authors Disclosures of Potential Conicts of Interest

The author indicated no potential conicts of interest.
DOI: 10.1200/JCO.2006.07.6810

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Fatigue in palliative care patients an EAPC approach

Lukas Radbruch* Department of Palliative Medicine, RWTH Aachen University, Aachen, Florian Strasser* Department of Internal Medicine, Cantonal Hospital, St. Gallen, Frank Elsner Department of Palliative Medicine, RWTH Aachen University, Aachen, Jose Ferraz Gonalves Department of Palliative Care, Portuguese Institute of Oncology, Porto, Jon Lge Department of Behavioral Sciences in Medicine, University of Oslo, Oslo, Stein Kaasa Palliative Medicine Unit, Department of Oncology, St Olavs Hospital, Trondheim, Friedemann Nauck Department of Palliative Medicine, University of Gttingen, Gttingen, Patrick Stone Department of Mental Health, St Georges Hospital Medical School, London and the Research Steering Committee of the European Association for Palliative Care (EAPC) Fatigue is one of the most frequent symptoms in palliative care patients, reported in .80% of cancer patients and in up to 99% of patients following radio- or chemotherapy. Fatigue also plays a major role in palliative care for noncancer patients, with large percentages of patients with HIV, multiple sclerosis, chronic obstructive pulmonary disease or heart failure reporting fatigue.This paper presents the position of an expert working group of the European Association for Palliative Care (EAPC), evaluating the available evidence on diagnosis and treatment of fatigue in palliative care patients and providing the basis for future discussions. As the expert group feels that culture and language inuence the approach to fatigue in different European countries, a focus was on cultural issues in the assessment and treatment of fatigue in palliative care. As a working denition, fatigue was dened as a subjective feeling of tiredness, weakness or lack of energy. Qualitative differences between fatigue in cancer patients and in healthy controls have been proposed, but these differences seem to be only an expression of the overwhelming intensity of cancer-related fatigue. The pathophysiology of fatigue in palliative care patients is not fully understood. For a systematic approach, primary fatigue, most probably related to high load of proinammatory cytokines and secondary fatigue from concurrent syndromes and comorbidities may be differentiated. Fatigue is generally recognized as a multidimensional construct, with a physical and cognitive dimension acknowledged by all authors. As fatigue is an inherent word only in the English and French language, but not in other European languages, screening for fatigue should include questions on weakness as a paraphrase for the physical dimension and on tiredness as a paraphrase for the cognitive dimension. Treatment of fatigue should include causal interventions for secondary fatigue and symptomatic treatment with pharmacological and nonpharmacological interventions. Strong evidence has been accumulated that aerobic exercise will reduce fatigue levels in cancer survivors and patients receiving cancer treatment. In the nal stage of life, fatigue may provide protection and shielding from suffering for the patient and thus treatment may be detrimental. Identication of the time point, where treatment of fatigue is no longer indicated is important to alleviate distress at the end of life. Palliative Medicine 2008; 22: 1322.
Key words: fatigue; palliative care; cancer-related fatigue; recommendations
Introduction
Fatigue is a frequent, almost ubiquitous symptom in cancer patients as well as in noncancer patients with progressive
Address for correspondence: Professor Dr Lukas Radbruch, Department of Palliative Medicine, RWTH Aachen University, 52074 Aachen, Germany. E-mail: lradbruch@ukaachen.de *Both authors contributed equally to the paper.
life-threatening diseases such as multiple sclerosis, amyotrophic lateral sclerosis or chronic heart or lung disease. Fatigue has a major impact on the quality of life in these patients. The prevalence and impact of fatigue often have not been recognized by physicians.1 In a US survey, more than half of the patients reported that they had never talked about fatigue with their physician and the two most frequent reasons for this were the doctors failure to offer interventions and the patients lack of awareness of effective treatments.2
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14 L Radbruch et al. However, fatigue has received more attention in recent years, as quality of life has increasingly been used as an endpoint in oncological trials. In addition, research on anaemia and cachexia has provided some insight into the pathophysiology of fatigue. The role of proinammatory cytokines in cachexia and fatigue is under investigation (reviewed in35). Cancer trials using erythropoietin found less fatigue with increased haemoglobin levels (reviewed in6,7). The National Institute of Health has included fatigue together with pain and depression in their call for increased awareness in symptom management in cancer,8 and the 6th Framework Programme on Research, Technological Development and Demonstration of the European Union has taken this up in the call for research proposals. Fatigue also is coming into focus in palliative care research. Pharmacological treatment of opioid-induced sedation with methylphenidate or other drugs has suggested that fatigue may be relieved in palliative care patients.9,10 In the light of the increased awareness of fatigue, the question can be raised whether fatigue has reached the point that cancer pain management passed 20 years ago: awareness of the problem leading to clear and easy treatment guidelines, providing adequate symptom relief for most patients. On the other hand, it has been argued that fatigue is fundamentally different from other symptoms, as it may be an inevitable part of the end of life itself. A consensus position on fatigue is an important rst step towards developing recommendations for clinical practice and a research agenda. Recognizing the need for a struc-tured approach, the Research Network of the European Association for Palliative Care (EAPC) has initiated an expert working group on fatigue in palliative care, to provide consensual positions and dene areas where consensus is not available. The authors decided to present a comprehensive review on fatigue in palliative care patients. This paper represents the position of the working group. It establishes the importance of adequate recognition, assessment and treatment of fatigue in palliative care. The focus of this paper is on patients with far advanced cancer or at the end stages of other progressive diseases receiving palliative care. The expert group feel that since culture and language inuence the approach to fatigue in different European countries, it is important to acknowledge cultural issues wherever appropriate. The expert group formulated statements that reect consensus in the expert group wherever possible, supported by evidence where available and the need for discussion and further research in other areas. Draft statements were based on the workshop discussions and rened in an ongoing email discussion among the authors. For each statement, the literature was searched using Medline (Pubmed) and palliative care textbooks by one of the authors (LR) with appropriate search strategies for evidence supporting or refuting the statement. The statements were further rened wherever the evidence necessitated adaptation or change. Other reviews and expert papers on fatigue in cancer patients have been published recently1117 and these reviews will be referred to if possible. Evidence-based guidelines have been presented by the National Comprehensive Cancer Network (NCCN)18 for cancer patients, collating predominantly nonpharmacological treatment options for fatigue. Epidemiology and impact of fatigue Fatigue is one of the most frequent symptoms in palliative care patients, impairing quality of life considerably. Fatigue is reported by not only a majority of patients with advanced cancer, but also many cancer survivors, patients with cardiac failure or with HIV/AIDS. Fatigue in cancer and noncancer palliative care patients is under-recognized, under-assessed and under-treated. Fatigue is one of the most frequent symptoms of cancer and cancer treatment. Fatigue (84%), weakness (66%) and lack of energy (61%) were three of the ve most frequent symptoms in a study of 1000 patients in an American palliative care program.19 Fatigue has been reported in up to 99% of patients following radiotherapy or chemotherapy (review in11,20). Seventeen to 56% of long-term survivors report fatigue as one of the major symptoms impairing quality of life even months after treatment has ended (review in11). In interviews with parents of children who had died from cancer, fatigue was the most common symptom affecting 57% of patients.21 Physical fatigue prevents participation in preferred activities and impedes activities of everyday living. Cognitive fatigue complicates activities such as reading or driving a car and thus prevents leisure activities. Fatigue often is associated with affective disturbances and patients feel listless, depressed, irked or paralyzed. In many cancer patients
Methodology
An expert working group of the EAPC met in November 2003 to evaluate the available evidence on diagnosis and treatment of fatigue in palliative care patients. The expert group did not follow a formal consensus process. The expert group also decided against an attempt to produce evidencebased guidelines. The authors felt that there is not enough consensus on many fatigue topics. Even the denition of fatigue is not used unanimously in trials and publications, preventing comparison of outcomes. Most available evidence on treatment options has been gathered in cancer patients undergoing chemotherapy and it is not clear how much of this data is transferable to palliative care patients. A purely evidencebased approach would also not be able to integrate results from qualitative research, which can provide valuable insights into symptom burden and the need for treatment in patients with fatigue.
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Fatigue in palliative care patients 15 fatigue impedes quality of life signicantly. Patients undergoing chemotherapy rated fatigue as the symptom with the highest impact on daily living, with 91% of fatigued patients stating that fatigue prevented them from leading a normal life.22 Patients felt that fatigue affected their daily life more than pain after chemo- or radiotherapy, whereas physicians believed that pain adversely affected their patients more than fatigue.1 Fatigue also plays a major role in palliative care for noncancer patients. More than half of the patients with multiple sclerosis describe fatigue as one of their most troubling symptoms (reviews at2325). Fatigue has also been reported for the majority of patients with chronic obstructive pulmonary disease26 and heart failure.27 Approximately half of the HIV-patients suffer from fatigue.28,29 As with cancerrelated fatigue, the aetiology often is multifactorial.30 Despite being a common symptom, fatigue has not received much attention from palliative care specialists compared with other symptoms such as pain or dyspnoea. Both nonspecialized and specialized physicians frequently consider fatigue as a natural trait of advanced, incurable illness that has to be endured. Treatment options for fatigue are often perceived as scarce and reduction of patient activities is often the only advice given. The consensus group felt that inadequate assessment skills and insufcient knowledge about multidimensional treatment options can lead to nonrecognition, under-assessment and under-treatment of fatigue in the vast majority of patients. Denition of fatigue As a working denition fatigue is dened as a subjective feeling of tiredness, weakness or lack of energy. Qualitative differences between fatigue in cancer patients and in healthy controls have been proposed. However, these differences seem to be only an expression of the overwhelming intensity of cancer-related fatigue. In the nonmedical setting, fatigue can have various meanings. In humans and animals, it can be used as a noun for the temporary loss of strength and energy resulting from hard physical or mental work. In materials (especially metals), it can mean the state of being weakened by long stress. It can also be used as a verb to mean to exhaust or tire through overuse or great strain or stress (http://www.hyperdictionary.com, access date 19 September 2006). In the medical context of cancer, different denitions have been proposed for fatigue. National Comprehensive Cancer Network denes cancer-related fatigue as a distressing, persistent, subjective sense of tiredness or exhaustion related to cancer or cancer treatment that is not proportional to recent activity and interferes with usual functioning (www.nccn.org/physician_gls/PDF/fatigue.pdf, access date 19 September 2006). A similar denition has been used for fatigue in multiple sclerosis: a subjective lack of physical and/or mental energy that is perceived by the individual or caregiver to interfere with usual and desired activities.23 The Oncology Nursing Society denes cancer-related fatigue as a feeling of debilitating tiredness or total lack of energy that can last for days, weeks or months; commonly caused by anaemia, fatigue is the side effect of chemotherapy that affects patients the most more than nausea, pain or depression; symptoms include feeling weak or worn out, having difculties climbing stairs, walking short distances and performing simple daily tasks; proper nutrition, light exercise, short naps and medications may help alleviate the fatigue (http://www.cancersymptoms.org/glossary.shtml, access date 19 September 2006). Glaus has stressed the qualitative difference of cancerrelated fatigue to fatigue in everyday life: Fatigue in cancer patients is a subjective feeling of unusual tiredness, affecting the body (physical), the emotions (affective) and the mental function (mental), persisting for several weeks and relieved only partially or not at all with rest or sleep. Fatigue in healthy people is a subjective feeling with circadian rhythm, which may be pleasant and normally is relieved by rest.31 Fatigue has also been dened as a clinical syndrome. The Fatigue coalition has suggested the use of the International Classication of Diseases-10 (ICD-10) criteria for the denition of cancer-related fatigue requiring signicant fatigue, diminished energy or increased need to rest, disproportionate to any recent change in activity level to be present every day or nearly every day for two consecutive weeks out of the last month (Table 1). Five out of ten additional symptoms
Table 1 Denition of fatigue in the international classication of diseases (ICD-10)32

A1 and at least ve out of A2A11 have been present for most days in at least two consecutive weeks in the past month A A1 A2 A3 A4 A5 A6 A7 A8 A9 A10 A11 Signicant fatigue, diminished energy or increased need to rest, disproportionate to any recent change in activity level Generalized weakness, limb heaviness Diminished concentration or attention Decreased motivation or interest to engage in usual activities Insomnia or hypersomnia Experience of sleep as unrefreshing or nonrestorative Perceived need to struggle to overcome inactivity Marked emotional reactivity (such as sadness, frustration, irritability) to feeling fatigued Difculty completing daily tasks attributed to feeling fatigued Perceived problem with short-term memory Postexertional malaise lasting several hours The symptoms cause clinically signicant distress or impairment in social, occupational or other important areas of functioning Evidence from history, physical examination or laboratory ndings, that symptoms are a consequence of cancer or cancer treatment Symptoms are not primarily a consequence of comorbid psychicatric disorders such as major depression, somatization disorder, somatoform disorder or delirium
B C D
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16
L Radbruch et al. means absence or loss of strength. Asthenia includes three different major symptoms: (1). fatigue or lassitude dened as easy tiring and decreased capacity to maintain performance; (2). generalized weakness dened as the anticipatory sensation of difculty in initiating a certain activity and (3). mental fatigue dened as the presence of impaired mental concentration, loss of memory and emotional lability.46 Finally, fatigue has been described not as a clinical symptom, but as a behavioural concept, where the symptom is part of a continuum ranging from tiredness to fatigue and then to exhaustion.47 These stages are related to dened behavioural patterns. Nonadaptation will lead to progression towards exhaustion, at least in patients with normal haemoglobin levels. These differences in the concepts of fatigue present an obstacle to producing a common denition of fatigue in Europe. Nevertheless, agreement on a working denition is clearly necessary. The working denition of fatigue should be simple and should take into account that fatigue in palliative care is a symptom that may be caused by the underlying disease, its treatment or by other comorbidities. For this paper, the following working denition is used: Fatigue is a subjective feeling of tiredness, weakness or lack of energy. This denition corresponds closely to the fatigue subscale of the quality of life questionnaire of the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30 version 3) that is calculated from the three questions have you felt weak?, were you tired? and did you need to rest?.48,49 This pragmatic approach facilitates comparable working denitions in different European languages, as the EORTC QLQ-C30 has been translated and validated in more than 50 languages. The working denition does not include any qualitative difference between cancer-related fatigue and fatigue in other settings, as the inability to relieve fatigue with rest as well as interference with function seem to be indicators of the intensity of fatigue rather than criteria for the quality of fatigue. Cancer-related fatigue usually is considered a negative emotion. However, in a German study, two out of 117 patients with chronic pain commented that they found it pleasant.50 The working denition relies on the subjective assessment of the patient only. Currently no objective measurement of fatigue is feasible, though objective activity assessment for weakness as a subdimension of fatigue has been proposed. However, as palliative care focuses on the subjective condition of the patient, the subjective assessment should be the indicator for treatment. There seems to be considerable overlap between fatigue and depression.51 Weakness and tiredness are among the predominant symptoms of depression and feeling depressed often is part of the affective dimension of fatigue. However, there are some symptoms that are reported only with depression (such as sustained feelings of worthlessness, recurrent thoughts of death) and some symptoms are specic for fatigue (such as postexertional malaise).51
such as generalized weakness, diminished concentration, insomnia or hypersomnia and unrestorative sleep are required for the diagnosis.32 The authors emphasize that fatigue must cause signicant distress or impairment, is to be associated with cancer or cancer treatment and must not be due to a comorbid psychiatric disorder. This denition is similar to that used for Chronic Fatigue Syndrome (CFS), which has been described as a specic illness in its own right and is probably caused by central nervous dysfunction (review in33). The threshold of six symptoms (fatigue and ve others) and the time span of at least two weeks have been chosen arbitrarily, with the intention of capturing various causes of fatigue, but so as not to render the diagnosis trivial.34 The authors found that although 37% of cancer patients reported fatigue for at least two weeks in the previous month, only 17% fullled their strict criteria for cancer-related fatigue syndrome. However, since 79% of the patients reported debilitating fatigue,32 it may be that this rather strict denition of the fatigue syndrome excludes many patients who should have been assessed and treated for fatigue. The International Classication of Diseases-10 criteria have been dened to recognize the fatigue syndrome in all stages of cancer from active treatment to advanced stages as well as to survivorship, but may be of limited value for diagnosis of fatigue in the palliative care setting, where the prevalence of concomitant psychological disorders is high.35,36 Some authors state that cancer-related fatigue is qualitatively different from the fatigue that everyone feels after exercise,32,3739 and cancer patients report that they are less likely to recover from fatigue during sleep. A self-report described cancer-related fatigue as totally unlike even the most profound fatigue of an otherwise well person.40 However, the consensus group emphasized that cancerrelated fatigue does not seem to be qualitatively different from fatigue in healthy humans, but simply represents one end of a continuum of intensity. Less severe fatigue in cancer patients may also be relieved by rest. Fatigue is not uncommon in the general population. A prevalence of fatigue up to 28% has been found in unselected patient groups treated by general practitioners.41,42 Pawlikowska et al. looked at the prevalence of fatigue in a general population and found that fatigue is continuously distributed in the community. Substantial fatigue lasting six months or longer was reported by 18% of the respondents.43 Stone et al. dened severe fatigue as an intensity score in excess of the 95th percentile of a healthy control group and found the prevalence of severe fatigue to vary between 15% in recently diagnosed breast cancer patients and 78% in patients receiving inpatient palliative care.44 Mendoza et al. found that healthy controls consistently rated fatigue levels as lower than cancer patients using a variety of different fatigue instruments.45 The second edition of the Oxford Textbook of Palliative Medicine uses the concept of asthenia and nds that fatigue is only one of the dimensions of asthenia: Astenos (Greek)
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Fatigue in palliative care patients 17 There also seems to be some overlap between fatigue and the cachexia and anorexia syndrome, and both may be reported by the patient concomitantly.52 As with depression, these symptoms represent distinct entities and efforts should be made to assess and treat them separately. However, it has been suggested that investigation of symptom clusters involving fatigue instead of fatigue as an isolated symptom may be the next step in research in symptom control.53,54 Pathophysiology of fatigue Primary fatigue is hypothesized to be related to the tumour itself. This may either be through peripheral mechanisms such as energy depletion or by central mechanisms such as dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis or serotonin metabolism. These mechanisms may ultimately be related to high levels of cytokines. Cancer-related concurrent syndromes and comorbidities such as anaemia, cachexia, fever, infections or metabolic disorders as well as sedative drugs for symptom control can produce secondary fatigue. The pathophysiology of cancer-related fatigue is not fully understood. In most patients, throughout the disease trajectory, many different causes will contribute to the development of fatigue.55 For a systematic approach, the expert group suggests a differentiation between primary fatigue, probably related to high cytokine load and secondary fatigue from cancer- or treatment-related concurrent syndromes and comorbidities (Figure 1). In advanced cancer, many factors are likely to contribute to fatigue. The relative contribution of each cause will uctuate throughout the disease trajectory, thus challenging too simplistic primary and secondary concepts in clinical practice. In a quantitative review of 18 studies with 1037 participants, signicant positive correlations were found between fatigue and circulating levels of inammatory markers. However, 31 out of a total of 58 correlation estimates in these studies were not signicant.56 High cytokine concentrations have been reported in association with fatigue in patients undergoing radio- and chemotherapy as well as in cancer survivors.57,58 However, another study with women with uterine cancer receiving curative external radiation therapy found no correlation of fatigue intensity and levels of interleukin-1 (IL-1) and tumour necrosis factor (TNF) and even a negative correlation between fatigue and interleukin-6 (IL-6) level.59 Simple assessment of circulating cytokine concentrations alone may not be sufciently reliable. In one study, signicantly higher serum levels of markers associated with proinammatory cytokine activity were found in fatigued breast cancer survivors compared with nonfatigued survivors. These markers included IL-1 receptor antagonist (IL-1ra), soluble TNF receptor type II (sTNF-RII) and neopterin as a
Figure 1
Algorithm for diagnosis of fatigue in palliative care patients.
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18 L Radbruch et al. measure of macrophage activity.60 Signicant correlations between fatigue and IL-1ra and between fatigue and neopterin have been conrmed in a review.56 However, in survivors from lymphoma with high levels of fatigue 410 years after bone marrow transplantation, no correlation of fatigue intensity with cytokine levels or levels of cytokine markers was found.61 Increased levels of vascular endothelial growth factor and soluble intercellular adhesion molecule-1 (sICAM-1) were related to increased fatigue following anthracycline-based chemotherapy in patients with advanced breast cancer.62 The pathophysiology of cytokine-related primary fatigue includes both peripheral and central components. Peripheral mechanisms may be related to energy imbalance, such as altered muscular metabolism and central mechanisms may involve changes in the neural function of the HPA axis and neuronal systems underlying arousal and fatigue.38 Peripheral energy depletion following reduced intake of food has been postulated as a cause of fatigue.63 Adenosine triphospate has been used with good effect on fatigue and cachexia in an open-label, randomized controlled trial,64 leaving the discussion open whether energy delivery or stimulation of P2 purinergic-receptors caused the effects. It is not clear whether energy depletion in fatigued patients is mainly a manifestation of concomittant cachexia. Another hypothesis on primary fatigue relies on evidence from animal studies suggesting a reex circuit with the reduction of somatic muscle tone from vagal afferent stimulation. Intraperitoneal injection of IL-1 induced sickness behaviour with decreased activity and increased sleep in rats and abdominal vagotomy abolished or attenuated this response.63 However, evidence in support of this vago-somatic inhibitory reex is scant. Comparing patients with cancer-related fatigue with healthy volunteers, Davis et al. found a reduction of central drive in the cancer group, whereas resting twitch force in the biceps muscle was similar and postfatigue twitch force was even greater in the cancer group, indicating less physiological fatigue in the cancer patients.65 These results point to a predominantly central change as the cause of cancer-related fatigue. Dysregulation of the HPA axis has been suggested as a possible central mechanism of primary fatigue. The diurnal cortisol rhythm was subtly, but signicantly changed in fatigued breast cancer survivors with a less rapid decline in cortisol levels in the evening hours.66 Compared with nonfatigued survivors, the cortisol response to stress was blunted in this patient group.67 Fatigue also may be linked to serotonin metabolism in the brain. The 5-hydroxytryptamine (5-HT) transporter, the main mechanism for removal of 5-HT from the synaptic space, is up-regulated by increased levels of TNF.63 Concurrent syndromes and comorbidities may further drain the reduced resources of energy and increase the feeling of fatigue and lack of energy. Proinammatory cytokines such as IL-1, IL-6, TNF or interferon play a major role in the pathophysiology of cachexia, anaemia, fever and infection, all of which can cause or aggravate fatigue (Table 2).68 Cachexia does not only result from reduced nutritional intake, but has been predominantly linked to a profound change in metabolism, with increased proteolysis in skeletal muscle and increased synthesis of acute phase proteins in the liver.69,70 The involvement of cytokines in cancer-related anorexia and cachexia have been extensively researched (reviews in4,69). Anaemia clearly is a cause of fatigue in cancer patients and anaemic patients are more fatigued than nonanaemic
Table 2
Laboratory parameters for differential diagnosis of fatigue

Parameter Haemoglobin, transferrin, ferritin, iron, erythropoetin Calcium (and albumin), magnesium, phosphate Creatinine, bilirubin TSH, free T3 and T4 WBC (white blood cell count), C-reactive protein ACTH, cortisol, free testosterone, melatonin Vitamin B1, vitamin B6, vitamin B12 Interleukin 1, interleukin 6, TNF- (tumour necrosis factor)
Comorbidities Anaemia Electrolytes Organ dysfunction Hypothyroidism Infection Hormones Vitamin deciency Cytokine load
Cortisol requires a 24-h prole Markers for increased cytokine load might be better suited than cytokines themselves: IL-1 receptor antagonist (IL-1ra), soluble tumour necrosis factor receptor type II (sTNF-RII) and neopterin (macrophage activity marker)
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Fatigue in palliative care patients 19 patients.71 High cytokine levels diminish erythropoetin secretion and blunt the erythropoetin response to cancerrelated anaemia. Treatment of anaemia with erythropoetin can result in alleviation of fatigue (reviewed in6). However, as the association between haemoglobin level and fatigue intensity is only weak, it has been hypothesized that impaired functionality of the haemoglobin instead of just lower levels may be responsible for fatigue.72 However, investigating oxyhaemoglobin dissociation as an indicator of the function of the haemoglobin, no differences were found between cancer patients and healthy controls. Other metabolic disorders such as hypothyroidism, hypogonadism,73 dehydration or electrolyte disturbances such as hypercalcaemia, hepatic, cardiac or renal failure, sleep disorders, anxiety or emotional stress may contribute to cancer-related fatigue,74 and treatment of these causes may alleviate fatigue considerably. New anti-neoplastic therapies may be associated with novel causes for secondary fatigue. Hypomagnesaemia following anti-neoplastic treatment with cetuximab, a monoclonal antibody to the epithelial growth factor receptor has been reported recently as a cause of secondary fatigue.75,76 Depression has been linked with fatigue and fatigue is one of the main symptoms of major depression.77 Fatigue can also be aggravated by other cancer- or treatment-related symptoms. In a group of breast cancer survivors, fatigue was signicantly correlated with dyspnoea, insufcient sleep and depression, with these three variables accounting for a total of 46% of variance in fatigue.78 Many drugs with sedative properties regularly used in palliative care such as opioid analgesics, benzodiazepines, anti-depressants or anti-convulsants can add to the fatigue load. As with cancer, fatigue and sleep disturbances have multiple causes in most patients with HIV infection and AIDS.30 Increased levels of IL-1 and TNF from HIV infection may lead to sleep disturbances and fatigue (reviewed in79). Anti-viral treatment with cytokines may boost fatigue dramatically.8083 Anaemia,84 dysregulation of growth hormone85 or hypothyroidism86 have also been implicated in the pathophysiology of fatigue with HIV. Whereas some work has been done on the pathophysiology of cardiac cachexia,87 only little research is available on the pathophysiology of fatigue in patients with cardiac failure. Cachexia-related loss of skeletal muscle may contribute to fatigue in these patients. Reduced muscle strength and endurance has been linked to changes in histology and metabolism in patients with chronic heart failure.88 These changes seem to be related to imbalances of anabolic and catabolic factors. The cause of this shift is not clear, but may be due to continuous haemodynamic stress from decreased peripheral perfusion. Fatigue may be aggravated by the ergoreex from metabolic stimulation of ergoreceptors in the muscle, causing increased ventilation and sympathetic activation after exercise. Fatigue in chronic progressive disease has also been described as part of the cytokine-induced sickness behaviour together with other symptoms such as loss of appetite, sleepiness, fever and aching joints.89 This seems to be a physiological adaptive response reorganizing priorities to facilitate recovery from an infection. Chronic sickness behaviour from inappropriate prolonged activation of the immune system may offer an explanation for chronic fatigue in a wide range of chronic diseases, ranging from Alzheimers disease to stroke. Assessment of fatigue A physical and cognitive dimension seem to be acknowledged by all authors. Weakness seems to be useful as a paraphrase for the physical dimension and tiredness for the cognitive dimension. Screening for fatigue should include questions on weakness and tiredness such as Do you feel unusually tired or weak? or How weak are you? / How tired are you? Multidimensional specic questionnaires should be used for research projects on fatigue. Assessment of fatigue should depend on subjective selfevaluation by the patient, substituted by estimations of carers or medical staff only where self-assessment is not possible. As with the denition of fatigue, various approaches to assessment have been proposed. Fatigue may be regarded as a single symptom, as a symptom cluster or as a clinical syndrome. For the single-symptom approach, single item scales (do you get tired for no reason?) have been proposed. For the symptom cluster approach, checklists and questionnaires with multiple dimensions have been validated (review in,90 Table 3). Using the clinical syndrome approach the physician has to assess fatigue with a checklist following the denition of the ICD-10. Many instruments have been constructed for the symptom cluster approach. Some of these instruments are rather long such as the Functional Assessment of Cancer Therapy Fatigue (FACT-F)91 with 47 items (although the 13-item fatigue subscale can be used as a stand-alone questionnaire). The Piper fatigue inventory has recently been shortened to 22 items.92 The Multidimensional fatigue inventory was constructed with 20 items.93 Some instruments such as the fatigue subscale of the FACT do not cover the different dimensions of fatigue. The brief fatigue inventory (BFI) was constructed in a similar fashion to the brief pain inventory. It assesses severity and impairment from fatigue using only 9 questions. However, the BFI taps only a single dimension described as severity of fatigue.45 The EORTC QLQ-C30 includes a subscale on fatigue with three items.48 The EORTC and FACT quality of life questionnaires and the BFI are available in many languages. Although there is no generally accepted denition of fatigue, it is widely recognized as a multidimensional construct. Glaus described physical, cognitive and affective dimensions of cancer-related fatigue.94,95 Other authors have
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20 L Radbruch et al. described interference with function, vigour, mood, reduced activity, reduced motivation or distress from fatigue as additional dimensions of cancer-related fatigue, usually in connection with the development of assessment instruments (Table 3). A physical and a cognitive dimension seem to be acknowledged by all authors. Weakness seems to be useful as a paraphrase for the physical dimension and tiredness for the cognitive dimension. However, semantic problems impede the discussion about denitions and assessment tools. Fatigue is inherent only in the English and French languages, but not in other European tongues (Table 4). In all European countries, fatigue has been used frequently in oncology research and assessment of fatigue has been introduced in many oncology trials. However, it is not clear how much explanation about fatigue patients receive and whether the concept of fatigue is understood by patients with native languages other than English or French. Even if the oncology or palliative care specialist has adequate understanding of fatigue, he may not be able to transfer this knowledge and understanding to a patient who is not familiar with the concept. Patients not included in oncological research will only rarely learn of fatigue. Translation of fatigue into other languages where the term is not commonly used is not without pitfalls. Glaus et al. stated that for German-speaking patients, fatigue would be translated with Ermdung or Ermdbarkeit, whereas Mdigkeit would rather be equivalent with tiredness.39 Other European languages may have similar problems with translation. Even with adequate care in translation, equivalent words in other languages may not always cover the different dimensions of fatigue. Care has to be taken that the translated questionnaire covers the same dimensions as the original versions. Patients in a German validation study clearly related fatigue more with cognitive and affective areas than with physical exhaustion and cut-off points for worst fatigue differed in the German and English versions of the BFI.50 It should be assumed that translation of fatigue into other languages will nd similar differences and problems. The expert group recommends a differentiated assessment of fatigue depending on the setting. Screening for fatigue in nonspecialized settings such as oncology departments or general practice should be done with single-item questions such as Do you feel unusually tired or weak?. Screening in specialized services such as palliative care units should include questions on weakness and tiredness as the two main dimensions of fatigue at initial assessment and on regular follow-up. Documentation systems such as the modied Edmonton symptom assessment score96 or the minimal documentation system97 that include weakness and tiredness are recommended for routine use in specialized services. Patients with high scores (severe weakness/ tiredness, NRS 5) should receive special attention, to detect reversible causes of fatigue or to identify distress associated with perceived fatigue. If fatigue is a priority syndrome for care, they may be asked to complete a standardized multidimensional questionnaire or (preferably) be interviewed to assess the areas and scope of impairment. Research projects on fatigue should follow a more detailed approach. Specic questionnaires such as the BFI or the anaemia and fatigue subscale of the FACT should be completed at study entry, before and after interventions and at study completion. Cognitive impairment may prevent self-assessment with standardized questionnaires. Patients with mild cognitive impairment will be able to self-assess fatigue on simple categorical scales, but patients with moderate or severe impairment may not be able to do so. The expert group recommends assessment of fatigue by carers or staff in these patients, taking into account that carers tend to overestimate and staff tend to underestimate fatigue severity. Children also may not be able to self-assess fatigue with standardized scales or questionnaires. As with pain assessment, school children and adolescents usually will be able to use the same fatigue assessment instruments as adults, but smaller children will lack the ability for abstract thinking required for the assessment scales. No instruments have been developed for assessment of fatigue in children yet. The expert group recommends assessment by parents or by staff in these children, using behavioural observations such as changes of the sleep-wake times, frequent dozing, continuous lack of interest or concentration difculties. The cognitive dimension of fatigue may be tested with psychomotor tests such as nger tapping or more complex methods such as the battery used for assessment of driving ability.98 However, these tests will only have limited value in a palliative care setting, as cognitive or physical impairment will prevent participation of the vast majority of patients in such tests. Trying to assess the physical dimension of fatigue with objective measures, for example with an ergometer, has been without much success in patients with advanced cancer. However, newer electronic physical activity meters are currently being evaluated in clinical trials. Using devices that record postural changes and other aspects of physical activity, information about the activity level of patients in a palliative care setting may be obtained. This may signify the beginning of a change from subjective self-assessment of the patient to more complex assessment using subjective assessment of impairment together with objective information on physical and cognitive activity. Treatment of fatigue Secondary causes for fatigue should be treated causally if possible. Causal treatment of primary fatigue with anticytokine or anti-inammatory pharmacological approaches is under investigation although is currently lacking both promising results and a favourable risk-benet relationship.
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Table 3
Items Translated and validated in many languages Translated and validated in many languages Only in English language Example Scales
Assessment instruments for fatigue in palliative care
Instrument
EORTC QLQ C30
V2.0176 Four-step VRS: not at all, a little, quite a bit, very much Five-step NRS: 0, not at all; 4, very much Adjective wording scales (22 items), open questions (ve items)
FACT An and F91
Piper fatigue scale92
Did you need to rest? Have you felt weak? Were you tired? I feel fatigued I feel weak all over I am frustrated with being too tired to do the things I want to do To what degree is the fatigue that you are feeling now causing you distress? To what degree are you now feeling lively/listless? Eleven-step NRS: 0, no fatigue, 10, as bad as you can imagine English, German and Japanese languages, other translations in the process of validation English and Italian versions
BFI45
Thirty items, among them three questions on fatigue Thirteen items (FACT-F), Seven items (FACT-An), used together with the 27 items of the FACT-G Twenty-seven items, behavioural/severity (six items), affective meaning (ve items), sensory (ve items), cognitive/mood (six items), ve additional items Ten items, intensity (three items), impairment (six items)
Fatigue symptom inventory177,178 Thirteen items, intensity (four items), duration (two items): interference with functional status (seven items)
Eleven-step NRS: 0, not at all fatigued; 10, as fatigued as I could be
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I feel t Physically, I feel only able to do a little I feel very active Eighty-three items, short form with 30 items (currently tested), general dimension (six items), physical dimension (six items), emotional dimension (six items) mental dimension (six items) vigour (six items) Twenty items, general fatigue, physical fatigue, reduced activity, reduced motivation, mental fatigue Twenty-three items, intensity (three items), physical dimension (11 items), affective dimension (ve items) cognitive dimension (three items) sleeping problems (single item) Did you experience weakness, loss of strength? Did you experience difculties in concentrating? Did you feel sad? I get tired for no reason Single item Single item
Multidimensional fatigue symptom inventory179
Have you felt unusually tired or fatigued in the last week? (yes, no Please rate your fatigue (weariness, tiredness) by circling the one number that best describes your fatigue right now. Rate the level of fatigue on the day you felt most fatigued during the past week Rate how much, in the past week, fatigue interfered with your general level of activity I feel sluggish My arms feel weak I feel tense Five-step VRS: not at all, a little, moderately, quite a bit, extremely
English, Estonian, Finnish, French for Canada, Hebrew and Lithuanian language versions
Multidimensional fatigue inventory93
Seven-step Lickert Scale: 1, yes that is true; 7, no, that is not true
English, Dutch, French, German, Danish and Swedish language versions
Fatigue assessment questionnaire95
Four-step VRS: not at all, a little, quite a bit, very much VAS for intensity: I did not feel unusually tired at all I felt extremely tired, exhausted
English and German language versions
I get tired for no reason180
English language only
Fatigue in palliative care patients 21
Rhoten fatigue scale181
Four-step VRS (none or a little of the time to most or all of the time) Ten-point NRS ((0, not tired, peppy; 10, total exhaustion)
VRSVerbal rating scale NRSNumerical rating scale VASVisual analogue scale
22 L Radbruch et al.
Table 4 Fatigue equivalents in different European languages
Language English (British) French Italian German Swiss Portuguese Norwegian Irish (Gaelic) Fatigue Fatigue Fatigue Stanchezza Ermdbarkeit, Ermattung Mde, Bedusselt Fraqueza, Cansao, Fadiga Trtt Buibhestas Other translation
Tiredness? Exhaustion? Weakness, tiredness, fatigue
Most patients will require symptomatic treatment for fatigue with pharmacological and/or nonpharmacological interventions. In the nal stage of life, fatigue may provide protection and shielding from suffering for the patient and treatment of fatigue may be detrimental. Identication of the time point where treatment of fatigue no longer is indicated is important to alleviate distress at the end of life. The vast majority of patients with cancer-related fatigue do not receive adequate treatment. In a survey of patients
after chemo- or radiotherapy, only 27% reported that their oncologist had recommended any treatment for fatigue.1 This is partly due to barriers to reporting fatigue in the patients, but also to inadequate skills and knowledge of physicians. Treatment of the underlying cause should be initiated in patients with secondary fatigue (Figure 2). Disease stage and life expectancy have to be considered to balance possible risks and potential benets of causal therapy. Taking into account the possible role of cytokines in the pathophysiology of fatigue, there may be a role for pharmacological approaches directed at targeting excessive cytokine concentrations. Thalidomide as an antagonist of TNF has been suggested as a treatment of cachexia in cancer4,99 and AIDS.100 Thalidomide showed a benecial effect on weight loss and quality of life in a single small randomized trial with cachectic cancer patients.101 However, the cytokine antagonist pentoxiphylline had no signicant effect on cachexia in randomized trials in HIV102 or cancer patients.103 Thalidomide, pentoxiphylline or other drugs interfering with cytokine synthesis such as rolipram have not been used in clinical trials on fatigue yet and sedation as one of the major side effects of thalidomide makes its use for the treatment of fatigue unlikely. No change in fatigue was reported in the randomized trial of thalidomide for cancer cachexia.101
Figure 2
Algorithm for treatment of fatigue in palliative care patients.
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Fatigue in palliative care patients 23 For most patients, causal treatment of primary or secondary fatigue will not be effective enough or will take too long. For these patients, symptomatic treatment should be considered. Symptomatic treatment should comprise pharmacological and nonpharmacological interventions. The expert group discussed the need for treatment with respect to the stage of the patients illness. It should be kept in mind that in the terminal stage of life fatigue might be considered a normal response, protecting and shielding the patient from suffering and facilitating the transfer from life to death. In the nal hours and days of life, effective treatment of fatigue could produce a cruel relapse into the full dramatic experience of the disease when sedation, weakness and emotional deprivation are reduced. Identifying the time point where vigorous treatment of fatigue is no longer indicated is important to alleviate distress at the end of life. Treatment of secondary fatigue Treatment of anaemia with erythropoetic agents effectively increases haemoglobin levels, thereby alleviating fatigue, but usually life expectancy is too short in palliative care patients to pursue this option. The efcacy of treatments for cachexia, depression, uid or electrolyte imbalances, fever or infection on fatigue have not been investigated, but should be considered in patients with fatigue related to these underlying causes. Some causes of secondary fatigue such as anaemia, depression, infection, dehydration, malnutrition, hypercalcaemia, hypomagnesiaemia or treatment with opioids or other sedative drugs can be treated and effective causal treatment should alleviate fatigue. The treatment of anaemia with erythropoetic agents such as erythropoetin or darbepoetin alfa has been a recent focus of interest in oncology. Fatigue has been named as the predominant symptom of anaemia and treatment with erythropoetic agents has been specically directed to alleviate cancer- and treatment-related fatigue.104 Randomized trials with darbepoetin71 and erythropoetin7,105 have consistently shown reduced levels of fatigue with increasing haemoglobin concentrations. Other reviews have conrmed the efcacy of erythropoetic agents.6,106 Treatment of anaemia is recommended for cancer patients with haemoglobin levels below 12 g/dL.107 However, treatment with erythropoetin will take up to 12 weeks to take effect and many patients in palliative care will not have a life expectancy to match this. Considering also the high costs of erythropoetin treatment and potential complications such as thrombosis or pure red cell aplasia, it is not surprising that palliative care physicians seem to make little use of erythropoetic agents. There was consensus in the expert group that blood transfusions may also increase haemoglobin levels effectively, and may be indicated for palliative care patients with fatigue related to anaemia. The effects of blood transfusions are short-term and transfusions often have to be repeated, sometimes several times per week. Potential transfusion complications, nancial and resource burden, all conspire to make routine transfusion unsuitable as a rst-line treatment approach. However, in selected patients repeated blood transfusions may have a role in management. As with blood transfusions, no clinical trials are available for treatment of other secondary causes of fatigue, even though published guidelines stress the importance of causal therapy wherever possible.74,108 The use of antibiotics has sometimes been considered controversial in palliative care. In such patients, infection does not always lead to antibiotic therapy. Some palliative care programs will not support the use of antibiotics in their patients, whereas others use them with the aim of symptom control. The expert group stated that treatment of fever or infections with antipyretic or antibiotic drugs may be indicated to treat fatigue-related impairment. The cachexia-anorexia syndrome (CAS) has been investigated intensively in recent years. However, effective treatment strategies are still scarce. Increasing the caloric intake alone does not seem to improve CAS. Nutritional supplementation with anti-inammatory polyunsaturated fatty acid or eicosapentanoic acid seems to be benecial in preclinical and phase II trials (review in109). However, three recent randomized trials failed to prove a benecial effect in patients with CAS.110112 Megestrol acetate was shown to improve appetite compared with placebo in several randomized trials113115 and compared with dronabinol in one trial.116 In some of these studies there was also an improvement in quality of life. However, three randomized trials failed to nd any benet for fatigue.115,117,118 Cyproheptadine, hydrazine sulfate and cannabinoids have all been suggested as treatments for anorexia but clinical trials have found no benet for appetite or energy levels (review in119,120). Corticosteroids have been shown to increase appetite and daily activity in a randomized trial in advanced cancer patients but with no effect on subjective fatigue.121 After prolonged treatment with corticosteroids, insulin resistance (aggravating cachexia), proximal myopathy (causing muscle weakness) and increased risk for infections (and cytokine activity) may aggravate fatigue. Recent data from animal trials have suggested the beta2agonists clenbuterol and formoterol as potential therapeutic tools for the CAS, probably via an inhibitory effect on the ATP-ubiquitin-dependent proteolytic system of skeletal muscles.122 Prostaglandin inhibitors such as celecoxib also seem to reverse wasting in the animal model123 and clinical trials are ongoing. However, the benet of these drugs on fatigue has not been investigated yet. As discussed above, there is considerable overlap between depression and fatigue in patients with advanced cancer and treatment with anti-depressants may alleviate fatigue in cancer patients with major depression. However, in a randomized controlled trial, paroxetine did not lead to a reduction of fatigue in patients with breast cancer receiving chemotherapy, even though depression was reduced signicantly compared
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24 L Radbruch et al. to placebo.124 Sedation may be a side effect of anti-depressant therapy, counteracting any potential effects on fatigue. Other causes of fatigue such as hypothyroidism, dehydration, electrolyte imbalances (eg, hypercalcaemia or hypomagnesemia) or other metabolic disorders should also be treated even though little evidence from randomized trials is available on the efcacy of these treatments. In a randomized trial, comparing 1000 versus 100 ml saline subcutaneously, there was no signicant difference in improvement of fatigue between the groups.125 Symptomatic nonpharmacological treatment Aerobic exercise effectively alleviates fatigue in patients receiving cancer treatment. Other nonpharmacological interventions have been investigated less thoroughly. Strategies on energy conservation and restoration may be useful and counselling for these strategies should be offered. Nonpharmacological treatment options include provision of information, keeping a diary, energy expenditure planning and physical exercise. Most patients will try to counteract exhaustion and fatigue with prolonged periods of rest.126 This may even be augmented by healthcare professionals. In a British survey, the most common advice on fatigue was to take more rest and relaxation.127 However, rest often will not restore energy and persistent reduction of physical activity may even promote fatigue. Counselling on coping strategies should be an effective intervention in these patients. The effect of physical exercise for cancer patients has been investigated in many clinical trials. Several reviews and meta-analyses have accumulated strong evidence that aerobic exercise will reduce fatigue levels in cancer survivors and patients receiving cancer treatment.128,129 Recent studies support the use of resistance training or anabolic exercise.130 However, most trials have been done in patients with breast cancer and good performance status. Only little information is available on patients with far advanced disease and impaired performance status. A 50-min group exercise program twice a week for six weeks reduced fatigue in cancer patients with short life expectancy.131 The expert group states that these patients are likely to benet from exercise training, but that training has to be adapted to reduced performance status, for example sessions with sitting up at the bedside several times per day might be considered adequate training for a bedridden patient. Other nonpharmacological interventions have been investigated less thoroughly. A sleep intervention has been investigated in patients with breast cancer. Using an individualized sleep promotion plan with four components: sleep hygiene, relaxation therapy, stimulus control and sleep restriction techniques patients were able to maintain normal sleep and manage fatigue during chemotherapy.132 Other recommendations from guidelines on fatigue have been the keeping of a diary on daily activities and fatigue and counselling for energy conservation principles. Energy conservation should include planning of daily activities with prioritizing of activities. Patients should learn to do the most important things when their individual energy levels are highest and delegate less important tasks to others.11,37,74 This should be supported by energy restoration strategies such as ensuring adequate rest and nutrition, reducing stress through meditation or relaxation and participating in enjoyable activities. Other nonpharmacological interventions have been used for the treatment of fatigue in patients receiving cancer treatment. Clinical trials on the use of aromatherapy and massage,133 psychotherapy,134 relaxation therapy135 or participation in support groups136,137 have been published. Even when these trials did show some effect on fatigue, it is not clear whether this can be extended to the palliative care setting. Complex multidimensional intervention programmes may be benecial compared to more restricted approaches. An intervention designed to minimize or prevent attentional fatigue through regular participation in activities that engage fascination was shown to be effective in two small controlled trials after breast cancer surgery.138,139 In patients undergoing autologous blood stem cell transplantation, a comprehensive coping strategy programme with counselling, education, written material, an audio tape providing information and instruction in guided imagery and relaxation proved effective compared to the control group.140 In a randomized study an intervention consisting of an information pack, a fatigue diary and monthly coaching from support nurses who visited patients at home was found to be more effective than the usual support.141 In another recent paper patients participating in a programme with physical exercise, relaxation and body awareness training and massage reported signicant relief of fatigue.142 However, training comprised 9 h per week for six weeks and the feasibility of such programmes in advanced cancer must be questioned. Only a minority of palliative care patients will be able and willing to spend so much time on a training programme. No studies have been published on the efcacy of training programmes for patients with advanced cancer and impairment of physical and cognitive function. Symptomatic pharmacological treatment Treatment with methylphenidate (investigated predominantly in opioid-induced sedation and cancer-related fatigue) and modanil (in advanced neurological diseases and AIDS) may reduce fatigue. The efcacy of other stimulant drugs such as pemoline or donepezil as well as the efcacy of corticosteroids on fatigue have been less well investigated. Research on symptomatic treatment of fatigue in palliative care patients has concentrated on stimulant drugs such as methylphenidate, modanil, pemoline and donazepil. Although there is evidence from randomized trials on some of these drugs, the routine use of these drugs in palliative care patients was considered controversial in the expert
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Fatigue in palliative care patients 25 group. Reluctance to recommend the routine use of stimulant drugs in fatigued patients partly came from the evaluation of available evidence as being too poor, and partly from differences about the concept of fatigue that might not be susceptible to pharmacological treatment. Methylphenidate is an amphetamine derivate. It acts by enhancing monoaminergic transmitters in the synaptic gap, either by blocking uptake of dopamine or by facilitating catecholamine release.143 Methylphenidate has been shown to improve cognitive function in patients receiving continuous opioid infusions.144 Methylphenidate has a rather low bioavailability (1152%) and a short half-life of ~2 h. After metabolization in the liver the inactive metabolites are excreted renally. Methylphenidate has been approved for the treatment of depression and of attention-decit disorder, but is not available in all European countries. Its usefulness for the treatment of depression in palliative care has been described,145,146 as a fast onset of anti-depressant activity is required for patients with restricted life expectancy. Methylphenidate has been reported to be effective in several trials for the treatment of opioid-induced sedation147149 and for fatigue in advanced cancer patients.9,150,151 Methylphenidate and exercise both reduced fatigue, increased functional ability and stabilized cognitive function in melanoma patients undergoing interferon treatment, whereas cognitive function deteriorated in the exercise-only group.152 However, a recent placebo-controlled trial challenged these positive results, as methylphenidate and placebo both improved fatigue with no signicant advantage of methylphenidate.153 Similarly, donepezil was not superior to placebo in a recent randomized trial.154 With regard to the high placebo response rate, it may be important to identify cancer patients who will benet from methylphenidate or other drugs more than from other treatment options. Less information is available on fatigue in noncancer diseases. Methylphenidate and pemoline were effective in the treatment of fatigue in patients with AIDS, with 41% responding to methylphenidate and 36% responding to pemoline compared with a 15% response rate with placebo.155 In a report on a patient with myotonic dystrophy, methylphenidate improved daytime sleepiness and cognitive impairment.156 No difference was reported comparing methylphenidate and placebo in elderly patients with fatigue.157 Treatment with methylphenidate usually is initiated with 510 mg in the morning. With monitoring of response and side effects, the dose may be titrated up to 4060 mg per day distributed into morning and midday doses. In a recent report patient-controlled oral titration with 5 mg methylphenidate every 2 h as needed showed fast relief of fatigue and other parameters in advanced cancer patients,10 however, this was not reproduced in a subsequent placebo-controlled trial.153 Side effects may be dose limiting and include nervousness, jitteriness, agitation and sometimes cardiac side effects such as arrhythmia and tachycardia. Modanil acts via the inhibition of GABA, thereby promoting the release of excitatory neurotransmitters such as dopamine, norepinephrine and serotonin in the sleep-wake regulation centres of the central nervous system.158,159 Modanil is a racemat with a half-life of ~15 h after multiple dosing. After metabolization in the liver, the inactive metabolites are excreted renally. Modanil was approved by the FDA in 1998 for the treatment of daytime sleepiness in patients with narcolepsy. In Europe modanil is released for the same indication. Modanil has been used in trials for treatment of fatigue in advanced neurological diseases such as multiple sclerosis,160162 amyotrophic lateral sclerosis,163 myotonic dystrophy164 Parkinsons diseases165 and in patients with AIDS/HIV.166 Modanil also reduced opioid-induced sedation in a retrospective survey.167 No direct comparison of modanil and methylphenidate is available. Only four studies were randomized and blinded.161,162,164,165 One of these studies did not show any difference against placebo in the relief of fatigue in multiple sclerosis162 and another one failed to improve daytime somnolence in Parkinsons disease.165 However, some evidence seems to point towards modanil as a treatment option for fatigue in palliative care. Studies with modanil against cancer-related fatigue are currently under way. A starting dose of 200 mg per day is recommended for modanil. In some patients titration to effect will be required with dosages up to 400 mg. In older patients or patients with impaired liver function a lower starting dose of 100 mg should be used. Major side effects can be agitation, nervousness, sleep disturbances, nausea or diarrhoea. Pemoline acts via the same mechanism as methylphenidate, increasing the amount of monoaminergic transmitters in the synaptic gap. Pemoline was as effective as methylphenidate in the treatment of fatigue in patients with AIDS and was superior to placebo.155 However, potential liver toxicity has limited the use of pemoline. Donepezil is a centrally acting acetylcholinesterase inhibitor, approved for symptomatic treatment of Alzheimers disease. Opioid-induced sedation may be related to functional decits of acetylcholine and preliminary studies with donepezil have suggested at least short-term benet in patients treated with opioids.168 Donezepil also was effective for treatment of opioid-induced sedation in an uncontrolled trial.169 A prolonged elimination half-life of 70 h or more and a high plasma protein binding of 96% may make its use problematic in palliative care patients. Amantadine, a central acting drug with effects on cholinergic, dopaminergic, adrenergic and glutamatergic neurotransmission has been used for treatment of fatigue in multiple sclerosis in several older, small, placebo-controlled studies, showing modest but signicant benets of this drug (reviewed in170). Anecdotal observation and very limited data from controlled trials support the use of low-dose corticosteroids
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26 L Radbruch et al. in fatigued patients with advanced disease and multiple symptoms.74 In a randomized trial in patients with advanced cancer, methylprednisolone 32 mg resulted not only in increased appetite, but also in improved daily activity in 21 of 31 patients.121 Low-dose prednisone in daily doses up to 10 mg led to improvement in several quality-of-life dimensions in patients with bone metastases from prostate cancer.171 Other randomized trials found no signicant benet on strength172 and no or only transient improvement of weakness.173,174 Fatigue was not a primary outcome parameter in these studies and the evidence on the impact of steroids on fatigue is still pending. However, the expert group agreed that the experience in clinical practice is that steroids such as methylprednisolone or dexamethasone are effective in relieving fatigue for a short period of time, usually one or two weeks and that they may be used to alleviate fatigue for well-dened goals, for example allowing the patient to spend a holiday or Christmas time with his family. Research agenda on fatigue Research into the underlying pathophysiology of the fatigue syndrome and suitable animal models is paramount as prerequisites for translational clinical research. Basic research should aim for the identication of central and peripheral mechanisms of fatigue in cancer and other diseases. Basic and clinical research should extend from cancerrelated fatigue to fatigue in other patients in the palliative care setting, for example patients with amyotrophic lateral sclerosis or geriatric patients. A major drawback of the research on fatigue in palliative care is the lack of suitable animal models for fatigue.38 A model of motivated motor activity has been developed, where mice are trained to run on a wheel voluntarily for extended periods of time. Once trained, the effect of interventions can be monitored.175 However, compared with the wealth of different animal models in pain research, where studies can be tailored to the pathophysiology of the pain syndrome, a lack of similar models has hampered research on fatigue considerably. Basic research is required to clarify the role of cytokines and of neurotransmitters in the sleep-wake cycle, and to identify central and peripheral mechanisms of fatigue in cancer and other diseases. Research is also needed on the similarities and discrepancies between fatigue in palliative care and CFS, major depression or cachexia. Considering that excessive cytokine production is a possible cause of fatigue in cancer patients, it stands to reason that drugs interfering with cytokine synthesis (eg, pentoxiphylline, rolipram and thalidomide) or TNF-antibodies (eg, etanercep and iniximab) or antibodies against other cytokines (eg, anti-IL-6) may become effective treatment options (reviewed for use in cancer-related anorexia and cachexia in4). The efcacy of these agents for cancer-related fatigue is currently being investigated in clinical trials, but preliminary results challenge the potential of these drugs as general remedies for fatigue. Future research with these drugs may focus on the efcacy in selected patient groups in palliative care. Most research on cancer-related fatigue has been done in cancer survivors or patients undergoing chemo- or radiotherapy. Little evidence is available on the efcacy of interventions in the palliative care setting. Interventions such as physical or cognitive training programmes may not be suitable for palliative care patients. For treatment of fatigue in palliative care patients available interventions should be adapted and specic interventions developed taking into account the limited resources of these patients. There is a need for clinical trials on the efcacy of these interventions in patients with advanced cancer. Whereas a wealth of information has been published on the treatment of cancer-related fatigue, only limited research has been undertaken on fatigue in advanced cancer patients or in noncancer palliative care patients. As with the pathophysiology of fatigue, specic efforts should be directed towards the investigation of interventions for treatment of fatigue in these groups. This will be even more important considering the increasing percentage of noncancer patients requiring and receiving palliative care in many countries. There will be specic research questions in this area, for example, to what extent diminished energy levels and decreasing physical and cognitive resources might be deemed normal with old age and whether a threshold can be identied where fatigue in the elderly requires assessment and treatment.
Conclusions
This paper of the expert working group of the EAPC has discussed the denition of fatigue and collated the available evidence on assessment and treatment. Most management strategies have been developed for the treatment of fatigue in survivors or for the treatment of fatigue arising as a side effect of cancer treatment. Transfer of these approaches into clinical palliative care practice is paramount. It is likely that some adaptation to these treatment options might provide relief of fatigue in palliative care patients. Research on fatigue should focus on the evaluation of the efcacy of available treatment options in the palliative care setting. In addition basic research is needed on the pathophysiology of fatigue, with the aim of identifying new causal and symptomatic approaches to the treatment of fatigue in palliative care. However, one of the major strengths of palliative care is the consideration of the individual preferences and needs of the patient. This has to be applied to the assessment and treatment of fatigue as to any other symptom in palliative care. The severity and impact of fatigue may change in the course of the disease trajectory. Following guidelines blindly
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Fatigue in palliative care patients 27 without consideration may not only be without benet, but may adversely affect patients. For most patients discontinuation of fatigue treatment in the nal stage of life should be discussed. In the terminal stages fatigue may be considered an acceptable nal common path, shielding and protecting the patient from what otherwise might be overwhelming emotional and physical distress. Balancing the impact of fatigue and the advantages and disadvantages of fatigue treatment in the individual situation is an important skill for palliative care specialists and should receive adequate attention in training and clinical practice. Treating fatigue vigorously in those patients who benet and withdrawing or withholding assessment and treatment procedures from those patients who do not benet will provide optimal care for the large number of palliative care patients with fatigue. Acknowledgements The Research Steering Committee of the European Association consists of Franco De Conno (Chair), Augusto Caraceni, Nathan Cherny, Carl Johan Frst, Jose FerrazGonalves, Geoffrey Hanks, Stein Kaasa, Sebastiano Mercadante, Juan Manuel Nunez Olarte, Lukas Radbruch, Carla Ripamonti, Friedrich Stiefel and Florian Strasser. The authors would like to thank Jose Pereira for his engagement and support of the experts work. The meeting of the expert group was supported by an unrestricted educational grant from the Grnenthal company.
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169 Bruera E, Strasser F, Shen L, et al. The effect of donepezil on sedation and other symptoms in patients receiving opioids for cancer pain: a pilot study. J Pain Symptom Manage 2003; 26: 104954. 170 Schwid SR, Murray TJ. Treating fatigue in patients with MS: one step forward, one step back. Neurology 2005; 64: 11112. 171 Tannock I, Gospodarowicz M, Meakin W, Panzarella T, Stewart L, Rider W. Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response. J Clin Oncol 1989; 7: 5907. 172 Moertel CG, Schutt AJ, Reitemeier RJ, Hahn RG. Corticosteroid therapy of preterminal gastrointestinal cancer. Cancer 1974; 33: 16079. 173 Popiela T, Lucchi R, Giongo F. Methylprednisolone as palliative therapy for female terminal cancer patients. The Methylprednisolone Female Preterminal Cancer Study Group. Eur J Cancer Clin Oncol 1989; 25: 18239. 174 Della Cuna GR, Pellegrini A, Piazzi M. Effect of methylprednisolone sodium succinate on quality of life in preterminal cancer patients: a placebo-controlled, multicenter study. The Methylprednisolone Preterminal Cancer Study Group. Eur J Cancer Clin Oncol 1989; 25: 181721. 175 Ottenweller JE, Natelson BH, Gause WC et al. Mouse running activity is lowered by brucella abortus treatment: a potential model to study chronic fatigue. Physiol Behav 1998; 63: 795801. 176 Bjordal K, de Graeff A, Fayers PM et al. A 12 country eld study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specic module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group. Eur J Cancer 2000; 36: 1796807. 177 Hann DM, Jacobsen PB, Azzarello LM et al. Measurement of fatigue in cancer patients: development and validation of the fatigue symptom inventory. Qual Life Res 1998; 7: 30110. 178 Hann DM, Denniston MM, Baker F. Measurement of fatigue in cancer patients: further validation of the Fatigue Symptom Inventory. Qual Life Res 2000; 9: 84754. 179 Stein KD, Martin SC, Hann DM, Jacobsen PB. A multidimensional measure of fatigue for use with cancer patients. Cancer Pract 1998; 6: 14352. 180 Kirsh KL, Passik S, Holtsclaw E, Donaghy K, Theobald D. I get tired for no reason: a single item screening for cancerrelated fatigue. J Pain Symptom Manage 2001; 22: 9317. 181 Rhoten D. Fatigue and the postsurgical patient. In Norris C ed. Concept clarication in nursing. Rockville: Aspen Systems, 1982: 277300
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Letter to the Editor
The importance of a word: how to translate breakthrough

Portenoy and Hagen defined breakthrough pain as a transitory increase in pain to greater than moderate intensity, which occurred on a baseline pain of moderate intensity or less.1 Although the term breakthrough pain includes a heterogeneous group of pains, it is widely used and usually its meaning is well understood by palliative care and pain specialists. However, there has been some difficulty in finding a translation of breakthrough pain in other languages, such as the Latin languages.2 The term episodic pain was suggested to overcome that difficulty,2 but apparently it was not successful. Therefore, in those languages there are other words or expressions being used. For example, some years ago, dor incidental (incident pain) was perhaps the term most commonly used to refer to breakthrough pain in Portugal. But incident pain is not a good term for translating breakthrough pain, because this term refers to a subtype of breakthrough pain caused by an incident, such as a movement.1 In Italian, there isnt a single word in use that is equivalent to breakthrough pain. One option in Italian is dolore episodico intenso (Sebastiano Mercadante, personal e-mail), meaning severe episodic pain. In French, there is the same problem and accs douloureux paroxystique is often used (Marilne Filbert, personal e-mail), meaning paroxysmal painful bout. The same problem certainly exists in other languages, both Latin and non-Latin ones. Since the end of the nineties, I have been using the word irruptiva in Portuguese as a translation for breakthrough (dor irruptiva meaning breakthrough pain). In fact, that word means to penetrate or appear suddenly,3 a meaning close to breakthrough. Some time later in a meeting of the Research Steering Committee of the European Association for Palliative Care, I mentioned this to the Spanish doctor Juan Manuel Nuez-Olarte, who also found the translation adequate and one that could be used in Spanish, and so he enthusiastically adopted it. Rapidly the term dolor irruptivo spread among Spanish palliative care physicians. Nowadays, the terms dor irruptiva and dolor irruptivo are used in Portugal and Spain, respectively, by all doctors working in palliative care and pain therapy, probably without any knowledge of its source.
Other Latin and non-Latin languages contain words similar to the Portuguese word irruptiva. However, those words may not be currently in use and are not even included in all dictionaries, but they exist. For example, the Italian word irruttivo and the French word irruptif have the same meaning as the Portuguese word irruptivo. However, when I tried to look them up in some Internet dictionaries, I was unsuccessful. Probably, the same is true with other languages. Although there may be some controversy regarding the definition of breakthrough pain and recognizing that the term is an umbrella that covers a heterogeneous reality, it is well established through use, and all palliative and pain doctors use and understand it. It is somewhat similar to the famous phrase, though I cannot define an elephant, I can recognize one when I see it. Therefore, a single word equivalent to breakthrough accepted in each language could be useful. Acknowledgement The author would like to thank the Portuguese League Against Cancer for funding the translation of this letter. Jos Antnio Ferraz Gonalves Unidade de Cuidados Paliativos Rede Instituto Portugus de Oncologia, Rua Dr. Antnio Bernardino de Almeida, 4200-072 Porto, Portugal
Email: ferrazg@netcabo.pt or ferrazg@ipoporto.min-saude.pt
References
1 Portenoy, RK, Hagen, NA. Breakthrough pain: definition, prevalence and characteristics. Pain 1990; 41: 273 281. 2 Mercadante, S, Radbruch, L, Caraceni, A, et al. Episodic (breakthrough) pain: consensus conference of an expert working group of the European Association for Palliative Care. Cancer 2002; 94: 832839. 3 Grande Dicionrio da Lngua Portuguesa. Lisboa: Publicaes Alfa, S.A., 1991.
Downloaded from http://pmj.sagepub.com by Jos Antnio Ferraz Gonalves on March 27, 2008 2008 SAGE Publications. All rights reserved. Not for commercial use or unauthorized distribution.
10.1177/0269216307087141
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Support Care Cancer (2008) 16:321327 DOI 10.1007/s00520-007-0316-x
Use of chemotherapy at the end of life in a Portuguese oncology center

Jos Ferraz Gonalves & Carmen Goyanes
Received: 19 February 2007 / Accepted: 11 July 2007 / Published online: 22 August 2007 # Springer-Verlag 2007
Abstract Goals of work Chemotherapy plays a major role in the treatment of cancer. However, it is sometimes thought of as being taken too far, being used in many cases close to death. The purpose of this study is to determine the proximity of chemotherapy use to the patients death in our hospital. Materials and methods This study comprised the analysis of the charts of 1,064 patients aged over 16 years with solid tumors who died in 2002 and were treated at the Porto Section of the Portuguese Institute of Oncology. Main results Four hundred ten of the 1,064 patients (39%) underwent chemotherapy. Fifty-two percent of those that underwent chemotherapy did so in the last 6 months of their lives, 31% in the last 3 months, 13% in the last month, and 3% in the last week. In the context of the total cohort of 1,064, the percentages of those that underwent chemotherapy was 20, 12, 5, and 1%, respectively. By multivariate analysis, age <65 years, breast and lung cancers, and metastases were positively associated with chemotherapy; kidney cancer and comorbidity were associated with a lower probability of undergoing chemotherapy. Three hundred sixty-one patients (34%) were admitted to the palliative care unit of the hospital. Conclusion It was concluded that in this hospital, chemotherapy is not used as close to death as often as most professionals feel and the literature reports. There are various possible explanations for this discrepancy; one of them may be the influence of health care systems. It would
be useful to see what is happening in other countries with different health care systems. Keywords Chemotherapy . Advanced cancer . End of life . Symptom Control . Palliative care
Introduction The evolution of chemotherapy as a method for cancer treatment, from the second half of the twentieth century onwards, provided an important improvement to the survival prospects of many patients. Its impact on the cure of not only mainly hematological cancer but also on some solid tumors is very positive. As an adjuvant treatment of some cancers, such as breast and colorectal cancer, it also has an important positive influence on the survival of many patients. Even when cure is an unattainable aim, it is possible to usefully prolong the life of many patients with some types of cancers that are responsive to chemotherapy. However, there are a number of cancers for which the probability of improvement is very small, such as pancreas or liver cancers and melanoma. The probability of a response drastically diminishes, even with usually chemoresponsive cancers, if patients have already been treated with chemotherapy, sometimes with a number of different regimens. Another problem is the toxicity of chemotherapy, which can be very important and even endanger the life of some patients. Therefore, chemotherapy should be used judiciously when the probabilities of a successful outcome are reasonable because the cancer is responsive and the patient is fit enough. However, many patients see chemotherapy as their only hope and insist on undergoing it despite the objective data.
:* & C. Goyanes F. Gonalves (*) ( C.) Goyanes J. Ferraz Gonalves Department of Medical Oncology, Portuguese Institute of Oncology, Rua Dr. Antnio Bernardino de Almeida, Porto 4200-072, Portugal e-mail: ferrazg@netcabo.pt
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Appropriately withdrawing or withholding chemotherapy in patients with advanced cancer does not mean abandoning them. Usually, those patients are in greater need of help than beforehand due to their multiple problems, which are not only physical but also psychological, social, and existential. For them, palliative care may be the best option. There is the idea that chemotherapy is often prolonged more than is desirable or beneficial to patients and that they are not referred to palliative care as often and as soon as they should be. However, there is only a small amount of data on this issue in medical literature and, as far as we know, none concerning Portugal. As this is a very important issue, a revision of the charts of all non-pediatric patients with a solid tumor who had died during 2002 was done, with the primary aim being to ascertain the time interval between the last chemotherapy procedure and death.
ments scheduled, their non-attendance is always investigated via contact by telephone or mail to find out what happened and if the cause of non-attendance was death, then the date is input in the hospital records but not the cause or place of death. In such cases, the place of death was classified as unknown for this study. As regards the cause of death, if the patient died outside of the hospital and the chart showed a deterioration of the patients condition, then the cause of death was classified as progressive disease; if, however, it is not possible to ascertain the cause of death or doubts remain, then the cause of death was classified as unknown. Descriptive statistics methods were used for the statistical analysis of the data. The comparisons between the study groups were performed using the MannWhitney test for continuous variables and the chi-square test for categorical variables. Logistic regression was used for multivariate analysis. P <0.05 was considered significant.
Materials and methods Results The Porto section of the Portuguese Institute of Oncology is the largest Portuguese oncological center. It is a public hospital that serves all of northern Portugal, with a catchment population of about 3 million people. About 4,000 new patients are admitted every year. There are also general hospitals that treat cancer patients in that region. Often cancer patients that have been treated in other hospital choose to be treated or are referred to this center to undergo active antineoplastic treatments. However, the opposite is quite uncommon; patients treated at our hospital are sometimes referred to other hospitals to be closer to their families when they are near to the end of life but not to undergo aggressive treatments such as chemotherapy, radiotherapy, or surgery. This center includes a 20-bed palliative care unit (PCU). As is usual in PCUs chemotherapy is not used as a method of palliation. Using the hospitals computer records, a list of patients diagnosed with a solid tumor that died in 2002 was made. Patients younger than 16 years who were treated by the pediatrics service were not included. The data collected included demographic data, primary tumor, the extension of the disease, comorbidity, treatments, whether chemotherapy was given, when the last course of chemotherapy was initiated and its last cycle, what was the line of the last chemotherapy and its aim (palliative vs curative), whether chemotherapy was postponed due to toxicity, the cause and place of death, and the reference to the PCU. Cancers with a frequency 2% were classified as others. The method used to record the date of patients death at our hospital is as follow: when the patients die at the hospital, deaths are immediately recorded; when patients die in other locations, given that there are always appointOf the 1,356 patients who were recorded as aged over 16 years and having died in 2002 with a solid tumor, 184 did not actually die in 2002, 39 had no cancer, 35 died before diagnosis, and the charts of 34 patients could not be found. Therefore, this study includes the remaining 1,064 patients. The median age was 69 years with a range from 23 to 99. Other demographic data are shown in Table 1. Antineoplastic treatment was given to 911 patients (86%): 690 (65%) underwent surgery and 488 (46%) underwent radiotherapy. The use of chemotherapy Four hundred ten patients (39%) underwent chemotherapy. The median between the beginning of the last chemotherapy regimen and death was 268 days (range, 2 to 8,965 days), and the median interval between the last cycle of chemotherapy and death was 168 days (range, 1 to 8,715 days); details of this interval are shown in Table 2. Chemotherapy was considered palliative in 366 patients (89%) and curative in 44 (11%). The chemotherapy was first-line for 272 patients (66%), second-line for 94 (23%), third-line for 32 (8%), and higher than third-line for 12 (3%). In 187 patients (46%), chemotherapy was delayed, at least once, due to toxicity. Chemotherapy was used from 1 to 4,860 days, median 120.5 days: 36 patients (9%) underwent only one cycle of chemotherapy; 29 (7%) from one cycle to 30 days; 101 (25%) 2 to 3 months; 97 (24%) 3 to 6 months; and 147 (36%) more than 6 months. By univariate analysis, the probability of undergoing chemotherapy was influenced by: age, with patients younger
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Support Care Cancer (2008) 16:321327 Table 1 Demographic data (n=1,064) Gender Male Female Residence Big city Small town Rural area Distance from the hospital <30 km 30 to 100 km 100 to 200 km >200 km Professiona 1 2 3 4 5 Unknown Cancer Head and neck Breast Colorectal Stomach Lung Prostate Esophagus Cervix Bladder Endometrium Melanoma Primary unknown Kidney Other
a
323 Table 2 Interval between the last chemotherapy and death Number of days Number of patients on chemotherapy Percent patients on chemotherapy Percent all patients (n =1,064) 1 4 7 8 19 39
583(55) 481(45) 350(33) 297(28) 417(39) 397(37) 314(30) 224(21) 129(12) 49(5) 108(10) 63(6) 309(29) 510(48) 25(2) 170(16) 161(15) 111(10) 86(8) 80(8) 76(7) 44(4) 39(4) 36(3) 33(3) 33(3) 27(3) 22(2) 146(14)
1 to 7 8 to 30 31 to 90 91 to 180 >180 Total
11 41 75 85 198 410
3 10 18 21 48 100
residence; in other words, chemotherapy was used irrespective of whether the place of residence was an important city, a small town, or a rural area. The mean age of those who underwent chemotherapy was 60.5 years against 70.4 years for those who did not (p < 0.001). To compare our data with other studies, the population was divided into two groups: patients under 65 years and patients aged 65 years or more. Details of the interval between the last chemotherapy and death are shown in Table 4. As can be seen, there was a number of patients who underwent chemotherapy very close to death in both groups. However, there is a significant difference (p =0.035) between the two age layers. In the multivariate analysis, only age <65, breast and lung cancers, and metastases were positively associated with chemotherapy. Kidney cancer and comorbidity were associated with a lower probability of undergoing chemotherapy (Table 5). Cause and place of death Three hundred sixty-one patients (34%) were admitted to the PCU where they were monitored from 1 to 1,338 days, median of 34 days. The overall most frequent cause of death was progressive disease, which occurred in 453 (69.3%) of the patients that did not undergo chemotherapy, and in those who underwent chemotherapy, it was the cause of death in 366 (89%) (Table 6). In 520 patients (49%), the place of death was unknown. Presumably, most of these patients died at home. The places of death that we do know were 234 (22%) in the PCU, 236 (22%) in other services of the hospital, 49 (5%) at home, 17 (2%) at other hospitals, and 8 (1%) at other places. Fifty-three percent of the patients who underwent chemotherapy died in our hospital, while only 38% of those who did not die here (p <0.001).
The professional levels were defined according to the Graffar index [18]. Level 1 is the highest and includes enterprise director, professionals with a university degree, etc. Level 5 includes undifferentiated workers.
than 65 years undergoing chemotherapy more often than those older than 65 years; gender, with women being more likely to undergo chemotherapy than men; profession, with the more affluent undergoing chemotherapy more often; cancer type; metastases; and comorbidity, with patients with comorbidity excluded more often from the chemotherapy protocols (Table 3). As regards cancer type, patients with gastric, head and neck, and kidney and prostate cancers were less likely to undergo chemotherapy, whereas breast and lung cancers were more likely to undergo chemotherapy. Patients with metastatic cancer had a higher probability of undergoing chemotherapy than those with locally advanced cancer. The probability of undergoing chemotherapy was not influenced by the distance of the patients residence from the hospital and the place of
Discussion The main goal of this study was to examine how close chemotherapy use is to the patients death. The overall
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Table 3 Differences between patients who did and did not undergo chemotherapy by univariate analysis Chemotherapy Yes (n =410) N (%) Gender Male Female Age <65 65 Residence Big city Small town Rural place Distance from the hospital <30 km 30 to 100 km 100 to 200 km >200 km Professiona 1 2 3 4 5 Unknown Cancer Stomach Breast Head and neck Esophagus Lung Colorectal Bladder Primary unknown Kidney Endometrium Prostate Cervix Melanoma Other Metastases Locally advanced Brain Lung Liver Bone Peritoneum Comorbidity
a
P value No (n =654) N (%)
203(35) 207(43) 243(56) 167(26) 143(41) 125(42) 142(34) 154(39) 124(40) 90(40) 42(33) 29(59) 48(44) 26(41) 122(40) 179(35) 6(24) 24(28) 98(61) 43(25) 15(34) 50(63) 50(45) 18(50) 11(41) 4(18) 12(36) 15(20) 10(26) 16(48) 44(30) 247(40) 37(67) 111(59) 105(54) 116(59) 48(49) 181(31)
38(65) 274(57) 188(44) 466(74) 207(59) 172(58) 275(66) 243(61) 190(60) 134(60) 87(67) 20(41) 60(56) 37(59) 187(60) 331(65) 19(76) 62(72) 63(39) 172(75) 29(66) 30(37) 61(55) 18(50) 16(59) 18(82) 21(64) 61(80) 29(74) 17(52) 102(70) 366(60) 18(33) 77(41) 88(46) 82(41) 51(51) 401(69)
0.006
<0.001
0.052
0.506
0.008
0.035 <0.001 <0.001 0.536 <0.001 0.136 0.150 0.811 0.047 0.795 <0.001 0.092 0.233 0.025 0.169 <0.001 <0.001 <0.001 <0.001 0.033 <0.001
The professional levels were defined according to the Graffar index [18]. Level 1 is the highest and includes enterprise director, professionals with a university degree, etc. Level 5 includes undifferentiated workers.
percentage of patients undergoing chemotherapy (39%) at this center is very similar to the percentage of the AragonChing et al. [1] study (38%), but our percentage is higher in the last 6 months of life, 52 vs 43%. However, in the last month, only 5% of our patients underwent chemotherapy,
contrasting with the 26% in the Aragon-Ching et al. study. In a study by Emmanuel et al. [2] with patients aged over 65 years, in 1996, 33% of the patients underwent chemotherapy in the last 6 months of life, 23% in the last 3 months, and 9% in last month in cancer decedents in
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Support Care Cancer (2008) 16:321327 Table 4 Interval between the last chemotherapy and death according with age Number of days Number and percent of patients on chemotherapy, n (%) <65 years 1 to 7 8 to 30 31 to 90 91 to 180 >180 Total
a
325
Percent of the total of each age layer % <65 yearsa 1.4 5.1 13.0 12.0 24.8 65 years* 0.8 3.0 3.0 5.2 14.4
65 years 5(3) 19(11) 19(11) 33(20) 91(55) 167(100)
6(3) 22(9) 56(23) 52(21) 107(44) 243(100)
Total number of patients under 65=431; total number 65 years or more=633
Massachusetts, and in California, the percentages were 26, 20, and 9%, respectively. These percentages are much higher than ours: 12, 7, and 4%, respectively, for patients aged 65 years and over. Another study including only patients aged 65 years and older who underwent chemotherapy showed that, in 1996, 18.5% of the patients were still receiving chemotherapy 2 weeks before death [3]. This too differs from the 14% of patients aged 65 years and older who underwent chemotherapy in the last month of life at our hospital. The reasons for the differences existing between the percentage of patients that undergo chemotherapy in the USA and Portugal are not clear. Probably, the differences in the results of the studies are due to a combination of reasons. Differences in the types of cancers, namely, the inclusion of hematological neoplasms in one study [2], which tend to be treated with chemotherapy more often and until a later stage, or possible differences in comorbidity could contribute to the differences observed. Perhaps, different diagnosis and prognosis disclosure practices result in different attitudes regarding possible treatments. Differences in the health systems, with a public and universal system in Portugal and a predominantly
Table 5 Factors associated with chemotherapy by multivariate analysis OR Cancer Breast Lung Kidney Metastases Brain Lung Peritoneum Liver Bone Comorbidity Age <65 95% CI P value
private practice in the USA can result in substantial differences in the decisions to initiate and/or maintain chemotherapy. In the Portuguese public system, doctors do not have any incentive to provide treatments considered unnecessary. On the other hand, in USA, health care providers are likely to be reimbursed for ordering chemotherapy [4], which can be an incentive to initiate or maintain chemotherapy, perhaps facilitating patients requests. Maybe a public system largely generates more streamlined expenses. Could this explain, at least in part, the huge differences in health care expenses? It would be important to see data from other countries with different health systems. In the study of Emmanuel et al. [2], cancers that tend to be unresponsive were as likely as responsive tumors to receive chemotherapy, although the former were more likely to have only a short course of therapy. At our hospital, that also happened to some point. However, there were significant differences with most patients with breast and lung cancers, which are responsive cancers although in different manners, undergoing chemotherapy more often, whereas only a few patients with kidney cancer, which respond poorly, underwent chemotherapy. Comorbidity is also a factor that negatively influences the decision to perform chemotherapy, which was expected and observed by others [3]. Women underwent chemother-
Table 6 Causes of death 2.80 2.94 0.30 1.95 1.82 1.80 1.91 1.78 0.67 2.96 1.874.20 1.754.95 0.090.98 1.953.69 1.262.62 1.142.85 1.332.74 1.232.57 .0510.89 2.233.94 <0.001 <0.001 0.046 0.041 0.001 0.012 <0.001 0.002 0.006 <0.001 Progressive disease Drug toxicity Postoperative complication Digestive hemorrhage Sepsis Other Unknown Total Overall group n (%) 819(77.0) 13(1.2) 12(1.1) 9(0.8) 8(0.8) 439(3.7) 164(15.4) 1064(100) Chemotherapy group n (%) 366(89.0) 10(2.4) 2(0.5) 3(0.7) 1(0.2) 5(1.2) 23(5.6) 410(100)
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apy more often than men, as in the Aragon-Ching et al. study [1], although in our study, the difference was not significant in the multivariate analysis. Profession was also significant in the univariate analysis but not in multivariate analysis. Therefore, there seems to be a fair distribution of resources, as socioeconomics variables were irrelevant in the decision to use chemotherapy, and gender, profession, distance, and place of residence were not significant in the option of chemotherapy, different to the findings of others [5]. However, as in other studies [57], age was an independent factor that significantly influenced the decision to initiate chemotherapy. This is perhaps based on a common sense judgment, although it is not an evidence-based decision. The toxicity of chemotherapy is well demonstrated in this study through the 46% patients whose treatment was postponed at least once due to toxicity. Chemotherapy can even be a cause of death, as occurred in our study where almost all deaths due to drug toxicity were due to chemotherapy. Chemotherapy is in fact an aggressive weapon that can cause major toxicity. Therefore, it should be used cautiously only and when there is a reasonable probability of success and reasonable patient fitness. However, that which a physician perceives as aggressive treatment may be perceived to be routine care by patients [4]. Patients often have unrealistic expectations from chemotherapy. Many think that chemotherapy can make them live longer and that the probability of cure is moderately high or high, even when this is not the case [8]. Patients and their families can call on it as a last, desperate remedy, as a last resource to prolong life even in the face of a very low probability of benefit and with the possibility of major toxicity [9, 10]. Doctors confronted with this situation can agree to do one or two cycles of chemotherapy. On the other hand, many doctors have difficulties in communicating bad news [9], mainly telling patients that antineoplastic treatment is no more beneficial and that it is better to change to symptomatic treatment; this can be seen as something that can affect hope [10]. Pharmaceutical companies run campaigns that influence all participants in the decision-making process: doctors, patients, and families [11]. Patients and families may hear about the efficacy of a treatment for their disease and request a trial, even if it is not adequate for their specific case [11]. In other cases, the explanations for the use of chemotherapy at the end of life can be related with the well-known difficulty in accurately calculating patients survival. Doctors tend to be over-optimistic and overestimate the survival of patients [12]. There is also some uncertainty regarding the responsiveness to chemotherapy in particular cases. In view of this uncertainty, it is usual to try one or two cycles of chemotherapy to assess its effect and thus the usefulness of continuing with it.
The prolongation of life is not chemotherapys only goal, as it can also be used to palliate symptoms and so improve the quality of life [13]. In fact, a number of studies have shown that chemotherapy can improve the quality of life of patients with lung [13, 14], colorectal [15], ovary [8], and pancreas [16] cancers, despite low objective responses. This is the rationale for the use of chemotherapy in some cases. Although the quality of life, as stated by patients, seems to be related with the gap between expectations and what actually occurs [17], patients can show a significant improvement in quality of life despite unrealistically high expectations relative to the results of chemotherapy [8]. To explain this, Doyle et al. [8] hypothesized that unrealistic expectations can be related to the patients way of coping with stress, to not acknowledge the prospect of dying from the disease, and to poor doctorpatient communication. The usefulness of chemotherapy in the palliation of symptoms despite expected low objective responses raises the issue that the cooperation between oncologists and palliative care specialists can result in many cases in better outcomes for their patients than if they work apart. The results of our hospital seem to compare favorably with the results of others, concerning the appropriateness of the use of chemotherapy at the end of life, as it seems to be used less often in patients near death. The use of chemotherapy seems appropriately related to the probability of response as per cancer type and negatively related in the presence of comorbidity. However, in this study, it is not possible to find out if patients who would benefit from chemotherapy did not undergo it. This study has a number of weaknesses. As described in the Materials and methods section, at this hospital, there is a cancer register system and whenever a patient misses an appointment, he or she is contacted by telephone or mail to find out what happened. This is not a perfect system and probably there are a number of cases missed, but this is the only possible way of detecting deaths. However, the number obtained is high enough to allow conclusions to be drawn in regard to this center. The high number of unknown places and causes of death are due to that system. In particular, the difference between the cause of death being classified as progressive disease in patients who underwent chemotherapy and those who did not is due probably to the fact that those patients that underwent chemotherapy were more closely monitored by the hospital and more often died in the hospital. Our data might not be generalizable to the whole country because the study was performed in an oncological center; therefore, it is not a population-based study, and because the center has a PCU, in a country where palliative care is not widely available, and the impact that this fact has on the decision to initiate chemotherapy is unknown.
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Support Care Cancer (2008) 16:321327 327 7. Hurria A, Naeim A, Elkin E, Limaye S, Grover A, Hudis C, Pearce C, Robson M (2007) Adjuvant treatment recommendations in older women with breast cancer: a survey of oncologists. Crit Rev Oncol Hematol 61:255260 8. Doyle C, Crump M, Pintilie M, Oza AM (2001) Does palliative chemotherapy palliate? Evaluation of expectations, outcomes, and costs in women receiving chemotherapy for advanced ovarian cancer. J Clin Oncol 19:12661274 9. Slevin ML, Stubbs I, Plant HJ et al (1990) Attitudes to chemotherapy: comparative views of patients with cancer with those of doctors, nurses, and general public. BMJ 300:14581460 10. Yellen SB, Cella DF (1995) Someone to live for: social wellbeing, parenthood status and decision-making in oncology. J Clin Oncol 13:12551264 11. Jirillo A, Boscaro M, Passeto LM, Monfardini S (2005) Chemotherapy at the end of life: an open question. Tumori 91:104105 12. Glare P, Virik K, Jones M et al (2003) A systematic review of physicians predictions in terminally ill cancer patients. BMJ 327:195200 13. Ellis PA, Smith IE, Hardy JR, Nicolson MC, Talbot DC, Ashley SE, Priest K (1995) Symptom relief with MVPP (mitomycin C, vinblastine and cisplatina) chemotherapy in advanced non-smallcell lung cancer. BJC 71:366370 14. Cullen MH, Billingham LJ, Woodroffe CM et al (1999) Mitomycin, ifosfamide, and cisplatin in unresectable non-smallcell lung cancer: effects on survival and quality of life. J Clin Oncol 17:31883194 15. Cunningham D, Pyrhnen S, James RD et al (1998) Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet 352:14131418 16. Burris HA, Moore MJ, Andersen MJ et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:24032413 17. Wan GJ, Counte MA, Cella DF (1997) The influence of personal expectations on cancer patients report of health-related quality of life. Psycho-Oncol 6:111 18. Graffar M (1956) Une mthode de Classification Social dchantillon de la population. Courier 6:455459
Conclusion The use of chemotherapy near the end of life seems to be less frequent at this hospital when compared with other reports. There are a number of possible explanations to this, including health systems differences, that is why, studies in other countries would be useful to clarify this important point. It is not possible, on the other hand, to see in this study if chemotherapy was in some cases inappropriately withheld or withdrew nor was it possible to gauge the possible influence of the availability of a PCU on the decision process. There is always a balance that must be made between the benefits and burdens, but the variables are often largely uncertain.
Acknowledgements This work was supported in part by the North Portugal Section of the Portuguese League against Cancer.
References
1. Aragon-Ching JB, Cohn JB, Cohn A (2003) Chemotherapy at the end of life. Proc Am Soc Clin Oncol 22(abst 3119) 2. Emanuel EJ, Young-Xu Y, Levinsky NG, Gazelle G, Saynina O, Ash AS (2003) Chemotherapy use among Medicaire beneficiaries at the end of life. Ann Intern Med 138:639643 3. Earle CC, Neville BA, Landrum MB, Ayanian JZ, Block SD, Weeks JC (2004) Trends in the aggressiveness of cancer care near the end of life. J Clin Oncol 22:315321 4. Matsuyama R, Reddy S, Smith TJ (2006) Why do patients choose chemotherapy near the end of life? A review of the perspective of those facing death from cancer. J Clin Oncol 24:34903496 5. Earle CC, Venditti LN, Neumann PJ, Gelber RD, Weinstein MC, Potosky AL, Weeks JC (2000) Who gets chemotherapy for metastatic lung cancer. Chest 117:12391246 6. Harlan LC, Clegg LX, Trimble EL (2003) Trends in surgery and chemotherapy for women diagnosed with ovarian cancer in the United States. J Clin Oncol 21:34883494
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Validation of a Consciousness Level Scale for Palliative Care

F Gonalves Palliative Care Unit Network, Portuguese Institute of Oncology, Porto, MJ Bento Epidemiology Service, Portuguese Institute of Oncology, Porto, M Alvarenga, I Costa and L Costa Palliative Care Service, Portuguese Institute of Oncology, Porto The main objective of this study is to validate a Consciousness Scale for palliative care. The scale was named Consciousness Scale for palliative care (CSPC). The validation had two phases: 1) face validity the scale was assessed by seven healthcare professionals, both doctors and nurses, experienced in palliative care; 2) reliability and construct validity performed by four investigators, two nurses and two doctors. The construct validation was performed by comparing the CSPC with a Visual Analogue Scale (VAS) of 100 mm, anchored in the terms awake and unarousable, and then with the Glasgow Coma Scale (GCS). In this study, all four observers completed 44 periods of observation relative to 38 patients resulting in a total of 176 observations. In the phase of face validation, there were no discrepancies in relation to the issue: the scale provides measures for measurement; the scale can be useful to clinical practice; the scale can improve communication among professionals and the scale is easy to use. As a measure of internal consistency, Cronbachs was found to be very high (0.99). The inter-rater reliability was also very high with an intraclass correlation coefficient of 0.99 (P < 0.001). The correlation of the CSPC to the VAS was 0.94 (P < 0.001) and the CSPC to the GCS was 0.82 (P < 0.001). The CSPC can be a very useful tool for assessing consciousness in palliative care patients. It is very ease to use, not time consuming and can be used with minimal training. Communication between professionals can be improved in the clinical setting and in the research environment. Palliative Medicine (2008); 22: 724729
Key words: consciousness; consciousness level scale; palliative care; sedation
Introduction
A large percentage of palliative care patients undergo temporary or definitive changes in their consciousness level. This can be due to the involvement of the central nervous system brought on by cancer, metabolic alterations, infections, medication or a combination of these factors. When it is caused by medication, the level of consciousness can be intentionally affected or not. When intentional, with the aim of controlling suffering, the action is called palliative sedation. Sedation in palliative care is a very important task. It has been under discussion for more than a decade. Chater et al.1 defined sedation as the intention to deliberately induce and maintain deep sleep, but not deliberately causing death, in very specific circumstances. However, the objective is to control suffering (physical or psychological
Correspondence to: Dr Ferraz Gonalves, Instituto Portugus de Oncologia, UCP-R, Rua Dr. Antnio Bernardino de Almeida, 4200-072 Porto, Portugal. Email: ferrazg@ipoporto.min-saude.pt or ferrazg@netcabo.pt
symptoms, existential distress, etc.) and not the level of sedation. Hence, the deepness of sedation should be, such as to acceptably control, the cause of suffering, which cannot be controlled by any other means. No validated palliative care scale to measure the level of consciousness exists. The absence of such a scale is one of the reasons why data from studies, such as those dealing with sedation, are difficult to compare. Therefore, a reliable consciousness level scale could improve communication between professionals, making the comparison of data of different studies easier, and it would be useful to clinical practice and research in general. The purpose of this study is to develop and validate such a scale for palliative care. The scale developed herein is called the Consciousness Scale for Palliative Care (CSPC). Consciousness has two dimensions: wakefulness and awareness.2 There are other scales that measure cognitive function, and therefore awareness, for example, the minimental state examination,3 and others. The intention of that scale is to primarily measure wakefulness and not the content of consciousness.
10.1177/0269216308094104
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Consciousness Level Scale for Palliative Care
725
Methods
This study was conducted at the Palliative Care Service of the Porto Section of the Portuguese Institute of Oncology. The study was approved by the ethics committee of the institution. As this study was non-interventional and there was no added risk to patients, a written informed consent was waived. The design of the scale To identify other existing level of consciousness scales, a MEDLINE search was done for the period January 1970 to September 2003, using the following keywords: coma scale, coma assessment, sedation scale and sedation assessment. Reference lists of the resulting articles were reviewed. Although there are many scales used in different environments, only a small number were assessed for reliability and validity, which was also observed by others.4,5 Most of them were designed for use in intensive care units (ICU) or on neurological patients. None have been designed for or studied in a palliative care setting. None of the identified scales are suited to use in a palliative care setting for a large number of reasons, the most relevant being:

nosis, metastases, sedative medication and if the patient was intentionally sedated or not. The study had two phases. In phase 1, face/content validity was carried out. Seven healthcare professionals experienced in palliative care, three doctors and four nurses, not involved in the design of the scale, applied the scale to about 20 patients each in order to familiarise themselves with it. They then answered the following questions using a five-point scale ranging from strongly agree to strongly disagree:

Does the scale measure what it is intended to measure? Can the scale be useful to clinical practice? Can the scale improve communication among healthcare professionals with regard to consciousness level? Is the scale easy to use?

Most of the scales used in ICU include the assessment of items such as anxiety or agitation.611 Other scales used in ICU have items related to compliance with mechanical ventilation.6,1113 Some scales were designed for neurological conditions; therefore, they contain items that are irrelevant to our purpose.1417 Some scales were designed to focus on particular conditions and therefore contain items that are only of relevance to such conditions.1822 Some were designed for children.23,24 Many do not have the levels of the scale clearly defined, or these are not mutually exclusive.25,26
Although the existing scales were considered inadequate for use in palliative care, they included the elements that should be used in a new scale. There are, therefore, elements common to all these scales. In fact, following the study of those scales, the CSPC was constructed based on the responses to the stimuli ranked in a logical manner. The chosen responses are mutually exclusive. The stimuli, which are common to many scales, are simple and also performed in a logical progression: first observation then, if required, vocal stimulus and finally painful stimulus. This study included bedridden patients over 18 years of age, on a convenience basis. A patient may be included more than once if observations are carried out at least 48 h apart. The data collected included age, gender, diag-
The investigators were asked to give suggestions that might improve the scale, if they thought the scale could be improved. In phase 2, reliability and construct validation were performed. Because there is not any golden standard to evaluate consciousness level against which the CSPC can be compared, a criterion validation could not be performed. Therefore, we had to perform a construct validation of the scale, comparing it with other tools we think can measure consciousness level, as is usually the case in these types of study. A visual analogue scale (VAS) and the Glasgow Coma Scale (GCS) were used, as was the case in similar studies undertaken in different settings, such as in an ICU environment.4,6,7,13 The VAS was assessed by drawing a perpendicular mark on a 100 mm horizontal line based on the terms awake and unarousable, and then the distance between the left end of the line and the mark was measured in millimetres. The data were collected by four investigators involved in the study: two doctors and two nurses. All four investigators underwent a training period with the VAS for evaluating consciousness level, to familiarise with the scale. Each patient was simultaneously observed by three investigators, one doctor and two nurses. One investigator interacted with the patient, as per the instructions set forth in the appendix, and rated the patient, whereas the other two observed and rated the patient independently: two scored using the CSPC and one using the VAS. In all, 15 min later, the other doctor performed the GCS, recording the score of each item (motor and verbal responses, and eye opening). A rotation system was used so that each healthcare professional performed all the roles a similar number of times, except with regards to the GCS, which was always performed by the doctors and always by the doctor who did not participate in the first part of evaluation.
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Table 2 Distribution of consciousness scale for palliative care scores between raters
Scores 1 1st rater 1 2 3 4 5 6 9 2 0 0 0 0 2 2 9 0 0 0 0 3 0 0 5 0 0 0 2nd rater 4 0 0 1 3 0 0 5 0 0 0 0 6 0 6 0 0 0 0 0 7
Statistical analysis

Cronbachs was performed to measure internal consistency.27 The intraclass correlation coefficient was used to measure the degree of concurrence between raters.28 The association between the CSPC, VAS and GCS was evaluated using Spearmens .29 The non-parametric Wilcoxon rank sum test was used to compare CSPC values with previously identified subgroups (gender, age, use of sedatives).30
Results
In this study, all four observers made 44 periods of observation relative to 38 patients, resulting in 176 observations. None of the patients was subject to more than two periods of observation. The demographic data of those patients are detailed in Table 1. Forty-two patients (96%) were medicated with one or more drugs with sedative effects: 91% opioids, 57% neuroleptics, 43% benzodiazepines and 30% others. Six patients were intentionally sedated: 1 was at level 4, 3 at level 5 and 2 at level 6 of the scale. There was, in those patients, 100% coincidence between the two raters of the scale.
Therefore, the range of responses went from strongly agree to the middle of the scale, without any disagreements. Internal consistency As a measure of internal consistency, the Cronbachs was very high (0.99). Inter-rater reliability The scores recorded by the raters are displayed in Table 2. The same score on the scale was selected in 39 cases (89%). In the five cases where a different score was selected, the difference was always not more than one level of the scale. The degree of agreement between raters with regard to the scale was, therefore, very high, with an intraclass correlation coefficient of 0.99 (P < 0.001). There were no significant within-subject differences in subgroups (age, gender) when analyzed by the Wilcoxon rank sum text. The median age of the patients (68 years) was used to divide this item into two groups. In women and those aged over 68 years, the scores coincided. The analysis of the group that used sedatives was not performed because 96% of the patients were using them. Construct validity The correlation of the CSPC to the VAS and GCS was very high (Table 3). The correlation coefficient of the CSPC to the VAS was 0.94 (P < 0.001) for the first observer and 0.95 (P < 0.001) for the second. The correlation coefficient of the scale to the GCS was 0.82 (P < 0.001) for the first observer and 0.85 (P < 0.001) for the second. Note that the coefficient of the CSPC to
Table 3
Scales CSPC1CSPC2 CSPC1VAS CSPC2VAS CSPC1GCS CSPC2GCS
Face validity The results for face validity were as follows:

The scale measures what it is intended to measure. Mean = 1.7 (range: 1 to 2). The scale can be useful to clinical practice. Mean = 1.6 (range: 1 to 3). The scale can improve communication among healthcare professionals: Mean = 2.0 (range: 1 to 3). The scale is easy to use. Mean = 1.6 (1 to 2).
Demographic data
No. (%)
Table 1
Gender Male Female Primary Gynaecologic Colorectal Head and neck Gastric Astrocytoma Lung Melanoma Other
19 (50) 19 (50) 8 6 5 3 3 2 2 9 (21) (16) (13) (8) (8) (5) (5) (24)
Correlation between scales

0.98 0.96 0.96 0.88 0.88 P <0.001 <0.001 <0.001 <0.001 <0.001
Age: median of 68 years (range: 3882).
CSPC1 and CSPC2 are the 1st and 2nd ratings of the scale. CSPC, Consciousness Scale for Palliative Care; VAS, Visual Analogue Scale; GCS, Glasgow Coma Scale.
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Consciousness Level Scale for Palliative Care 727 the GCS was negative due to the scales scoring being inverted in relation to each other; in other words, the best score of the CSPC is the lowest, whereas the best score of the GCS is the highest. There are potential limitations to the use of the CSPC. As it relies on the patients auditory and visual acuity, it is not suitable for use on patients with major impairment of these senses. The intensity of the stimuli can vary with the observer; in other words, louder voices or more firm pinching of the trapezius might eventually result in different scores. Patients can have a not normal score simply because they were normally sleeping, but this is common to all scales. Nevertheless, the CSPC can be a very useful tool for assessing consciousness in palliative care patients. It is very ease to use, not time consuming and can be performed with minimal training. Communication between healthcare professionals can be improved in the clinical setting and in a research environment by the lack of ambiguity of the levels and of the method of interaction with the patient. However, the scale should be evaluated in other locations in a palliative care setting to confirm the results achieved by this study.
Discussion
An ideal assessment tool should be inexpensive, easy to learn and easy to use by doctors and nurses at bedsides. This last aspect is particularly important in palliative care because it is practised in many settings and by healthcare professionals from heterogeneous backgrounds. Yet, the assessment tool should undergo rigorous testing to show validity and reliability. Probably, the most used scale is the Ramsay Scale. This scale was developed in an ICU to control the level of sedation with alphaxalone-alphadolone and published in the British Medical Journal in 1974.25 The scale was really a secondary aspect of the article; however, since then, it has been widely used in many settings without undergoing any process of validation. This was carried out recently.31 Although that scale has been extensively used, it has been criticised for many reasons,32 the criticisms most relevant to palliative care being: the six levels of the Ramsay scale are not mutually exclusive; patients may be restless or agitated (level 1), whereas at the same time being responsive only to light physical or loud auditory stimulus (level 4 and 5) and the sedation levels are not clearly defined or fully inclusive. The goal of this study was the development and validation of a scale with the above-described characteristics, in an attempt to avoid the drawbacks of the Ramsay scale and other scales. The structure of the scale is very ease to use and the levels are clearly defined, with a phase of observation and, if required, consecutive phases of verbal interaction and of physical stimulation. The scale can be administered in a few seconds, using common and unambiguous stimuli in a logical sequence. The stimuli are also standardized, which does not happen with most scales. The inter-rater reliability of the scale was very good for all patients, with coincident scores in almost 90% of the cases, and in the few cases without coincidence, the difference was never greater than one level. In women and in patients aged over 68 years, there was complete agreement in the scores, as well as among the six patients who were intentionally sedated. As no gold standard exists for sedation, against which the CSPC could be compared to validate it, the validation of the CSPC was performed by correlating it to a VAS based on the terms awake and unarousable and the GCS, which is a scale that was designed to assess the prognosis of coma after head injury33 but which is widely used in many settings to assess the consciousness level. The correlation of the CSPC to the VAS and the GCS was very high.
References
1 Chater, S, Viola, R, Paterson, J, Jarvis, V. Sedation for intractable distress in the dying a survey of experts. Palliat Med 1998; 12: 255269. 2 Laureys, S. The neural correlate of (un)awareness: lessons from the vegetative state. Trends Cogn Sci 2005; 19: 556559. 3 Folstein, MF, Folstein, SE, McHugh, PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975; 12: 188189. 4 Ely, EW, Truman, B, Shintani, A, Thomason, JW, Wheeler, AP, Gordon, S, et al. Monitoring sedation status over time in ICU patients: reliability and validity of the Richmond Agitation-Sedation Scale (RASS). JAMA 2003; 289: 29832991. 5 Jacobi, J, Fraser, G, Coursin, DB, Riker, RR, Fontaine, D, Wittbrodt, ET, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adults. Crit Care Med 2002; 30: 119141. 6 Sessler, CN, Gosnell, MS, Grap, MJ, Brophy, GM, ONeal, PV, Keane, KA, et al. The Richmond Agitation-Sedation Scale: validity and reliability in adult intensive care unit patients. Am J Respir Crit Care Med 2002; 166: 13381344. 7 Devlin, JW, Boleski, G, Mlynarek, M, Nerenz, DR, Peterson, E, Jankowski, M, et al. Motor Activity Assessment Scale: a valid and reliable sedation scale for use with mechanically ventilated patients in an adult surgical intensive care. Crit Care Med 1999; 27: 12711275. 8 Riker, RR, Picard, JT, Fraser, GL. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999; 27: 13251329. 9 Detriche, O, Berr, J, Massaut, J, Vincent, JL. The Brussels Sedation Scale: use of a simple clinical sedation scale
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undergoing haemodiafiltration. Intensive Care Med 1995; 21: 342347. Checketts, MR, Gilhooly, CJ, Kenny, GNC. Patientmaintained analgesia with target-controlled alfentanil infusion after cardiac surgery: a comparison with morphine PCA. Br J Anaesth 1998; 80: 748751. Irwin, MG, Thompson, N, Kenny, GNC. Patientmaintained propofol sedation. Anaesthesia 1997; 52: 525530. Malviya, S, Voepel-Lewis, T, Huntington, J, Siewert, M, Green, W. Effects of anesthetic technique on side effects associated with fentanyl oralet premedication. J Clin Anesth 1997; 9: 374378. Ambuel, B, Hamlett, KW, Marx, CM, Blumer, JL. Assessing distress in pediatric intensive care environments: the COMFORT scale. J Pediatric Psychol 1992; 17: 95109. Ramsay, MAE, Savege, TM, Simpson, BRJ, Goodwin, R. Controlled sedation with alphaxalone-alphadolone. BMJ 1974; 2: 656659. De Jonghe, B, Cook, D, Appere-De-Vecchi, C, Guyatt, G, Meade, M, Outin, H. Using and understanding sedation scoring systems: a systematic review. Intensive Care Med 2002; 26: 275285. Bland, JM, Altman, DG. Cronbachs alpha. BMJ 1997; 314: 572. Anlisis de la concordancia. In: Palls, JMA, Villa, JJ, (Eds), Mtodos de investigacin: clnica e epidemiolgica, segunda edicin. Madrid: Ediciones Harcourt S.A., 2000; p. 321325. Relation between two continuous variables. In: Altman, DG, (Ed), Practical statistics for medical research. 1st ed. London: Chapman and Hall, 1991; p. 277324. Comparing groups continuous data. In: Altman, DG, (Ed), Practical statistics for medical research, 1st ed. London: Chapman and Hall, 1991; p. 179228. Yate, PM, Thomas, D, Short, SM, Sebel, PS, Morton, J. Comparison of infusions of alfentanil or pethidine for sedation of ventilated patients of the ITU. Br J Anaesth 1986; 58: 10911099. Hansen-Flaschen, J, Cowen, J, Polomano, RC. Beyond the Ramsay Scale: need for a validated measure of sedating drug efficacy in the intensive care unit. Crit Care Med 1994; 22: 732733. Teasdale, G, Jennett, B. Assessment of coma and impaired consciousness. Lancet 1974; 13: 8184.
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can avoid excessive sedation in patients undergoing mechanical ventilation in the intensive care unit. Br J Anaesth 1999; 83: 698701. Chaudhri, S, Kenny, GNC. Sedation after cardiac bypass surgery: comparison of propofol and midazolam in the presence of a computerized closed loop arterial pressure controller. Br J Anaesth 1992; 68: 9899. Riker, RR, Fraser, GL, Cox, PM. Continuous infusion of haloperidol controls agitation in critically ill patients. Crit Care Med 1994; 22: 433440. Mallick, A, Smith, SN, Bodenham, AR. Local anaesthesia to the airway reduces sedation requirements in patients undergoing artificial ventilation. Br J Anaesth 1996; 77: 731734. Riker, RR, Fraser, GL, Simmons, LE, Wilkins, ML. Validating the Sedation-Agitation Scale with the bispectral index and Visual Analog Scale in adult ICU after cardiac surgery. Intensive Care Med 2001; 27: 853858. Wijdicks, EFM, Kokmen, E, OBrien, PC. Measurement of impaired consciousness in the neurological intensive care unit: a new test. J Neurol Neurosurg Psychiatry 1998; 64: 117119. Stanczak, DE, White, JG, Gouview, WD, Moehle, KA, Daniel, M, Novack, T, et al. Assessment of level of consciousness following severe neurological insult: a comparison of the psychometric qualities of the Glasgow Coma Scale and the Comprehensive Level of Consciousness Scale. J Neurosurg 1984; 60: 955960. Sugiura, K, Muraoka, K, Chishiki, T, Baba, M. The Edinburg-2 Coma Scale : a CSPC for assessing impaired consciousness. Neurosurgery 1983; 12: 411415. Benzer, A, Mitterschiffthaler, G, Marosi, M, Luef, G, Phringer, F, De La Renotiere, K, et al. Prediction of non-survival after trauma: Innsbruck Coma Scale. Lancet 1991; 338: 977978. Miller, DR, Martineau, RJ, Hull, KA, Vall, F, LeBel, M. Optimizing sedation following major vascular surgery: a double-blind study of midazolam administered by continuous infusion. Can J Anaesth 1994; 41: 782793. Sanchez-Izquierdo-Riera, JA, Caballero-Cubedo, RE, Perez-Vela, JL, Ambros-Checa, A, CantalapiedraSantiago, JA, Alted-Lopez, E. Propofol versus midazolam: safety and efficacy for sedating the severe trauma patient. Anesth Analg 1998; 86: 12191224. Eddleston, JM, Pollard, BJ, Blades, JF, Doram, B. The use of propofol for sedation of critically ill patients
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Consciousness Level Scale for Palliative Care 729 Appendix

Nvel 1 2 3 4 5 6 Level 1 2 3 4 5 6 Portuguese version Acordado/a Acorda quando chamado/a pelo seu nome e permanece acordado durante a conversao Acorda quando chamado/a pelo seu nome mas adormece durante a conversao Reage com movimentos ou abrindo brevemente os olhos, mas sem contacto visual, quando chamado/a pelo seu nome Reage a belisco no trapzio No reage English translation Awake Awakens when called by his/her name and stays awake during conversation Awakens when called by his/her name but falls asleep during conversation Reacts with movement or brief eye opening, but without eye contact, when called by his/her name Reacts to trapezius muscle pinching Does not react
Procedures for assessment:

Stimulation Patient is awakened, calm or agitated, without the need for any external stimulus Patient is not spontaneously alert. Patient is called loudly by name Patient is not spontaneously alert and does not react to voice. A firm pinching of the trapezius muscle is applied Score Level 1 Levels 2, 3 and 4, according to the reaction observed Level 5 and 6, according to the reaction observed
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Support Care Cancer (2010) 18:359366 DOI 10.1007/s00520-009-0661-z
ORIGINAL ARTICLE
Attitudes toward assisted death amongst Portuguese oncologists

Ferraz Gonalves
Received: 10 January 2009 / Accepted: 13 May 2009 / Published online: 1 June 2009 # Springer-Verlag 2009
Abstract Background The attitudes and practise of doctors concerning euthanasia and assisted suicide have been the subject of studies performed in many countries. However, these issues have not been studied properly in Portugal. Materials and method This study is a survey of 450 Portuguese oncologists by postal means and personal contact. Results The response rate was 33% (143). Only 13% would practise euthanasia with the present law in force forbidding such practise, and 24% would do so if it were legalised; 39% favoured its legalisation and 36% would like to have the option of euthanasia if they had a terminal disease. About assisted suicide, 15% would do it with the current law in force forbidding such action and 25% would do so if it were made legal; 32% favoured its legalisation and 24% would like to have that option if they had a terminal disease. There was one case of euthanasia and no cases of assisted suicide. The most important factor related with the acceptance of euthanasia and assisted suicide was religion, with non-practising Catholics accepting such practises more often than practising Catholics. The Portuguese oncologists have a very positive view on the potential role of palliative care in preventing many requests for euthanasia and assisted suicide. Conclusion Portuguese oncologists are mainly against the practise of euthanasia and assisted suicide and the number of requests is also relatively low; consequently, the number of episodes of assisted death is also apparently very low. Keywords Assisted death . Euthanasia . Assisted suicide . End-of-life decisions . Palliative care
F. Gonalves (*) Instituto Portugus de Oncologia, UCP-R, Rua Dr. Antnio Bernardino de Almeida, 4200-072 Porto, Portugal e-mail: ferrazg@ipoporto.min-saude.pt
Attitudes toward assisted death amongst Portuguese oncologists At the end of life, there are often many problems and complex situations which require decisions involving ethical issues. Some of the problems that physicians face when their patients are near the end of life include what to do when a patient requests euthanasia or physician-assisted suicide, withholding or withdrawing treatment including nutrition and hydration, how to respond to requests by families relative to incompetent patients, and the use of drug therapy to control suffering with the potential to hasten death. Studies have been performed in various countries on the opinion and the practises of doctors concerning end-of-life situations [111], and the discussion of those issues, in which euthanasia and physician-assisted suicide, primarily, has been very strong. In Portugal, however, the discussion has not undergone significant public debate, except at periods of time coinciding with the modification of legislation or with news of debate occurring in other places. Probably, this issue may be the topic of greater discussion in the future. Euthanasia and or physician-assisted suicide have being legalised in some countries or states, such as Australia (not currently in force), Holland, Belgium, Switzerland, and Oregon (USA). In Portugal, the Penal Code does not specifically mention the words euthanasia or assisted suicide but it states: Article 131 (homicide) Anyone who kills another person shall be liable to imprisonment for a term of 8 to 16 years. Article 133 (homicide in special circumstances) Anyone who is moved to kill another person under the influence of an understandable violent emotion, compas-
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sion or despair, or for any other reason of significant social or moral scope that appreciably diminishes the culprits culpability, shall be liable to imprisonment for a term of 1 to 5 years. Article 134 (homicide at the victims request) Anyone who kills a person in response to that persons serious, vehement and expressed request, shall be liable to imprisonment for a term of up to 3 years. Article 135 (incitement or assistance in committing suicide) Anyone who incites another person to commit suicide, or aids that person to that end, shall be liable to imprisonment for a term of up to 3 years, whether the suicide is attempted or successful. Therefore, under the Portuguese law, euthanasia and assisted suicide are not permitted. However, the legislator distinguishes between a homicide with other motivations and the homicide motivated by compassion or at the victims request, determining a lower punishment in these cases. The opinions and the testimonies of Portuguese physicians are not known, but they are essential to that debate. This lack of knowledge regarding what doctors think can lead to speculation. For example, sometimes people say that the practise of euthanasia in Portugal is not rare, but that is not my idea based on my practise and on the contact I have with my colleagues. Faced by this uncertainty, I believe that is worthwhile to try to find out what is really happening. That is the reason why this exploratory study was performed.
Materials and methods After the study of questionnaires used in other countries, namely, those kindly sent to me at my request by Helga Kuhse [5], Frederich Stiefel [12], David Doukas [13], and Diane Meier [14], a new questionnaire was developed. As all the questionnaires consulted were different from each other, some choices had to be made with the selection of questions, which had to be clear and informative and not too many. After the design of the questionnaire, it was submitted to face validation by 15 doctors, mainly oncologists. They were asked to complete the questionnaire and comment on the relevance and coherence of the questions and also suggest any necessary alterations. Minor alterations were made when considered pertinent, based on those suggestions. The questionnaires included questions concerning demographic data, euthanasia, assisted suicide and palliative care. Questions on other end-of-life issues were included in the questionnaire, but they will be
presented in another paper. The questions referring to euthanasia and assisted suicide were identical and can be seen in Table 1. The definitions of euthanasia and assisted suicide proposed in this study are shown in Table 2. As there is no consensus on those definitions, the definition was constructed from what was viewed as being the main elements of various definitions, which would ensure the concept was clearly defined. For example, the definition of euthanasia includes the intentional killing of the patient by a doctor as is the case with many definitions, such as those used by Bittel et al. [12] and Materstvedt et al. [15]; the aspect of the explicit, repeated, informed and well-considered request is identical to the Materstvedt et al. definition [15]; advanced disease is a common element; and without pain is included in the definitions of, for example, Bittel et al. [12] and Gielen et al. [16]. The questionnaires were sent by mail to all doctors belonging to the Portuguese Society of Oncology (PSO), included on a list provided by the board of that society. Four hundred eight doctors were surveyed in total. A letter explaining the reasons and the importance of the study and assuring the anonymity of replies was enclosed with the questionnaire; a prepaid envelop without any code or other means of identifying the person that sent it back was also included. Three weeks later, a new letter was sent to all doctors asking those who had still not replied to please do so. During this process, it was concluded that many doctors working in oncology did not belong to the PSO. The total number of such doctors is obviously unknown. Forty-two of these doctors working at different hospitals and whose position on these issues were not publicly known, were personally invited to fill in the questionnaire. They were provided with a questionnaire, letter and prepaid envelop identical in every way to those that had previously been sent by mail. Three weeks later, they were contacted again and asked to complete and return the questionnaire if they had not already done so. This study was approved by the Bioethics Service of the Faculty of Medicine of Porto University. An initial analysis was performed for statistical purposes, to identify coding errors, inconsistencies and the presence of missing categories or small numbers, and corrections were made where needed. An exploratory analysis of the data was performed so as to describe the sample. The variables were analysed by graphical methods, proportions and means. To evaluate the existence or not of associations between categorical variables the chi-square test was used. The level of significance was deemed to be 0.05. SPSS (Statistical Package for Social Sciences) version 14.0 statistical software was used to analyse the data.
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Support Care Cancer (2010) 18:359366 Table 1 Questions on euthanasia and assisted suicide 361
Considering the definition of euthanasia (or assisted suicide) presented, please answer the following questions: 1. Portuguese legislation does not allow the practice of euthanasia (or assisted suicide). Even so, are there any circumstances in which you would practise it? Yes No I do not have a definite opinion 2. If legislation allowed the practice of euthanasia (or assisted suicide), would you practise it? Yes No I do not have a definite opinion 3. Have you ever been requested to perform euthanasia (or assisted suicide)? Yes No About how many? 4. Have you received a request for euthanasia (or assisted suicide) in the last year? Yes No How many? 5. Have you ever practised euthanasia (or assisted suicide) in the sense of the above-stated definition? Yes No How many times? 6. Do you think that euthanasia (or assisted suicide) should be permitted by Portuguese law? Yes No I do not have a definite opinion 7. If you had an incurable and progressive disease, which inexorably led to death, would you like to have the available option of euthanasia (or assisted suicide)? Yes No I do not have a definite opinion The questionnaire included one set of seven questions on euthanasia and another identical set on assisted suicide. The definition of euthanasia or assisted suicide was presented above each set.
Results From the total of 450 questionnaires sent, 12 were returned because the doctor had moved house or had died. One hundred forty-three (33%) of the remaining 438 questionnaires were sent back completed. Table 3 shows the demographic data of the doctors who sent back the questionnaire. The questionnaires had been completed in a careful and consistent manner. Not much data was
missing, though religion was the data variable most omitted. However, 132 (92%) reported their religion. Of those, 126 (96%) were Catholic and 121 of them declare themselves as practising or non-practising Catholics. Therefore, in the analysis concerning religion, only this group of 121 was considered because the other groups were too small. The age and gender of 80% of the non-respondent doctors were known. The gender comparison of those who
Table 2 Definitions of euthanasia and assisted suicide Euthanasia: the deliberate termination without pain of the life of a person who has an incurable, advanced and progressive disease that will inexorably lead to death, at his or her explicit, repeated, informed and well-considered request, through the administration of one or more drugs in lethal doses. Assisted suicide: assistance in the suicide of a person with an incurable, advanced and progressive disease that will inexorably lead to death, at his or her explicit, repeated, informed and well-considered request, prescribing the drugs and giving him or her the necessary instructions on their use.
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362 Table 3 Demographic data Age (years) 3145 4665 >65 Gender Female Male Marital status Married/common-law partnership Living alone Religion Catholic Agnostic Atheist Catholics Non-practising Practising Main specialisation Surgery Medical oncology Radiotherapy Other Working place Institute of Oncology Hospital Other Region Large city Other How many people with terminal diseases do you see per year? 05 630 >30
Support Care Cancer (2010) 18:359366 Total 142 50 69 23 142 51 91 142 124 18 132 126 4 2 121 66 55 143 59 54 20 10 142 82 37 23 141 123 18 141 32 54 55 22.7 38.3 39.0 87.2 12.8 57.7 26.1 16.2 41.3 37.8 14.0 7.0 54.5 45.5 95.5 3.0 1.5 87.3 12.7 35.9 64.1 35.2 48.6 16.2 No. %
responded with those who did not respond was as follows: females 51 (35.1%) vs. 80 (32.5%); male 91 (64.1%) vs. 166 (68%). These differences were not significant (p = 0.49). The distribution of gender by age groups can be seen in Table 4. Only the difference between age groups of female doctors was significant with the youngest responding more often.
Table 4 Gender distribution by age groups
Euthanasia Only 13% of Portuguese oncologists stated that they would practise euthanasia in some circumstances under the present law which forbids it, and if euthanasia were legal the number would increase to 24%. However, the rate of doctors without a defined opinion also increased (Table 5).
Age (years)
Female Resp. n (%) N-resp. n (%) 18 (22.5) 50 (62.5) 12 (15.0)
Male Resp. n (%) N-resp. n (%) 24 (14.5) 86 (51.8) 56 (33.7)
Resp. respondent, N-resp. nonrespondent
<46 46-65 >65
27 (52.9) 23 (45.1) 1 (2.0)
> 0.001
23 (25.3) 46 (50.5) 22 (24.2)
0.06
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Support Care Cancer (2010) 18:359366 Table 5 Euthanasia Question Total Yes (%) No (%) I do not have a definite opinion no. (%) 12 (8.4) 18 (12.6) 27 (19.0) 33 (23.1) Practising vs. nonpractising Catholic p 0.005 0.004 <0.001 <0.001 363
Portuguese legislation does not allow the practise of euthanasia. Even so, are there any circumstances in which you would practise it? If legislation allowed the practise of euthanasia, would you practise it? Do you think that euthanasia should be permitted by Portuguese law? If you had an incurable and progressive disease, which inexorably led to death, would you like to have the available option of euthanasia?
143 143 142 143
19 (13.3) 34 (23.8) 55 (38.7) 51 (35.7)
112 (78.3) 91 (63.6) 60 (42.3) 59 (41.3)
Twenty-nine doctors (21%) received a varying number of requests to commit euthanasia (Table 6), six (4%) in the previous year. Only one doctor (0.7%) did actually commit euthanasia; that doctor had received three requests, though none in the previous year. Higher rates were observed in the following, relative to other questions: 39% of doctors think that euthanasia should be legalised and 36% would like to have the option of euthanasia if they had an incurable and progressive disease which would inexorably lead to death (Table 5). The rate of doctors without a defined opinion concerning these issues was also higher. No correlation between euthanasia and age, gender, marital status, specialisation, work place and region of practise was found. The factor most consistently related to the acceptability of euthanasia was religion, with statistically significant differences between practising and non-practising Catholics in regard to all questions included in Table 5; with the latter agreeing to it more often, although the number of those who do not agree to it is higher in both groups. Another statistically significant factor concerning whether doctors would practise euthanasia if permitted by law was the number of patients with incurable and progressive diseases observed per year, wherein those seeing more than
30 such patients replied affirmatively less often, but also replying that they had no defined opinion more often (p = 0.035). There was also a tendency for those aged over 65 years to reply negatively to the questions on euthanasia, although the correlation was not statistically significant. This group was the one with the least replies of non-defined opinion. Assisted suicide Regarding the questions on the practise of assisted suicide under current Portuguese legislation and if it were legalised, the answers are similar to those given for euthanasia. However, there are a lower number of doctors who think that assisted suicide should be legalised and also a lower number that would like to have that option at the end of life. In this last question, there is also a higher number of doctors without an opinion, than that in regard to euthanasia (Table 7). Only five doctors (3.5%) have been requested to practise assisted suicide: two have received one request, one received four and another six. One of those requests was in the previous year. No doctor practised assisted suicide. The most significant statistical difference concerning the acceptability of assisted suicide was again provided by the doctor being a practising Catholic or notwith nonpractising Catholics approving of assisted suicide more often, though they did not have an opinion on the issue in greater numbers. Another statistically significant association was between age and the legalisation of assisted suicide, with those aged over 65 years being more often against it (p =0.027), and none did not have an opinion. There was also an association in the same direction between age and the possibility of having the option of assisted suicide if the doctor had a terminal disease (p =0.029); but here, some doctors did not have an opinion. It was also observed that doctors older than 65 years tend to be more
Table 6 Number of requests for euthanasia received in the last year Number of requests 0 1 2 3 46 >6 Number of doctors 110 4 9 6 5 5 139 % 79.1 2.9 6.5 4.3 3.6 3.6 100
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364 Table 7 Assisted suicide Questions Total Yes (%) No (%)
I do not have a definite opinion (%) 16 (11.3) 17 (12.0) 23 (16.3) 37 (25.9)
Practising vs. non-practising Catholic p 0.001 0.005 0.001 0.005
Portuguese legislation does not permit the practise of assisted suicide. Even so, are there any circumstances in which you would practise it? If legislation allowed the practise of assisted suicide, would you practise it? Do you think that assisted suicide should be permitted by Portuguese law? If you had an incurable and progressive disease, which inexorably led to death, would you like to have the available option of assisted suicide?
142 143 142 143
21 (14.8) 36 (25.4) 45 (31.9) 34 (23.8)
105 (73.9) 89 (62.7) 73 (51.8) 72 (50.3)
often against the other questions about assisted suicide, although the correlations were not significant. This age group was the one that provided the least no-opinion answers. No correlations between assisted suicide and gender, marital status, specialisation, work place, region of practise and the number of cases seen per year were found. Palliative care Most doctors believe that palliative care could prevent euthanasia and assisted suicide requests: 12 doctors (8.4%) believed that such care could prevent all requests; 102 (71.3%) most requests; 19 (13.3%) some requests; four (2.8%) not at all; six (4.2%) had no opinion.
Discussion In this study, most Portuguese oncologists reject euthanasia and assisted suicide. The rate of requests and the rate of doctors accepting requests are lower than that observed in most studies performed in other countries, on different continents, although the results of those are heterogeneous [13, 5, 7, 10, 11, 1721]. The differences can reflect the cultural factors of doctors, patients and their families, including religious beliefs. The low level of debate on these issues in Portugal possibly reflects the low level of consideration that such issues presently have in this country. The fact that the doctors were oncologists may have influenced the results, since, although they are more exposed to terminal patients and suffering, they tend to oppose the practises of assisted death [22].The possibility of a bias induced by the low rate of replies cannot be excluded. The requests for euthanasia and assisted suicide were focused on a few doctors, some of them with an exceptional number of requests compared with the majority that did not
receive any requests at all. This might be related to the attitude of those doctors toward their patients; maybe they have a closer and more intimate relationship with their patients than others, allowing a deeper expression of patients feeling. The rate of Portuguese oncologists who support the legalisation of assisted death, 39% for euthanasia and 32% for assisted suicide, is roughly in the middle of the rates observed in a recent review of the attitudes observed in European countries [16]. In Portugal, the rate of oncologists who support assisted suicide is lower than that supporting euthanasia, as found in the study of Pasterfield et al. [23], but it is the reverse of the results of most studies [16]. It was observed that doctors who favour the legalisation of euthanasia and assisted suicide were greater in number than those who would practise it if it were legalised. These data follow the same trend as that observed in the study of Cohen et al. [22], carried out in Washington where 54% thought that euthanasia should be legalised in some situations, but only 33% would want to practise it, while in relation to assisted suicide, the rates were 53% and 40%, respectively. Those data can be interpreted by some doctors as recognition of the patients right to assisted death; however, the doctor maintains the right to refuse to provide such assistance. Those positions are, however, a minority in Portugal. More doctors wish to have the option of euthanasia available if they had a terminal disease than those who would practise it on patients, but the same does not occur with assisted suicide. In the study of Howard et al. [18] a similar difference, although lower, was observed. The most consistent relationship between the pro and con opinions in various questions concerning euthanasia and assisted suicide and demographic factors was that concerning religion. In fact, there were very significant differences between practising and non-practising Catholics. This may result from the fact that in Portugal most people have been christened and have had a Catholic education, and so they see themselves as Catholic, that is,
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Support Care Cancer (2010) 18:359366 365
they are inserted into Catholic culture and tradition, but they do not show firmness in their convictions, so they consider themselves as non-practising Catholics. The result of this is that, probably, people adopt positions that are against those usually accepted by convinced Catholics, namely the moral doctrine of the Catholic Church. The influence of religion on these issues seems to be very important and was also observed in other studies. In Oregon, the variables significantly associated with the willingness to participate in assisted suicide included the Jewish affiliation, no religious affiliation and other nonChristian affiliations; whereas the unwillingness to participate in assisted suicide was a Catholic affiliation or other Christian affiliation [1]. In a study in Washington, religious beliefs were also a reason for being against euthanasia and assisted suicide [22]. In another study, the Catholics and the very religious were less likely to desire that euthanasia or assisted suicide be performed on themselves [18]. However, in a study conducted by the German Association for Palliative Medicine religious convictions did not play a significant role in the decision-making process [19]. In this study, however, the rate of positive responses, 9.6%, was very low reflecting the common position of palliative care physicians who are usually against assisted death [16]. It was also observed that the over 65 years age group opposed euthanasia and assisted suicide more often than other age groups. The finding that older doctors more frequently oppose assisted death than younger ones is common in studies on these issues [20, 21]. Perhaps this association is due to their education, which was at a time when the ethical principle that dominated all others was undoubtedly beneficence, and when the doctors attitude to patients was mainly paternalistic. The primacy of the respect for autonomy is more recent, with the possible extension of the concept to include the right to choose the way of dying. In general, the answers that reveal more indecision were those concerning the option for euthanasia or assisted suicide by the doctors themselves if they had a terminal disease. This suggests that it is more difficult to decide in their own cause than when the decision concerns others. It seems that the problems concerning euthanasia are more relevant among both doctors and patients, taking into consideration the number of requests indicated by doctors, than those related to assisted suicide. Maybe this is because euthanasia has more visibility. In fact, in Portugal, the few discussions on assisted death are usually limited to euthanasia. The Portuguese oncologists looked very positively on the value of palliative care in responding to the problems of patients with advanced chronic diseases and its potential in preventing many requests for assisted death. This is a very important and encouraging aspect for the development of
palliative care in a country where only a few teams are working in this field. An important potential limitation of this study is the low percentage of questionnaires received. It was lower than that of studies with similar questions carried out in other countries [1, 2, 5, 17, 18]. However, it is higher than that usually observed in studies carried out in Portugal using questionnaires sent by mail to doctors [24]. The meaning of this is unknown, but it does indicate general disinterest by the Portuguese public and Portuguese doctors in surveys. In fact, there are other examples of studies with even lower reply percentages [24]. The sensitivity of the topic could make some fear for being identified and their opinions and practises being made public, even if anonymity was guaranteed in the cover letter sent together with the questionnaire. Or does it mean that there is no reflection on these issues? It is probably a combination of factors. Some of those factors identified above were associated to a lower percentage of replies, although the results are not completely consistentthese factors being related to the doctors population, the inquiry being anonymous or the sensitivity of the theme [25, 26]. However, so long as the number of replies is sufficiently high to perform statistical analysis, the only problem that exists is if those who did not reply were significantly different to those who did. Therefore, although a low rate of replies increases the probability of bias, there is not necessarily an association between the reply rate and bias [26]. In this study, only the distribution of females by age groups was significantly different in regards to those who responded and those who did not. Even so, the results can be deemed nonrepresentative of the opinion of the population studied. However, this is the best approach made until now regarding the opinion of Portuguese oncologists on euthanasia and assisted suicide and we believe that these results deserve consideration.
Conclusion Most Portuguese oncologists are against assisted death. In parallel, there seems to be a reduced number of requests for assisted death, based on the physicians answers. Positive responses to requests for assisted death seem to be quite rare. Portuguese oncologists value the potentially positive role of palliative care in the treatment of patients with incurable and advanced chronic diseases thereby preventing at least many cases of requests for assisted death. Religion greatly influences the attitudes of Portuguese oncologists as regards their opinions on assisted death.
Acknowledgements I would like to thank Prof. Rui Nunes, as advisor of the Masters Degree in Bioethics from where this work was extracted;
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366 Prof. Henrique de Barros and Dr. Joselina Barbosa and Dr. Milton Severo from the Epidemiology Service of the Faculty of Medicine of Porto University for their help in data extraction and statistical analysis; Helga Kuhse, Frederich Stiefel, David Doukas and Diane Meier for making available the questionnaires used in their studies; and The Portuguese League against Cancer for funding the study.
Support Care Cancer (2010) 18:359366 14. Meier DE, Emmons CA, Wallenstein S, Quill T, Morrison RS, Cassel CK (1998) A national survey of physician-assisted suicide and euthanasia in the United States. N Engl J Med 338:1193 1201. doi:10.1056/NEJM199804233381706 15. Masterstvedt LJ, Kaasa S (2002) Euthanasia and physicianassisted suicide in Scandinaviawith a conceptual suggestion regarding international research in relation to the phenomena. Palliat Med 16:1732. doi:10.1191/0269216302pm470oa 16. Gielen J, van der Branden S, Broeckaert B (2008) Attitudes of European physicians toward euthanasia and physicianassisted suicide: a review of the recent literature. J Palliat Care 24:173184 17. van der Maas PJ, van der Wal G, Haverkate I et al (1996) Euthanasia, physician-assisted suicide, and other medical practices involving the end of life in the Netherlands, 19901995. N Engl J Med 335:16991705. doi:10.1056/NEJM199611283352227 18. Howard OM, Fairclough DL, Daniels R, Emanuel EJ (1997) Physician desire for euthanasia and assisted suicide: would physicians practise what they preach? J Clin Oncol 15:428432 19. Mller-Busch HC, Oduncu FS, Woskanjan S, Klaschik E (2004) Attitudes on euthanasia, physician-assisted suicide and terminal sedationa survey of the members of the German Association for Palliative Medicine. Med Health Care Philos 7:333 339. doi:10.1007/s11019-004-9349-9 20. Miccinesi G, Fisher S, Paci E et al (2005) Physicians attitudes towards end-of-life decisions. A comparison between seven countries. Soc Sci Med 60:19611974. doi:10.1016/j.socscimed.2004.08.061 21. Ryynnen O-P, Myllykangas M, Viren M, Heino H (2002) Attitudes towards euthanasia among physicians, nurses and the general public in Finland. Public Health 116:322 331. doi:10.1016/S0033-3506(02) 00556-5 22. Cohen JS, Fihn SD, Boyko EJ, Jonsen AR, Wood RW (1994) Attitudes toward assisted suicide and euthanasia among physicians in Washington state. N Engl J Med 331:8994 23. Pasterfield D, Wilkinson C, Finlay IG, Neal RD, Hulbert NJG (2006) Ps views on changing the law on physician-assisted suicide and euthanasia, and willingness to prescribe or inject lethal drugs: a survey from Wales. Br J Gen Pract 56:450452 24. INFARMED Informao cientfica sobre medicamentos: relatrio. [Scientific information on medicaments: report] http://www. i n f a r m e d . p t / p o r t a l / p a g e / p o r t a l / I N FA R M E D / MONITORIZACAO_DO_MERCADO/OBSERVATORIO/ INTRODUCAO_DE_FICHEIROS/ICM_rel_preliminar.pdf (accessed in April 2007). 25. Edwards P, Roberts I, Clarke M, DiGuiseppi C, Pratap S, Wentz R, Kwan I (2002) Increasing response rates to postal questionnaires: systematic review. BMJ 324:11831185. doi:10.1136/ bmj.324.7347.1183 26. Asch DA, Jedrziewski K, Christakis NA (1997) Response rates to mail surveys published in medical journals. J Clin Epidemiol 50:11291136. doi:10.1016/S0895-4356(97) 00126-1
References
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Support Care Cancer (2010) 18:12711277 DOI 10.1007/s00520-009-0743-y
ORIGINAL ARTICLE
Attitudes toward end-of-life situations other than euthanasia and assisted suicide among Portuguese oncologists
Jos Antnio Ferraz Gonalves
Received: 10 January 2009 / Accepted: 10 September 2009 / Published online: 6 October 2009 # Springer-Verlag 2009
Abstract Background The aim of this study was to determine the attitude of Portuguese oncologists toward end-of-life situations other than euthanasia and assisted suicide. Methods This study used a survey of 450 Portuguese oncologists by postal means and personal contact. Main results The response rate was 33% (143). Only 7.7% doctors would give lethal doses of drugs to someone with an incurable, advanced, and progressive disease that is unable to make decisions, at the request of a family member or other close person. However, 30 doctors (21.3%) would prefer, in the event they were in such a situation, that the drugs be given them at their request. None of the 12.4% who have received such requests admitted to committing any of those acts. Almost 70% of the doctors would withdraw life support measures at the patient's request if the same had an incurable, advanced, and progressive disease, and a further 14% would do it in certain circumstances, but only 41% would withdraw measures such as nutrition and hydration. Fewer doctors would withdraw such measures including nutrition and hydration at a family member's request or on their own initiative. Religion has a major influence on the doctors' opinion. Most doctors (96.5%) agreed with the administration of drugs for symptom control even foreseeing that they could shorten life. Conclusion Most Portuguese oncologists respect patients' autonomy, favoring the withdrawal of life support treatment at the patients' request when appropriate and much less do so on the request of others or by their own initiative. They
J. A. F. Gonalves (*) Instituto Portugus de Oncologia, UCP-R, Rua Dr. Antnio Bernardino de Almeida, 4200-072 Porto, Portugal e-mail: ferrazg@ipoporto.min-saude.pt
appropriately do not confuse those practices with symptom relief even when hastened death can be envisaged. Keywords End-of-life decisions . Life-terminating acts without explicit request of patient . Treatment withdrawal . Symptom control The most discussed end-of-life issues are probably euthanasia and assisted suicide. However, doctors, patients, and families face many other situations requiring difficult decisions. Examples of those are decisions about withholding and withdrawing life-supporting treatments at the patient's request or, if the patient is not competent, how to respond to eventual requests by family members and whether or not a doctor or a healthcare team can decide unilaterally. Should nutrition and hydration be considered as treatment or as basic care, that is, may they be withheld or withdrawn in certain circumstances, or never? There are also issues concerning the provision of lethal doses of drugs to terminate the life of patients without their explicit request, also referred to as involuntary or nonvoluntary euthanasia depending on whether the patient is competent or not, although this designation is not appropriated because euthanasia implies a patient's request. Other issues are the administration of drugs to relieve suffering, even when this carries the possibility of shortening life, and palliative sedation. All those situations sometimes generate difficult decisions, and health professionals should have clear perception in relation to those issues. The withholding or withdrawing of lifeprolonging treatments or symptom control in a terminal patient even if death can be foreseen are, in the appropriate circumstances, legitimate acts that must be accomplished. Those acts are of a completely different nature to euthanasia or assisted suicide because they are intended to
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relieve suffering or avoid prolonging the process of dying rather than directly causing the patient's death. Many doctors use the argument of the principle of double effect to justify such actions and separate them from euthanasia. This implies, as far as medicine is concerned, that a doctor can make a correct action even if he/she foresees that a bad consequence can also occur without being his/her intention, if there is no other alternative. However, the issue of intentions is problematic because they cannot be objectively evaluated. Therefore, in my view, there is no need to invoke the principle of double effect to justify acts like withholding or withdrawing treatments or symptom control in a terminal patient even if death can be foreseen. The problem should be defined in terms of the adequacy of the means used, after the evaluation of the benefits to and burdens on the patient and the patient's will. Those issues have been studied in several countries [1 5]. For example, in Holland, in a famous study sponsored by the Dutch government [2] on acts that terminate life, it was observed that the administration of drugs in lethal doses without explicit request from the patients occurred in 0.8% of all deaths. In a deeper analysis made later regarding the circumstances surrounding those cases, 27% of the doctors answered that they had carried out one of those acts at least once and 32% had never done it but could imagine a situation where they might. According to those doctors, in almost all cases, the patient was suffering unbearably with no possibility of improvement, as the possibilities of palliation had been exhausted. The authors of that study hold the view that such acts can be a response to the injustice of a patient's situation, when he/she is unable to make an explicit request, thereby having to suffer to the end when their doctors, who may have been responsible for treatment for a long time, and their families agree on the termination of their life, in a country where euthanasia is usually not punished; they add that the lifetime shortened by such a practice is usually lower than that related to euthanasia. On the other hand, such acts can be seen as homicide and they illustrate the slippery slope that would emerge if euthanasia were accepted. As another example, in an Australian study, 6.4% of the doctors stated that they had terminated the life of patients without their explicit request [1]. In this study, not all patients were incompetent, and some doctors declared that discussion would have done more harm than good. This is a strange way of thinking because it means that discussing the problem with the patients is more harmful than killing them. The law and the practices regarding end-of-life issues are changing, namely, in Europe and the United States, with greater openness towards assisted death. In Portugal, endof-life problems have not deserved much attention in studies. However, it is important to know what doctors
think and feel about them and consequently what they do, as was the case in other countries. Doctors of some specialties, such as oncologists, are faced with those problems in their everyday practice, so they are particularly well suited to explore such questions. The data presented in this paper are part of an exploratory study that also included questions on euthanasia and assisted suicide, the results of which were presented in a separate paper [6].
Methods The questionnaire was developed for this study partially based on other published papers kindly sent to me at my request by the authors [1, 79]. After the design of the questionnaire, it was submitted to face validation by 15 doctors, mainly oncologists. They were asked to complete the questionnaire and comment on the relevance and coherence of the questions and also suggest any necessary alterations. Minor alterations were made when considered pertinent, according to those suggestions. The questionnaires were sent by mail to the 408 doctors belonging to the Portuguese Society of Oncology (PSO) included on a list provided by the board of that society and to 42 oncologists not belonging to the PSO and whose positions on these issues were not publicly known. The members of the PSO received the questionnaire with a letter explaining the reasons and the importance of the study and assuring the anonymity of replies by mail; a prepaid envelop without any code or other means of identifying the person replying was also included. Three weeks later, a new letter was sent to all doctors asking those who had still not replied to please do so. The other oncologists were personally invited to fill in the questionnaire. They were provided with a questionnaire, letter, and prepaid envelop identical in every way to those that had previously been sent by mail. Three weeks later, they were contacted again and asked to complete the questionnaire if they had not already done so. The questionnaires contained questions concerning demographic data, administration of drugs to incompetent patients, withdrawal of life support treatments including feeding and nutrition, and symptom control with the risk of hastened death. Questions on euthanasia and assisted suicide issues were included in the questionnaire, but they were presented in another paper. This study was approved by the Bioethics Service of the Faculty of Medicine of Porto University. An initial analysis was performed for statistical proposes in order to identify coding errors, inconsistencies, and the presence of missing categories or small numbers, and corrections where made where needed. An exploratory
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Support Care Cancer (2010) 18:12711277 1273 Table 1 Demographic data Total Age (years) 3145 4665 >65 Gender Female Male Marital status Married/common-law partnership Living alone Religion Catholic Agnostic Atheist Catholics Nonpracticing Practicing Main specialty Surgery Medical oncology Radiotherapy Other Working place Institute of Oncology Hospital Other Region Large city Other How many people with terminal diseases do you see per year? 05 630 >30 132 126 4 2 121 66 55 143 59 54 20 10 142 82 37 23 141 123 18 141 32 54 55 22.7 38.3 39.0 87.2 12.8 57.7 26.1 16.2 41.3 37.8 14.0 7.0 54.5 45.5 95.5 3.0 1.5 142 50 69 23 142 51 91 142 124 18 87.3 12.7 35.9 64.1 35.2 48.6 16.2 Number Percentage
analysis of the data was performed so as to describe the sample. The variables were analyzed by graphical methods, proportions, and means. To evaluate the existence or not of associations between categorical variables, the chi-square test was used. The level of significance was deemed to be 0.05. The Statistical Package for Social Sciences (SPSS) version 14.0 statistical software was used to analyze the data.
Results From the total of 450 questionnaires sent out, 12 were returned because the doctors concerned had either moved house or died. Of the remaining 438 questionnaires, 143 (33%) were sent back filled in. Table 1 shows the demographic data of the doctors who returned the questionnaire. These have been filled in a careful and consistent manner. There was not much missing data, but religion was the variable most frequently omitted. Even so, 132 (92%) reported their religion. Of those, 126 (96%) were Catholic and 121 of them declared themselves to be practicing or nonpracticing Catholics. Therefore, in the analysis concerning religion, only this group of 121 were considered because the others groups were too small. The age and gender of 80% of the doctors that did not reply were known. The comparison by gender of those who replied with those who did not was as follow: females 51 (35.1%) vs. 80 (32.5%); males 91 (64.1%) vs. 166 (68%). These differences were not significant (p =0.49). The distribution of gender by age groups can be seen in Table 2. Only the difference among the age groups of female doctors was significant with the youngest responding more often. Incompetent patients All the opinions about giving lethal doses of drugs to incompetent patients were favored only by a small minority of doctors. Only 11 doctors (7.7%) would give lethal doses of one or more drugs to someone with an incurable, advanced, and progressive disease unable to make decisions, at the request of a family member or other close person. However, 30 doctors (21.3%) would prefer, in the event that they were in such a situation, that the drugs were given to them at the request of a family member or other close person (Table 3); but there were also more doctors without an opinion in relation to this hypothetical situation. Twelve doctors (8.4%) have received that type of request and four of them had received between one and three requests in the previous year. No doctor committed any of those acts. However, 24 doctors (17.3%) favored that those acts should be permitted by legislation.
In the similar question on drugs' administration, though by the doctors' initiative, there were more affirmative answers to the hypothesis of the doctor personally being in that situation than to the doctor having to do such to a patient. Once again, there were more doctors without an opinion in the event that the doctor is personally in that situation, although the difference is not statistically significant (Table 3). However, the number of positive answers was lower than in the scenario of drugs given on request. Also, no doctor has committed any one of those acts. Nineteen (13.5%) were of the opinion that those acts should be permitted by legislation. In those questions, statistically significant differences between doctors in different work places were observed,
195
1274 Table 2 Distribution of gender by age groups Age (years) Female Resp., no. (%) <46 4665 >66 27 (52.9) 23 (45.1) 1 (2.0) N-resp., no. (%) 18 (22.5) 50 (62.5) 12 (15.0) >0.001 p
Support Care Cancer (2010) 18:12711277 Male Resp., no. (%) 23 (25.3) 46 (50.5) 22 (24.2) N-resp., no. (%) 24 (14.5) 86 (51.8) 56 (33.7) 0.06 p
Resp. respondent, N-resp. nonrespondent
with the doctors working in the institutes of oncology being less favorable to the administration of drugs at the family's request (p =0.035) and surgeons being more often pro permission being granted through legislation (p =0.030). Nonpracticing Catholics favor that practice more often than practicing Catholics if they were in the position of the patient in those conditions and the request having been made by a family member, but there were also more doctors without an opinion (p =0.016). No association between the administration of lethal drugs to incompetent patients and age, sex, marital status, the region of practice, the specialty, and the number of situations of terminal diseases the doctor treats per year were observed. Treatment withdrawal Almost 70% of the doctors would withdraw life support measures at the patient's request if the same had an incurable, advanced, and progressive disease, and an additional 14% would do it in certain circumstances, but only 41% would withdraw measures such as nutrition and hydration. Fewer doctors would withdraw those measures
at a family member's request or by their own initiative (p < 0.0001); in the case of nutrition and hydration at a family member's request, the difference was not statistically significant; but in cases involving doctor or healthcare initiative, there was a significant difference (p =0.03). The totals for the withdrawal of those measures at family members' request and on the doctor's initiative are identical or very close (Table 4). In relation to the withdrawal of life support measures at the patient's request, there were statistically significant differences between practicing and nonpracticing Catholics (p =0.039), with practicing Catholics wanting to do it less often and basing the decision more on circumstances. There was also a significant difference (p =0.033) among doctors associated to the number of times they were confronted with situations of terminal diseases, with those who see more patients in that phase more readily accepting the withdrawal of support. The opinion about withdrawal of nutrition and hydration differed significantly according to the doctors' specialty (p < 0.001), with 100% of radiotherapists against withdrawal. Work place was also associated with a significant difference
Table 3 Incompetent patients Questions Total Yes, no. (%) No, no. (%) I do not have a defined opinion, no. (%) 3 (2.1)
Would you give one or more drugs in lethal doses to someone unable to make decisions because of impaired consciousness and suffering from an incurable, advanced, and progressive disease that would inexorably lead to death, at the request of a family member or other close person? Do you think that those acts should be allowed by the legislation? (referring to the question above) If you had an incurable, advanced, and progressive disease that would inexorably lead to death and you were unable to make decisions because of impaired consciousness, would you like that a doctor give you one or more drugs in lethal doses, at the request of a family member or other close person? Would you give one or more drugs in lethal doses to someone unable to make decisions because of impaired consciousness and suffering from an incurable, advanced, and progressive disease that would inexorably lead to death, by your own initiative (not on the request of anybody)? Do you think that those acts should be allowed by the legislation? (referring to the question above) If you had an incurable, advanced, and progressive disease that would inexorably lead to death and you were unable to make decisions because of impaired consciousness, would you like that a doctor give you one or more drugs in lethal doses, based only on his or her judgment?
143
11 (7.7)
121 (85.2)
139 141
24 (17.3) 30 (21.3)
92 (66.2) 80 (56.7)
23 (16.5) 31 (22.0)
139
6 (4.3)
124 (89.2)
9 (6.5)
141 139
19 (13.5) 14 (10.1)
101 (71.6) 100 (71.9)
21 (14.9) 25 (18.0)
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Support Care Cancer (2010) 18:12711277 Table 4 Treatment withdrawal Question Total Yes, no. (%) No, no. (%) In certain circumstances, no. (%) 20 (14.1) 1275
Do you think that in relation to someone with an incurable, advanced, and progressive disease that would inexorably lead to death, it is legitimate to withdraw support of life measures at his or her explicit, repeated, informed, and well-pondered request? Would you withdraw measures such as feeding and hydration? (referring to the question above) Do you think that in relation to someone with an incurable, advanced, and progressive disease that would inexorably lead to death, who is unable to make decisions because of impaired consciousness, it is legitimate to withdraw support of life measures at the request of a family member or other close person? Would you withdraw measures such as feeding and hydration? (referring to the question above) Do you think that in relation to someone with an incurable, advanced, and progressive disease that would inexorably lead to death, who is unable to make decisions because of impaired consciousness, it is legitimate to withdraw support of life measures by the unilateral decision of the doctor or the healthcare team? Would you withdraw measures such as feeding and hydration? (referring to the question above)
142
95 (66.9)
27 (19.0)
142 142
58 (40.8) 52 (36.6)
84 (59.2) 66 (46.5) 24 (16.9)
141 143
44 (31.2) 52 (36.6)
97 (68.8) 66 (46.2) 25 (17.5)
136
39 (28.7)
97 (71.3)
(p =0.027), with doctors of the institutes of oncology being more often against withdrawal of nutrition and hydration than doctors from other hospitals, but this may be due to the influence of the radiotherapists because they are concentrated in those institutes; doctors from other work places were the least in favor. There was no relationship between withdrawal of life support, namely, nutrition and hydration, and age, gender, marital status, and the region of practice. The withdrawal of life support at the request of families or another close person is associated with a significant difference in relation to specialties (p =0.040), with 75% of radiotherapists against the withdrawal under those circumstances. That difference increases in regard to nutrition and hydration withdrawal, with 100% of radiotherapists answering no (p =0.003). In relation to withdrawal by the doctor or on the health team's initiative, there are no significant differences, except in what concerns nutrition and hydration, with practicing Catholics being more often against (p =0.009) and, again, 100% of radiotherapists also against it (p =0.013). Symptom control As regards the question of the administration of drugs for symptom control even foreseeing that they could shorten life, 138 (96.5%) agreed with it, four admitted it in certain circumstances, one had no opinion, but none answered negatively. And on the hypothesis of the doctor being in that suffering situation, 100% would like for someone to administer a drug that would relieve their suffering even if it could shorten their lives.
Discussion It seems that there is a broad consensus among Portuguese oncologists as regards the questions on incompetent patients included in this study. Only a few doctors would give drugs in lethal doses to an incompetent patient at the family' request; and even less would give them on their own initiative. Although some of them had received those requests, not one doctor did so. A few more, but even so only a few, favored the legalization of these kinds of acts. The questions concerning what doctors would want if they were in the patients' position are those that most frequently had no opinion answers. As it happens, on the other hand, many more doctors would like drugs to be administered to them at their family's request than those who would do it to their patients, suggesting that some doctors would want, in regard to themselves, that others take a decision, the responsibility for which they are not prepared to take. A much lower number would like the decision to be taken unilaterally by a doctor, suggesting that they fear the possibility of abuse. A small minority agree with the legalization of those acts, which are now legal in Holland [10]. This is an evolution of the Dutch law once again interpreted by many as proof of the slippery slope that is created through the very significant danger of the legalization of assisted death. The vast majority of oncologists agree with the withdrawal of life support treatment at the patient's request, under the circumstances defined in the questionnaire, although they agreed less often when the questions were about withdrawing feeding and hydration. Probably, most
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of those see feeding and hydration as basic care and not as treatments. However, in regard to the withdrawal of those treatments at the families' request or by the doctor's own initiative, the number of positive answers was identical but much lower than when it was at the patient's request. Therefore, it seems that doctors effectively respect patients' autonomy and that many think that others, namely, themselves, do not have the legitimacy to make those decisions. Here again, the fear of abuse may have played a role. In an Australian study [1], 36% of doctors said that they had already taken a decision to withhold or withdraw treatments, 81% with the explicit intention of hastening death. This is a dubious statement because when life support treatments are withheld or withdrawn it is predictable that death occurs sooner, but it is appropriate in certain circumstances. Therefore, the problem of intention is an equivocal one. Once again, the problem should be put on the adequacy of the means used, after the evaluation of the benefits and burdens to the patient and the patient's will. Religion was the factor that most consistently influences the answers on incompetent patients and the withdrawal of treatments, with practicing Catholics opposing more those acts than nonpracticing Catholics. In a country where most physicians have been christened and have had a Catholic education, and so they say they are Catholics, many, in particular the nonpracticing Catholics, probably do not have firm convictions. Physicians' religiosity is a factor that has been consistently observed in various studies as related with their opinions and attitudes regarding end-of-life issues [1114]. The difference between areas of specialty was curious, particularly in relation to radiotherapy, and the 100% that were against the withdrawal of feeding and hydration. The reasons for this difference are not clear, but we can speculate that doctors of that specialty probably accompany patients near the end of life less often, so they do not face these problems in this phase. This hypothesis seems to be supported by the observation that doctors who more frequently face such situations more often favor the withdrawal of life support treatment. Almost all oncologists would give a drug for symptom relief even if they foresaw that life could be shortened. In their own case, all would like for the drugs to be given to them. Therefore, there were no doubts on this issue and no confusion with other acts as regards giving drugs with the explicit or implicit aim of killing the patient. In other studies [1, 3], some doctors who gave drugs for symptom relief had the partial intention of hastening death. However, in one of those studies [3], the relatively low doses of opioids and the high number of patients who were on opioids before made the authors raise doubts whether the doctors were correct in attributing death-hastening effects to their practices. The authors comment further that unfounded concerns may have resulted in less than optimal
symptom management in the care of those dying patients [3]. This is a very important topic because at the end of life the primary role of physicians is to control patients' suffering. Therefore, the right drugs in the right doses should be given in order to control that suffering, even if the doctor fears that there is a risk of death. Once again, it is the balance of benefits and burdens and the patient's will that should govern our acts. Taking all the results together, the logical conclusion is that Portuguese oncologists have clear concepts about endof-life issues. Almost all are against the administration of drugs in lethal doses to incompetent patients. On the other hand, they are prepared to withdrawal life support measures at the request of a patient with an incurable, advanced, and progressive disease. They are also prepared to administer drugs for symptom control even when foreseeing that they could shorten life. Therefore, it seems that there is no confusion at all with the concepts. In relation to the withdrawal of artificial nutrition and hydration, there is a larger division among doctors, but this is also a more controversial issue. About 60% of doctors accompany less than 30 terminal patients per year. The doctors included in this study are medical oncologists, surgeons, and radiotherapists and, although they accompany many patients, surgeons and radiotherapists usually only assist a few in the terminal phase. In this phase, medical oncologists are the doctors who treat most patients. Even so, the contact of doctors working in oncology with the reality of patients with far advanced disease is a frequent event. A potential limitation of this study is the low percentage of questionnaires received. It was lower than that of studies in other countries [1, 3, 1517], but the percentage is not low compared to the universe of other studies performed in Portugal [18]. However, so long as the number is high enough to perform statistical analysis, the only problem that exists is if those who did not reply are significantly different from those who did. Therefore, although a low rate of replies increases the probability of bias, there is not necessarily an association between the reply rate and bias [19]. In this study, only the distribution of females by age groups was significantly different between those who replied and those who did not. Therefore, we believe that, even with a low rate of replies, these results deserve consideration and these are the only data collected until now regarding the opinion of Portuguese oncologists about end-of-life issues.
Conclusion Most Portuguese oncologists favor the withdrawal of life support treatments at the patients' request but much less do
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Support Care Cancer (2010) 18:12711277 1277 6. Gonalves F (2009) Attitudes toward assisted death amongst Portuguese oncologists. Support Care Cancer (in press) 7. Bittel N, Neuenschwander H, Stiefel F (2002) Euthanasia: a survey by the Swiss Association for Palliative Care. Support Care Cancer 10:265271 8. Doukas DJ, Waterhouse D, Gorenflo DW, Seid J (1995) Attitudes and behaviours on physician-assisted death: a study of Michigan oncologists. J Clin Oncol 13:10551061 9. Meier DE, Emmons CA, Wallenstein S, Quill T, Morrison RS, Cassel CK (1998) A national survey of physician-assisted suicide and euthanasia in the United States. N Engl J Med 338:11931201 10. Englert Y (2004) Belgiumevolution of the debate. Em: Euthanasia. Volume II. National and European perspectives. Council of Europe Publishing, Strasbourg, pp 1324 11. Lee MA, Nelson HD, Tilden VP, Ganzini L, Schmidt TA, Tolle SW (1996) Legalizing assisted suicideviews of physicians in Oregon. N Engl J Med 334:310315 12. Cohen JS, Fihn SD, Boyko EJ, Jonsen AR, Wood RW (1994) Attitudes toward assisted suicide and euthanasia among physicians in Washington state. N Engl J Med 331:8994 13. Howard OM, Fairclough DL, Daniels R, Emanuel EJ (1997) Physician desire for euthanasia and assisted suicide: would physicians practice what they preach? J Clin Oncol 15:428432 14. Wenger NS, Carmel S (2004) Physicians' religiosity and end-oflife care attitudes and behaviours. Mt Sinai J Med 71:335343 15. Back AL, Wallace JI, Starks HE, Pearlman RA (1996) Physicianassisted suicide and euthanasia in Washington state: patient requests and physician responses. JAMA 275:919925 16. Ganzini L, Nelson HD, Schmidt TA, Kreamer DF, Delorit MA, Lee MA (2000) Physicians' experience with the Oregon death with dignity act. N Engl J Med 324(20):557563 17. Edwards P, Roberts I, Clarke M, DiGuiseppi C, Pratap S, Wentz R, Kwan I (2002) Increasing response rates to postal questionnaires: systematic review. BMJ 324:11831185 18. INFARMED. Informao cientfica sobre medicamentos: relatrio [Scientific information on drugs: report]. Available at http://www. infarmed.pt/portal/page/portal/INFARMED/MONITORIZACAO_ DO_MERCADO/OBSERVATORIO/INTRODUCAO_DE_ FICHEIROS/ICM_rel_preliminar.pdf. Accessed April 2007 19. Asch DA, Jedrziewski K, Christakis NA (1997) Response rates to mail surveys published in medical journals. J Clin Epidemiol 50:11291136
so on the request of others or by their own initiative. However, many of those do not favor the withdrawal of feeding and hydration, probably because they see them as basic care. The majority is against the administration of drugs in lethal doses to incompetent patients and they do not confuse those practices with symptom relief, even when hastened death can be possible. Religion is the factor that most influences the attitudes of Portuguese oncologists in relation to end-of-life decisions.
Acknowledgements I would like to thank Prof. Rui Nunes, as advisor of the Master's Degree in Bioethics from where this work was extracted; Prof. Henrique de Barros, Dr. Joselina Barbosa, and Dr. Milton Severo from the Epidemiology Service of the Faculty of Medicine of Porto University for their help in data extraction and statistical analysis; Helga Kuhse, Frederich Stiefel, David Doukas, and Diane Meier for making available the questionnaires used in their studies; and the Portuguese League against Cancer for funding the study.
References
1. Kuhse H, Singer P, Baume P, Clark M, Rickard M (1997) End-oflife decisions in Australian medical practice. Med J Aust 166:191196 2. Pijnenborg L, van der Maas PJ, van Delden JJ, Looman CWN (1993) Life-terminating acts without explicit request of patients. Lancet 341:11961199 3. Bilsen J, Norup M, Delians L et al (2006) Drugs to alleviate symptoms with life shortening as a possible side effect: end-of-life care in six European countries. J Pain Symptom Manage 31:111121 4. van der Heide A, Deliens L, Faisst K, Nilstun T, Norup M, Paci E, van der Wal G, van der Maas PJ, on behalf of the EURELD consortium (2003) End-of-life decision-making in six European countries: descriptive study. Lancet 362:345350 5. Buiting HM, van Delden JM, Rietjens AC, Onwuteaka-Philipsen BD, Bielsen J, Fischer S, Lfmark R, Miccinesi G, Norup M, van der Heide A, on behalf of the EURELD-Consortium (2007) J Pain Symptom Manage 34:305313
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European Journal of Pain 14 (2010) 545.e1545.e10
Contents lists available at ScienceDirect
European Journal of Pain

journal homepage: www.EuropeanJournalPain.com
Reliability study in ve languages of the translation of the pain behavioural scale Doloplus
G. Pickering a,b,c,*, S.J. Gibson d, S. Serbouti e, P. Odetti f, J. Ferraz Gonalves g, G. Gambassi h, H. Guarda i, J.P. Hamers j, D. Lussier k, F. Monacelli f, J.M. Prez-Castejn Garrote l, S.M. Zwakhalen j, D. Barneto m, Collectif Doloplus e, B. Wary e
a
CHU Clermont-Ferrand, Centre de Pharmacologie Clinique, F-63003 Clermont-Ferrand, France Inserm, CIC 501, UMR 766, F-63003 Clermont-Ferrand, France Univ. Clermont1, F-63001 Clermont-Ferrand, France d National Ageing Research Institute, Parkville, Australia e Palliative Care Unit, Regional Hospital, Metz-Thionville, France f Unit of Geriatrics, Department of Internal Medicine and Medical Specialties, University of Study, Genoa, Italy g Palliative Care Unit, Portuguese Cancer Institute, Porto, Portugal h Centro Medicina Invecchiamento, Universit Cattolica Sacro Cuore, Rome, Italy i Centro de Sade da Lapa, Lisboa, Portugal j Department of Health Care and Nursing Science, Maastricht University, The Netherlands k Division of Geriatric Medicine and Center for research on pain, Mc Gill University, Montreal, Canada l CSS Clinica Barceloneta, C/Pescadores, Barcelona, Spain m Santa Creu de Vic Hospital, Barcelona, Spain
b c
a r t i c l e
i n f o
a b s t r a c t
Non-verbal pain assessment scales are useful tools for pain evaluation in persons with communication disorders and moderatesevere dementia. The Doloplus was one of the rst scales to be developed and validated as a pain assessment tool in older adults with dementia. This study aims at evaluating the translation of the Doloplus scale in ve languages, as regards testretest and inter-rater reliability. Results show that both tests are good or excellent for the English, Italian, Portuguese and Spanish versions and moderate for the Dutch version. These results bring a unique opportunity to include the translated Doloplus scale in daily assessment of elderly persons with communication disorders, and future studies should focus on enriching the validation of the scale in each language. 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.
Article history: Received 2 June 2008 Received in revised form 10 August 2009 Accepted 10 August 2009 Available online 10 September 2009 Keywords: Pain assessment Cognitive impairment Elderly
1. Introduction Persistent pain is recognised as a very common problem in longterm aged care facilities, affecting up to 80% of residents (Roy, 1986; Parmelee et al., 1993; Gibson and Helme, 2000). Undetected or under-treated pain can have serious adverse effects on frail older adults including poorer cognitive performance, reduced quality of life, increased depression and functional disability (Gibson, 2007; Leong et al., 2007; Scherder et al., 2008). In the adult population, the group at most risk of undetected pain and poor pain manage-
^timent 3C, * Corresponding author. Address: Clinical Pharmacology Centre, Ba CHU, Hopital G Montpied, 63001 Clermont-Ferrand cedex, France. Tel.: +33 0 4 73 17 84 16; fax: +33 0 4 73 17 84 12. E-mail address: gisele.pickering@u-clermont1.fr (G. Pickering).
ment are frail older persons with communication problems, and particularly those with dementia (Pickering et al., 2000; Marzinski, 1991). There is mounting evidence to show that older adults with dementia receive less analgesic medication than cognitively intact adults, despite the presence of similar levels of disease or injury (Scherder and Bouma, 1997; Horgas and Tsai, 1998; Pickering et al., 2006; Gibson, 2007). The identication and treatment of pain depends on appropriate pain assessment and this is often a very difcult task in those with dementia. Self-report is generally recognised as the de facto gold standard for pain assessment, but verbal communication skills are often lost or compromised in those with moderatesevere dementia. Non-verbal pain assessment methods provide an alternative strategy, and may be the preferred assessment choice in cases of moderatesevere dementia (Hadjistavropoulos et al., 2007). Recent reviews of the literature catalogue more than 20 observer-rated behavioural pain assessment tools that have
1090-3801/$36.00 2009 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ejpain.2009.08.004
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been developed for specic use in older persons with dementia. A few of the most researched alternate measures are: Abbey Pain Scale (Abbey et al., 2004), Checklist of Non-verbal Pain Indicators (Feldt, 2000), Discomfort in Dementia of the Alzheimers type (Hurley et al., 1992), Non-Communicative Patients Pain Assessment Instrument (Snow et al., 2004), Pain Assessment Checklist for Seniors with Limited Ability to Communicate (Fuchs-Lacelle and Hadjistavropoulos, 2004), Pain Assessment in the Dementing Elderly (Villanueva et al., 2003), Pain Assessment In Advanced Dementia (Warden et al., 2003) and the Doloplus (Wary et al., 2001). The French version of the Doloplus behaviour rating scale was one of the rst scales to be developed in older adults with dementia (Wary and Collectif, 1999) and has been validated in a group of 510 residents (Lefevre-Chapiro and Collectif, 2001; Wary et al., 2001). Validation of the French version of the Doloplus scale included testretest reliability (Spearmans correlation coefcient is >0.75 on all items of the Doloplus scale (r = 0.750.94), inter-rater reliability (r = 0.90), internal consistency (Chronbachs alpha = 0.82) and concurrent validity (r = 0.65), when compared with self-rated pain using a visual analog scale among patients who can complete self-report measures (Lefevre-Chapiro and Collectif, 2001; Wary et al., 2001). Considering the need for reliable and valid tools for older persons with moderatesevere cognitive impairment, the aim of the current study was to examine the intra (testretest) and inter-rater reliability of the translation of the Doloplus scale into English, Dutch, Italian, Portuguese and Spanish, in a large multicultural sample of older persons with moderatesevere cognitive impairment. See Tables S1S5, see the online version at doi:10.1016/j.ejpain.2009.08. 004. 2. Method This is a multicentre study of the translated version of the Doloplus scale in ve languages. 2.1. Measures Doloplus was used to assess pain: the Doloplus scale consists of ten items, each scored on 03 point scales, ve somatic, two psychomotor and three psychosocial items. It takes only about 23 min to complete by French teams and has sufcient items to avoid missing idiosyncratic pain expressions that may be specic to pain with cognitive disorders. Prior to the study Doloplus was translated. The main difculty in the translation of scales is indeed to maintain the content equivalence of the original instrument in the translated version and there is no gold standard of translation techniques in international research. The French version of the scale has been translated from French to another language (forward translation) and the reverse (backward translation) (Cull et al., 1998; MOT, 1997). Two independent bilingual health professionals (their mother tongue is the second language) translated independently the questionnaire into their native tongue. A reconciliation meeting was conducted to obtain a consensus version. Then two native French speakers who were blinded to the original version retranslated the new scale into French. The last step of the translation procedure was the pre-testing of the translated instrument using a small sample of elderly persons with communication disorders with a nal debrieng summary including all participants. Besides pain scores, demographic information (e.g. age, gender) was gathered from all the participants and recorded on a case report form. Cognitive status of all residents was evaluated using the Mini Mental State Examination (MMSE) (Folstein et al., 1975). This test ranges from 0 to 30 points and is widely
used to screen for cognitive impairment. Efforts were made to have the MMSE assessment undertaken as close to the pain assessment as possible and while most evaluations were taken in the preceding week, in a few isolated cases the evaluation was up to 3 months old. At the end of the study, the qualitative opinion of the participating physicians concerning the acceptability of the Doloplus scale was sought with special regard to its ease of use. 2.2. Ethics committee The protocol was approved by the French Ethics Committee. When required, it was also approved by the local Ethics Committee and informed consent of the patient or surrogate consent was obtained. Informed consent was obtained by a doctor not involved in the pain evaluation. This protocol did not change the normal care of the patients and might even have improved it, as the protocol created a dynamic awareness among the staff to pain assessment in the institution where pain was systematically evaluated. 2.3. Investigators Nine teams (one for Dutch and two for each of the other languages) have been selected on the basis of their experience and competence in geriatrics and in pain evaluation of elderly patients with communication disorders. Each team tested the scale in their native language with at least 40 elderly persons. 2.4. Patients Males and females aged 65 or above, with communication disorders, with or without suspected pain, were included. Any change in behaviour (posture and movement, facial expression, prostration, loss of appetite, vocal complaint, psychological and behavioural disturbances) was also an inclusion criteria. Pain is always a potential cause of behaviour changes and even though pain might not be the most likely cause of behavioural change, it must always be considered as a potential cause in patients with dementia. The enrolment of patients without suspected pain was aimed at overcoming the misdiagnoses of pain in patients affected by dementia. Excluded from the protocol were: patients who had acute pain needing immediate pharmacological pain management (patient with any major behavioural changes, obvious sign of distress and agitation, or complaining overtly) or who had recent analgesic treatment (within the previous 4 h), or who refused to participate. Finally, we excluded patients when they were agitated and could not be observed quietly for a few minutes by the physicians of the unit in order to have an adequate scoring of the Doloplus scale. The level of agitation was assessed clinically (interference with and opposition to daily care) and/or by administration of the neuropsychiatric inventory scale (NPI with cut off >40/120). Withdrawn from the protocol were: any patient who had a change of treatment between the retest evaluations or a change of treatment between the evaluations of both practitioners, any patient who refused to participate after having given informed consent. The decision to initiate analgesics or to administer a rescue dose was essentially based on a clinical evaluation indicative of obvious pain and based on a Doloplus score >15. 2.5. Procedure Prior to the start of the study, the teams met in order to discuss the inclusion/exclusion criteria and the methodology. They were
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provided with the Doloplus video, instructions for the use of the Doloplus scale, the agreement of the French ethics committee, and the recommendation that only two physicians should be involved per team. An important recommendation was that the physicians should get fully accustomed to, and condent in, the use of the scale before starting the study. Considering the polymorphism of elderly patients, the training consisted of a number of evaluations with the help of the paper and video backups. B. Wary and the collective Doloplus team who have 10 years experience in using the Doloplus scale recommended that before starting the study, the teams should allow themselves a few days to become familiar with the scale, to include it in the clinical routine of the ward, to assess 810 elderly patients with communication disorders and to discuss collectively between all raters the Doloplus scores obtained. On the day of the study, pain assessment was implemented during the provision of the usual care in order to integrate it as much as possible to the customary routine of the unit. Selection of the patients took place on the days where both physicians were available and was done after the round by the team of the ward. At least 40 patients per team were required and were assessed twice by a trained physician (rater 1) at initial contact (t0) and again 4 h later (t4) without any treatment in between, and the same patient was assessed once by a second physician at t0 (rater 2). Observations were timed to avoid potentially painful experiences, such as movement or invasive nursing care. During the study, each physician assessed the patients by observing them for a few minutes prior to scoring the Doloplus scale. The raters were blind to each others ratings and undertook the observation and completion of the Doloplus scale in a sequential fashion. There was no discussion between the raters about the scores they obtained and no access to each others scores nor to their own previous score in the case of retest assessments (for rater 1). The assessment is easier and quicker if the investigator is familiar with the patient, especially concerning facial expressions and body movement; all physicians were familiar with the patient in our study and provided daily medical care. The test took an average of 5 min per patient to be performed. The study protocol did not disrupt nor change the normal care of the patients.
4. Results 4.1. Completion of the scales The nine teams recruited at least 40 patients each. In each of the eight teams, two physicians took all the training assessments with about eight patients. In the Dutch team, four physicians used the scale with about two patients as a pilot training exercise. In all teams, the same physicians undertook all the evaluations of the study thereafter. The assessment scales were completed in 406 patients, but due to missing data or patients being excluded because of an implemented treatment in the course of the study, statistics were undertaken on the complete data of 342 patients. Data from the 64 patients that were excluded from the study comprised: 10 patients were excluded because of severe agitation assessed clinically and through Neuro Psychiatric Inventory, 16 patients needed a treatment for acute pain and were withdrawn from the evaluation and data were not fully completed or missing in 38 subjects (9% of our population). Several les per team were not analysed, mainly because one out of the 40 items had not been lled in properly or there was a missing date of birth or MMSE score. Looking for the report of missing data in the literature on scales validation the rate of missing data is not always indicated. In CNPI scale validation, Feldt, 2000; report 8% missing data, a rate quite comparable to ours. There were no signicant differences between the settings concerning missing data and withdrawals (p value = 0.996). No patient refused to consent to participate. 4.2. Demographical data Seventy percentage women and 30% men (16% single, 25% married, 3% divorced and 56% widowed), aged 82 2 years old were included by nine teams in ve languages across six countries; Australia, Canada, Italy, Portugal, Spain and The Netherlands. Demographical data are presented in Table 1 for each of the ve languages and detail the institution where the patient lives, his/ her handicap (incapacity), age, gender and marital status. MMSE (SD) ranged from 0 to 12 for all patients: 2(4) for Dutch, 12(10) for English, 12(5) for Italian, 4(7) for Portuguese and 8(9) for Spanish settings.
3. Data analysis In each language, data collected with the scale administered by the same physician, on two occasions at 4 h intervals (t0 and t4) were used to explore the testretest reliability. A 4-h interval was chosen because it is the usual interval of time for pain assessment in clinical practice. In our study, the Doloplus scale scores at t0 were compared with their t4 scores using Student t-test. In each language, the data collected independently by two trained physicians (raters 1 and 2) were compared using Student t -test. Kappa statistics (Landis and Koch, 1977) were calculated for each item of the Doloplus scale. Kappa coefcient is a statistical measure of inter-rater reliability. It is generally thought to be a more robust measure than simple percent agreement calculation. A Kappa value higher than 0.81 typically indicates excellent inter-rater reliability, between 0.61 and 0.80 the test is good and between 0.41 and 0.60 it is moderate. Testretest and inter-rater reliabilities were evaluated with the Pearson and the Intra-class correlation coefcients: coefcients above 0.75 are considered as good to excellent. Differences between the settings concerning missing data and withdrawals have been compared with Chi square. We chose a per protocol analysis rather than an intentionto-treat (ITT) analysis of the data in order to obtain a reliable validation of the translation with only complete case report forms.
Table 1 Demographical data. Language Number of residents Institution (%) Nursing home Long-term care setting Rehabilitation Home dwelling Acute care Other Incapacity (%) Dementia Aphasia Behavioural disorders Other Age in years (SD) Male n (%) Marital status (%) Single Married Divorced Widowed Dutch 40 English 90 Italian 88 Portuguese 57 Spanish 67
100 0 0 0 0 0 100 0 0 0 80 (6.9) 7 (17.5) 3 25 5 67
52 44 0 0 3 1 81 2 1 16 84 (7.8) 30 (33) 8 36 2 54
84 0 13 0 0 3 45 37 18 0 81 (7.7) 27 (45) 19 22 5 54
65 0 0 2 0 33 44 2 26 28 84 (8.4) 9 (16) 32 24 0 44
0 78 21 0 0 1 57 18 13 12 82 (10) 26 (39) 19 28 3 50
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Table 2 (A) Testretest and inter-rater correlations of pain scores. (B) Kappa analysis of the items of the Doloplus scale. Language (A) Pain score Mean total score (SD) Rater 1 Rater 2 Retest rater 1 Pearson correlation coefcient Inter-rater Test/retest Intra-class correlation coefcient Inter-rater Test/retest (B) Kappa analysis of the Doloplus scale (Kappa values) Somatic reactions Somatic complaints Protective posture Protection of sore areas Expression Sleep patterns Psychomotor reactions Activities of daily living Mobility Psychosocial reactions Communication Social life Problems of behaviour Dutch English Italian Portuguese Spanish
5.4 (4.4) 4.1 (3.8) 4.9 (4.4) 0.75 0.57 0.75 0.62
8.3 (6.0) 8.8 (6.5) 7.9 (6.0) 0.94 0.95 0.89 0.83
12.7 (6.5) 12.7 (6.8) 12.7 (6.7) 0.97 0.98 0.97 0.98
6.1 (7.0) 6.2 (7.0) 6.0 (7.0) 0.97 0.99 0.95 0.95
6.0 (4.9) 6.3 (4.6) 6.0 (4.9) 0.92 0.96 0.84 0.83
0.19 0.31 0.35 0.4 1 0.56 0.5 0.47 0.43 0.25
0.67 0.51 0.56 0.62 0.84 0.79 0.75 0.68 0.62 0.59
0.81 0.96 0.95 0.91 0.79 0.84 0.93 0.85 0.96 0.92
0.66 0.75 0.68 0.82 0.68 0.82 0.72 0.75 0.65 0.81
0.62 0.87 0.59 0.53 0.58 0.47 0.61 0.85 0.59 0.55
4.3. Pain scores comparison Mean total pain scores obtained with the Doloplus scale by raters 1 and 2, and correlations across languages are presented in Table 2. Pearson and intra-class correlation coefcients show very good to excellent results for four languages, English, Italian, Portuguese and Spanish: the Pearson correlation coefcient ranges from 0.95 to 0.99 for testretest reliability and from 0.92 to 0.97 for inter-rater reliability; the intra-class correlation coefcient ranges from 0.83 to 0.98 for testretest reliability and from 0.84 to 0.97 for inter-rater reliability. Dutch correlations are fair to moderate, inter-rater reliability is 0.75 and testretest reliability is 0.57 (Pearson) or 0.62 (intra-class). 4.4. Kappa correlation of the scales across languages Results obtained for somatic, psychomotor and psychosocial reactions, a total of 10 items, have been correlated across languages using the Kappa test. Kappa value for each of the 10 items ranges from 0.51 to 0.84 for the English scale, 0.790.96 for the Italian scale, 0.650.82 for the Portuguese scale, and 0.470.85 for the Spanish scale. For these languages, somatic reactions (including somatic complaints, protective posture, protection of sore areas, expression and sleep patterns) range from 0.51 to 0.96; psychomotor reactions (including activities of daily living and mobility) range from 0.47 to 0.93; psychosocial reactions (including communication, social life and problems of behaviour) range from 0.55 to 0.96. Concerning the Dutch scale, there is a large heterogeneity of results ranging from 0.19 to 1. All of the participating physicians considered the scale to be easy to use once they were familiar with it. 5. Discussion The aim of the present study was to validate the translation of the Doloplus scale in ve languages, with regard to testretest
and inter-rater reliability. Results show that reliability tests and correlations are good or excellent for the English, Italian, Portuguese and Spanish versions, while the reliability correlations are fair to moderate but more heterogeneous for the Dutch scale. There are indeed discrepancies in the kappa values of the different items of the scale between the Dutch and the other language scales and a number of factors may have contributed to this discrepancy. It is very unlikely that the ndings are linked to the translation itself as all ve translations have been similarly carried out using the same method. The participation of only one team and training being performed on a lesser number of residents may be potential factors. Another reason might be linked to differences in the samples under study within each language group, but our sample is too small to relate the ndings to the specic type of institution, the level of incapacity, the severity of cognitive impairment or cultural impacts on facial or body expression of pain. Although we should be careful with the interpretation of the results of Table 2, the lowest kappa values were obtained when the total scores were lowest. Hence the Italian scale demonstrates highest mean pain scores with highest kappa values, while the Dutch sample had the lowest total score and lowest kappa values. This would suggest that the Doloplus scale might display better reliability in cases where pain is present and a lower inter-rater agreement with lower pain scores or with more severe dementia. This novel nding needs to be addressed in a larger, more heterogeneous sample as the current results are limited to raters who are familiar with their patients and limited to participants who are not agitated and do not have severe acute pain. Increasing the size of the sample in future studies would help remove these concerns and strengthen the widespread use of Doloplus. Also, this scale has never been validated in agitated patients and the study of Doloplus in this population would be an important topic for further research. There are important issues requiring further investigation in the near future. First, sensitivity of the scales must be studied with respect to the identication of pain in each language. Specicity of each scale in differentiating pain from other types of emotion or distress must also be sought, as well as internal consistency and
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congruency. Socio-cultural factors should be considered and this applies especially to Latin American Spanish and Portuguese populations, although potential linguistic adaptations of the Doloplus scale appear to be minor. Several projects in Anglo-Saxon and American English or South American Spanish and Portuguese languages are in preparation for these adaptations of the scale and other reliability studies are being completed, including, German, Chinese, Japanese, Arabic and Czech. Although the participating physicians considered the scale to be easy to use once familiar with the tool, their opinion should be sought with a standardized evaluation in future studies. The opinion of nurses, physical therapists, psychologists and more generally of health care professionals taking care of elderly patients with dementia and communication disorders will also be important to collect. Indeed Doloplus has been rated by Dutch nurses as being the least useful of the scales when examined in a comparative study (Zwakhalen et al., 2006), while in France, the Doloplus scale is now included in the Ministry of Health ofcial guidelines for pain evaluation of persons with communication disorders and dementia (called Mobiqual). Indeed, it is present in the package for pain evaluation in the elderly that is distributed to health care professionals of all nursing homes to raise awareness of the need for systematic pain evaluation especially when communication disorders are present. The reliability testing of the English, Italian, Portuguese and Spanish translations of the Doloplus scale allows a unique opportunity to include this scale in the daily pain assessment and in studies concerning elderly persons with communication disorders. Compared to other scales, the strong psychometric properties of the Doloplus have already been acknowledged and it has been recommended as the preferred choice among the scales that are currently available. Herr et al. (2006) describe the Doloplus as comprehensive, covering ve of the six behaviour categories proposed by the American Geriatrics Society. The scale was also considered to be clear, requiring a short time to be administered but was lacking validation in languages other than French. In a recent study (Zwakhalen et al., 2006), similar issues were recognized, namely, satisfactory stability on retest, good correlation with visual analog scale test, good levels of internal consistency. A commonly recognized pitfall has always been the lack of adequate information on parameters of validity like inter-rater and testretest reliability, in languages other than French. Finally, the Doloplus scale is cited, but not thoroughly examined, by the (Stolee et al., 2007) review because reliability and validity data are missing. Our study provides evidence that the Doloplus scale is a reliable and easy to use instrument but the validity of the scale must be assessed in larger samples in order to undertake a full construct validation in each language. Furthermore, the follow-up of a larger sample would add greater condence in the psychometric properties of the behavioural pain assessment scales in each language. Future studies should also focus on improving the scale in each language, in order to optimize pain evaluation in the population of elderly persons with communication disorders, since these scales are intended for use in this highly dependent and vulnerable group. Acknowledgements The Doloplus team thanks all the persons who participated in this study, patients and staff of the nursing homes. We wish to thank Grnenthal-France Laboratories who have generously
helped and supported all the steps of this study. There are no conicts of interest. References
Abbey J, Piller N, Bellis de A, Esterman A, Parker D, Giles L, et al. The Abbey pain scale: a 1-min numerical indicator for people with end stage dementia. Int J Palliat Nurs 2004;10:614. Cull A, Sprangers M, Bjordal K, Aaronson N. On behalf of the EORTC quality of life study group. EORTC quality of life study group translation procedure. Brussels: EORTC; 1998. Feldt KS. The checklist of nonverbal pain indicators. Pain Manag Nurs 2000;1:1321. Folstein MF, Folstein SE, McHugh PR. Mini-mental state: a practical method for grading the cognitive state of patients for the clinician. J Psychiatric Res 1975;12:18998. Fuchs-Lacelle S, Hadjistavropoulos HD. Development and preliminary validation of the pain assessment checklist for seniors with limited ability to communicate (PACSLAC). Pain Manag Nurs 2004;1:3749. Gibson SJ, Helme RD. Cognitive factors and the experience of pain and suffering in older persons. Pain 2000;85(3):37583. Gibson SJ. IASP global year against pain in older persons: highlighting the current status and future perspectives in geriatric pain. Expert Rev Neurother 2007;7(6):62735. Hadjistavropoulos T, Herr K, Turk DC, Fine PG, Dworkin RH, Helme R, et al. An interdisciplinary expert consensus statement on assessment of pain in older persons. Clin J Pain 2007;23(Suppl. 1):S143. Herr K, Bjoro K, Decker S. Tools for assessment of pain in nonverbal older adults with dementia: a state-of-the-science review. J Pain Symptom Manage 2006;31(2):17092. Horgas AL, Tsai PF. Analgesic drug prescription and use in cognitively impaired nursing home residents. Nurs Res 1998;47(4):23542. Hurley AC, Volicer BJ, Hanrahan PA, Houde S, Volicer L. Assessment of discomfort in advanced Alzheimer patients. RINAH 1992;15:36977. Landis JR, Koch GG. A one-way components of variance model for categorical data. Biometrics 1977;33:6719. Lefevre-Chapiro S, Collectif Doloplus. The Doloplus scale evaluating pain in the elderly. Eur J Pall Care 2001;8(5):1913. Leong IY, Farrell MJ, Helme RD, Gibson SJ. The relationship between medical comorbidity and self-rated pain, mood disturbance, and function in older people with chronic pain. J Gerontol A Biol Sci Med Sci 2007;62(5):5505. Marzinski LR. The tragedy of dementia: clinically assessing pain in the confused nonverbal elderly. J Gerontol Nurs 1991;17(6):258. Medical Outcomes Trust. Trust introduces new translation criteria. Trust Bull 1997;5:14. Parmelee PA, Smith B, Katz IR. Pain complaints and cognitive status among elderly institution residents. J Am Geriatr Soc 1993;41(5):51722. Pickering G, Eschalier A, Dubray C. Pain and Alzheimers disease. Gerontology 2000;46(5):23541. Pickering G, Jourdan D, Dubray C. Acute versus chronic pain treatment in Alzheimers disease. Eur J Pain 2006;10(4):37984. Roy R. A psychosocial perspective on chronic pain and depression in the elderly. Soc Work Health Care 1986;12(2):2736. Scherder EJ, Bouma A. Is decreased use of analgesics in Alzheimer disease due to a change in the affective component of pain. Alzheimer Dis Assoc Disord 1997;11(3):1714. Scherder EJ, Eggermont L, Plooij B, Oudshoorn J, Vuijk PJ, Pickering G, et al. Relationship between chronic pain and cognition in cognitively intact older persons and in patients with Alzheimers disease. The Need to Control for Mood. Gerontology. 2008;54(1):5058. Snow AL, Weber JB, OMalley KL, Cody M, Beck C, Bruera E, et al. NOPPAIN: a nursing assistant administered pain assessment instrument for use in dementia. Dement Geriatr Cogn Disord 2004;17:2406. Stolee P, Hillier LM, Esbaugh J, Bol N, Mckellar L, Gauthier N, et al. Pain assessment in a geriatric psychiatry program. Pain Res Manag 2007;12(4):27380. Villanueva MR, Smith TL, Erickson JS, Lee AC, Singer CM. Pain assessment for the dementing elderly (PADE): reliability and validity of a new measure. J Am Med Dir Assoc 2003;4:18. Warden V, Hurley AC, Volicer L. Development and psychometric evaluation of the pain assessment in advanced dementia (PAINAD) scale. J Am Med Dir Assoc 2003;4:915. Wary B, Collectif Doloplus. Doloplus, une chelle pour valuer la douleur. Soins Grontologie 1999;19:257. Wary B, Serbouti S, Collectif Doloplus. Doloplus 2. Validation dune chelle dvaluation comportementale de la douleur chez la personne ge. Douleurs 2001:2. Zwakhalen SM, Hamers JP, Berger MP. The psychometric quality and clinical usefulness of three pain assessment tools for elderly people with dementia. Pain 2006;126(13):21020.
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545.e6 Table S1 English version of the Doloplus2 scale.
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545.e8 Table S3 Italian version of the Doloplus2 scale.
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Thalidomide for the Control of Severe Paraneoplastic Pruritus Associated With Hodgkins Disease
Ferraz Gonc alves, MD1
American Journal of Hospice & Palliative Medicine 27(7) 486-487 The Author(s) 2010 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/1049909110362523 http://ajhpm.sagepub.com
Abstract A 22-year-old woman with nodular sclerosis type II Hodgkin lymphoma diagnosed in June 2001. She initially underwent chemotherapy with 6 cycles of ABVD (adriamycin, bleomycin, vincristine, dacarbazine) regimen, leading to clinical remission. As it relapsed, she was again treated with 2 different chemotherapy regimens. In November 2003, she underwent bone marrow autotransplantation, but it relapsed after 2 months. After that, she was treated with chemotherapy in monotherapy until November 2005. In December 2005, she was referred to palliative care. Her main symptom was very severe pruritus that interfered with all aspects of her life, making her scratch continuously and interfering in all aspects of her life. She was treated with loratadine, hydroxyzine, prednisolone, paroxetine, mirtazapine, cimetidine, and ondansetron, individually and in various combinations. She also underwent ultraviolet phototherapy. All trials failed and her pruritus remained at level 8 of 10 most of the time. In April 2006, she started on thalidomide, 200 mg at night. The pruritus significantly improved to a level of 3 of 10 but did not disappear completely. She was at last able to sleep properly at night. She remained with a low level of pruritus until her death in July 2008, at the same dose of thalidomide. Keywords Hodgkins disease, palliative care, itch, thalidomide
Clinical Case
A 22-year-old woman with nodular sclerosis type II Hodgkin lymphoma diagnosed in June 2001. She initially underwent chemotherapy with 6 cycles of ABVD (adriamycin, bleomycin, vincristine, dacarbazine) regimen, leading to clinical remission. However, it soon relapsed and she was again treated with chemotherapy: the ESHAP (etoposide, solumedrol, high-dose ara-C, cisplatin) and MOPP (mechlorethamine, oncovin, procarbazine, and prednisone) regimens. In November 2003, she underwent bone marrow autotransplantation, but it relapsed after 2 months. After that, she was treated with chemotherapy in monotherapy until November 2005. In December 2005, she was referred to palliative care. She was a young woman with a good performance status (ECOG 2). Her principal symptom was very severe pruritus that interfered with all aspects of her life, making her scratch continuously. She was unable to sleep properly due to pruritus. She would take more than 1 cold shower during the night to obtain transient relief from the pruritus. Her body was covered with lesions, many of them ulcerated. She was not jaundiced and blood tests of liver function were normal. A biopsy of a skin ulcer was compatible with scratching lesions. She was treated with loratadine, hydroxyzine, prednisolone, paroxetine, mirtazapine, cimetidine, and ondansetron, individually and in various combinations. She also underwent
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ultraviolet phototherapy. All trials failed and her pruritus remained at level 8 of 10 most of the time. She was also being treated with morphine, sodium picosulphate, zolpidem, and diazepam. In April 2006, she started on thalidomide, 200 mg at night. The pruritus significantly improved to a level of 3 of 10 but did not disappear completely. She was at last able to sleep properly at night. She remained with a low level of pruritus until her death in July 2008, at the same dose of thalidomide.
Discussion
Cutaneous manifestations of Hodgkins disease are common; most are nonspecific and can be present in over 50% of patients. The most well-recognized paraneoplastic finding is severe pruritus.1 Sometimes it is the presenting symptom of Hodgkins disease, but it is usually a sign of far advanced disease. Sometimes it persists after disease remission.2 In a
1
s de Oncologia, Porto, Portugal Instituto Portugue
Corresponding Author: s de Oncologia, UCP-R, Rua Dr. Anto nio Ferraz Gonc alves, Instituto Portugue Bernardino de Almeida, 4200-072 Porto, Portugal. Email: ferrazg@ipoporto.min-saude.pt; ferrazg@netcabo.pt
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Gonc alves few cases the pruritus of Hodgkins disease is due to liver involvement and colestasis, but this patient was not jaundiced and the blood tests on liver function were normal. Recommended treatment of pruritus related with Hodgkins disease includes palliative chemotherapy, corticosteroids, cimetidine, and mirtazapine.2 This patient underwent all these treatments and others without any benefit. Thalidomide, a drug synthesized in 1954, was used extensively as a sedative, tranquilizer, and antiemetic. Thalidomide was the cause of multiple congenital abnormalities mainly concerning the limbs when used during gestation, sometimes after only a single dose.3 Because of these effects, it was withdrawn from markets at the beginning of the 1960s. Later on, the drug proved to be effective in the treatment of erythema nodosum leprosum. Nowadays, it is used for the treatment of many diseases and symptoms, namely in advanced cancer, such as anorexia. There are very rigid rules in women with reproductive potential to prevent its use during pregnancy. The antipruritic activity of thalidomide can be secondary to the inhibition of tumor necrosis factor alpha.4 Another possibility is that its antipruritic effect results from its central depressive action.5 This nonspecific action seems more likely as thalidomide has proven to be effective in the relief of pruritus originating from very different causes. Besides teratogenicity, the major adverse effect of thalidomide is peripheral neuropathy. Other frequent adverse effects include rash, dizziness, constipation, tremor, mood changes, headache, and thromboembolism.3 This patient had none of those adverse effects. Thalidomide enhances the activity of alcohol, barbiturates, and chlorpromazine, and raises the serum levels of paracetamol, increasing its toxicity.6 Drugs that cause sedation or neuropathy should be used carefully, as well as drugs that decrease the efficacy of oral contraceptives.6 Recently, Rubinstein and Duvic found that the pruritus of Hodgkins disease is commonly associated to Staphylococcus aureus colonization and that antibiotic therapy can significantly reduce the pruritus.1 We do not know whether this patient could have benefited from antibiotic therapy because this information was not available at the time and S aureus was not detected. Korfitis and Trafalis describe 4 patients, 3 with lymphoma and 1 with multiple myeloma, with intense
487 generalized pruritus who improved with carbamazepine.7 Carbamazepine has previously been reported to alleviate pruritus associated to multiple sclerosis but not as far as I know in any other cases.4 Could carbamazepine have been a solution for this young woman? Although, thalidomide has been described in several situations as an effective drug for pruritus, this is the first time that its effect was described in Hodgkins disease, as far as I know.
Conclusion
Pruritus may be a very distressing symptom. It is relatively frequent in Hodgkin disease and sometimes its control is very difficult as it was in this young woman. In such cases, thalidomide should be considered a potentially useful alternative. Declaration of Conflicting Interests
The author(s) declared no conflicts of interest with respect to the authorship and/or publication of this article.
Funding
This work was supported in part by the North Portugal Section of the Portuguese League against Cancer.
References
1. Rubinstein M, Duvic M. Cutaneous manifestations of Hodgkins disease. Int J Dermatol. 2006;45(3):251-256. 2. Twycross R, Greaves MW, Handwerker H, et al. Itch: scratching more than the surface. QJM. 2003;96(1):7-26. 3. Franks ME, Macpherson GR, Figg WD. Thalidomide. Lancet. 2004;363(9423):1802-1811. 4. Summey BT, Yosipovitch G. Pharmacologic advances in the systemic treatment of itch. Dermatol Ther. 2005;18(4):328-332. 5. Daly BM, Shuster S. Antipruritic action of thalidomide. Acta Derm Venereol. 2000;80(1):24-25. 6. Wu JJ, Huang DB, Pang KR, Hsu S, Tyring SK. Thalidomide: dermatological indications, mechanisms of action and side effects. Br J Dermatol. 2005;153(2):254-273. 7. Korfitis C, Trafalis TD. Carbamazepine can be effective in alleviating tormenting pruritus in patients with haematological malignancy. J Pain Symptom Manage. 2008;35(6):571-572.
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ARTIGOS PUBLICADOS COMO MEMBRO DO RESEARCH STEERING COMMITTEE DA ASSOCIAO EUROPEIA DE CUIDADOS PALIATIVOS
SPECIAL ARTICLE
Strategies to Manage the Adverse Effects of Oral Morphine: An Evidence-Based Report

By Nathan Cherny, Carla Ripamonti, Jose Pereira, Carol Davis, Marie Fallon, Henry McQuay, Sebastiano Mercadante, Gavril Pasternak, and Vittorio Ventafridda for the Expert Working Group of the European Association of Palliative Care Network
Abstract: Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia. The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of denitive, evidence-based comparative data. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. This study presents evidencebased recommendations for clinical-practice formulated by an Expert Working Group of the European Association of Palliative Care (EAPC) Research Network. These recommendations highlight the need for careful evaluation to distinguish between morphine adverse effects from comorbidity, dehydration, or drug interactions, and initial consideration of dose reduction (possibly by the addition of a co analgesic). If side effects persist, the clinician should consider options of symptomatic management of the adverse effect, opioid rotation, or switching route of systemic administration. The approaches are described and guidelines are provided to aid in selecting between therapeutic options. J Clin Oncol 19:2542-2554. 2001 by American Society of Clinical Oncology.
CCORDING TO THE World Health Organization guidelines for patients with pain of moderate severity or greater, opioid analgesics are the mainstay of cancer pain management.1 For patients with moderate to severe pain, oral morphine is conventionally the opioid of choice.1 This recommendation was derived by virtue of availability, familiarity to clinicians, established effectiveness, simplicity of administration, and relative inexpensive cost. It is not based on proven therapeutic superiority over other options. Guidelines for the use of oral morphine have been presented
From the Cancer Pain and Palliative Medicine Service, Department of Oncology, Shaare Zedek Medical Center, Jerusalem, Israel; Rehabilitation and Palliative Care Division, National Cancer Institute, and Fondazione Floriani, Milan; Palliative Care Department, National Cancer Institute, Palermo, Italy; Countess Mountbatten House, Southampton; Department of Palliative Care, Western General Hospital, Edinburgh; Pain Research Department, Nufeld Department of Anaesthetics, University of Oxford, The Churchill Oxford Radcliffe Hospital, Oxford, United Kingdom; Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY; and Division of Palliative Medicine, University of Alberta, Edmonton, Canada. Submitted October 18, 2000; accepted January 30, 2001. Address reprint requests to Nathan Cherny, MBBS, FRACP, Director Cancer Pain and Palliative Medicine, Department of Oncology, Shaare Zedek Medical Center, Jerusalem, Israel; email: chernyn@netvision.net.il. 2001 by American Society of Clinical Oncology. 0732-183X/01/1909-2542
by a previous expert working group,2 and an update is in preparation. Successful pain management with opioids requires that adequate analgesia be achieved without excessive adverse effects. By these criteria, a substantial minority of patients treated with oral morphine (10% to 30%) do not have a successful outcome because of (1) excessive adverse effects, (2) inadequate analgesia, or (3) a combination of both excessive adverse effects along with inadequate analgesia.2 The management of excessive adverse effects remains a major clinical challenge. Multiple approaches have been described to address this problem. The clinical challenge of selecting the best option is enhanced by the lack of studies comparing various therapeutic approaches to manage these problems. Indeed, this aspect of opioid therapeutics has become a focus of substantial controversy. Given this situation, the Steering Committee of the European Association of Palliative Care (EAPC) Research Network felt that clinicians would benet from evidencebased clinical-practice recommendations by an Expert Working Group. A panel of experts including Carla Ripamonti (cochair), Nathan Cherny (cochair), Jose Pereira, Henry McQuay, Gavril Pasternak, Sebastiano Mercandante, Vittorio Ventafridda, Carol Davis, and Marie Fallon were invited to participate. They met in Oporto, Portugal, in February 1998, where they reviewed all the available data, discussed the evidence, and discussed what practical recommendations could be derived from it. On the basis of the
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Table 1. Gastrointestinal Common Opioid-Induced Adverse Effects Nausea Vomiting Constipation Xerostomia Urinary retention Postural hypotension Drowsiness Cognitive impairment Hallucinations Delirium Respiratory depression Myoclonus Seizure disorder Hyperalgesia Itch Sweating
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dine by blocking the depressant action of pethidine and allowing the convulsant activity of norpethidine to become manifest.7,8 If naloxone must be administered to a patient receiving pethidine, it should be diluted and slowly titrated while appropriate seizure precautions are taken. Route Related There is very limited evidence to suggest differences in adverse effects associated with specic routes of systemic administration. Compared with oral morphine administration, small studies have demonstrated less nausea and vomiting with rectal9 and subcutaneous administration.10 Three studies comparing transdermal fentanyl to oral morphine demonstrated less constipation among the patients receiving transdermal fentanyl. It is not clear as to whether this is a route- or drug-related effect.11-13 For reasons that are not well explained, there is striking interindividual variability in the sensitivity to adverse effects from morphine and other opioid drugs. Genetic variability clearly affects the sensitivity to opioid analgesia, particularly related to codeine,14,15 dihydrocodeine16 and, possibly, oxycodone,17 and it is reasonable to assume that the genetic background plays a similarly important role in the predisposition to adverse effects. Some of this variability is related to comorbidity. Aging is associated with altered pharmacokinetics particularly characterized by diminished clearance and volume of distribution. This has been well evaluated for morphine18 and fentanyl.19,20 In studies of morphine use among elderly patients with chronic cancer pain, the older patients required lower doses than their younger counterparts, but they did not exhibit an enhanced risk for opioid-induced adverse effects.21,22 Studies among patients with postoperative pain similarly found that age was a major predictor of lower morphine dose requirement.23 In patients with impaired renal function there is delayed clearance of an active metabolite of morphine, morphine-6-glucuronide.24 Anecdotally, high concentrations of morphine-6-glucuronide have been associated with toxicity25-27; however, in a prospective study of patients with opioid-induced delirium or myoclonus, no relationship to renal function was observed.28 Patients with liver disease may have decreased clearance of meperidine, pentazocine, and propoxyphene that may result in increased bioavailability and prolonged half-lives, which may result in plasma concentrations higher than normal.29,30 Regarding morphine, mild or moderate hepatic impairment has only minor impact on morphine clearance31,32; however, advanced disease may be associated with reduced elimination.33 Patient Related
Autonomic
CNS
Cutaneous
content and conclusions of that meeting, Drs Cherny and Ripamonti drafted these recommendations that have since been approved by all participating experts.
OPIOID-INDUCED ADVERSE EFFECTS
Successful opioid therapy requires that the benets of analgesia clearly outweigh treatment-related adverse effects. This implies that a detailed understanding of adverse opioid effects and the strategies used to prevent and manage them are essential skills for all involved in cancer pain management. The adverse effects that are frequently observed in patients receiving oral morphine and other opioids are summarized in Table 1.
FACTORS PREDICTIVE OF OPIOID ADVERSE EFFECTS
Overall, there is very little reproducible evidence suggesting that any one opioid agonist has a substantially better adverse effect prole than any other does. Pethidine (meperidine) is not recommended in the management of chronic cancer pain because of concerns regarding its side effect prole. Accumulation of norpethidine after repetitive dosing of pethidine can result in CNS toxicity characterized by subtle adverse mood effects, tremulousness, multifocal myoclonus and, occasionally, seizures.3,4 Although accumulation of norpethidine is most likely to affect the elderly and patients with overt renal disease, toxicity is sometimes observed in younger patients with normal renal function.5,6 The most serious toxicity associated with pethidine is norpethidine-induced seizures. Naloxone does not reverse this effect, and indeed, could theoretically precipitate seizures in patients receiving pethi-
Drug Related
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Table 2. Comorbidity That May Mimic Opioid-Induced Adverse Effects
Cause Adverse Effects
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CNS Cerebral metastases Leptomeningeal metastases Cerebrovascular event Extradural hemorrhage Metabolic Dehydration Hypercalcemia Hyponatremia Renal failure Liver failure Hypoxemia Sepsis/infection Mechanical Bowel obstruction Iatrogenic Tricyclics Benzodiazepines Antibiotics Vinca alkaloids Flutamide Corticosteroids Nonsteroidal antiinammatory drugs Chemotherapy Radiotherapy
Drowsiness, Drowsiness, Drowsiness, Drowsiness, Drowsiness, Drowsiness, Drowsiness, Drowsiness, Drowsiness, Drowsiness, Drowsiness,
cognitive cognitive cognitive cognitive cognitive cognitive cognitive cognitive cognitive cognitive cognitive
impairment, nausea, vomiting impairment, nausea, vomiting impairment impairment impairment impairment, impairment impairment, impairment, impairment impairment,
nausea, vomiting nausea, vomiting, myoclonus nausea, vomiting, myoclonus nausea, vomiting
Nausea, vomiting Drowsiness, cognitive impairment, constipation Drowsiness, cognitive impairment Nausea and vomiting Constipation Constipation Agitated delirium Nausea, drowsiness Nausea, vomiting, drowsiness, cognitive impairment Nausea, vomiting, drowsiness
Drug Interactions Patients who require opioid analgesia for chronic pain related to cancer or other chronic disorders commonly suffer from conditions requiring other medications that may increase the likelihood of adverse effects by several distinct mechanisms. Commonly, the adverse effects of the other medication may be synergistic or cumulative to those associated with opioid medications (Table 2). Drugs that may alter opioid absorption, metabolism, or clearance of opioid analgesics have recently been reviewed.34 Dose Related Among adverse effects, there is substantial variability in their dose response. A dose-response relationship is most commonly evident regarding the CNS adverse effects of sedation, cognitive impairment, hallucinations, myoclonus, and respiratory depression. Even among these, however, there is very substantial interindividual variability to many of these effects. Additionally, as tolerance develops to some effects, the spectrum of adverse effects varies with prolonged use. Commonly, patients who have had prolonged opioid exposure have a lesser tendency to develop sedation or respiratory depression, and the predominant CNS effects become the neuroexcitatory ones of delirium and myoclo-
nus. Gastrointestinal adverse effects generally have a weaker dose-response relationship. Some, like nausea and vomiting, are common with the initiation with therapy but are subsequently unpredictable with resolution among some patients and persistence among others. Constipation is virtually universal, and it demonstrates a very weak dose relationship and no tolerance over time. Opioid Initiation and Dose Escalation After the initiation of an opioid or after dose escalation some adverse effects appear transiently and spontaneously abate. This phenomenon has been well demonstrated in a prospective study on the effect of morphine dose escalation on cognitive performance.35 This study demonstrated that cognitive impairment associated with the initiation of opioid therapy or dose escalation commonly improved after 7 days. This phenomenon, although often described, has not been formally studied regarding other adverse effects such as nausea, vomiting, and delirium.
DIFFERENTIAL DIAGNOSIS
Adverse changes in patient well-being among patients receiving opioids are not always caused by the opioid. Adverse effects must be differentiated from other causes of
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for patients who cannot otherwise attain an acceptable balance between relief and side effects.42 There is great interindividual variability in the response to all adjuvant analgesics and, for most, the likelihood of benet is limited. Furthermore, many of the adjuvant analgesics have the potential to cause side effects that may be additive to the opioid-induced adverse effects that are already problematic. In evaluating the utility of an adjuvant agent in a particular patient setting, one must consider the likelihood of benet, the risk of adverse effects, the ease of administration, and patient convenience. 3. The application of a therapy targeting the cause of the pain. Specic antitumor therapies, such as radiotherapy, chemotherapy, or surgery targeting the cause of cancerrelated pain can provide substantial relief and thus lower the need for opioid analgesia. The analgesic effectiveness of radiotherapy is documented by abundant data and a favorable clinical experience in the treatment of painful bone metastases,43-45 epidural neoplasm,44 and headache attributable to cerebral metastases.46-48 In other settings, however, there is a lack of data, and the use of radiotherapy is largely anecdotal. Despite a paucity of data concerning the specic analgesic benets of chemotherapy,49,50 there is a strong clinical impression that tumor shrinkage is generally associated with relief of pain. Although there are some reports of analgesic effect even in the absence of signicant tumor shrinkage,51-53 the likelihood of a favorable effect on pain is generally related to the likelihood of tumor response. Surgery may have a role in the relief of symptoms caused by specic problems, such as obstruction of a hollow viscus,54-57 unstable bony structures,58-60 and compression of neural tissues.61-63 Bone pain may similarly be relieved by systemically administered local treatments, including bisphosphonates64,65 or radiopharmaceuticals such as strontium-89.66 4. The application of a regional anesthetic or neuroablative intervention. The results of the World Health Organization analgesic ladder validation studies suggest that 10% to 30% of patients with cancer pain do not achieve a satisfactory balance between relief and side effects using systemic pharmacotherapy alone.67-72 Anesthetic and neurosurgical techniques may reduce or eliminate the requirement for systemically administered opioids to achieve adequate analgesia. In general, regional analgesic techniques such as intraspinal opioid and local anesthetic administration or intrapleural local anesthetic administration are usually considered rst because they can achieve this end without compromising neurologic integrity. Neurodestructive procedures, however, are valuable in a small subset of patients; and some of these procedures, such as celiac plexus blockade in patients with pancreatic cancer,
comorbidity that may develop in the treated patient and from drug interactions. Common causes of comorbidity that may mimic opioid-induced adverse effects are presented in Table 2. Indeed, the appearance of a new adverse change in patient well-being that occurs in the setting of stable opioid dosing is rarely caused by the opioid alone, and an alternate explanation should be vigorously sought. Since polypharmacy is common among patients with advanced cancer, it is essential to scrutinize medication records and patient reports of drug administration to evaluate for possible drug interactions or some other drug-related explanation for the reported symptoms.
OVERVIEW OF ALTERNATIVE APPROACHES TO TREATING OPIOID ADVERSE EFFECTS
In general, four different approaches to the management of opioid adverse effects have been described: 1. Dose reduction of systemic opioid 2. Symptomatic management of the adverse effect 3. Opioid rotation (or switching) 4. Switching route of systemic administration Reducing the dose of administered opioid usually results in a reduction in dose-related adverse effects. When patients have well controlled pain, gradual reduction in the opioid dose will often result in the resolution of dose-related adverse effects while preserving adequate pain relief.36 When opioid doses cannot be reduced without the loss of pain control, reduction in dose must be accompanied by the addition of an accompanying synergistic approach. Four approaches are commonly applied: 1. The addition of a nonopioid coanalgesic. The analgesia achieved from nonopioid coanalgesics from the nonsteroidal anti-inammatory class of agents is additive and often synergistic with that achieved by opioids. This is supported from a number of prospective studies37-40 and from one retrospective drug utilization survey.41 Nonopioid coanalgesics, particularly the nonsteroidal anti-inammatory agents, have the potential to cause side effects that may be additive to the opioid-induced adverse effects that are already problematic. In evaluating the utility of one of these agents in a particular patient setting, one must consider the likelihood of benet, the risk of adverse effects, the ease of administration, and patient convenience. 2. The addition of an adjuvant analgesic that is appropriate to the pain syndrome and mechanism. Adjuvant analgesics, drugs that have a primary indication other than pain but which are analgesic in some conditions, may be combined with primary analgesics to improve the outcome Dose Reduction of Systemic Opioid
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may have a favorable enough risk:benet ratio that early treatment is warranted. The application of these approaches will be the subject for future Expert Working Group reports. In general, consideration of invasive approaches requires a word of caution. Interpretation of data regarding the use of alternative analgesic approaches and extrapolation to the presenting clinical problem requires care. The literature is characterized by the lack of uniformity in patient selection, inadequate reporting of previous analgesic therapies, inconsistencies in outcome evaluation, and paucity of long-term follow-up. Furthermore, reported outcomes in the literature may not predict the outcomes of a procedure performed on a medically ill patient by a physician who has more limited experience with the techniques involved. Symptomatic Management of the Adverse Effect Symptomatic drugs used to prevent or control opioid adverse effects are commonly employed. Most of these approaches are based on cumulative anecdotal experience. With few exceptions, the literature describing these approaches is anecdotal or expert opinion. Very few studies have prospectively evaluated efcacy, and no studies have evaluated the toxicity of these approaches over the long term. In general, this approach involves the addition of a new medication. Implicitly, polypharmacy adds to medication burden and invokes associated risks of adverse effects, drug interaction, and diminished compliance.73 Opioid Rotation (Also Called Opioid Switching or Substitution) Over the past 10 years, numerous clinicians and cancer pain services have reported successful reduction in opioid side effects by switching from the currently administered opioid to an alternative opioid.74-88 This approach has been termed opioid rotation,78,89 and it is also commonly referred to as opioid switching or opioid substitution. Using this approach, the reporting clinicians have described improvements in cognitive impairment, sedation, hallucinations, nausea, vomiting, and myoclonus. The biologic basis for the observed intraindividual variability in sensitivity to opioid analgesia and adverse effects is multifactorial. Preclinical studies show that opioids can act on different receptors or subtype receptors,78,90-99 and individual receptor proles may inuence the analgesia as well as the side effects. The genetic makeup of the individual plays and important role in analgesia for some opioids,14-16,100-103 and similar phenomena may contribute to variability in adverse-effect sensitivity. This approach requires familiarity with a range of opioid agonists and with the use of the opioid dose conversion tables when switching between opioids. It is important to
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appreciate, however, that doses calculated using such tables may not be accurate among patients tolerant to opioids. This inaccuracy is explained to some extent by the large SDs observed in many of the initial relative potency studies that formed the scientic basis for the development of these tables.104 Furthermore, the phenomenon of incomplete cross-tolerance can lead to unanticipated potency in a new agent, even when from the same general class of opioid analgesic. The use of the opioid dose conversion tables is critical to this strategy. Guidelines for switching and rotating opioids are presented in Appendix A, and a dose conversion table appears in Appendix B. While opioid rotation has the practical advantage of minimizing polypharmacy, outcomes are variable and somewhat unpredictable. While many patients will have an improved balance between analgesia and side effects, in some cases, patients may have an unimproved or worse outcome with the new agent that may necessitate a further trial of rotation or a change in therapeutic strategy. Indeed, in one prospective survey, 20% of patients needed to undergo two or more switches until a satisfactory outcome was achieved.77 Limited data indicates that some adverse effects among patients receiving oral morphine can be relieved by switching the route of admission to the subcutaneous route. In one small study, this phenomenon was reported for nausea and vomiting10; in another study, there was less constipation, drowsiness, and nausea.105
INITIAL MANAGEMENT OF THE PATIENT RECEIVING ORAL MORPHINE WHO PRESENTS WITH ADVERSE EFFECTS
Switching Route of Systemic Administration
Among the experts, there was consensus regarding the initial steps in the management of adverse effects. Distinguish Between Morphine Adverse Effects From Comorbidity or Drug Interactions
This step requires careful evaluation of the patient for factors outlined in Table 2. If present, these factors should be redressed. Metabolic disorders, dehydration, or sepsis should be treated, nonessential drugs that may be producing an adverse interaction should be discontinued. This situation requires a high level of clinical vigilance with close follow-up. Often, symptomatic measures to provide relief of the distressing symptoms will be required until improvement in patient well-being is observed. Consider Dose Reduction If the patient has good pain control, consider reducing the morphine dose. If the adverse effect is mild to moderate,
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Constipation Scope of the problem. Data from prospective studies indicates that chronic constipation is observed in 40% to 70% of patient receiving oral morphine for chronic cancer pain.9,11,13,114-121 Opioid-induced constipation can be exacerbated by metabolic alterations (diabetes, hypercalcemia, hypokalemia, uremia, hypothyroidism), dehydration, advanced age, reduced physical activity/immobility, low-uid and/or low-ber diet intake, difculty reaching the bathroom, mechanical obstruction, neurologic disorders, autonomic failure, drugs with anticholinergic action such as ondansetron, diuretics, anticonvulsants, iron, vinca alkaloids, and some antihypertensive drugs.124,125 Symptomatic management. These are no studies to indicate the superiority of one laxative over another in the management of opioid-induced constipation. Commonly, recommendations have been made on the basis of personal experience and clinical observations. These recommendations are generally unsupported by any prospective study or even systematic evaluation of retrospective data. Among the agents that have been suggested are docusate, senna, bisacodyl, phenophthalein, and lactulose. Prospective data has demonstrated efcacy of senna126 and oral naloxone.127-129 Opioid rotation. In one small series, opioid rotation of morphine to methadone resulted in a reduction in constipation.130 Switching route. Reduction in constipation was not reported in any of the studies on changes in morphine route of administration. Switching drug and route. Three recent crossover studies have demonstrated a reduced tendency to constipation among patients treated with transdermal fentanyl compared with oral morphine.11-13 Sedation Scope of the problem. Data from prospective studies indicates that sedation or drowsiness is observed in 20% to 60% of patients receiving oral morphine for chronic cancer pain.9,11,13,114-121 Symptomatic management. The data indicating the merit of amphetamine psychostimulants is limited. In a single-dose study, dextroamphetamine antagonized opioidinduced sedation and cognitive impairment in postsurgical patients.131 Several small controlled clinical trials of methylphenidate demonstrated efcacy in reducing drowsiness and confusion.132-137 Positive outcomes were also observed in a small open label study of these agents in adolescents with chronic cancer pain.138 All authors note that these agents can produce adverse effects such as hallucinations, delirium or psychosis, decreased appetite, tremor, and
this may be achieved by reducing the morphine dose by 25% to 50%. This recommendation is based on the known dose-response relationship for some opioid adverse effects such as drowsiness, delirium and myoclonus as derived from pharmacokinetic/pharmacodynamic studies106-108 and clinical observations.87,109-113 In the setting of severe adverse effects, particularly neurotoxicity, often a complete cessation of morphine will be needed to allow circulating morphine levels to fall sufciently for the adverse effects to resolve. Once resolution has occurred, consideration can be given to recommencing morphine at a lower dose or switching to an alternative opioid in accordance with the data presented below.
SPECIFIC ADVERSE EFFECTS: BEYOND THE INITIAL STEPS
Beyond these initial steps, the Expert Working Group concluded that a range of reasonable options commonly coexisted. In the sections below, the Expert Working Group summarizes the existing data regarding symptomatic management, opioid rotation, and switching the route of systemic opioid administration in the management of specic adverse effects and presents a rational approach to prudent decision making. Nausea and Vomiting Scope of the problem. Data from prospective studies indicates that chronic nausea is observed in 15% to 30% of patient receiving oral morphine for chronic cancer pain.9,11,13,114-121 Symptomatic management. These are no studies to indicate the superiority of one antiemetic over another in the management of opioid-induced nausea. Commonly, recommendations have been made on the basis of the inferred mechanism of opioid-induced nausea. These recommendations are unsupported by any prospective study or even systematic evaluation of retrospective data. Among the agents that have been suggested are metoclopramide, haloperidol, prochlorperazine, dimenhydrinate, phenothiazine, transdermal scopolamine, cisapride, ondansetron (and other 5-HT3 antagonists), and dexamethasone (and other corticosteroids). Opioid rotation. In ve reports, the prevalence and severity of nausea and vomiting were substantially reduced by switching to an alternative opioid.77,78,83,84,86 Switching route. In two small studies, the switch from oral to subcutaneous morphine produced signicantly less nausea10,105 and vomiting.10 There is conicting data regarding the effect of switching to the rectal route.9,122,123 If present, this effect is small.
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tachycardia. These drugs are contraindicated in patients with a history of psychiatric disorders and are relatively contraindicated in patients with a history of substance abuse or with paroxysmal tachyarrhythmias. Switching route. In one small study, the switch from oral to subcutaneous morphine produced signicantly less drowsiness.105 Opioid rotation. In ve reports, the prevalence and severity of drowsiness and/or sedation were substantially reduced by opioid rotation.76,78,80,84,86 Scope of the problem. Mild cognitive impairment is common after the initiation of opioid therapy or dose escalation.35,139 There is no data on the prevalence of severe opioid-induced cognitive failure or delirium. Symptomatic therapy. Neuroleptics, specically haloperidol, are most commonly recommended in the symptomatic management of patients with delirium. When associated with severe agitation, a benzodiazepine is often coadministered.140 These recommendations largely derive from the extensive experience and studies in the management of acute delirium in the medically ill.140-145 Anecdotal experience among cancer patients supports this approach.146,147 Opioid rotation. Delirium or agitated confusion was reported to improve after opioid rotation in ve retrospective series.77,78,80,85,86 In the only prospective study of its type, Maddocks et al83 switched patients who developed delirium while taking oral or subcutaneous morphine to a continuous subcutaneous infusion of oxycodone, with resolution of the delirium in eight of 13 patients. Switching route. Reduction in delirium was not reported in any of the studies on changes in morphine route of administration. Scope of the problem. Myoclonus may occur in patients on chronic opioid therapy, and it seems to be dose related in a unpredictable manner. In a small study of patients receiving more than 500 mg morphine per day, 12 of 19 had signicant myoclonus.148 A study of patients with morphine-related adverse effects indicated that the prevalence of myoclonus was threefold higher among patients receiving oral morphine than among those receiving parenteral morphine, suggesting a role of metabolite production by the liver.28 Symptomatic management. There are no prospective studies on the treatment of opioid-induced myoclonus. Consequently, current recommendations for the treatment of myoclonus are empiric and anecdotal. Agents that have been recommended include baclofen,149-151 diazepam152,153 Myoclonus Cognitive Failure
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and clonazepam,154-156 midazolam,157,158 valproic acid,155,156 and dantrolene sodium.159 Opiod rotation. Improvement in myoclonus after opioid rotation, commonly with total resolution of the symptom, is reported in ve retrospective series.77,78,84,86,87 Switching route. Reduction in myoclonus was not reported in any of the studies on changes in morphine route of administration. Scope of the problem. Data from prospective studies indicate that chronic itch is observed in 2% to 10% of patient receiving oral morphine for chronic cancer pain.9,11,13,114-121 Symptomatic management. There are no prospective studies on the treatment of opioid-induced pruritus. Consequently, current recommendations for the treatment of pruritus are empiric and anecdotal. Antihistamines are commonly recommended. Anecdotal positive experience has been reported with paroxetine.160 Opioid rotation. There are conicting data suggesting that fentanyl and oxymorphone are less likely to produce histamine release.161,162 A case where persistent morphineinduced itch resolved after switching opioid has been reported.163 Switching route. Reduction in pruritus was not reported in any of the studies on changes in morphine route of administration.
SELECTING BETWEEN THERAPEUTIC OPTIONS IN THE MANAGEMENT OF OPIOID ADVERSE EFFECTS
Pruritus
The members of the Expert Working Group concluded that there were inadequate data to formulate specic recommendations regarding the management of morphine side effects, and they recognized that even among expert clinicians there is considerable variability in individual practices. Despite this, they agreed on six factors to be taken into consideration when considering therapeutic options in the management of morphine adverse effects: 1. Convenience: Compliance with analgesic therapy is enhanced when the treatment program is simple.73 In general, polypharmacy should be minimized whenever possible. 2. Availability: Drug availability is highly variable between countries and the range of available therapeutic options strongly inuences clinical decision making. 3. Cost: Some opioid formulations, nonsteroidal antiinammatory drugs, adjuvant analgesics, and symptomatic remedies are expensive. This must be considered when budgetary constraints exist, and when insurance coverage is limited.
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5. The efcacy of switching routes of administration in management of adverse effects 6. Comparative studies randomizing patients between various approaches In summary, the following conclusions can be drawn from this study: 1. There is no sound evidence from well-designed clinical trials of the superiority of one opioid over another regarding the side effect prole and/or analgesic prole. 2. There are now numerous reports describing improvement or resolution in adverse effects from morphine after switching to an alternative opioid. Data derived from observational studies and reports of opioid rotation indicate substantial intraindividual variability in analgesic effect and propensity to adverse effects. 3. When opioid rotation is applied in the setting of unacceptable adverse effects, the selection of an alternative opioid is largely empiric. A pure opioid agonist such as oxycodone, methadone, hydromorphone, and fentanyl is recommended. The outcome is not predictable and several different agents may need to be tried sequentially. 4. Despite the presence of multiple recommendations for the symptomatic management of opioid-induced adverse effects, the level of evidence supporting specic efcacy is very low. 5. Clinical research is needed to more formally evaluate the relative merits of these approaches.
ACKNOWLEDGMENT
We wish to acknowledge the Steering Committee of the Research Network of the EAPC who have participated in review and preparation of this manuscript: Franco De Conno (Chair), Augusto Caraceni, Nathan Cherny, Carl Johan Fu rst, Jose Antonio Ferraz Gonc alves, Geoffrey Hanks, Stein Kaasa, Sebastiano Mercadante, Juan Manuel Nunez Olarte, Philippe Poulain, Lukas Radbruch, Carla Ripamonti, Friedrich Stiefel, Peter Thomas. Additionally, we acknowledge the AIRC (Italian Association for Research in Cancer), the Portuguese Association of Palliative Care, and the Portuguese League against Cancer Association for Pain Control for supporting the Expert Working Group.
4. Familiarity: Clinician bias favors the selecting of options with which the clinician has greatest familiarity and experience. Since the most familiar option may not be the best option, clinicians should be sensitive to this bias and should familiarize themselves with a range of therapeutic options, including facility with all of the opioid drugs available in their country. Of critical issue is the need to be familiar with the use of the dose conversion tables in the calculation of doses when switching between different opioids and between routes of opioid administration. 5. Availability of appropriate experience and expertise: If invasive procedures are considered, it is important to consider the availability of local expertise. The outcome of invasive techniques is very operatordependent, and outcomes reported in the literature may not predict the outcomes of a procedure performed by a physician who has more limited experience with the techniques involved. 6. Patient preference: In some situations, patients may have strong preference for an option of adding another medication or switching to an alternative monotherapy. Therapeutic options should be presented to the patient, and patient preferences should weigh into nal decision making.
DIRECTIONS FOR FUTURE RESEARCH
The Expert Working Group identied the need for prospective research using validated outcome measures of pain and adverse effects to evaluate: 1. The efcacy of opioid-sparing approaches with the use of nonopioid and adjuvant analgesics and invasive approaches, including regional drug delivery and neuroablative techniques 2. The efcacy of dose reduction in the management of adverse effects 3. The efcacy of specic strategies in the symptomatic management of adverse effects 4. The efcacy of opioid rotation in management of adverse effects
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APPENDIX A
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Guidelines for Switching and Rotating Opioids

1. Use dose conversion tables. When switching from one opioid to another in na ve patients, dose conversion tables are used to calculate the dose of the new opioid. Ensure that the table being used relates to the management of chronic pain. Tables used in acute pain management generally depict single-dosing, which cannot be applied in the chronic pain setting. In tolerant patients, the possibility of incomplete cross-tolerance makes the use of a simple conversion on the basis of dose conversion tables potentially hazardous. 2. Dose conversion tables are guidelines only. It must be noted that the values depicted in dose conversion tables are guidelines only. There exists large interindividual variability in response to various opioids, and this variability cannot be captured in these tables. Recent studies indicate a wide range of dose ratios relative to morphine. However, with the exception of methadone, current literature does not clarify the exact ranges. A suggestion, which is not supported by strong evidence, would be to decrease the dose of the new opioid by an additional 30% to 50%. This would accommodate the variability in most cases and address the phenomenon of a lack of complete cross-tolerance when switching from one opioid to another. 3. Dosing with the new opioid. The initial goal when switching opioids is to convert the patient to the new drug safely. As noted above, incomplete cross-tolerance may result in a patient who is far more sensitive to the new agent than expected. Thus, it is suggested that clinicians be conservative in their calculations when switching between opioids. It is advisable to start at doses of the new opioid lower than those predicted by the dose conversion tables, monitor patients closely during the switch-over period and titrate to clinical effect. If pain is not well controlled, the dose can be increased, whereas if the patient experiences adverse effects such as excessive somnolence, the dose may need to be titrated down. It is always better to start at a lower dose and then titrate upward than to start with a dose that is too high. Close monitoring of patients during the switch is crucial.
APPENDIX B Dose Conversion Table of Opioids in the Setting of Cancer Pain Management
Opioid Relative Equianalgesic Doses
Morphine122,123,164-166
10 mg PO: 7-10 mg PR 10 mg PO: 3-5 mg SC or IV Morphine 10 mg PO: hydromorphone 2 mg PO Hydromorphone 2 mg PO: hydromorphone 1 mg SC or IV Morphine 10 mg PO: oxycodone 7.5 mg PO Oxycodone 10 mg PO: oxycodone 5 mg SC or IV N.B.the ratio depends on the dose of previous opioid. 3 If morphine 30 mg to 90 mg PO use ratio of 4:1 (ie, morphine 30 mg is approximately equivalent to 7 mg of methadone 3 If morphine 90 to 300 mg PO use ratio of 8:1 (ie, morphine 300 mg PO is approximately equivalent to 35 mg methadone PO) 3 If morphine 300 mg PO use ratio of 12:1 (ie, morphine 400 mg PO is approximately equivalent to 35 mg methadone PO) If previous morphine dose is much higher than 300 mg, the dose ratio will be higher than 12:1 Readers are referred to tables distributed by the manufactures for dose ratios related to transdermal fentanyl. Wide ranges are noted in these tables. A dose ratio of morphine SC: fentanyl SC of 100:1 is suggested for parenteral fentanyl.
Hydromorphone74,75,167,168
Oxycodone120,166,169,170
Methadone82
Fentanyl171,172
NOTE. Doses are depicted to indicate relative potency, ie, morphine 10 mg PO is approximately equivalent in potency to hydromorphone 2 mg PO. This would give an equianalgesic dose ratio of morphine to hydromorphone of 5:1. Abbreviations: PO, oral route; SC, subcutaneous route; IV, intravenous route; PR, rectal route.
REFERENCES
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Support Care Cancer (2001) 9:477488 DOI 10.1007/s005200100244
S P E C I A L A RT I C L E
Friedrich Stiefel Maria Die Trill Alexandre Berney Juan Manuel Nunez Olarte Darius Razavi
Depression in palliative care: a pragmatic report from the Expert Working Group of the European Association for Palliative Care
Published online: 22 May 2001 Springer-Verlag 2001 Friedrich Stiefel, Maria Die Trill, Alexandre Berney, Juan Manuel Nunez Olarte, Darius Razavi, and the members of the Steering Committee of the Research Network of the European Association for Palliative Care The named authors are the invited experts who make up the Expert Working Group mentioned in the title, which is chaired by F. Stiefel and co-chaired by J. Olarte The members of the Steering Committee of the Research Network of the European Association for Palliative Care are: Franco De Conno (Chair), Augusto Caraceni, Nathan Cherny, Carl Johan Frst, Jos Antonio Ferraz Gonalves, Geoffrey Hanks, Stein Kaasa, Sebastiano Mercadente, Juan Manuel Nunez Olarte, Philippe Poulain, Lukas Radbruch, Carla Ripamonti, Friedrich Stiefel F. Stiefel () Psychiatry Service, University Hospital Lausanne, 1011 Lausanne, Switzerland e-mail: frederic.stiefel@inst.hospvd.ch Tel.: +41-21-3141090 Fax: +41-21-3141098 M.D. Trill Psycho-Oncology Unit, University General Hospital Gregorio Maranon, Madrid, Spain
A. Berney Psychiatry Service, University Hospital, Lausanne, Switzerland J.M.N. Olarte Palliative Care Service, University General Hospital Gregorio Maranon, Madrid, Spain D. Razavi Psychiatric University Clinic, Hpital St. Anne, Brussels, Belgium
Abstract Our objective in this study was to summarize the relevant knowledge on depression in palliative care and to provide a framework for clinical, scientific and educational efforts at improving its management. The Research Steering Committee (RSC) of the European Association of Palliative Care (EAPC) established an Expert Working Group (EWG) to address the issue of depression in palliative care. Each invited expert was allocated a specific topic and was asked to review the literature. These reviews were presented during the Sixth Congress of the EAPC in 1999 and then discussed in a closed meeting with members of the RSC. Based on these reviews, and the discussions that followed their presentation, a first draft of the paper was produced and circulated among the invited experts and members of the RSC who had been present at the meetings. After some debate the manuscript was revised, and a second draft was circulated, this time also to RSC members who had not attended the meetings. All persons consulted have agreed on this final version of the report. The EWG concluded that the current level of evidence did not lend itself to the development of clinical guidelines and decided to publish the results of their work as a pragmatic report. The report is divided into four sections, focusing on detection, training and nonpharmacological and phar-
macological treatment of depression in palliative care. For each of these sections, general considerations are addressed on the basis of the literature review and of clinical experience and a short description of unresolved issues and recommendations is provided. Underdetection and undertreatment of depression is a serious problem in palliative care. Training of the nonpsychiatric staff should therefore have the highest priority. A proactive, flexible and comprehensive strategy embracing clinical, scientific, and educational aspects is advocated. Keywords Depression Palliative care Detection Treatment Staff training
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Introduction
The European Association for Palliative Care (EAPC) is a multiprofessional association for persons involved in palliative care. The EAPC has specific networks for issues related to education, ethics, policy questions and research. The Research Steering Committee (RSC) of the research network of the EAPC initiates Expert Working Groups (EWG) to address specific topics, to summarize relevant knowledge, to develop recommendations, and to identify priorities for future research. So far, the topics covered by EWGs have been concerned with morphine administration [38], pain assessment tools [13], breakthrough cancer pain [65], management of bowel obstruction [83], the use of corticosteroids in palliative care [28], and strategies to manage adverse effects of oral morphine [15]. The meetings of the EWG on Depression in Palliative Care were held during the Sixth Congress of the EAPC in Geneva (2224 September 1999). In four open workshops1 the invited experts reviewed relevant aspects of depression in palliative care, with particular reference to detection, training, and nonpharmacological and pharmacological treatment. A closed meeting with the experts and members of the RSC was organized a day after the congress to discuss these topics in detail. A first version of this paper summarizing the presentations and the subsequent discussions was drafted by the Chair and circulated to the Co-Chair, the invited experts and the members of the RSC who attended the closed meeting. After revision, a second version circulated, this time also to members of the RSC who had not been able to attend the closed meeting. Only unanimous conclusions have been included in this final version, which is based as far as possible on scientific evidence. Since a large part of the knowledge on this topic is not yet supported by scientific evidence, the EWG concluded that the current level of evidence did not lend itself to the development of clinical guidelines [110]. The results of the work are therefore presented as a pragmatic report based on a literature review by the invited experts, their clinical experience, and the expertise of the members of the RSC. The literature review was provided by the experts and completed by the Chair with the aid of such conventional sources as Medline. The review cannot therefore be regarded as exhaustive. For each of the aspects specified above a summary of relevant knowledge will be presented, followed by an account of the unresolved issues and the recommendations for clinical practice and future research. The aim of the paper is to provide a framework for clinical,
1 The workshops were chaired by F. Stiefel and co-chaired by J.M. Nunez Olarte. Detection of depression in palliative care was presented by D. Razavi, Psychotherapeutic treatments by M. Die Trill, and Pharmacological treatments by A. Berney. Educational aspects was presented by D. Vuille (replacement) and then discussed by F. Stiefel
scientific and educational efforts to improve the management of depression in palliative care. Background The topic depression in palliative care was chosen by the RSC because psychiatric disorders are frequent in palliative care, often remain undetected and untreated, and add considerably to the burden of suffering on patients who are already facing severe physical and psychosocial problems [77, 94]. The RSC considered the topic psychiatric disorders in palliative care was too broad to be treated by an EWG and decided first to address a specific disorder and then utilize a similar approach for other psychiatric disorders frequently observed in palliative care. Since most of the literature on depression in palliative care is related to adult cancer patients and most of the patients in palliative care suffer from malignant diseases (WHO [112]), this paper draws largely on experience with adult cancer patients. However, there are many other diseases, such as cardiovascular, neurological, metabolic and rheumatological diseases, in which depression is also a relevant topic. The recommendations with modifications where necessary should therefore also be useful for patients with nonmalignant diseases. In addition, this first EWG on a specific psychiatric disorder in palliative care could serve as a model for other EWGs addressing psychiatric disorders of pediatric and geriatric patients. General aspects of depression in palliative care Two major paradigms exist in current clinical practice for defining depression: (1) the general phenomenon of depressive symptoms and (2) specific depressive disorders defined by diagnostic criteria [104]. While the general medical sector tends to conceptualize depression according to the former definition, a large proportion of mental health specialists conceptualize depression according to the second one [82]. These two paradigms have different implications for clinical care and treatment response. For example, antidepressant treatment has proved to be beneficial for patients with depression, but not for those with a depressive symptomatology attributable to an adjustment disorder [5]. The EWG was given a mandate to focus on major depression in palliative care and has therefore based its work on the established diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association [1], the most widely used diagnostic system (Table 1). The prevalence of depression in palliative care varies, depending on type and stage of disease, setting and population characteristics [62], and has been reported as 3.758% [11, 21, 99]. Among hospitalized cancer pa-
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479 Table 1 DSM-IV criteria of major depressive episode.a Five (or more) of the following symptomsb have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) depressed mood or (2) loss of interest or pleasure
Depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g. feels sad or empty) or observation made by others (e.g., appears tearful) Markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observations made by others) Significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day Insomnia or hypersomnia nearly every day Psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down) Fatigue or loss of energy nearly every day Feelings of worthlessness or excessive and inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick) Diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others) Recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
a Adapted from the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) (APA) b The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
The symptoms are not due to direct physiological effects of a substance or a medical condition, and are not better accounted for by bereavement
tients with significant levels of physical impairment, at least one quarter of patients with advanced disease suffer from a clinically relevant and treatable depressive illness [7, 53, 54, 75, 102]. Unfortunately, only a minority of these patients receive the necessary pharmacological treatment [53, 59, 95]. The undertreatment of depression has different reasons [5, 6]. Among them are the difficulties of physicians to talk with patients about their emotions [61], or the belief even among mental health professionals that depression is somehow inevitable in the terminally ill [25]. It is unfortunate that health care professionals and the public agree that depressive illness should be treated in the physically healthy but remain skeptical about the treatment of depression in patients with severe somatic diseases. In the palliative care setting depression and pain often coexist and influence each other. A close correlation between long periods of pain and depressive feelings has been demonstrated, a correlation that may be due to neurotransmitter changes, but also to psychological exhaustion [93]. On the other hand, pain-free periods are known to give patients new strength and to lower the incidence of mood disturbances and suicidal ideation [85]. It is very difficult to establish a diagnosis of depression in an individual suffering from unrelieved pain, and pain perception on the other hand may be influenced by depressed mood. Many of the symptoms of depression, such as sleep and appetite disturbances or loss of energy and fatigue, are also associated with unrelieved pain and disappear when analgesia is achieved [9]. Adequate treatment of pain is therefore most important in the management of depression in palliative care.
Detection of depression in palliative care

The undertreatment of depression in palliative care is closely related to the fact that depression remains undetected in a substantial number of patients [72, 99]. Some studies have found that depression remains unrecognized in more than 50% of depressed medically ill patients [56, 69]. The difficulty lies in differentiating depression from other psychiatric disorders, such as acute stress reactions or adjustment disorders and from normal reactions such as grief, or from somatic states that may mimic depression [16]. The psychiatric interview, conducted by an experienced consultation-liaison mental health professional who is familiar with patients with advanced disease, would certainly be the gold standard for detection of depression in this patient population [29, 75]. However, in most settings mental health specialists are not part of the palliative care team or their number is very limited. Detection of depression in palliative care by the treating physicians and nurses is therefore crucial. The medical staff need specific knowledge, skills and instruments to detect depression in palliative care. Training in psychiatric issues is complex, however, and various factors hamper effective educational efforts (see section on Training, below). Most scientific approaches to the problem have concentrated on the use of screening instruments to detect depression. Screening is designed to detect a given disturbance early; it picks up false-positive and false-negative cases and is not diagnostic in confirming caseness. The instrument that has been most widely utilized and evaluated in the palliative care setting is the Hospital Anxiety and Depression Scale
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(HADS) [113]. This self-report scale is especially suitable for the medically ill, since it does not include the somatic symptoms of depression, such as fatigue, pain or insomnia, which may also be caused by the illness or its treatment [60]. Several studies have concluded that the HADS is a simple, sensitive and specific tool that can be used to screen for adjustment, depressive, and anxiety disorders [37, 51, 52, 79]. However, there are several problems associated with the use of the HADS in daily clinical practice. First, the sensitivity and specificity of the instrument depends on cut-off points, which may change in different patient populations (e.g. inpatients, outpatients, young and elderly patients, patients differing in stage and type of disease) [45, 76]. Second, as with any other instrument, higher sensitivity is associated with lower specificity and higher specificity with lower sensitivity. Third, the HADS is a screening instrument for adjustment disorders with anxious and depressed mood, as well as for major depression or dysthymic and anxiety disorders. Since the types of intervention needed to treat these disorders differ, the HADS lacks a diagnostic component that would allow the diagnosis of major depression. Fourth, the HADS is an instrument based on self-report: acute stress reactions contribute to relatively high rates of false-positive results and social desirability, to false-negative results [96]. Its suitability for use as a screening instrument for depression in palliative care has therefore been called in question [35]. There are studies comparing different screening instruments [43, 45, 52], such as the HADS [113], the Zung Self-Rating Depression Scale [24], the General Health Questionnaire (GHQ) [30], and the Rotterdam Symptom Checklist (RSC) [20]. However, the aforementioned problems associated with screening remain the same. Diagnostic instruments for the detection of psychiatric disorders, including depression, also exist. The Prime MD to mention one widely used and validated instrument has been designed to diagnose six major psychiatric disorders (including depression) prevalent in primary care and consists of a one-page patient questionnaire and a structured diagnostic interview conducted by the physician [91]. This instrument has not been adapted and validated for palliative care. A two-step screening and diagnostic procedure for depression in palliative care has not yet been developed. Unresolved issues When all these difficulties associated with screening are taken into account, it becomes clear that no suitable instrument is available for the detection of depression in palliative care. Several issues therefore remain unresolved (Table 2). It remains unknown whether training in how to diagnose depression may be an alternative to the use of screening instruments or whether screening should
Table 2 Detection of depression in palliative care: unresolved issues Should efforts concentrate on screening instruments or on comprehensive, educational strategies? Are specific mental disorders or psychological distress the focus of detection? Since detection is not a one-point procedure, how should it be conceptualized longitudinally? How can somatic symptoms of depression be taken into account in a medically ill patient population? Intra- and interindividual variations in symptom thresholds, language barriers and personality traits hamper uniform detection procedures The roles of the specialized mental health professionals remain undefined
be implemented as an isolated act. It also remains unclear whether screening should focus on specific disorders, how often it should be repeated over time, and how the somatic symptoms of depression should be taken into account. In addition, the screening of patients who are unable to communicate because of language barriers, personality traits or severe depressive states also remains an unresolved problem. The inter- and intraindividual variations in the threshold of psychological suffering and adaptation make it impossible to conceive of screening as a one-point procedure [78, 79]. Finally, the roles of the specialist nurse clinician [102] and of the consultation-liaison mental health professional have to be defined. In one study only 3 out of 106 patients receiving antidepressants were referred to mental health specialists [53]. Several other factors affect the diagnosis of depression. Among them are the diagnostic criteria: if diagnostic criteria differ, prevalence rates will of necessity also differ [47]. The same holds true for symptom severity thresholds, which may differ depending on instruments and clinical judgments [107]. In addition, inclusion and exclusion of somatic symptoms of depression or their substitution with psychological symptoms affect diagnosis prevalence rates. A flexible approach could be to exclude physical symptoms in the diagnosis of depression if they are probably due to physical disease or its treatment and to include them if they are more likely to be part of the depressive symptomatology [8]. Recommendations As mentioned above, empirical studies addressing these questions are lacking; the following recommendations are therefore based on the clinical experience of the EWG and the literature (Table 3). Since palliative care settings vary widely with regard to patients and health care delivery characteristics, recommendations for the detection of depression also vary. For example, ambula-
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481 Table 3 Detection of depression in palliative care: recommendations The setting (patient and care delivery characteristics) should influence detection strategies; flexibility is most important The wait-and-see policy should be replaced by a proactive strategy characterized by trial and error Implementation of screening should be complemented by training and a comprehensive management strategy Close collaboration with specialized mental health professionals from consultation-liaison psychiatry is mandatory Comparison of different strategies should be the focus of future research Referral policy to mental health professionals should be defined depending on the local circumstances
tory patients would have to be screened with different threshold levels than would inpatients, and any referral policy will depend on existing resources in terms of mental health specialists. Nevertheless, the current policy of wait and see should be replaced by a proactive clinical, scientific and educational strategy characterized rather by trial and error. All screening procedures should be complemented by staff training and by close cooperation with consultation-liaison psychiatry. Consultation-liaison psychiatry services are usually staffed by mental health specialists from different professional backgrounds, such as psychiatry, psychology, nursing and social work. With regard to future research, comparison of different strategies should be favored, for example, implementation of screening or diagnostic instruments versus training in clinical judgement. Definition of local referral policies is also recommended.
Staff training
The assessment and treatment of psychiatric disorders depend on the ability to address sensitive issues, such as emotional states, illness representations, and relationships, which it may be difficult to ask about in patients with advanced disease. The highest levels of agreement between patients self-reported depressive symptoms and staff members perceptions are found when patients report few or no depressive symptoms, with only 14% concordance in the severe ranges of depression [64]. These results are similar to those of studies on the correlations between patients and health care professionals in their perception of pain [93], illustrating that adequate assessment is based on communication and not on intuition alone. Communication, on the other hand, is not just a natural gift, but can be influenced and improved by training [26, 58, 80]. Other important aspects of training are related to staff members knowledge about how to diagnose depression, how to identify underlying etiolo-
gies, including organic factors, and how to differentiate depression from normal and other pathologic states. While the link between diagnosis and treatment of depression may seem obvious, clinical experience and scientific evidence from noncancer populations indicate that less than a quarter of diagnosed depressed patients receive effective treatment [3, 67]. In advanced disease this percentage is probably even lower, since the reluctance to prescribe antidepressants seems to be even greater in such patients [53]. Finally, monitoring of treatment and its adverse effects is often neglected and delays the reaction (changes of treatment modalities) to nonresponsiveness. In summary, many different factors hamper effective management of depression in palliative care and make training of the staff necessary. They can be identified as recognition barriers, diagnostic barriers, and treatment barriers related to patients, physicians, or health care system characteristics [31]. Up to now, only a few projects and studies have addressed the issue of training in the management of depression for nonpsychiatric health professionals [72]. While physicians seem to be aware of their need for improvement in diagnosing depression, effective strategies are difficult to design and to evaluate [36]. In a randomized study, a brief educational intervention did not significantly improve residents ability to detect depressed patients; nevertheless it had changed the residents attitudes and knowledge relevant to the care of depressed patients by the time they were followed up 6 months later [50]. In another randomized controlled trial, the training of specialist nurses led to a six-fold improvement in their ability to recognize patients with depression compared with nurses who had not had the training; the psychiatric referral rate increased five times, with a three- to four-fold reduction in the incidence of depression in the intervention group [58]. However, the accumulating load on specialist nurses and the tendency to delegate psychological care are major disadvantages of such models. It has also been demonstrated that specific interviewing behaviors, such as posing open-ended questions, periodically summarizing the information supplied by the patient, and responding to nonverbal and emotional cues, led to greater recognition of depression [2, 84]. These findings support the view that training in communication skills promoting such an interview behavior is important. In the Groningen Primary Care Study recognition of psychological disorders was not associated with better patient outcome; the authors concluded that recognition was necessary, but not sufficient, unless primary care physicians had the skills to provide appropriate treatment [100]. This view has been supported by other studies [31, 48]. Comprehensive strategies are therefore needed, and the provision of an antidepressant algorithm [18] or of diagnostic criteria alone seems not to be sufficient. First studies investigating comprehensive educational strategies designed to improve detection and treatment of depression in the physi-
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cally ill are currently under way [72, 73]. Such comprehensive strategies should also define referral policies for mental health staff by outlining the limits of nonpsychiatric competence. If staff members encounter difficult cases, for example if there is diagnostic uncertainty, suicidality, an important psychiatric comorbidity or unresponsiveness to treatment, referral to specialized mental health professionals should be the rule [6]. Unresolved issues Unresolved issues in staff training are listed in Table 4 and include the following. First, the lack of trained mental health specialists who are interested in palliative care remains a serious problem, especially with regard to training. Historically, psychiatry and somatic medicine have developed separately, and the emergence of psychiatric liaison services in general hospitals is relatively recent. Such services exist mainly in large hospitals and those affiliated to universities [109]. This lack of mental health specialists hampers educational efforts despite the strong support for interdisciplinarity within the palliative care movement. Second, even in settings where mental health specialists are part of the palliative care team, the choice of training strategies for the detection and management of depression are based on personal preferences and skills. Working with personal preferences may involve such advantages as increased motivation of the trainer, but they may not meet the needs of the staff, in which case they will be ineffective. Finally, the question remains whether patients, family members, nurses, physicians or other team members should be the target of training interventions. It also has to be determined whether communication skills, diagnostic skills or prescription behavior should be their main focus of these interventions. Such studies are difficult to conduct, since they involve both health care professionals and patients and outcomes are influenced by a variety of confounding variables. Recommendations Based on the studies reviewed and on clinical experience, the transfer of knowledge (e.g. of diagnostic criteria) alone may be a necessary but not a sufficient condition of improvement in the management of depression in palliative care. Other important training aspects concern the staffs ability to develop appropriate communication skills. The EWG therefore recommends complementing the transfer of knowledge with training in communication skills. Such training courses have proved to be effective if their duration and content are adapted to the type of work performed and if they are consolidated over time [80]. Finally, the EWG recommends that future research should focus on the evaluation and comparison of
Table 4 Staff training in the management of depression in palliative care: unresolved issues How should the transfer of knowledge be organized given the lack of mental health professionals working in palliative care? What are the most effective strategies for the training of nonpsychiatric staff? Who should be the main target of training interventions and what should be their main focus? Table 5 Staff training in the management of depression in palliative care: recommendations Transfer of knowledge is a necessary, but not sufficient, element Education should also include training in communication skills Future research should compare different educational interventions
different, comprehensive training interventions. Again, close collaboration with specialized mental health professionals from consultation-liaison psychiatry (CL-Psychiatry) is especially crucial (Table 5).
Nonpharmacological treatments
Prior to the discussion of treatment, the issue of prevention will be addressed. Since depression is associated with different factors, such as psychological and physical symptom distress, ineffective coping styles, and poor social support [17, 24, 37, 46, 70], preventive interventions could possibly have an impact. Up to now such attempts have not been very successful. In nontargeted interventions, a reduction in depression scores for patients in psychoeducational groups was achieved; the reduction did not seem to be clinically significant [27]. The same holds true for other interventions, which failed to reduce the incidence of depression [12, 32, 105, 111]. In order to have an impact, preventive interventions will most probably have to be targeted at patients at risk. Treatment of depression should not be restricted to the prescription of a psychotropic medication. The empathy and support of significant others and of the medical team are as important as the psychopharmacological treatment [33, 77]. In addition to basic but very important nonspecific therapeutic interventions, such as support and information, specific psychotherapeutic interventions have been proposed for the treatment of depression in patients with severe and life-threatening diseases [19, 27, 89, 90]. However, only in a few studies on psychotherapy in the medically ill has the methodology been comprehensively described. Information on such important aspects as how randomization was achieved or how sample size, power and confidence intervals were calculated is most often lacking [23]. It is difficult to compare these studies, since timing and duration of interventions
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vary, description of the practitioners providing the interventions is lacking, and study samples and outcome measures differ. Despite these difficulties, a recent metaanalysis of 30 trials of psychological interventions in depressed patients with cancer (10 trials were excluded because of missing data) demonstrated that interventions targeted at patients at risk or with significant psychological distress were associated with clinically powerful effects; group therapy was found to be more effective than individual therapy [87]. Most of the studies demonstrating the efficacy of psychotherapeutic techniques in depressed patients with cancer are based on group formats and cognitive-behavioral, time-limited models that have emphasized coping strategies, psychological strengths, personal control, relaxation training and cognitive restructuring [19, 27, 89, 90]. Some psychotherapeutic models have combined structured cognitive behavioral techniques with an existential approach [89], while others have reported the efficacy of a treatment package combining behavioral and pharmacological therapies [40]. Even though structured treatments have proved to be more effective in the reduction of depression than nonstructured treatments [68], clinical experience suggests that more psychodynamically oriented treatments may also be beneficial in the palliative care setting [33]. Unresolved issues Before we can rely exclusively on scientific evidence when implementing psychotherapeutic programs in palliative care, the following issues need to be considered (Table 6). First, preventive interventions cannot yet be conceptualized. Second, it is necessary to ask whether the quantitative approaches used for the scientific evaluation of psychotherapeutic interventions are optimal for studying the complex topic of psychotherapy with patients who are facing the highly individual and existential issues of life and death. Outcome measures of depression that define the success of a given intervention in palliative care have yet to be defined. Third, it remains unknown whether psychotherapeutic interventions, such as group therapies and structured treatments implemented by trained counsellors that have been empirically tested, are beneficial for the majority of patients or whether they should be used in selected populations in specific clinical and cultural embeddings [19]. Fourth, a final interesting question concerns the key elements of psychotherapeutic interventions. It is well known from psychotherapeutic research that many nonspecific factors common to different interventions, such as empathy, providing information and support, and mutual emotional involvement, are key elements of psychotherapeutic progress [44, 86, 92]. Given all the reasons described above and the complexity of the palliative care patients, highly
Table 6 Nonpharmacological treatment of depression in palliative care: unresolved issues Preventive interventions will have to be targeted, but the profile of patients at risk for depression remains unknown Many methodological aspects (e.g., concerning outcome) of psychotherapeutic intervention studies, are still controversial, and many of the studies in the palliative care setting have methodological flaws Efficacy of psychotherapeutic interventions has been demonstrated, but effectiveness studies are still lacking Nonspecific elements of psychotherapeutic interventions, such as empathy, favoring emotional expression and information are known to be beneficial, yet remain to be evaluated Table 7 Nonpharmacological treatment of depression in palliative care: recommendations Implementation of psychological treatments should be based on clinical and scientific evidence at this point in time Training of nonpsychiatric staff (see recommendations for training) is currently the most effective strategy to improve the situation of the depressed patient in palliative care Future research should focus on effectiveness studies and the unspecific therapeutic elements that can be offered by nonpsychiatric staff Psychotherapeutic efforts should also include the patients significant others
structured treatment modalities have to be regarded with caution despite the empirical evidence of their usefulness [97]. Recommendations It is suggested that at this point in time, the implementation of psychological treatment should not be based on scientific evidence alone, and both highly structured psychotherapeutic treatments and other treatment modalities for which there is clinical although not yet empirical evidence of effectiveness can be recommended. In view of the persisting lack of mental health professionals working in palliative care, training of the nonpsychiatric staff is currently the most effective strategy to improve nonpharmacological treatment of the depressed patient with advanced disease. The above-mentioned training in communication skills is a basic requirement in reaching this goal; however, it is only one element in improving the psychological care of the depressed patient in palliative care. Future research should focus on the effectiveness and role of nonspecific elements of the psychotherapeutic process. Owing to the high levels of depression in significant others of patients in palliative care [39], they too, should benefit from these efforts (Table 7).
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Psychopharmacological treatment
In most cases, management of major depression also involves pharmacological treatment. There has been considerable progress in the development of new antidepressants with a more favorable side effect profile facilitating their use in the medically ill and the elderly [5, 66]. Despite these developments, clinical utilization of these substances remains stable over time and is restricted to a small minority of patients with advanced disease [95]. A recent study on the prescription of antidepressant medication in palliative care found that only 10% of the patients admitted to a palliative care inpatient unit were treated with an antidepressant. In the majority of cases, the medication was initiated during the final 2 weeks of life, consequently leaving insufficient time for the medication to have any therapeutic effect [53]. Barriers to the use of antidepressants derive from the patient (e.g., lack of compliance, fear of side effects) or from the physician (e.g., lack of training, unfamiliarity with these substances) [49]. Thus, there is a considerable gap between the progress in the development of newer antidepressants and their utilization. Even when the diagnosis of depression has been established and initiation of psychopharmacological treatment seems obvious, less than a quarter of depressed psychiatric patients receive effective treatment [31, 67]. It is difficult to imagine that the situation in the palliative care setting is any better. Although there are many reports on the efficacy of antidepressants in depressed patients with advanced somatic disease, only a few controlled studies have been conducted [5]. These placebo-controlled double-blind studies support the clinical experience indicating that these substances improve depressive symptoms and quality of life [41, 81, 103]. If such treatment is indicated, these medications should be prescribed in a dose that guarantees therapeutic efficacy (therapeutic range). Medications should be changed if there is no appropriate response after a 2- to 3-week treatment period with a therapeutic dosage [5]. After resolution of the depressive state, they should be continued for at least 46 months and slowly tapered [88]. The era of antidepressants started with agents with effects on multiple receptor systems, then progressed to selective agents with single pharmacological mechanisms, and we now have drugs that again offer multiple receptor actions but also selective mechanisms, reducing side effects while maintaining clinical efficacy [5]. Because older and newer antidepressants are equally efficacious [88, 106], both adverse effect profiles and pharmacological properties (half-life, interactions, accumulation in hepatic and renal impairment) should determine the one selected. The newer (serotoninergic) agents have fewer side effects; some of them are available in liquid forms for patients with difficulties in swallowing and can be considered as first-line treatment in the presence of med-
ical illness [4]. Tricyclics or tetracyclics (mianserin) may still be useful, for example in patients with concomitant insomnia and neuropathic pain [57]. The reader is reminded that tricyclic agents have anticholinergic and antihistaminic properties and should therefore be used with caution in the elderly, in patients with advanced or cardiovascular disease, and in those also being treated with opiates [8]. Different tricyclics and serotoninergic agents are significant inhibitors of the isoenzyme CYP2D6 [101], which catalyzes the conversion of codeine into morphine, and thus may almost completely abolish its analgesic action [22]. There has been a recent interest in phytotherapeutic agents (hypericum extracts) for depression of moderate intensity [74]; no studies have yet been conducted with these substances in palliative care. Finally, mirtazepine, one of the newest agents with both serotoninergic and noradrenergic actions, seems to be well tolerated in the elderly [34], but again has not been studied in the palliative care setting. Amphetamines (psychostimulants) have also been used for the treatment of depression in palliative care. They are known to improve arousal, energy, ability to concentrate and depressive symptoms [42]. They have a rapid onset of action (within 2 days) and may therefore be useful for patients with limited survival [71]. Several open trials and also randomized double-blind placebocontrolled studies in depressed medically ill patients have led to the conclusion that amphetamines are effective in relieving depressive symptoms, especially in adjustment disorders (but also major depression) and in women [42, 55, 108]. They should not be prescribed to agitated or anxious patients [10, 42]. During the latent period before antidepressants take effect, alternative treatments with benzodiazepines [40, 98] and neuroleptics [63] may also be considered, especially for patients in the terminal phase of their life. Unresolved issues Some of the unresolved issues are listed in Table 8. Studies comparing different classes of medications for different clinical situations, such as for rapid relief of symptoms or rapid onset of action until antidepressant treatment is effective, are still lacking, and clinical experiences remain somehow controversial. Such studies with higher numbers of patients would be of great importance, but are not easy to conduct because of recruitment difficulties, drop-outs and intercurrent disease and treatment variables [41]. Finally, various factors hampering effective psychopharmacological treatment remain unknown.
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485 Table 8 Psychopharmacological treatment of depression in palliative care: unresolved issues Effectiveness studies comparing different agents are still lacking The value of alternative substances, such as amphetamines, for patients with limited survival times remains unknown A variety of patient-, physician- and health care-related factors hamper effective pharmacological treatment; yet they have not been identified and targeted in intervention studies Table 9 Psychopharmacological treatment of depression in palliative care: recommendations Antidepressants should be utilized without delay once the diagnosis of major depression has been established Until effectiveness or if survival time is very limited, amphetamines, benzodiazepines and neuroleptics should be considered Strategies to improve pharmacological treatment should not be conceptualized separately, but should be part of an comprehensive management strategy Future research should attempt to identify and target factors that hamper effective pharmacological treatment Table 10 Conclusions Undertreatment and underdetection of depression in palliative care remains a major problem impairing the quality of life of the patients and their significant others A proactive and comprehensive approach should be favored. Such an approach addresses detection and treatment of depression in palliative care and training, and consists in clinical, scientific and educational strategies A flexible approach should be adopted to the implementation of general guidelines, depending on the setting Close collaboration with specialized mental health professionals is highly recommended Clinical experience and scientific evidence should be considered when psychological treatment modalities are implemented Studies evaluating different comprehensive approaches should be initiated
Conclusions
Depression in palliative care is a most complex topic, being associated with many unresolved issues as well as a lack of scientific evidence. The major problem remains the underdetection and undertreatment of the disorder, both of which are related to a variety of different factors, only some of which have been identified (Table 10). A proactive approach to this problem should include clinical, scientific and educational aspects and address detection and treatment of depression in palliative care in a comprehensive manner. Such an approach would overcome the shortcomings of isolated actions, which lose their impact in targeting the individual levels of the problem separately. In order to achieve these objectives, interdisciplinary cooperation with specialized mental health professionals from consultation-liaison psychiatry and psychooncology will be necessary.
Acknowledgment The authors wish to thank Heidi Blumhuber for her help in organizing this expert working group and for her continuous support of the Research Network of the European Association for Palliative Care.
Recommendations There is enough clinical and scientific evidence to justify exploiting the benefit of these medications, even in a terminal stage of disease (see Table 9) [14]. Medication should be started without delay, like any other therapy aimed at symptom control. In patients with limited life expectancy, amphetamines may be considered. For the relief of suffering until antidepressants are effective and in anxious and depressed patients, benzodiazepines and neuroleptics may also be useful. Strategies to improve pharmacological treatment cannot be conceptualized separately, but should be part of a comprehensive management strategy based on a proactive but thoughtful approach with due consideration for all aspects of depression in palliative care. Future research should focus on interventions directed at barriers that hamper adequate prescription of antidepressants.
References
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Vol. 23 No. 3 March 2002
Journal of Pain and Symptom Management 239
Special Article
Pain Measurement Tools and Methods in Clinical Research in Palliative Care: Recommendations of an Expert Working Group of the European Association of Palliative Care
Augusto Caraceni, MD, Nathan Cherny, MBBS, FRACP, Robin Fainsinger, MD, Stein Kaasa, MD, Philippe Poulain, MD, Lukas Radbruch, MD, Franco De Conno, MD, and the Steering Committee of the EAPC Research Network
Rehabilitation and Palliative Care Unit (A.C., F.D.C.), National Cancer Institute of Milan, Milan, Italy; Pain & Palliative Medicine Service (N.C.), Shaare Zedek Medical Center, Jerusalem, Israel; Palliative Care Program (R.F.), Royal Alexandra Hospital, Edmonton, Alberta, Canada; Palliative Medicine Unit (S.K.), University Hospital of Trondheim, Trondheim, Norway; Analgesia Consult Service (P.P.), Institut Gustave-Roussy, Paris, France; and Anesthesiology Clinic (L.R.), University of Cologne, Cologne, Germany
Abstract An Expert Working Group was convened under the auspices of the Steering Committee of the Research Network of the European Association of Palliative Care to review the status of the use of pain measurement tools (PMTs) in palliative care research conducted in a multilingualmulticenter setting. Based on a literature review and on the experts opinion, the present work recommends that standardized methods should be applied for the use of PMTs in research in palliative care. Visual analogue scales, numerical rating scales, and verbal rating scales are considered valid to assess pain intensity in clinical trials and in other types of studies. Among the multidimensional questionnaires designed to assess pain, the McGill Pain Questionnaire and Brief Pain Inventory are valid in many multilingual versions. Specic recommendations for PMT use and administration, depending on the study type and aim, are reviewed. Special population requirements specic of clinical situations encountered in palliative care (elderly, terminal, cognitively impaired patients, pediatric patients) are also considered. J Pain Symptom Manage 2002;23:239255. U.S. Cancer Pain Relief Committee, 2002. Key Words Palliative care, pain, pain measurement, clinical trials
Introduction
Address reprint requests to: Augusto Caraceni, MD, Neurology Unit, Rehabilitation and Palliative Care Unit, National Cancer Institute of Milan, via Venezian 1, 20133 Milan, Italy. Accepted for publication: June 19, 2001.
U.S. Cancer Pain Relief Committee, 2002 Published by Elsevier, New York, New York
Pain is among the most common and distressing symptoms encountered by patients with advanced cancer and other terminal illnesses. The relief of pain is a clinical task at the very heart of the endeavor of palliation. The challenge of
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this task is to achieve effective relief with minimal side effects and to deliver this service to all patients in need of these interventions. Success in meeting this challenge requires delineation of the scope of the problem, characterization of the pain syndromes, determination of optimal therapeutic strategies, identification of barriers to implementation of effective strategies, determination of strategies to overcome these obstructions, and the monitoring of outcomes for purposes of continual quality improvement. Evidence-based medicine requires the testing and evaluation of strategies to assure their effectiveness and to define optimal approaches for all contingent indications. Through this approach, ineffective strategies are to be discarded and effectual strategies are submitted to trials against competing options to determine the best approach to serve as the standard for future comparison. It is incumbent upon palliative care practitioners to participate in the challenge of clinical research to enhance the efficacy of palliative practices to the benefit of our patients and their families.1 Interpretation of research data requires that the data be valid and recorded in an interpretable format. In clinical studies on pain, valid and reliable outcomes should be used. Furthermore, in order to compare data between studies, a standardization of outcomes, namely, pain measures, will increase the validity of the comparisons. Many approaches to the measurement of pain attributes have evolved over the past four decades. Some of them have been applied to cancer pain and palliative care,2 but the selection and application of these approaches in palliative care has often been capricious and idiosyncratic. The lack of uniformity in the approach to outcome measurement in evaluating chronic pain conditions has diminished from the ability to draw meaningful conclusions from much of the published literature.35 This article reports the results of the work of an Expert Working Group which was convened under the auspices of the European Association of Palliative Care (EAPC) Research Network to prepare recommendations for the measurement of pain in palliative care research.
teriorating health and multiple symptoms. At the end of life, cognitive impairment of variable severity is common. These factors impact both the ability to extrapolate pain management data derived from other clinical contexts with relatively healthy patient populations and the ability to conduct clinical research. They specifically influence the processes of data collection necessary for prospective studies. Research methodologies must be sensitive to these considerations. Specific recommendations will be made for approaches suitable for patients with cognitive impairment and for children. No valid instrument is applicable at the moment for the assessment of pain in the cognitively impaired. A behavioral scale has been recently designed for pain assessment in the cognitively impaired patient and its validation is ongoing (DOLOPLUS, Bernard Wary, personal communication).
Study Types
The working group defined six types of pain studies in palliative care, three descriptive study designs and three intervention designs (Table 1).
Descriptive Studies
Descriptive studies of pain are needed to define the prevalence and severity and scope of pain in various patient populations encountered in palliative care. These studies are performed to clarify clinical variability, pain course and prognosis, quality of care, and services. Depending upon the epidemiological method used, the results of these studies give information of varied generalizability. 1. Prevalence/severity studies: Pain is evaluated in a specific patient population to define its prevalence and severity.610
Table 1 Study Types

Descriptive Studies Prevalence/severity studies Trajectory studies Pain syndrome characterization Intervention Studies Phase I Phase II Phase III
Research Issues in Palliative Medicine

The patient populations that are the focus of palliative medicine are often frail, and have de-
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2. Trajectory studies: Pain is evaluated at repeated intervals in a defined patient population over time.11 3. Pain syndrome characterization: The clinical characteristics of pain and its relationship to clinical and investigation findings are collated to define and to describe specific pain syndromes.12
Covariates
A list of the covariates that are most relevant to pain studies in palliative care is provided in Table 2.
Description of Pain Measurement Tools (PMTs)

Pain is a subjective sensation which can be described according to several relevant features or attributes (quality, location, intensity, aversiveness, emotional impact, frequency, etc.). Among these attributes, intensity is recognized as one of the most relevant clinical dimension of the pain experience.13 Being a subjective experience, there is no objective method to measure pain. However, pain intensity can be measured in patients in a reliable and valid way by recording the self-rating of the sensation on different types of scales.1420 When considering pain assessement limited to the intensity dimension, PMTs should have a unidimensional structure. Since clinical pain is not only the product of a primary sensory modality, but rather, a complex human experience with functional, emotional, social, and spiritual components, multidimensional PMTs and health-related quality of life measures are also appropriate to address specific research questions related to the measurement of pain intensity. The measurement of pain for purposes of clinical research demand that the selected tool is valid and appropriate to the patient population and the study design. The Expert Working Group reviewed unidimensional and multidimensional pain measurement tools suitable for this purpose.
Intervention Studies
Intervention studies are needed to evaluate the effect of a therapeutic strategy. Pain management interventions may include primary therapies against the underlying pathology, analgesic drug therapy, invasive interventions, and psychological or social interventions. 1. Phase I studies: This term typically refers to drug interventions with new agents. The aim of the study is to define the maximal dose range that can be administered without excessive toxicity and to determine the acute toxicity profile of the agent. 2. Phase II studies: This term refers to prospective studies aimed at evaluating the impact of a study intervention with regard to the primary outcome, pain; secondary outcomes, such as quality of life and satisfaction; and costs, such as adverse effects and treatment-related resource utilization. In the evaluation of analgesic drugs, Phase I and II studies are often combined. In addition to essential pharmacokinetic data, pharmacodynamic effects including analgesia and adverse effects are measured. Pharmacokinetic/pharmacodynamic (PK/PD) studies correlate drug effects with measurement of plasma concentration in blood or other relevant compartments, such as cerebrospinal fluid. PK/PD studies may be performed with a single administration of a study drug or prolonged administration. 3. Phase III studies: This term refers to studies comparing the relative efficacy of two or more treatment approaches with a view to determining an optimal approach. These studies typically evaluate drugs with similar outcomes in phase II studies. Pain evaluation approaches must be appropriate for the study type and patient population that will constitute the subjects of the study.
Unidimensional Pain Measurement Tools

Three types of unidimensional pain measurement tools were considered, visual analogue scales (VAS), categorical verbal rating scales (VRS), and categorical numerical rating scales (NRS). All of these approaches are commonly used to measure pain intensity and are well validated in the cancer population.2127 VAS, VRS, and NRS are also commonly used to measure pain relief.25,27 When applied in the chronic nonmalignant pain or cancer pain populations, the unidimensional pain scalesVAS, NRS and VRS can be considered equivalent. The choice should
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Table 2 Recommendations for Clinical and Pain-Related Covariates to be Documented in Pain-Related Studies
Basic demographic data to be collected for all studies 1. Age 2. Sex 3. Disease diagnosis 4. Predominant pain mechanism: neuropathic, nociceptive (visceral or somatic), idiopathic 5. Performance status 6. Cognitive function: normal or impaired 7. Current analgesic therapy: Drug(s), dose(s), non-drug therapies Other covariates that may be relevant to specific study designs 1. Stage of disease at time of study 2. Sites of metastases 3. Place of care 4. Specific pain syndrome 5. Primary therapies (i.e., antitumor treatments among patients with cancer) 6. Co-existing psychological disorder (present vs. absent, specific diagnoses) 7. Measure of cognitive function (i.e., Mini Mental Status Examination Score)
be influenced by practical considerations based on available knowledge (see also Table 3).28 Numerous verbal rating scales exist and use different words in different languages. The verbal 15-level scale developed by Gracely et al. for rating experimental pain can be considered a ratio scale,14,15 but this is not proven for the many scales available in the literature. After much discussion of the issues related to translational validity of verbal rating scales, the Expert Working Group recognized that a simple intensity scale of none, mild, moderate, and severe is the most widely used in the clinical context, but also that scales with a larger number of intervals are more desirable, both in research and in clinical practice, because of higher sensitivity to treatment effects.15 A validated multilingual translation of the more simple VRS does not exist, but a valid multilingual six-level VRS is presented in Appendix 1.29 The VAS has been studied and is often considered an ideal scale, because it is continuous, approximates a ratio scale, and is more independent from language than verbal scales (although the choice of the extreme anchor words or end-phrases can be relevant).16,19,20,30 On the other hand, its validity more strongly depends on the appropriateness of administration method and of the instructions given to the study subjects.19,20 It is, therefore, more difficult to use than other scales. Evidence suggests that numeric rating scales are easier to apply and are associated with better compliance than the VAS.28,31 Based on the available evidence,17,28,32 the use of a standard 010 numeric rating scale and 100-mm horizon-
tal visual analogue scale can be recommended. Although these are typically administered with pen and paper, other valid approaches include the use of touch screens for VAS and NRS, sliding scales, and verbally administered numeric rating scales.20 For purposes of intervention studies, both pain intensity and pain relief can be measured.21,22 Pain relief can be measured by asking the patients to compare pain now with previous pain experiences. Pain relief measurement validity is limited to short-term intervention studies (24 hours or less); in chronic studies, its validity has been seriously questioned33 and the construct underlying its meaning in descriptive studies is uncertain.5,6,34,35
Multidimensional Pain Measuring Tools

Three multidimensional scales were considered, the McGill Pain Questionnaire, the Brief Pain Inventory, and the Memorial Pain Assessment Card. Although recognizing that other instruments exist36 or are under study,37,38 the Expert Working Group recommends the use of the Short form of the Brief Pain Inventory or the McGill Pain Questionnaire. Both of these tools are well validated in multiple languages and are thus suitable for application in an international setting. The Expert Working Group withheld recommendation of the Memorial Pain Assessment Card35 because it is not validated in languages other than English. The Brief Pain Inventory (BPI)39 is a simple and easy to administer tool that provides information about the history, intensity, location, and quality of pain. Numeric scales (range 0 to 10)
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Table 3 Evidence-Based Criteria Adopted for Recommending Pain Measurement Tools

Scale VAS Ease of Administration Kremer et al. 198131 Briggs et al. 199960 Validity Scott & Huskinsson 197616 Price et al. 199420 Jensen et al. 198628 Jensen et al. 198628 Jensen et al. 199318 Jensen et al. 199432 Jensen et al. 198628 Gracely et al. 197814 / De Conno et al. 199461 Wallenstein et al. 198025 Fishman et al. 198735 Feine et al. 199833 Serlin et al. 199540 / Twycross et al. 199649 Melzack 1975, 198550, 52 / Holroyd et al. 199262 Sensitivity to Treatment Effect Littmann et al. 198527 Joyce et al. 197564 Farrar et al. 200066 Validated in Palliative Care De Conno et al. 199461 Multilingual Validity NA
NRS 0-10
Kremer et al. 198130 Jensen et al. 198628
De Conno et al. 199461
Serlin et al. 199540
VRS
Jensen et al. 198628
/ Littman et al. 198527 Littman et al. 198527 Farrar et al. 200066
De Conno et al. 199461 De Conno et al. 199461
Bullinger et al. 199829 NA
Relief
NA
BPI
/ Twycross et al. 199648
? Twycross et al. 199649 Melzack 198552 De Conno et al. 199461
Twycross et al. 199649 Graham et al. 198051 Dudgeon et al. 199353 De Conno et al. 199461
McGill
NA. The expert consensus was that this instrument is more demanding than others
NA not available; Studies providing evidence for validity; Studies not providing evidence of validity; / Studies offering mixed results See text for full list.
indicate the intensity of pain in general, at its worst, at its least, and right now. A percentage scale quantifies relief from current therapies. A figure representing the body is provided for the patient to shade the area corresponding to his or her pain. Seven questions determine the degree to which pain interferes with function, mood, and enjoyment of life. The BPI is selfadministered and easily understood, and has been translated and validated in many different languages.4048 A Norwegian (S. Kaasa, personnal communication), and Spanish (J.M. Nunez-Olarte, personal communication) validation are ongoing. It is suitable for repeated evaluation of painthat is, weekly or biweeklybut its use for this purpose needs further study.49 The McGill Pain Questionnaire (MPQ)50 is a self-administered questionnaire that provides global scores and subscale scores that reflect
the sensory, affective, and evaluative dimensions of pain. It has been validated in cancer pain.51 A short form of the MPQ (SF-MPQ) was developed for use in research settings.52,53 The SF-MPQ consists of 15 representative words from the sensory (n 11) and affective (n 4) categories of MPQ. The Present Pain Index, verbal rating scale, and a visual analogue scale (VAS) measuring pain intensity is included. The 15 words are scored using a 4-point verbal rating scale, ranging from none, mild, moderate, to severe pain. The SF-MPQ correlates highly with the MPQ. Whereas the MPQ is available in many languages, the SF-MPQ is not.
Health-Related Quality of Life Measures

Several measures of health-related quality of life (HRQL) have been developed and internationally validated during the last decade.54 These measures are multi-dimensional and in-
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clude several domains, such as physical function, psychological function, social function, and various symptoms which are prevalent in advanced medical illnesses. Pain is included as a single item or as a dimension in many of these measures. The European Organization for Research and Treatment of Cancer (EORTC) quality-of-life questionnaire has been specifically designed for the use in oncology clinical trials in a multicenter multilingual setting55,56 and has a pain-related scale.57 By using a measure of HRQL, a more comprehensive picture of the patients total symptom burden and function might be obtained. This may be favorable when compared to using one scale or one measure for pain. However, HRQL instruments are long and can be difficult to complete for patients with reduced performance status. HRQL should be included in descriptive studies and in prospective phase III studies. At the moment, research in HRQL measures and pain is still insufficient to make specific recommendations on which tool should be used in pain-related studies.54,58,59
it is meant to measure (within the limited aims of our review, pain intensity). Human sensation has no external gold standard with which to compare empirical measures, and indirect methods of inferring validity are necessary. These may include concurrent validity with other supposedly valid measures,16,20,25,61 crossmodality matching,14,15 matching of experimentally-administered pain stimuli with clinical pain,19 and factor analysis.28,39,61,62 The pain intensity measures obtained with VAS, VRS, and NRS are valid; the assessment of pain relief has been demonstrated to be valid in the short-term assessment of analgesics25 and when used over intermediate periods of time,61 but it is problematic in longer-term evaluation.33,35 3. Sensitivity to treatment effect. Sensitivity to change can be considered one aspect of validity. The measure must be shown to be valid for the use for which it is recommended.63 For the use of PMTs in clinical trials, a scale should show changes in pain intensity when a change is expected. Sensitivity to treatment effects of VAS, NRS, and VRS for pain intensity and shortterm relief is well demonstrated.27,52,61,6466 The only study49 that evaluated repeated administration of the BPI in a clinical context demonstrated that clinical changes can be detected by this instrument, but did not specifically address sensitivity (for this reason, this point is associated with a question mark in Table 3). Data on the McGill Pain Questionnaire are variable.52,61 4. Validation studies in palliative care. Data on the validity and reliability of an instrument in the specific area of interest are relevant to establish its specific value and recommended use.51,53 5. Multilingual validity. The availability of multilingual and multicultural validity and reliability data is particularly relevant because these recommendations are made also to allow multicenter international trials. The specific use of different words as end-phrases or anchor points for the VAS has been shown to change the distribution of patient responses.30 No study is available that assesses how the translation of intensity describing words in another language may affect the VAS and NRS measuring properties. It is advisable that the words used are strictly intensity descriptors and repre-
Summary of Criteria Adopted for Recommendation

Table 3 summarizes some of the evidence that can be used to support the appropriateness of the PMTs considered. The use of a scale can be recommended according to several criteria. Practicality and appropriateness for palliative care studies were emphasized. 1. Ease of administration. This criterion has obvious practical implications. Between two instruments sharing all other psychometric properties the choice should favor the one that maximizes patients compliance. In this respect, the VAS may have disadvantages when compared with other instruments, especially in the elderly,31,60 although some have found that the percentage of incorrect responses with the VAS is higher but comparable with those obtained with other instruments.28 The BPI is usually considered easy to complete, but in one study that employed this questionnaire for clinical purposes, the percentage of missing responses and of noncompliant patients in repeated administration was relatively high.49 2. Validity. This criterion is fundamental and guarantees that the instrument measures what
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rating scale (none, mild, moderate, severe). Additional desired data include satisfaction with pain relief and whether or not pain level is acceptable. 3. Adult patients who are unable to communicate: Observer rating using 4-point VRS for pain now.
tions. Adequate cognitive function and ability to communicate should be inclusion criteria for PK/PD studies.
Phase I and II Studies

1. Adult patients with no cognitive impairment: Repeated measurement of pain at both long-term and short-term intervals is needed. Long-term changes in pain and pain-related interference with function can be measured using the Brief Pain Inventory-Short Form at intervals of 3 days to 2 weeks. Short-term changes in pain and pain relief should be measured using a standard VAS or 010 NRS administered at least three times daily for 4 days.18 Although data specific to the palliative care population are lacking, this recommendation is based on the evidence that averaging multiple measures of pain intensity across time maximizes the reliability and validity of pain assessments and is preferred to assessment of average pain over last 24 hours.18 In general, the working group recommends the NRS over the VAS because of data on better compliance. These measures should be applied more frequently depending on the study aim and on the agent under investigation.70,74,75 2. Multiple dose Phase II studies should incorporate measures of adverse effects and the impact of the intervention on quality of life. For Phase I and single dose studies, quality-of-life evaluation is not needed. There are inadequate data to make firm recommendations regarding the choice of measure to record data regarding adverse effects and quality of life. However, the EORTC QLQ-C30 is the only valid HRQL instrument available in a significant number of different languages.56 3. Adult patients with cognitive impairment: The Expert Working Group did not recommend that patients with cognitive impairment be candidates for Phase I/Phase II studies. The development of behavioral scales (Bernard Wary, personal communication), or simplified prorated scales to measure pain, satisfaction, distress, and adverse outcomes might provide valid assessments to obtain useful in-
Pain Syndrome Characterization

1. Adult patients with no cognitive impairment: Co-administration of both the Brief Pain Inventory-Short Form and the short form of McGill Pain Questionnaire is recommended. Together, these tools provide excellent coverage of quantitative and qualitative pain characteristics. These data should be integrated with detailed recording of the clinical narrative, pain characteristics, exacerbating and relieving factors, response to previous trials of analgesic therapies, findings of physical examination, and relevant imaging studies. 2. Adult patients with cognitive impairment or unable to communicate: The nature of the data needed for characterization of pain syndromes requires a level of detail that cannot be derived from these patient populations. The Expert Working Group recommends that adequate cognitive function should be an inclusion criteria for studies of pain syndrome characterization.
Pharmacokinetic/Pharmacodynamic (PK/PD) Studies

1. Adult patients with no cognitive impairment: The primary pain measures in these studies are pain intensity and pain relief; pain unpleasantness has also been studied.71 Both pain intensity and relief should be measured by using a standard VAS or 010 NRS. In general, the working group recommends the NRS over the VAS because of data on better compliance. These measures should be applied with a frequency appropriate to the agent under investigation.70,7274 2. Adult patients with cognitive impairment or unable to communicate: The nature of the data needed for PK/PD studies requires a level of compliance that can not be derived from these patient popula-
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formation from this population in intervention studies, but trial development is, at the moment, not recommended.
Phase III Analgesic Studies

1. These studies should be restricted to patients who are cognitively intact. 2. Repeated measurement of pain at both long-term and short-term intervals should be performed. Long-term changes in pain and pain-related interference with function should be measured using the Brief Pain Inventory-Short Form at intervals of 3 days to 2 weeks. Short-term changes in pain and pain relief should be measured using a standard VAS or 010 NRS administered at least three times daily for 4 days. In general, the Expert Working Group recommends the NRS over the VAS because of data on better compliance. 3. The Expert Working Group recommends that all Phase III studies incorporate measures of adverse effects, quality of life, and measure of satisfaction. The same observations on the instrument of choice made for Phase II studies apply. When a crossover design is incorporated, patient preference between the treatment arms should be ascertained.76
stood. Pain should be assessed from a multidimensional perspective by combining subjective and objective measurement tools, including self-report,77 behavioral measures, and physiologic indicators. Physiologic measures alone cannot be interpreted simply as pain, as they are also signs of stress.78 In children under the age of 5 and in those with developmental deficits, self-assessment is limited.79 In older children, the correlation between self-assessment and behavioral methods is variable.77 False replies and underrating are possible. As a result, a multidimensional approach is, in general, warranted.
Unidimensional Pain Measurement Tools

The VAS is generally the gold standard for children, as it is for adults. The scale has been adapted for children and is usually presented vertically. Particularly in the setting of palliative care, reliability of self-assessment will depend on the care with which it is applied to obtain measurements. NRS is used in children but they have to be old enough to count up to 10, which means they have to be school-aged children. Other tools are more useful in the preschool child. A VAS score can be obtained from a 3-year-old child, but the reply can be misleading, as at that age the child does not have the same abstract capacities of older children. They have a tendency to choose the extremities of the scale, whether for the VAS or another tool (such as the algocube). The Bieri Face Scale can be recommended80,81 as it is sensitive to pain intensity and less to emotions in comparison with the Smiley Analogue Scale.82,83 Indeed, recently it has been shown84 that scales with smiles or tears show higher rating scores than scales with neutral faces (as the Bieri scale). The number of faces is also important. Although some scales show up to 9 faces, the best choice may be a scale using from 5 to 6 faces, because of the childs cognitive capacities. The Bieri scale has a shorter version (Carl Von Baeyer, personal communication). The Poker Chip Tool representing four pieces of hurt has been used in acute pain.85
Pain Measurement Tools for Children

The following recommendations concerning pain assessment in children reflect the contribution of a separate study group organized by the EuroPain group. (List of EuroPain Collaborators: P. Poulain, MD, Chair, E. PichardLandri, MD, C. Wood, MD, M. Vieyra, PhD, H. H. Abu-Saad, MD, RN, G. Schaffer Vargas, MD.) Evaluation of pain in children is always delicate and notoriously difficult, because it depends on the level of cognitive development and psychological condition of the child. The reactions to prolonged pain, as seen in palliative care, may be characterized by withdrawal and are similar to depression in its manifestations. Pain measurement tools used in children must determine the presence and the severity of pain in various conditions. Most pain scales used in adults can also be used in children, provided they can be under-
Multidimensional Pain Measurement Tools

The McGill Pain Questionnaire and the McGill Pain Questionnaire-Short Form can be proposed to children over approximately 9 years of age. Drawings and body outlines are
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specific methods for communicating with children, useful for diagnosis and followup.86 The Pediatric Pain Assessment Tool has established content, convergent, discriminant, and construct validity.87 The tool has been validated for use in children with cancer and is being currently used to assess the effectiveness of pain management in pediatric palliative care. Behavioral pain assessment tools. Few behavioral measurement tools have been evaluated for their response to medication, and insufficient attention has been paid to the significance of behaviors in terms of level of pain.88 In younger children or in children with handicaps and communication problems, these are, nonetheless, the preferred tools. Various scales have been developed for postoperative pain, but pain behavior can be different in advanced disease. Scales that have been validated for use in chronic pain conditions include the DEGR scale for cancer pain89 and San Salvadour Scales90 for cognitively delayed children. The San Salvadour Scales90 has 22 items. Many of them depend on the childs response to manipulation during physical examination, basal state, and sleep. It is correlated with the level of autonomy. It has never been used in palliative care but the relevance of palliative care in neurologically disabled children can suggest its use in special populations. The DEGR scale89 consists of ten indicators divided into three subgroups, voluntary expression of pain, direct signs of pain and psychomotor alterations. Observation of the child is carried out at rest, on movement, and during social interaction and play. It has been validated in French for children with cancer aged 2 to 6 years. Translations in English and Spanish are available. At the moment, it is the only available measurement tool for prolonged pain in young children. It is appropriate for younger children in palliative care but lacks the benefit of self-report.
specific attention to the more difficult and ethically demanding situation. 1. Children with no cognitive impairment and old enough to understand: VAS, Faces scale, Poker Chip tool, MPQ, drawings. 2. Children with cognitive impairment: San Salvadour is a possibility in the absence of another tool that might apply to palliative care in the neurologically disabled child. To confirm this recommendation, further validation studies are necessary. 3. Children unable to communicate because of their age and poor physical status: DEGR. 4. For the younger children (2 years), the DEGR should be tried as no other scale is available or adapted.
Conclusions
The measurement of pain is a cardinal activity in palliative care research. The members of the Expert Working Group hope that these recommendations may assist researchers in project development. It is acknowledged that some of the recommendations address areas that have not been formally studied or validated, and are, therefore, open to study and criticism. The Expert Working Group did not attempt a systematic literature review but used a critical approach to give substantial examples for all the statements provided. All statements lacking specific references reflect the opinion of the expert consensus. When sufficient evidence existed, the recommendations underline that they should be used to implement state-of-the-art research in palliative care. The widespread application of these recommendations will facilitate greater standardization of outcomes and presentations of data, and will enhance the applicability and relevance of accumulated data to the palliative care patient population. These recommendations should also help in evaluating critically the available literature on the use of PMTs in research in palliative care. The Expert Working Group acknowledges that other study designs and methods are feasible beyond the ones reviewed. The present recommendations will be relevant to pain measurement in most study designs. Specific study
Practical Recommendations
Recommendations for children are more difficult because of the paucity of studies addressing pain in the palliative care of pediatric patients. As a result, the recommendations here below must be adapted to the study design with the same criteria used in adults, with
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requirements may necessitate research approaches that are not covered by our work.
Acknowledgments
EAPC Research Network Steering Committee members: Franco De Conno (Chair), Augusto Caraceni, Rehabilitation and Palliative Care Unit, Istituto Nazionale Dei Tumori, Milan, Italy; Nathan Cherny, Pain and Palliative Medicine Service, Shaare Zedek Medical Center, Jerusalem, Israel; Jos Antnio S. Ferraz Gonalves, Unidade de Cuidados Continuados, Instituto Portugus de Oncologia Porto, Portugal; Carl Johan Frst, Palliative Care Unit, Stockholm, Sweden; Geoffrey Hanks, Department of Palliative Medicine, Bristol Oncology Centre Bristol, Great Britain; Stein Kaasa, Palliative Medicine Unit University Hospital of Trondheim, Trondheim, Norway; Sebastiano Mercadante, Palliative Care Unit, Ospedale La Maddalena, Palermo, Italy; Juan Manuel Nuez Olarte, Unidad de Cuidados Paliativos, Hospital General Univ. Gregorio Maraon, Madrid, Spain; Philippe Poulain, Consultation D`Analgsie France Institut Gustave Roussy, Paris, France; Lukas Radbruch, Anesthesiologie, Klinik Universitt zu Kln, Cologne, Germany; Carla Ripamonti, Rehabilitation and Palliative Care Unit, Istituto Nazionale Dei Tumori, Milan, Italy; Friedrich Stiefel Service de Psychiatrie de Liaison, Lausanne, Switzerland. The authors wish to thank Heidi Bulmhuber for her help in organizing this expert working group and for her continuous support of the Research Network of the European Association for Palliative Care.
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strument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365376. 56. Kaasa S, Bjordal K, Aaronson N, et al. The EORTC core quality of life questionnaire (QLQC30): validity and reliability when analysed with patients treated with palliative radiotherapy. Eur J Cancer 1995;31A:22602263. 57. Klepstadt P, Borgchgrevink PC, Kaasa S. Effects on cancer patients health-related quality of life from start of morphine. J Pain Symptom Manage, 2000;20:1926. 58. Osoba D, Rodrigues D, Myles J, et al. Interpreting the significance of changes in health-related quality-of-life scores. J Clin Oncol 1998;16:139144. 59. Sloan JA, Loprinzi CL, Kuross SA, et al. Randomized comparison of four tools measuring overall quality of life in patients with advanced cancer. J Clin Oncol 1998;16:36623673. 60. Briggs M, CLoss JS. A descriptive study of the use of visual analogue scales and verbal rating scales for the assessment of postoperative pain in othopedic patients. J Pain Symptom Manage 1999;18:438446. 61. De Conno F, Caraceni A, Gamba A, et al. Pain measurement in cancer patients: a comparison of six methods. Pain 1994;57:161166. 62. Holroyd KA, Holm JE, Keefe FJ, et al. A multicenter evaluation of the McGill Pain Questionnaire: results from more than 1700 chronic pain patients. Pain 1992;48:301311. 63. American Educational Research Association APA, National Council on Measurement in Education. Standards or educational and psychological testing. Washington DC: American Psychological Association, 1985:98. 64. Joyce CRB, Zutshi DW, Hrubes V, Mason RM. Comparison of fixed interval and visual analogue scales for rating chronic pain. Eur J Clin Pharmacol 1975;8:415420. 65. Jensen MP, Turner JA, Romano JM, Fisher LD. Comparative reliability and validity of chronic pain intensity measures. Pain 1999;83:157162. 66. Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL. Defining the clinically important difference in pain outcome measure. Pain 2000;88:287294. 67. Maiani G, Sanavio E. Semantics of pain in Italy: the Italian version of the McGill Pain Questionnaire. Pain 1985;22:399405. 68. De Benedittis G, Massei R, Nobili R, Pieri A. The Italian pain questionnaire. Pain 1988;33:5362. 69. Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999;81:129134. 70. Portenoy RK, Payne R, Coluzzi P, et al. Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study. Pain 1999;79:303312. 71. Price DD, von der Gruen A, Miller J, et al. A psychophysical analysis of morphine analgesia. Pain 1985;22:261269.
72. Inturrisi CE, Colburn WA, Kaiko RF, et al. Pharmacokinetics and pharmacodynamics of methadone in patients with chronic pain. Clin Pharmacol Ther 1987;41:392401. 73. Inturrisi CE, Portenoy RK, Max MB, et al. Pharmacokinetic-pharmacodynamic (PK-PD) relationships of methadone infusions in patients with cancer pain. Clin Pharmacol Ther 1990;47:565570. 74. Farrar JT, Cleary J, Rauck R, et al. Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients. J Natl Cancer Inst 1998;90:661666. 75. Max MB, Laska EM. Single-dose analgesic comparisons. In: Max MB, Portenoy RK, Laska EM, eds. The design of analgesic clinical trials, vol 18. New York: Raven Press, 1991:5595. 76. Max M, Portenoy RK. Pain research: designing clinical trials in palliative care. In: Doyle D, Hanks GWC, eds. Oxford textbook of palliative medicine, 2nd ed. Oxford: Oxford University Press, 1998:167178. 77. Champion GD, Goodenough B, Von Baeyer CL, Thomas W. Measurement of pain by self-report. In: Finley GA, McGrath PJ, eds. Measurement of pain in infants and children, vol 10. Seattle: IASP Press, 1998. 78. Sweet SD, McGrath PJ. Physiological measures of pain. In: Finley GA, McGrath PJ, eds. Measurement of pain in infants and children, vol 10. Seattle: IASP Press, 1998:5981. 79. Hammers JP, Abu-Saad HH, Van Den Hout MA, et al. The influence of childrens vocal expressions, age, medical diagnosis and information obtained from parents on nurses pain assessment and decisions regarding interventions. Pain 1996;65:5361. 80. Hicks CL, Von Baeyer CL, Spafford PA, van Korlaar I, Goodenough B. The Faces pain scalerevised: toward a common metric in pediatric pain measurement. Pain 2001;93:173183. 81. Bieri D, Reeve RA, Champion GD, et al. The faces pain scale for the self-assessment of pain experienced by children. Pain 1990;41:139150. 82. Wong DL, Baker CM. Pain in children: comparison of assessment scales. Ped Nurs 1988;14:917. 83. Pothmann R. Comparison of visual analogue scale (VAS) and a Smiley analogue scale (SAS). In: Tyler DC, ed. Advances in pain research and therapy. New York: Raven Press, 1990:9599. 84. Chambers CT, Giesbrecht K, Craig KD, et al. A comparison of faces scales for the measurement of pediatric pain: childrens and parents ratings. Pain 1999;83:2535. 85. Hester NK. The preoperational childs reaction to immunization. Nurs Res 1979;28:250255. 86. Poulain P, Pichard-Leandri E, Gauvain-Piquard A. Assessment and treatment of pain in children in palliative care. Eur J Palliative Care 1994;1:3135. 87. Abu-Saad HH, Pool H, Tulkens B. Further test-
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ing of the Abu-Saad pediatric pain assessment tool. J Advanced Nurs 1994;19:10631071. 88. McGrath PJ. Behavioral measure of pain. In: Finley GA, McGrath PJ, eds. Measurement of pain in infants and children, vol 10. Seattle: IASP Press, 1998:83102. 89. Gauvain-Piquard A, Rodary C, Rezvani A, Ser-
bouti S. The development of the DEGR: a scale to assess pain in young children with cancer. Eur J Pain 1999;3:165176. 90. Collignon P, Giusano B, Boutin AM, Combes JC. Utilisation dune echelle dheteroevaluation de la douleur chez le sujet severement handicape. Doul et Analg 1997;1:2732.
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Appendix 1 Valid Translations of the Verbal Rating Scale from SF-36 (with Permission)
French: Au cours de ces 4 dernires semaines, quelle a t lintensit de vos douleurs physiques? nulle trs faible faible moyenne grande trs grande English: How much bodily pain have you had during the past 4 weeks? none very mild mild moderate severe very severe Italian: Quanto dolore fisico ha provato nelle ultime 4 settimane? nessuno molto lieve lieve moderato forte molto forte Czech: Jak velk bolesti jste mel(a) v poslednich 4 tydnech? Zadn velmi mirn mirn stredni siln velmi siln Danish: Hvor strke fysike smerter har du haft i de sidste 4 uger? ingen smerter megen lette smerter lette smerter middelstrke smerter strke smerte meget strke smerter Dutch: Hoeveel lichamelijke pijn heeft u de afgelopen 4 weken gehad? geen heel licht licht nogal ernstig heel ernstig Finnish: Kuinka paljon ruumiillista kipua tai srky olette tuntenut viimeksi kuluneiden neljn viikon aikana? ei lainkaan hyvin liev liev kohtalaista vaikeaa erittin vaikeaa entourez la rponse de votre choix 1 2 3 4 5 6 circle one 1 2 3 4 5 6 indichi un numero 1 2 3 4 5 6 zakrouzkujte jedno cislo 1 2 3 4 5 6 soet kun n ring 1 2 3 4 5 6 omcirkel n cijfer 1 2 3 4 5 6 rengastakaa yksi numero 1 2 3 4 5 6
(continued)
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Appendix 1 Continued
German: Wie stark waren Ihre Schmerzen in den vergangenen 4 Wochen? Ich hatte keine Schmerzen Sehr leicht Leicht Mig Stark Sehr stark Hungarian: Milyen ers testi fjdalmai voltak az elmlt 4 hbten? nem voltak nagyon enyhe enyhe kzepes ers nagyon ers Norwegian: Hvor sterke kroppslige smerter har du hatt lpet av de siste 4 ukene? ingen meget svake svake moderate sterke meget sterke Polish: Jak bardzo odczuwali Panstwo w ciagu ostanich 4 tygodni bl fizyczny? Zadnego bardzo lagodny lagodny sredni silny bardzo silny Portuguese: Durante as ultimas 4 semanas teve dores? nenhumas muito fracas ligeiras moderadas fortes muito fortes Serbian: Da li ste osecali telesni bol, i ako jeste u kolikoj meri, tokom poslednje 4 nedelje? bez bola vro blag bol blag bol umeren bol tezak bol vrlo tezak bol Slovak: Ak vel k telesn bolesti ste mali v piebehu poslednych 4 tyzdnov? ziadne vel mi mierne mierne stredn vcsie tazk Bitte kreuzen Sie nur eine Zahl an 1 2 3 4 5 6 csak egy szmot jelljn meg! 1 2 3 4 5 6 sett ring rundt ett tall 1 2 3 4 5 6 zakresl jedno 1 2 3 4 5 6 circule uma 1 2 3 4 5 6 zaokruziti jedan broj 1 2 3 4 5 6 zakrzkujte jednu moznost 1 2 3 4 5 6
(continued)
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Appendix 1 Continued
Spanish: Tuvo dolor en alguna parte del curpo durante las 4 ltimas semanas? no ninguno s, muy poco s, un poco s, moderado s, mucho s, muchissimo Swedish: Hur mycket vrk eller smrta har Du haft under de senaste fyre veckorna? ingen mycket ltt ltt mttlig svr mycket svr Turkish: Gectigimiz bir ay (4 hafta) ierisinde ne kada bedensel agrilariniz oldu? hi ok hafif hafif orta hafiflikte asiri derecede ok asiri derecede marque un solo nmero 1 2 3 4 5 6 stt en ring runt en siffra 1 2 3 4 5 6 birinin etrafina daire cizin 1 2 3 4 5 6
In this questionnaire the scale is intended to evaluate pain during the previous 4 weeks. Different time frames can be chosen depending on the study requirements and aims.
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Episodic (Breakthrough) Pain

Consensus Conference of an Expert Working Group of the European Association for Palliative Care
Sebastiano Mercadante, M.D.1 Lukas Radbruch, M.D.2 Augusto Caraceni, M.D.3 Nathan Cherny, M.D.4 Stein Kaasa, M.D., Ph.D.5 Friedemann Nauck, M.D.6 Carla Ripamonti, M.D.3 Franco De Conno, M.D.3 the Steering Committee of the European Association for Palliative Care (EAPC) Research Network
Pain Relief and Palliative Care Unit, La Maddalena Cancer Center, Palermo, Italy.
2 Klinik fur Anasthesiologie und Operative Intensivmedizin, University of Koln, Koln, Germany. 3 Department of Rehabilitation and Palliative Care, National Cancer Institute, Milan, Italy. 1
BACKGROUND. Breakthrough pain is transitory exacerbation of pain that occurs in

addition to otherwise stable persistent pain. The wide differences in estimation of incidence reported in literature are probably because of different settings and meanings attributed to the denition of breakthrough pain.
METHODS. A panel of experts met to establish the actual knowledge on breakthrough pain, according to the evidence in literature and experience. They agreed that episodic or transient pain could be a more simple and adequate term in most languages, including English, French, Italian, and Spanish. RESULTS. A specic assessment and precise pain characterization are essential to plan the most appropriate treatments. Despite the relevance of this temporal pain pattern for the inuence on the outcome and quality of life, few controlled studies have been performed to give evidence of a specic approach. Several experiences have reported the possible efcacy of different drugs, route of administration, and modalities of administration in different circumstances. CONCLUSIONS. Prospective studies with previous treatments using similar terminologies are necessary to nd the most convenient therapeutic intervention, according to the temporal pattern characteristics and the pain mechanism involved. Cancer 2002;94:8329. 2002 American Cancer Society. DOI 10.1002/cncr.10249
Cancer Pain and Palliative Medicine, Share Zedek Medical Center, Jerusalem, Israel.
5 Palliative Medicine Unit, Trondheim University Hospital, Trondheim, Norway. 6 Palliative Medicine Unit, University of Bonn, Bonn, Germany.
KEYWORDS: cancer pain, breakthrough pain, incident pain, transient pain, opioids, nonsteroidal antiinammatory drugs (NSAIDs), pamidronate, transmucosal fentanyl, radiotherapy, spinal opioids.
Members of the Research Steering Committee of the EAPC: Franco De Conno (Chair), Augusto Caraceni, Nathan Cherny, Carl Johan Fu rst, Jose Ferraz Gonc alves, Geoffrey Hanks, Stein Kaasa, Sebastiano Mercadante, Juan Manuel Nunez Olarte, Philippe Poulain, Lukas Radbruch, Carla Ripamonti, and Friedrich Stiefel. Address for reprints: Sebastiano Mercadante, M.D., Pain Relief and Palliative Care Unit, La Maddalena Cancer Center, Via S. Lorenzo 312, 90146 Palermo, Italy; Fax: 39-091-6806909; E-mail: mercadsa@tin.it Received July 11, 2001; revision received July 11, 2001; accepted October 15, 2001. 2002 American Cancer Society
ain relief usually is achieved in most cancer patients using the World Health Organization guidelines for cancer pain management. However, it is well acknowledged that many patients continue to suffer from difcult pain syndromes with a typical temporal pattern.1,2 Breakthrough pain has been associated with a reduced likelihood for adequate pain control in some groups of cancer patients.3 6 The incidence of breakthrough pain has been estimated to be high (approximately 40 80% depending on the setting) in various surveys.2,711 The differences reported are probably because of different settings and meanings attributed to the denition of breakthrough pain. In an international survey of cancer pain characteristics and syndromes, large differences in the diagnosis of breakthrough pain by clinicians of different countries have been found, suggesting that this phenomenon is diagnosed differently in various countries.5 These controversial aspects, both semantic and clinical, were discussed in a consensus meeting of an expert working group from the Research Network of the European Association for Palliative Care during the 2nd International and Hellenic Conference on Pain Relief and Pallia-
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Episodic Pain in Cancer/Mercadante et al. TABLE 1 Differentiation of Episodic Pain

Episodic pain without signicant baseline pain (difcult pain problem) Episodic pain with signicant baseline pain (inadequate pain management) Any kind of pain Movement-related episodic pain Bone pain Neuropathic pain Visceral pain Somatic soft tissue pain Nonmovement-related episodic pain
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Neuropathic pain Visceral pain Somatic soft tissue pain
tive Care held in Athens in March 1999. The selected members of the expert panel were required to have specic clinical and research interests relating to the topic and to have published signicant articles on patients with cancer pain. Before the meeting, each selected expert prepared a report on various aspects, including epidemiology, denition, assessment, pain categorization, and treatment, according to the existing literature and his or her own experience. The material drawn from a systematic review of the various aspects was discussed. The chairs of this group were solicited to rene a draft. In the subsequent year, the position paper was circulated and then debated and extended to other external referees belonging to the steering committee of the research network, and further changes were made, according to new suggestions until a nal agreement was achieved in December 2000.
FIGURE 1. Algorithm for treatment of episodic (breakthrough) pain. WHO:

World Health Organization.
TERMINOLOGY
Breakthrough pain is dened as transitory exacerbation of pain that occurs in addition to otherwise stable persistent pain.2 This suggests a high pain intensity limited in time, that means a transient episode of uncontrolled pain. The denition of breakthrough pain is not agreed on among various researchers.2,12 For example, in the United Kingdom this term often is used as a sign of end-of-dose failure during dose titration. A relation between transient pain and baseline regimen has been found. End-of-dose pain occurs when the effect of opioids does not last until the next dose is scheduled. Moreover, the term is typically English and does not have any correspondent in other languages in Europe, especially in Latin countries, where patients and untrained physicians may have misconception of the denition of breakthrough pain. To increase the relevance in the clinical setting, a broader and less burdened term should be preferred, such as episodic or transient pain. These terms seem to be more simple and adequate in most languages, including English, French, Italian, and Spanish. In Table 1, typical episodic pain mechanisms are
listed. These could be useful for education and for establishing a common language among researchers; clinical conditions with varying underlying mechanisms requiring various approaches could be used to illustrate each mechanism.
ASSESSMENT
Patients with episodic pain and their treatment frequently have been described as a common group. The therapeutic approach, however, can change considerably according to the phenomenology and the pathophysiology of the episodic pain. An assessment algorithm is useful to categorize patients in groups according to the background pain conditions (Fig. 1). Patients with background pain that was described as unusually severe are considered to have uncontrolled background pain. Patients with controlled background pain who experienced one or more severe or excruciating episodes of pain during the past day may be classied as having controlled background pain and episodic pain (Fig. 2). A temporal distribution of opioid doses as needed has been reported. It has been attributed to a more intense diurnal activity.13 Conversely, an intraindi-
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FIGURE 2. Different temporal patterns

of episodic pain and continuous pain. Examples on the left side should be interpreted as inadequate pain management, whereas those on the right side as difcult pain problems. In the middle is an example of a mixed pattern.
vidual variation in the absorption of morphine or changes in volume of distribution during the day have been demonstrated, and there is a potential for a mismatch between uctuations in pain intensity and morphine blood concentration, as a consequence of a chronopharmacokinetic variability.14 This suggests a more accurate assessment, including not only intensity, frequency, and duration of episodic pain, but also quality of pain and alleviating or precipitating factors. The characteristics of this kind of pain suggest that it needs to be assessed with instruments aiming at measuring pain intensity over short periods of time. Although the traditional measures of pain intensity, including visual analog scales, numericl rating scales, and verbal rating scales, most likely are equivalent for this purpose, measurements should be performed frequently, at the onset and then at intervals until the episode evanishes spontaneously or after a specic treatment. The use of analgesics, the relation between the occurrence of the episode and the administration of drugs, and the onset of effect should be recorded.9 Onset and peak intensity, location, quality and predictability, and factors that precipitated them or provided relief once they occurred or able to prevent them also should recorded. An additional question should determine whether the episode represent an acute worsening of the chronic pain or was an entirely distinct phenomenon. The Brief Pain Inventory (BPI) is a useful tool to
evaluate the degree to which pain interferes with function and quality of life.5 It offers useful information for episodic pain, including several questions on pain intensity differentiating between average pain and worst pain as an indicator of episodic pain intensity. The Beck Depression Inventory, the Beck Anxiety Inventory, and performance status measures such as Eastern Cooperative Oncology Group and Karnofsky, are other well recognized instruments, which include physical and psychologic symptoms and the ability to function physically, although they do not assess specic questions on episodic pain.
PAIN CATEGORIZATION
The concluded pathophysiology can be categorized as the following: 1. Nociceptive if the pain is related to injured somatic or visceral structures, and is usually described as aching, sharp, or throbbing; 2. Neuropathic if the pain was related to an injury of a neural structure with a typical neuropathic pattern or aberrant characteristics (Fig. 3). Given the broad scope of pain syndromes that may be hidden under the cover of episodic pain, the importance of a differentiated diagnosis must be stressed. The most striking distinction could be made in movement-related pain and nonmovement-related pain (Table 1). The former case typically is associated to bone metastases. Patients have pain well controlled
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Episodic Pain in Cancer/Mercadante et al. TABLE 2 Specic Episodic Pain Problems

With (incident) movement-related pain With neuropathic pain With visceral pain With somatic soft tissue pain (mucositis) Oversedation at rest
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Paroxysmal pain with very short duration Tenesmus of colon or bladder Inability to take oral medication, inability to swallow
FIGURE 3. Algorithm for treatment of neuropathic breakthrough pain.
at rest and tend to prevent pain by limiting their movements, depending on the site of the painful bone metastases. As a consequence, autonomy and quality of life are highly compromised by this status. Incident pain usually has a sudden onset reaching a peak pain intensity within few minutes. Because the onset is quite predictable and can be considered volitional, these episodes are associated with a functional impairment on measures of mood and anxiety, and on scales of pain interferences with function.9 Nonvolitional movements, such as laughing, sneezing, coughing, or myoclonus, may also exacerbate skeletal pain. A Valsalva maneuver induced by coughing and sneezing can precipitate transient elevations in intracranial or spinal cord pressure. Because of the proximity of neural and somatic structures, neuropathic radicular pain often is exacerbated by volitional or nonvolitional movements, as typically observed in situations of epidural compression of the cord or nerve roots. Some other pains should be considered volitional rather than induced by a specic movement. Pain induced by swallowing or chewing in patients with mucositis or touching some hyperesthetic skin areas in patients with neuropathic or somatic pain conditions may precipitate a pain crisis. Mucositis renders patients unable to take oral medication or to swallow, inducing a decrease in food and uid intake. Tenesmus of colon and bladder are induced by attempts in defecation and micturition. Finally, episodic pain may be independent of the movement or volitional conditions. Transient episodes of spontaneous lancinating or burning pain are a common manifestation of neuropathic pain syndromes. These paroxysmal episodes commonly present with a short onset and duration
(seconds or minutes) and require a preventive therapy rather than an as-needed medication.15 Spontaneous muscular contractions of hollow organs (including the esophagus, intestine, gall bladder and their ducts, the urinary bladder, and the ureters) commonly result in paroxysmal transient pain exacerbations. Irritant factors or the obstruction of any hollow viscus may generate such pain with the typical colic pattern. Specic episodic pain mechanisms are listed in Table 2.
TREATMENT
Any temporal increase in pain intensity should be carefully considered, because it may be just a sign of inadequate pain management due to a wrong opioid dose or schedule. Treatment with adjuvant drugs should be optimized because they may be useful in improving basal analgesia and in preventing episodic pain. When exacerbations of pain occur or markedly worsen predictably before next scheduled dose of opioid, pain can be managed by increasing the basal dose or decreasing the interval between dosing until either favorable effects occur or intolerable and unmanageable adverse effects supervene. Dosing on an asneeded basis may be benecial for an appropriate increment in the regularly scheduled dose, when the transient events are attributable to a low daily basal dosage, for example, when rapid escalation is needed. The quantity of rescue medication can be summed to the previous 24 hours consumption to nd out the more appropriate dosage to prevent new episodes in the following days.16 Once an effective background has been provided, precipitating factors and measures able to prevent them, as well as palliative factors should be found, although this often results in a limitation in movement (Fig. 1).
Primary Therapies
The value of primary therapies, such as hormonal manipulation and chemotherapy, remains to be established. In patients with very advanced cancer, there is little justication for using chemotherapy, because of its toxicity. Orthotic devices, such as lightweight
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functional bracing, may be useful with upper extremity bone lesions, and surgical stabilization of the spine and extremities may substantially improve the quality of life, although the potential benets of surgical intervention must be tempered with patient survival. If suitable, surgical abdominal interventions may be helpful in resolving bowel obstruction and, as a consequence, colics associated with a difcult transit. Radiotherapy is a well recognized method to reduce pain from bone metastases. However, no studies to our knowledge have analyzed specically the effect on episodic pain.17
Nonopioid Analgesic Regimens

Different drugs have been used in controlling episodic pain according to specic pain mechanisms. Some algorithms have been designed as a way to facilitate the approach to patients with episodic pain (Figs. 2 and 3).
Antiinammatory drugs
Additive or synergic analgesia produced by nonsteroidal antiinammatory drugs (NSAIDs) and steroidal antiinammatory drugs can be useful in painful bone metastases or mucosal and skin lesions. The specic usefulness in bony pain has not been addressed appropriately. The chances of good pain control until death were high, and the negative inuence of incidental pain was lower when patients achieved a good response using NSAIDs, according to an individual variability in response to analgesics.6 Whereas longacting NSAIDs facilitating once- or twice-daily dosing should be favored in patients already taking multiple drugs, rescue doses of particular formulations (fast release, sublingually, or parenterally) of NSAIDs may be useful in controlling incidental pain when side effects from opioids administered as needed can be expected once the episodic pain disappears. Guidelines in the management of NSAIDs in the patient with cancer pain are largely empiric, drawn from clinical experience. Anecdotal experience has been reported on the use of steroids for this indication as well as for conditions of edema and swelling surrounding peripheral nervous structures.18
Other drugs
Various classes of drugs have been used in episodic pain according to the pain mechanism involved. These treatments have a rationale from the pathophysiologic point of view. However, to our knowledge, no controlled studies have been performed to gain scientic evidence. Spasmolytics such as butylscopolamine or octreotide also may be useful in abdominal colic super-
imposed to visceral pain, often associated with obstruction of the intestinal or urinary tract. Bisphosphonates represent a new class of drugs with inhibitory activity on bone resorption and on inammatory process. Recently, a review of Phase III studies and an evidence-based review have underlined that bisphosphonates are able to reduce both skeletal events and pain in metastatic bone disease without determining relevant adverse effects.19 A reduction in bone pain might potentially result in a reduction of incidental pain. Anecdotal experience reports that bisphosphonate cycles may be useful in reducing movement-related pain.20 However, to our knowledge to date no prospective studies have assessed the role of this class of drugs in preventing or reducing movement-related pain nor the number of rescue doses required with respect to placebo or other treatments. Predictable movement-related pain, such as those occurring with dressing changes or skin toilette, may be prevented with a light sedation using midazolam or ketamine. Ketamine has been found to be useful in neuropathic pain conditions poorly responsive to morphine21 and potentially may prevent pain exacerbations. However, psychomimetic effects are of concern. The regular use of some adjuvants, including antidepressants, antiarrhythmics, and anticonvulsants, have been used to prevent or alleviate paroxysmal burning or lancinating neuropathic pain, although to our knowledge controlled studies in this context are not available. In a recent review, the pain characteristics did not appear to predict the response to specic agents. However, studies were performed in noncancer patients.22,23 Some topical drugs, including capsaicin, aspirin, or a cream of eutectic mixture of local anesthetics, may reduce the input from peripheral nerve lesions.18 Topical application of opioids or local anesthetics is another option in pain due to mucositis or skin ulcers in which pain is precipitated with contact.24 Nitrous oxide has properties that might enable prompt control of episodic pain. It has been safely and effectively used with a 50:50 mixture of nitrous oxide and oxygen by a patient-controlled mechanism by mask in advanced cancer patients with episodic pain from bone metastases.25 The use of psychostimulant drugs such as methylphenidate has been demonstrated to allow patients to tolerate higher doses of opioids during the period between incident pain episodes.26 However, it should be used cautiously, especially in the rst 48 hours of treatment.
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Opioids
Patients with severe episodic pain typically are treated with an opioid drug. When baseline pain is well controlled, eventual increases in opioid dosage will result in oversedation at rest. The use of as-needed analgesia either to prevent an anticipated air of pain or to treat an established episode of pain is the standard symptomatic treatment. A rescue dose must have a rapidity of onset appropriate to the specic pain presentation, appropriate potency, and easy administration. Despite the large clinical experience on the use of opioids, there is limited scientic evidence because few randomized studies have dealt with this subject.
Routes of Administration Oral route

Typically, the rescue doses consist of an immediate release opioid preparation that is usually the same drug as that being administered on an around-theclock basis. The most effective dose remains unknown. Titration of the rescue dose according to the characteristics of the event should be attempted in an individual way to identify the most appropriate dose, although some clinicians suggest a dose roughly equivalent to 510% of the total opioid dose administered as needed every 23 hours.2 The time to peak effect for orally administered opioids is approximately 60 minutes and is not suitable for pains with a short onset and duration. Methadone may have a shorter peak effect.
dent on the level of absorption within the rectum. However, there is no clear anatomic demarcation between the portal and systemic drainage because of the presence of extensive anastomoses, and this may render the proportion of drug absorbed via portal vein difcult to predict. The absorption also depends on the preparation (aqueous or alcoholic solutions, suppositories, use of surfactants), bowel movements, pH of solutions used, and the presence of feces in rectal ampulla. As expected, considerable interindividual variation in bioavailability of morphine administered rectally have been reported. Whereas suppositories generally achieve peak effect within 60 90 minutes, liquid rectal formulations seem to have a shorter peak effect.31
Transmucosal
An oral transmucosal formulation of fentanyl in a matrix that dissolves when rubbed against the buccal mucosa has been developed recently. Transmucosal fentanyl provides a rapid onset of pain relief within 510 minutes,32 comparable to parenterally administered fentanyl. In controlled studies, most patients found this approach safe and effective for episodic pain.3336 Formulations incorporating 200, 400, and more will be available soon in Europe. Dose titration should be individualized, because there is a lack of relation between the effective dose of transmucosal fentanyl and xed schedule of opioids.34,35 Somnolence, nausea, and dizziness are the most common adverse effects associated with this fentanyl formulation. Transmucosal fentanyl was used safely and effectively during long-term treatment of episodic pain for cancer patients at home.37 In a recent pilot study, intranasal fentanyl in doses of 20 g recently has been reported to be effective in the management of episodic pain.38
Sublingual
This alternative route of opioid administration has limited value due to a lack of formulations, poor or irregular absorption of most drugs, and the inability to deliver high doses that are prevented by swallowing. Potent drugs such as sufentanil may be useful to delivery higher doses in lower volumes.27 When compared with morphine, lipophilic drugs such as buprenorphine, fentanyl, sufentanil, and methadone are relatively well absorbed through the buccal mucosa.28 30
Subcutaneous and intravenous route

The onset of action of noninvasive administration may be too slow, and better results may be obtained with a parenteral rescue dose. Subcutaneous administration is associated with a slower onset of effect than intravenous administration, but it should be considered equivalent in terms of efcacy, unless when high volumes are required.39 Opioids are commonly administered via a subcutaneous or intravenous cannula. Repetitive intramuscular injections are not recommended, because they are painful and do not offer pharmacokinetic advantages. Opioids suitable for subcutaneous infusion must be soluble, well absorbed, and nonirritant. Injection site should be changed every 37 days, depending on the type of needle used. Teon cannulas are better
Rectal
Rectal administration potentially offers the possible pharmacokinetic advantage of bypassing rst-pass metabolism by entering the system circulation via lower rectal veins. Rectal morphine is absorbed into the systemic circulation to an extent at least that of oral morphine.30 The use of small amount of liquid may prevent the diffusion into sigmoid colon and avoid the drainage by the superior rectal vein into the portal system. Therefore, the avoidance of rst-pass metabolism is depen-
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tolerated. Among opioids, methadone appears to be relatively irritating.40 More often, these approaches are used in conjunction with simple or sophisticated devices that the patients control to deliver a bolus on demand, set by physicians. The optimal candidates for intravenous or subcutaneous patient-controlled analgesia (PCA) are patients with intravenous or subcutaneous access with irregular or rapidly accelerating pain requiring an immediate treatment.41 The PCA device should be set initially to deliver a continuous infusion with the bolus dose at 25% of the hourly dose and with a lockout intervals of 2 hours. The bolus dose should be adjusted to provide supplementary analgesia to counter or minimize episodic pain.42,43 Cognitive impairment, technical expertise, drug-seeking behavior, and costs are the major drawbacks of this technique.41
with traditional drugs commonly used for cancer pain, including opioids, anticonvulsants, antidepressants, and NSAIDs, unless for transmucosal fentanyl. An attempt to clarify the cultural aspects between European and American people could contribute in homogenizing the language and denition of this phenomenon. Further prospective studies using similar terminologies are necessary to nd the therapeutic intervention, according to the temporal pattern characteristics and the pain mechanism involved.
REFERENCES
1. Hanks GW, Portenoy RK, MacDonald N. Difcult pain problems. In: Doyle D, Hanks GW, MacDonald N, editors. Oxford textbook of palliative medicine. Oxford, UK: Oxford Medical Publications, 1993:25774. Portenoy RK, Hagen NA. Breakthrough pain: denition, prevalence, and characteristics. Pain 1990;41:273 81. Banning A, Sjogren P, Henriksen H. Treatment outcome in a multidisciplinary cancer pain clinic. Pain 1991;47:129 34. Bruera E, Schoeller T, Wenk R, et al. A prospective multicenter assessment of the Edmonton staging system for cancer pain. J Pain Symptom Manage 1995;10:348 55. Caraceni A, Portenoy RK, et al An international survey of cancer pain characteristics and syndromes. Pain 1999;82: 26374. Mercadante S, Maddaloni S, Roccella S, Maddaloni S, Salvaggio L. Predictive factors in advanced cancer pain treated only by analgesics. Pain 1992;50:1515. Fine PG, Busch MA. Characterization of breakthrough pain by hospice patients and their caregivers. J Pain Symptom Manage 1998;16:179 83. Petzke F, Radbruck L, Zech D, Loick G, Grond S. Temporal presentation of chronic cancer pain: transitory pains on admission to a multidisciplinary pain clinic. J Pain Symptom Manage 1999;17:391 401. Portenoy RK, Payne D, Jacobsen P. Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 1999;81:129 34. Fine PG, Busch MA. Characterization of breakthrough pain by hospice patients and their caregivers. J Pain Symptom Manage 1998;16:179 83. Zeppetella G, ODoherty CA, Collins S. Prevalence and characteristics of breakthrough pain in cancer patients admitted to a hospice. J Pain Symptom Manage 2000;20:8792. Mercadante S. What is the denition of breakthrough pain? Pain 1991;45:107. Bruera E, MacMillian K, Kuehn N, et al. Circadian distribution of extra doses of narcotic analgesics in patients with cancer pain: a preliminary report. Pain 1992;49:311 4. Gourlay GK, Plummer JL, Cherry DA. Chronopharmacokinetic variability in plasma morphine concentrations following oral doses of morphine solution. Pain 1995;61:375 81. MacFarlane BV, Wright A, Benson HA. Chronic neuropathic pain and its control by drugs. Pharmacol Ther 1997;75:119. Portenoy RK. Treatment of temporal variations in chronic cancer pain. Semin Oncol 1997;243(Suppl.16):712. Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997;69:1 8. Portenoy RK. Adjuvant analgesic agents. Hematol Oncol Clin North Am 1996;10:10319.
2. 3. 4.
Invasive Techniques
Pain syndromes with episodic somatic and neuropathic mechanism have been resolved by intermittent or continuous administration of local anesthetic by a catheter. This is because of the nding that some locations are more readily accessible with respect to other areas receiving a signicant overlap in sensory innervation. The spinal administration of local anesthetics with an opioid may provide additional analgesia in patients unresponsive to systemic therapies. Individual titration seems to be mandatory to prevent the adverse effects of local anesthetics.42 Epidural clonidine is an important alternative. The benet seems to be more evident in patients with neuropathic pain.43 A percutaneous cordotomy may be indicated in a selected group of patients with refractory incident pain from bone metastases. However, the risk of serious complications, including mirror pain, general fatigue or hemiparesis, and respiratory depression, is high. Intrathecal phenol block, chemical neurolysis of intercostal nerves, and pituitary ablation have been used for cancer pain. The results of these invasive procedures are often suboptimal when considering the risk of serious side effects.17
5.
6.
7.
8.
9.
10.
11.
12. 13.
CONCLUSION
Episodic pain, that is, a transitory exacerbation of pain that occurs in addition to otherwise stable persistent pain, has been associated with a reduced likelihood for adequate pain control. Despite the variable incidence of this condition reported in several surveys, probably because this phenomenon is diagnosed differently in various countries, few prospective controlled study have assessed the efcacy of a treatment
14.
15. 16. 17. 18.
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19. Fulfaro F, Casuccio A, Ticozzi C, Riupamonti C. The role of bisphosphonates in the treatment of painful metastatic disease: a review of phase III trials. Pain 1998;78:157 69. 20. Mercadante S, Villari P, Ferrera P, Dabbene M. Pamidronate in incident pain due to bone metastases. J Pain Symptom Manage 2001;22:630 1. 21. Mercadante S, Arcuri E, Tirelli W, Casuccio A. The analgesic effect of intravenous ketamine in cancer patients on morphine therapy: a randomized controlled double-blind cross-over double dose study. J Pain Symptom Manage 2000;20:246 52. 22. McQuay HJ, Moore RA. An evidence based resource for pain relief. Oxford, UK: Oxford University Press, 1998. 23. Sindrup SH, Jensen TS. Efcacy of pharmacological treatment of neuropathic pain: an update and effect related to mechanism of action. Pain 1999;83:389 400. 24. Krajnik M, Zylicz Z, Finlay I, Luczak J, van Sorge AA. Potential uses of topical opioids in palliative carereport of 6 cases. Pain 1999;80:1215. 25. Keating HJ, Kundrat M. Patient-controlled analgesia with nitrous oxide in cancer pain. J Pain Symptom Manage 1996; 11:126 30. 26. Bruera E, Fainsinger R, MacEachern T, et al. The use of methylphenidate in patients with incident cancer pain receiving regular opiates. A preliminary report. Pain 1992;50:757. 27. Kunz KM, Theisen JA, Schoeder ME. Severe episodic pain: management with sublingual sufentanil. J Pain Symptom Manage 1993;8:189. 28. Coluzzi PH. Sublingual morphine: efcacy reviewed. J Pain Symptom Manage 1998;16:184 92. 29. Mercadante S, Arcuri E. Breakthrough pain in cancer patients. Pathophysiology and treatment. Cancer Treat Rev 1998;24:42532. 30. Ripamonti C, Bruera C. Rectal, buccal, and sublingual narcotics for the management of cancer pain. J Palliat Care 1991;7:30 5. 31. De Conno F, Ripamonti C, Saita L, et al. Role of rectal route in treating cancer pain: a randomized crossover trial of oral versus rectal morphine administration in opioid-naive cancer patients with pain. J Clin Oncol 1995;13:1004 8. 32. Cleary JF. Pharmacokinetic and pharmacodynamic issues in the treatment of breakthrough pain. Semin Oncol 1997; 24(Suppl.16):S16 39. 33. Christie JM, Simmonds M, Patt R, et al. Dose-titration, multicenter study of oral transmucosal fentanyl citrate for the
839
34.
35.
36.
37.
38.
39.
40.
41. 42. 43.
44. 45.
treatment of breakthrough pain in cancer patients using transdermal fentanyl for persistent pain. J Clin Oncol 1998; 16:3238 45. Farrar JT, Cleary J, Rauck R, Busch M, Nordbrock E. Oral transmucosal fentanyl citrate: randomized, double-blinded, placebo-controlled trial for treatment of breakthrough pain in cancer patients. J Natl Cancer Inst 1998;90:611 6. Portenoy RK, Payne R, Coluzzi P, et al. Oral transmucosal fentanyl citrate (OTFC) for the treatment of breakthrough pain in cancer patients: a controlled dose titration study. Pain 1999;79:30312. Coluzzi PH, Schwartzberg L, Conroy JD, Chaparata S, Gay M, Busch MA, et al. Breakthrough cancer pain: a randomised trial comparing oral transmucosal fentanyl citrate (OTFC) and morphine sulphate immediate release (MSIR). Pain 2001;91:12330. Payne R, Coluzi P, Hart L, Simmonds M, Lyss A, Rauck R, et al. Long-term safety or oral transmucosal fentanyl citrate for breakthrough cancer pain. J Pain Symptom Manage 2001; 22:575 83. Zeppetella G. An assessment of the safety, efcacy, and acceptability of intranasal fentanyl citrate in the management of cancer-related breakthrough pain: a pilot study. J Pain Symptom Manage 2000;20:253 8. Nelson KA, Glare A, Walsh D, Groh ES. A prospective, within-patient, crossover study of continuous intravenous and subcutaneous morphine for chronic cancer pain. J Pain Symptom Manage 1997;13:2627. Bruera E, Fainsinger R, Moore M, et al. Local toxicity with subcutaneous methadone. Experience of two centers. Pain 1991;45:1413. Mercadante S. Alternatives to oral opioids for cancer pain. Oncology 1999;13:21525. Ripamonti C, Bruera E. Current status of patient-controlled analgesia in cancer patients. Oncology 1997;11:373 80. Walsh T, Smith EM, Currie K, et al. A pilot study, review of literature, and dosing guidelines for patient-controlled analgesia using subcutaneous morphine sulphate for chronic cancer pain. Palliat Med 1992;6:21726. Mercadante S. Problems of long-term spinal opioid treatment in advanced cancer patients. Pain 1999;79:113 Eisenach JC, Du Pen S, Dubois M, et al. Epidural clonidine analgesia for intractable cancer pain. Pain 1995;61:3919.
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Pain and pain treatments in European palliative care units. A cross sectional survey from the European Association for Palliative Care Research Network
Pa l Klepstad Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Stein Kaasa Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway, Nathan Cherny Pain and Palliative Medicine, Shaare Zedek Medical Center, Jerusalem, Israel, Geoffrey Hanks Department of Palliative Medicine, Bristol Oncology Centre, Bristol, UK, Franco de Conno Istituto Nazionale dei Tumori, Milan, Italy and the Research Steering Committee of the EAPC+ The Research Network of the European Association for Palliative Care (EAPC) performed a survey of 3030 cancer patients from 143 palliative care centres in 21 European countries. The survey addressed pain intensity and the use of non-opioid analgesics, adjuvant analgesics and opioids. Patients were treated with analgesics corresponding to the WHO pain ladder step I (n 0/855), step II (n 0/509) and step III (n 0/1589). The investigators assessed 32% of the patients as having moderate or severe pain. In general there were small differences between pain intensities across different countries. Cancer primary sites and the presence of metastasis had only minor influences on pain intensity. The most frequently used nonopioid analgesics were NSAIDs (26%) and paracetamol (23%). Adjuvant analgesics or co/ of the patients were corticosteroids (39%), tricylic antidepresanalgesics used by 1% sants (11%), gabapentin (5%), bisphosphonates (4%), clonazepam (2%), carbamazepine (4%) and phenytoin (2%). The use of non-opioid analgesics and co-analgesics varied widely between countries. Opioids administered for mild to moderate pain were codeine (8%), tramadol (8%), dextropropoxyphene (5%) and dihydrocodeine (2%). Morphine was the most frequently used opioid for moderate to severe pain (oral normal release morphine: 21%; oral sustained-release morphine: 19%; iv or sc morphine: 10%). Other opioids for moderate to severe pain were transdermal fentanyl (14%), oxycodone (4%), methadone (2%), diamorphine (2%) and hydromorphone (1%). We observed large variations in the use of opioids across countries. Finally, we observed that only a minority of the patients who used morphine needed very high doses. Palliative Medicine 2005; 19: 477 /484
Key words: analgesics; cancer; opioid; pain; palliative care; survey
Introduction
Pain is one of the most frequent symptoms among cancer patients with metastatic disease. The prevailing principle for treatment of cancer pain is the WHO three-step pain ladder in which pain treatment is escalated from the use of non-opioids as the first step, through a second step using opioids for mild to moderate pain, up to the third step applying opioids for moderate and severe pain.1
*At the time of this study the members of the Research Committee of the EAPC were Franco de Conno (chair), Augusto Caraceni, Nathan Cherny, Jose Antonio Ferraz Goncalves, Carl Johan Fu rst, Geoffrey Hanks, Stein Kaasa, Sebastiano Mercadante, Juan Manuel Nunez Olarte, Lukas Radbruch, Carla Ripamonti and Frederic Stiefel. Address for correspondence: Pa l Klepstad, Department of Anaesthesiology and Acute Medicine, St. Olavs University Hospital, 7006 Trondheim, Norway. E-mail: pal.klepstad@ntnu.no
# 2005 Edward Arnold (Publishers) Ltd
Based on the WHO pain ladder, a more detailed European recommendation for the use of morphine and alternative opioids has been published by an expert committee of the European Association for Palliative Care (EAPC),2 which parallels its US counterparts guidelines for the treatment of cancer pain.3 Despite the widespread use and recognition of recommendations for the treatment of cancer pain, results from retrospective and prospective surveys consistently show that pain is still prevalent in patients with malignant disease. Cleeland et al . surveyed the intensity of pain in 1308 outpatients with metastatic cancer and observed that 42% of those with pain were not given adequate analgesic therapy.4 The inadequacy of cancer pain treatment was also demonstrated by an IASP Task Force on Cancer Pain survey which reported that among 1095 patients treated by pain specialists, 20% reported average pain intensity of ]/7 on a 10-point numerical rating scale and 67% reported worse pain of ]/7.5 A recent
10.1191/0269216305pm1054oa
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P Klepstad et al. phine, hydromorphone and hydrocodone. Doses were registered for those patients who used morphine. The investigators assessed the patients symptom severity over 24 hours applying a 4-point verbal rating scale with the descriptors none, mild, moderate or severe. The symptoms rated were pain, fatigue, generalized weakness, focal weakness, anxiety, anorexia, depression, confusion, constipation, diarrhoea, nausea, vomiting, sleep disturbance, dyspnoea, itching, hallucination and hiccups. Statistics All data are descriptive in character. Collection and organization of the data were performed at the Unit for Applied Clinical Research, Norwegian University of Science and Technology. The SPSS statistical software for Windows v.10.07 was used for all statistical analyses.
Norwegian survey observed that 13% of cancer patients on ongoing morphine treatment reported an average pain score of ]/7. These data suggest that there has been little improvement in pain treatment since the IASP task force project was completed.6 In 2000, the Research Network of the EAPC initiated a questionnaire survey among 141 palliative care centres in 21 European countries. One of the main objectives of the survey was to provide detailed information on the use of strong opioids and other key drugs by specialist palliative care services. This was a select sample of patients in the care of palliative care services, but the data provide some insights into the epidemiology of symptoms and the use of non-opioid and opioid analgesic drugs in a palliative care patient population across European countries.
Methods
Palliative care centres The project was organized by the Research Network of the EAPC. Palliative care centres were recruited from 15 states in the European Union (in June 2000), as well as Norway, Switzerland, Iceland, Israel, Romania and Cyprus. In each country a national co-ordinator recruited individual centres with a maximum of ten in each country. In the countries where the national coordinators identified more than ten palliative care centres, a representative selection based upon the distribution of palliative care programmes in that country was identified. Data on contributing centres, patient demographics and symptoms will be reported in a separate paper. Study period This was a cross-sectional survey performed during week 23 of the year 2000. All patients treated in the palliative care programme, either as in-patients or out-patients, during this week were eligible. Study procedure A physician or other health care professional completed a questionnaire for each patient currently in the care of the palliative care service. The questionnaire included the demographics, age, gender, cancer diagnosis and presence of metastasis. Current medications used for pain control at the time of inclusion into the study were recorded as yes or no in respect of predefined categories of medications. These categories included the non-opioid drugs: paracetamol, dipyrone, aspirin, NSAIDs, dexamethasone, prednisolone, other corticosteroids, amitriptyline, other antidepressants, gabapentin, carbamazepine, phenytoin and clonazepam. The opioid drugs recorded were codeine, tramadol, dextropropoxyphene, dihydrocodeine, morphine, fentanyl, methadone, oxycodone, diamor-
Results
Patients Reports were submitted on 3030 patients from 143 centres located in 21 countries. The patients were admitted to cancer hospital departments (8%), general hospital departments (28%), hospices (39%) or treated as outpatients (26%). The patients mean age was 66 years (0 /19 years: 24 patients; 20 /39 years: 127 patients; 40 /59 years: 798 patients; 60 /79 years: 1555 patients; 80 /99 year: 504 patients, /100 years: three patients). The majority of patients suffered from a malignant disease (94%). Other diseases were neurological (3%), respiratory (0.5%), cardiac (0.5%), renal (0.3%) or AIDS (0.3%). Among those patients with cancer, breast cancer was the most prevalent malignant diagnosis with lung cancer and colorectal cancer as the second and third most prevalent cancer diagnosis (Table 1). Some 30% of the patients had bone metastases. Liver and lung were the two other sites of metastasis observed in more than one-tenth of the patients (Table 2). Pain and other symptoms A total of 32% of the patients had pain of intensity that was moderate or severe (Table 3). The reported pain intensity varied between countries: on a 4-point scale, the lowest mean score of 1.6 was reported from Austria and the highest mean score of 2.6 was reported from Romania. However, in general there were small differences in pain intensity across different countries (data can be supplied from the first author). The percentage of patients who were considered to have moderate or severe pain were 11% of those receiving WHO pain ladder step I treatment (n 0/855), 30% for step II treatment (n 0/509) and 43% for step III treatment (n 0/1589). Overall, there were only minor differences in
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Table 1 Malignant diagnosis
Number of patients 471 395 349 214 201 189 134 121 114 87 71 54 44 37 32 25 18 228 59 2843 % 17 14 12 8 7 7 5 4 4 3 3 2 2 1 1 1 1 8 2 100
479
Table 3
Severity
Symptom severity: clinician assessment*

None (%) 31 16 17 40 43 52 54 57 65 70 70 79 84 91 92 95 96 Mild (%) 37 33 30 30 30 28 27 27 20 10 21 11 10 5 5 3 2 Moderate (%) 24 33 33 21 18 14 14 13 12 11 8 6 5 3 2 1 1 Severe (%) 8 18 20 9 9 5 6 4 4 9 2 3 2 1 1 1 0.5
Primary site Breast Lung Colorectal Prostate Female reproductive organs Head and neck Stomach Pancreas Haematological malignancy Bladder Renal Skin (including malignant melanoma) Oesophagus Sarcoma Brain Liver Thyroid Others Unknown Total
Pain Fatigue Generalized weakness Anxiety Anorexia Depression Constipation Poor sleep Dyspnoea Focal weakness Nausea Confusion Vomiting Diarrhoea Itch Hallucination Hiccups
*Overall severity for the past 24 hours.
pain intensities between different cancer diagnoses (data can be supplied from the first author). The only notable exception was for primary brain tumours, which were associated with reports of lower pain intensity than other sites. Pain severity was not influenced by the presence of bone, liver, lung or brain metastases (data can be supplied from the first author). Symptoms other than pain were prevalent in this population. Commonly reported symptoms of moderate or greater severity were generalized weakness (53%), fatigue (51%), anxiety (30%), anorexia (27%), constipation (20%), mood disorder (19%), lack of sleep (17%), dyspnoea (16%) and nausea (10%) (Table 3). Non-opioid analgesics NSAIDS and paracetamol were the most frequently used non-opioid analgesics. Acetylsalicylic acid (1%) and dipyrone (2%) were given only to a small number of patients. Use of adjuvant analgesics was commonplace. Various types of corticosteroids were used by 39% of the patients and dexamethasone was the most frequent choice. Less commonly used adjuvant analgesics were tricylic antidepressants, most often amitriptyline (11%), gabapentin
Table 2
Site Bone Liver Lung Peritoneum Brain Skin Pleural Others
(5%), bisphosphonates (pamidronate and clodronate) (4%), clonazepam (2%), phenytoin (2%), carbamazepine (4%), sodium valproate (1%), baclofen (1%), calcitonin (0.4%) and sodium channel blockers (lidocaine and mexiletine) (0.2%). The use of non-opioid analgesics and adjuvant analgesics varied widely between countries (Table 4). Opioid analgesics The opioids administered for mild to moderate pain were codeine (8%), tramadol (8%), dextropropoxyphene (5%) and dihydrocodeine (2%). Morphine was the most frequently used opioid for moderate to severe pain (oral normal release morphine: 21%; oral sustained-release morphine: 19%; iv or sc morphine: 10%). Other opioids used in the management of severe pain were transdermal fentanyl (14%), oxycodone (normal release oxycodone: 2%; sustained release oxycodone: 2%), methadone (2%), diamorphine (2%) and hydromorphone (1%). Of those patients receiving morphine, approximately three-quarters were treated with doses B/150 mg/24 hours, and only a very small minority used a dose /1000 mg (Table 5). Similar sets of data were not reported for the other opioids. The use of step II opioids varied across countries (Table 6). Codeine was not given to cancer patients in Austria and Portugal, while 25% of the patients from Greece received this drug. The Greek patients, however, did not use tramadol, a drug used frequently in Romania (23%), Italy (23%), Finland (17%), Portugal (14%) and Spain (13%). Also the prescription practice of another WHO step II drug, dextropropoxyphene, varied between countries. One quarter of Romanian patients received dextropropoxyphene, a drug not used at all in nine of the countries.
Localization of metastases
Number of patients 901 605 450 283 231 124 119 325 % 30 20 15 9 8 4 7 11
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Table 4
Total (n /3030) (19) (10) (46) (7) (2) (5) (2) (23) (4) (1) (1) (7) (2) (2) Netherlands (n /42) (36) (31) (25) (2) (5) (2) (5) (31) (7) (4) (39) (13) (1) Norway (n /121) Portugal (n /43) (28) (26) (49) (16) (5) (12) (4) (5) (5) (65) (22) (17) (2) (9) Italy (n /269) (4) (35) (54) (2) (6) (8) (3) (80) (20) (20) (40) (100) (60) Luxembourg (n /5) (1) (2) (3) (37) (8) (4) (4) (1) (1) (7) Romania (n /94) (12) (44) (32) (22) (10) (5) (1) (14) (1) (24) (5) (2) (30) (41) (23) (4) (5) (4) (1) (6) (15) (8) (45) (29) (43) (15) (6) (29) (1) (2) (33) Austria (n /59) Belgium (n /109) Cyprus (n /133) Denmark (n /88) Finland (n /139) France (n /160) Germany (n /101) UK (n /783) Greece (n /72) (15) (39) (28) (22) (6) (1) (3) (4) Spain (n /195) (16) (21)
Use of non-opioids by country (No. of patients (% of patients))

Iceland (n /72) (10) (28) (42) (15) (1) (1) (4) Sweden (n /168) (49) (20) (54) (5) (3) (5) (1) (5) Switzerland (n /65) (34) (32) (2) 11 28 0 0 20 16 4 1 0 2 3 7 20 0 0 30 11 0 0 1 1 3
Paracetamol NSAIDs Acetylsalicylic acid Dipyrone Corticosteroids TCA Gabapentin Bisphosphonates Clonazepam Phenytoin Carbamazepine Ireland (n /205) (18) (37) (0.5) (44) (6) (10) (5) (1) (5) (1) (10) (7) (3) (2) (13) (38) (5) 27 79 1 0 93 13 21 5 2 10 3 6 8 0 14 41 5 0 11 7 3 2 (6) (8) 10 94 0 0 206 32 16 20 0 0 9 5 3 0 0 4 1 1 2 0 0 0 15 13 0 0 11 1 2 1 0 2 0 47 16 1 0 38 9 5 0 0 0 5 12 11 0 0 21 7 2 5 0 2 2 Israel (n /107)
700 792 43 66 1179 337 152 132 57 64 108
(23) (26) (1) (2) (39) (11) (5) (4) (2) (2) (4)
0 11 0 6 27 4 1 3 1 0 5
16 9 0 1 36 5 2 0 1 2 3
60 38 0 0 30 5 1 1 0 9 2
38 13 0 0 57 19 15 2 0 0 0
8 40 2 0 51 11 6 6 1 2 9
28 23 1 3 68 37 11 9 29 0 3
(18) (14) (1) (2) (43) (23) (7) (6) (18)
2 33 0 30 41 23 4 5 4 1 6
261 222 37 1 228 89 30 30 1 16 24
(33) (28) (5) (0.1) (29) (11) (4) (4) (0.1) (2) (3)
266
Paracetamol NSAIDs Acetylsalicylic acid Dipyrone Corticosteroids TCA Gabapentin Biphosphonates Clonazepam Phenytoin Carbamexapine
11 41 0 0 30 30 9 5 0 1 13
32 42 0 11 85 9 14 7 6 9 6
(6) (44) (5) (7) (4) (3) (5) (3)
82 33 0 0 90 9 5 9 0 2 8
22 15 1 0 32 1 3 4 4 2 2
(49) (2) (5) (6) (6) (3) (3)
Distribution by countries for non-opioid analgesic drugs and co-analgesics used by /1% of the patients. Some patients may have received a non-opioid drug or a coanalgesic drug for indications other than pain.
Cross sectional survey from the European Association
Table 5
Dose (mg) B/30 /30 /60 /60 /150 /150 /300 /300 /600 /600 /1000 /1000 /1500 /1500
481
Distribution of daily doses of morphine

Morphine oral (%) 28 26 22 13 6 3 1 0.2 Morphine parenteral (%) 32 26 19 11 6 3 2 0.5
The formulation of morphine varied between countries. Oral normal release morphine is most frequently used in Ireland, Denmark and Norway, while Romania, Luxembourg, Iceland and Italy rarely use this formulation. The use of sustained release morphine varied from 3% in Greece to 43% in Iceland. The use of sc or iv morphine varied from B/5% in several countries (Cyprus, Finland, UK, Greece) to /30% in Austria and Portugal. Fentanyl was the most used opioid for moderate or severe pain in Belgium, Denmark, Greece and Netherlands. Oxycodone was most used in Denmark, Finland and Israel, hydromorphone most often used in Germany, Ireland and Switzerland and diamorphine was used only in Belgium and the UK. Opioids for severe pain were often combined with a non-opioid analgesic drug. Of the 1416 patients treated with a WHO step III opioid analgesic, 334 received paracetamol and 504 received a NSAID.
Discussion
This paper presents a cross-sectional survey of the incidence and intensity of pain and of the use of analgesic medications prescribed for pain in European palliative care units. The principal findings of the survey are that most patients are treated with moderate doses of morphine, that there is considerable variability between countries in the use of non-opioids, and a similar large variability between countries in the selection of opioids. In this survey about one-third of the patients were assessed as having moderate or severe pain. This result confirms that pain is still prevalent in cancer patients. The number of patients with pain observed in this palliative care patient population was similar to reported incidences of pain in other cancer patient populations, such as those treated as out-patients,4 or those admitted to a general hospital.6 The reasons why such a high proportion of patients had moderate or severe pain are not clear. Potential causes are lack of knowledge of adequate pain treatment,7,8 fear of prescribing opioids,9 or patient related barriers towards the use of opioids.10,11 Lack of compliance may cause inferior pain treatment, especially if opioids are prescribed on an as required
basis.12 Lack of treatment success may also be caused by failure to recognize specific cancer pain syndromes needing differential pain treatments. An IASP Task Force on Cancer Pain identified 22 pain syndromes as prevalent and observed that 40% of patients had some pain of neuropathic origin.5 These findings indicate that in some cases poor pain control is a result of inaccurate or inadequate diagnosis. The pain intensities were in general rather uniform across the different countries and were also similar to results obtained in US surveys.4 However, the pain ratings were slightly higher in some countries of which Romania had the highest pain scores. It is not clear why this should be, but potential explanations are differences in the availability of opioids because of legislative or economic restrictions, doctor or patient barriers against opioid use, differences in pain assessment or different expectations about acceptable pain relief. Patients with brain cancer had less pain compared to the other patients. For all other cancer diseases, the difference in pain from the lowest ratings (gastric and liver cancer) to the highest ratings (sarcoma and head and neck cancer) was only 0.5 on the 4-point pain verbal rating scale. Thus, cancer primary site had no major influence on pain intensities. This finding was surprising since it is assumed that highly invasive cancers generally cause a more intense pain stimulus. Previous studies have also reported that patients with bone metastases are subject to more intense pain.13 No association was observed between the presence of bone metastases and pain intensity in this survey. The explanation may be that increased pain caused by a more invasive cancer or by a metastasis is simply counterbalanced with higher opioid doses. Another explanation not addressed in this survey may be that pain related to bone metastases is more associated with breakthrough pain,13 which is not adequately assessed using a global pain assessment. The findings of only minor associations between pain intensity and cancer primary site suggest that clinicians should not over emphasize the implications of a particular cancer diagnosis or the presence of metastasis when considering the expected success of pain treatment. An interesting finding of this survey is the wide variation in use of analgesics across countries. This variability is evident for non-opioids, opioids for mild to moderate pain, and opioids for moderate and severe pain. The EAPC guidelines recommend morphine as the first choice step III opioid.2 Despite the EAPC recommendation, some countries such as Belgium (fentanyl), Finland (oxycodone), Greece (fentanyl) and Israel (fentanyl) do not use morphine as the opioid of first choice. Another interesting opioid in terms of differences in use between countries is diamorphine, which is exclusively used in Belgium and the UK. In the UK, diamorphine is the most frequently used opioid for
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Table 6
Total (n /3030) (3) (6) (7) (7) (13) (27) (2) (5) (3) Luxembourg (n /5) (17) (21) (29) (50) (2) (5) (2) Netherlands (n /42) Norway (n /121) (9) (4) (1) (2) Portugal (n /43) (19) (12) (30) (21) (1) (6) (2) (10) (8) (1) (3) (5) (34) (2) (35) (21) (24) (40) (15) (9) (17) (5) (15) (3) (19) (23) (2) (2) (1) (6) (1) (1) Austria (n /59) Belgium (n /109) Cyprus (n /133) Denmark (n /88) Finland (n /139) France (n /160) Germany (n /101) UK (n /783) Greece (n /72) (25) (7) (1) (7) (3) (4) (42) (1)
Use of opioids by country (No. of patients (% of patients))

Iceland (n /72) (19) (4) (1) (43) (6) (17) (1)
(2) (5) (5) (10) (34) (17) (5) (10) (25) (26) (20) (24) (4) (1) (4) (9) Romania (n /94) (7) (11) (12) (1) (11) (1) (10) (1) (6) (14) (2) (5) (23) (14) (26) (3)
(7) (5) (3) (9) (23) (21) (24) (19)
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Ireland (n /205) (22) (19) (8) (29) (29) (7) (1) (1) (1) (2) (2) (23) (15) (1) (2) (17) (12) (4) (0.4) (4) Israel (n /107) Italy (n /269) (38) (36) (127) (9) (1) (1) (10) (2) (1) (4) (0.5) (0.5) (2) (31) (29) (11) (15) (1) (3) (1) 77 73 24 18 2 2 21 0 3 2 8 1 1 4 23 20 8 31 31 7 0 0 1 1 0 1 0 2 4 45 33 10 1 10 0 0 62 39 3 0 0 6 0 1 (20) 0 0 0 0 0 0 1 (20) 1 (20) 0 0 0 0 7 9 12 21 0 0 1 0 2 1 0 0 0 4 38 35 13 18 1 3 1 0 1 13 1 0 1 7 8 5 13 9 0 0 0 0 6 0 1 2 0 0
Codeine Dextropropoxyphene Dihydrocodeine Tramadol Morphine oral normal release Morphine oral sustained release Morphine parenteral Fentanyl Oxycodone Methadone Hydromorphone Diamorphine Hydrocodone Other opioids (1) Spain (n /195) (11) (16) (13) (10) (6) (13) (4) (2) (0.5) (0.5)
227 155 53 229 520 561 302 417 111 66 62 52 4 89
(8) (5) (2) (8) (17) (19) (10) (14) (4) (2) (2) (2) (0.1) (3)
0 0 1 3 3 6 20 10 0 0 3 0 0 0
3 0 0 7 8 8 14 29 0 2 0 5 0 3
7 45 0 3 13 11 1 4 0 0 0 0 0 0
2 1 0 2 31 18 21 35 13 8 0 0 0 8
8 1 0 23 7 21 4 26 32 3 0 0 0 5
11 8 4 14 36 34 39 31 0 1 9 0 1 4
1 0 0 10 25 26 20 24 4 1 4 0 0 9
82 51 38 31 172 132 4 68 25 5 10 47 0 6
(10) (7) (5) (4) (22) (17) (0.5) (9) (3) (0.5) (1) (6)
18 5 1 0 5 2 3 30 0 1 0 0 0 0
14 0 0 3 1 31 4 12 0 1 0 0 0 3 Sweden (n /168) (11) (20) (15) (10) (1) (4) (2) (1) (4) (1) (1) (13)
(4) Switzerland (n /65) (28) (12) (14) (5) (2) (10) (8) (2) 0 7 10 0 0 11 0 0 22 13 24 0 0 3 21 32 25 19 0 11 0 0 26 8 0 4 1 1 18 33 25 17 2 0 6 0 4 2 7 1 1 22 18 8 9 3 0 1 6 0 5 1 0 0 0 1
Morphine oral immediate release Morphine slow release Morphine parenteral Fentanyl Oxycodone Methadone Hydromorphone Diamorphine Tramadol Codeine Dextroporopoxyphene Dihydrocodeine Hydrocodone Other opioids
(2)
Cross sectional survey from the European Association 483 sc opioid infusions. Diamorphine is preferred to morphine for parenteral administration because of its greater solubility. Few patients received methadone. The exception was observed in Romania, where methadone was the most used opioid for moderate to severe pain, however this may be related to the low cost of methadone in Romania. Methadone is a drug in which there has recently been much renewed interest and is recommended by several authorities as an alternative opioid in cases not successfully treated with morphine, especially for patients suffering from neuropathic pain.14 The use of step II opioids also varied considerably between countries. For example, the use of tramadol and dextropropoxyphene varied from no use in some countries to being the most frequently prescribed opioid drug in other countries (dextropropoxyphene: Cyprus and Romania; tramadol: Italy). The reasons for these large variations in the use of opioids for cancer pain across Europe are unclear. Potential factors are clinical traditions, price, education and legal or cultural barriers to the use of opioids. There also remains little available data from high quality studies / randomized controlled trials (RCTs) / in which head to head comparisons of opioids have been made. This lack of formal evidence,15 may be a cause of the variability in cancer pain treatment between countries. Another finding in the subsample of patients using morphine was that relatively few patients needed very high doses of morphine (Table 4). This observation may reflect that most patients are adequately treated with low or moderate doses of opioids, and similar experience has been reported before.16 However, the number of patients who still reported moderate or severe pain despite treatment with step III opioids suggests the possibility that some, at least, were receiving inadequate doses. Adjuvant analgesics were used in about one-fifth of the patients. Those used in /1% of patients were tricyclic antidepressants, bisphosphonates and anticonvulsants. The findings in this survey indicate that palliative care physicians in general apply the recommended co-analgesics for selected cases. The choice of adjuvant (i.e., gabapentin versus tricyclic antidepressant) varies between countries. All patients included in this study were in the care of a palliative care specialist service. Therefore, this study represents specialist practice in different European countries and it is not possible to draw inferences from these data about non-specialist practice in these countries. We recognize some limitations in this cross-sectional study. First, this study used observer ratings for symptom assessments. Observer assessments are known to underestimate pain intensity.17 If present, an under report of pain should result in a systematic error and therefore not jeopardize the validity of comparisons across countries, diagnoses, or different groups of medications. Second, in this survey we did not obtain data on the number of patients who refused inclusion or on the number of eligible patients who were not approached for study inclusion. Finally, we do not know if all non-opioids or adjuvant analgesics were prescribed with the intention of achieving improved pain control. For example, some patients may have been prescribed paracetamol for fever, corticosteroids for other diseases or anticonvulsants for prevention of epileptic seizures. In conclusion, this survey presents the first European epidemiological study on palliative care patients symptoms, use of non-opioid analgesics and use of opioids. We observed that one-third of the individual patients had clinically significant pain. There were large variations in the use of both non-opioids and opioids across countries, but the intensities of pain were still relatively evenly distributed across the participating countries. Cancer primary site and the presence of metastases had minor influence on pain intensity. Finally, we observed that for patients who used morphine, only a minority needed very high doses.
Acknowledgements The study was performed within the Research Network of the European Association for Palliative Care. In addition to the authors the following investigators participated in the study: study coordinator : K Torvik (Norway). National coordinators : R Likar (Austria), J Menten, (Belgium), J Kakas (Cyprus), L Pedersen (Denmark), E Kalso (Finland), P Poulain (France), L Radbruch (Germany), K Mystakidou (Greece), V Sigurdardottir (Iceland), T OBrien (Ireland), B Thill (Luxembuourg), B Zylics (Netherlands), J Ferraz Goncalves (Portugal), L Ionescu-Ca linesti (Romania), JM Nunes (Spain), CJ Fu rst (Sweden), F Porchet (Switzerland), K Done (UK). Coordinators at clinical sites : Austria: G Forche, JP Zoidl, H Retschitzegger, M Werni-Kourik, B Stapel, C Stabel. Belgium: A Verhoeve, P Cornil, M Faignaert, T van Iersel, J Menten, K Sterckx, R Veekhoven, K Claassens, C Bieke, J Indirjian, S Michael, B Pitsillides, R Christou, N Koupi. Denmark: M Mrk, A Bonde, L Pedersen, B Enig. Finland: T Saarto, J Ha nninen, T Leino. France: B Veronique, R Duclos, L Hacpille, G Laval, MHH Salamagne, P Vinan. Germany: M Cremer, F Nauck, G Hanekop, L Latasch, W Diemer, M Kloke, L Radbruch, C Bausewein, C Mu ller-Busch. UK: J Dale, D Alison, M Fallon, L Forman, C Sinnott, A Wilcock, C Regnard, M Nugent, K Forbes, C Higgs. Greece: K Mystakidou, E Tsiouri, A Kritikou, E Argiraki, T Christos, G Evgenia, E Kosmidou, M Tsitoura. Iceland: V Sigurdardottir, S Bjo rnsson, N Fredriksdottir, G Thorsdottir, H Helgadottir, E Hjo rleifsdottir. Ireland: L OSiorain, S Kingston, J Flemming, R McQuillan,
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484 P Klepstad et al. M Kearney, S Donelly, T McCormack, T OBrien. Israel: Y Zinger, R Gassner, M Bercovitch. Italy: E Arcuri, R Bortolussi, O Corli, M Gallucci, A Gottlieb, M Maltoni, M Visentin, G Zaninetta, F Zucco. Luxembourg: B Thill. Netherlands: AJM Wolf, RJ van Boxtel, Z Zylicz, R Voskamp, J Koningswoud-ten Hove, F Baar. Norway: N Magery, S Ottesen, S Jrgensen. Portugal: F Goncalves, AL Marques Goncalves, I Galrica Neto. Romania: C Bogdan, G Popescu, M Daniela, H Cristina. Spain: JM Nunez Olarte, G Maranon, A Tuca i Rodriguez, J Porta i Sales, C Centeno Cortes, M Nabal Vicuna, J Sanz Ortiz, N Peraz de Lucas, R Rodeles del Pozo, L Azuara Rodriguez. Sweden: G Eckerdal, I Fridegren, I Underskog, CJ Fu rst, A Janson, A-M Graavgaard, M Fahlstro m. Switzerland: A Levorato, D Anwar, S Pautex, G Gremaud, S Eychmu ller, H Gudat.
survey of cancer patients characteristics and syndromes. Pain 1999; 82: 263 /74. Klepstad P, Loge JH, Borchgrevink PC, Mendoza TR, Cleeland CS, Kaasa S. The Norwegian Brief Pain Inventory questionnaire: translation and validation in cancer pain patients. J Pain Symptom Manage 2001; 24: 517 /25. Warncke T, Breivik H, Vainio A. Treatment of cancer pain in Norway. A questionnaire study. Pain 1994; 57: 109 /16. Sloan PA, Donelly MB, Scwartz RW, Sloan DA. Cancer pain assessment and management by housestaff. Pain 1996; 67: 475 /81. Zenz M, Willweber-Strumpf A. Opiophobia and cancer pain in Europe. Lancet 1993; 341: 1075 /76. Paice JA, Toy C, Shott S. Barriers to cancer pain relief: fear of tolerance and addiction. J Pain Symptom Manage 1998; 16: 1 /9. Weiss SC, Emanuel LL, Fairclough DL, Emanuel EJ. Understanding the experience of pain in terminally ill patients. Lancet 2001; 357: 1311 /15. Miaskowski C, Dodd MJ, West C, et al . Lack of adherence with the analgesic regimen: a signicant barrier to effective cancer pain management. J Clin Oncol 2001; 19: 4275 /79. Mercadante S. Malignant bone pain: pathophysiology and treatment. Pain 1997; 69: 1 /18. Ripamonti C, Zecca E, Bruera E. An update on the clinical use of methadone for cancer pain. Pain 1997; 70: 109 /15. Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA 1995; 274: 1870 /73. Hanks GW, Twycross RG. Pain, the physiological antagonist of opioid analgesics. Lancet 1984; 1: 1477 /78. Zalon ML. Nurses assessment of postoperative patients pain. Pain 1993; 54: 329 /34.
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References
1 World Health Organisation. Cancer pain relief . Geneva: WHO, 1996. 2 Hanks GW, De Conno F, Cherny N, et al . Morphine and alternative opioids in cancer pain: the EAPC recommendations. Br J Cancer 2001; 84: 587 /93. 3 Jacox A, Carr DA, Payne R, et al . Management of cancer pain: adults quick reference guide , Volume 9. Rockville, MD. Agency for Health Care Policy and Research, US Department of Health and Human Services Publication, 1994. 4 Cleeland CS, Gonin R, Hateld AK, et al . Pain and its treatment in outpatients with metastatic cancer. N Engl J Med 1994; 330: 592 /96. 5 Caraceni A, Portenoy RK and a Working Group of the IASP Task Force on Cancer Pain. An international
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Palliative Medicine 2007; 21: 15 22
A cross sectional survey of the European Association for Palliative Care (EAPC) Research Network1
The members of the Research Steering Committee of the EAPC at the time of the study were Franco de Conno (chair), Augusto Caraceni, Nathan Cherny, Jose Antonio Ferraz Goncalves, Carl Johan Fu rst, Geoffrey Hanks, Stein Kaasa, Sebastiano Mercadante, Juan Manuel Nunez Olarte, Lukas Radbruch, Carla Ripamonti and Frederic Stiefel. Address for correspondence: Stein Kaasa, Pain and Palliation Research Group, Faculty of Medicine, Norwegian University of Science and Technology, 7006 Trondheim, Norway. E-mail: stein.kaasa@ntnu.no
# 2007 SAGE Publications 10.1177/0269216306072086
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Key words: organisation; palliative care; research
Patients in palliative care are elderly, frail and in decline with multisystem disease. These and other factors make palliative care research particularly challenging, and has been one of several reasons why relatively little systematic research has been performed. The European Association for Palliative Care (EAPC) is seeking to emphasise the importance of research. The present project is the first empirical multicentre study organised by the EAPC Research Network, with the aim of identifying the patient population using specialised palliative care, and identifying a network of palliative care services across Europe, able to participate in a multicentre collaboration for research. During a designated week in the autumn of 2000, data on patients were recorded from 143 centres. The survey was carried out by means of two questionnaires, one centre questionnaire and one patient questionnaire. Data were submitted on 3013 patients from 22 different European countries. Almost all patients had cancer (94%), while some had neurological disease (3%). The majority (75%) had been referred to a palliative care service during the six to seven months before the survey was performed. Very few patients had less than one week of expected survival (6%), the majority were expected to live one to six months, while as many as 16% were expected to live more than one year. The majority of the patients (27%) were fully ambulatory the ability to walk independently without any assistance. The majority of the patients (60%) received care as an outpatient, either at a traditional clinic in an outpatient cancer hospital (12%), in home-care programs from a specialised advisory service (24%), or external nursing care (24%). The population of patients included in this survey was not a sample of dying patients. There were a substantial number of patients with an anticipated life expectancy of more than six months. The study demonstrated a considerable enthusiasm for research in the palliative care community across Europe. The heterogeneity of the sample is evident, and this will need careful consideration for future clinical trials. This calls for an international consensus on how to report on patient characteristics within palliative care research. This is necessary in order to be able to evaluate the representativity of the study population, as well as to compare data between studies. The range of services encountered in the survey highlights the need for the organisational and clinical standards for palliative care, which can be audited. Palliative Medicine 2007; 21: 15 22
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Stein Kaasa Faculty of Medicine, Norwegian University of Science and Technology, Trondheim and Department of Oncology, St. Olavs University Hospital, Trondheim, Karin Torvik Department of Nursing, College of Higher Eduction, Oslo, Nathan Cherny Department of Oncology, Shaare Zedek Medical Center, Jerusalem, Geoffrey Hanks Department of Palliative Medicine, Bristol Haematology and Oncology Centre, Bristol and Franco de Conno Rehabilitation and Palliative Care, Istituto Nazionale Dei Tumori, Milano
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Patient demographics and centre description in European palliative care units
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Introduction
Palliative care is a relatively young discipline, and epidemiological data are essential in order to provide a credible evidence-base for clinical practice.1,2 There are particular difficulties in conducting clinical research in a palliative care environment. Patients are elderly, frail and in decline with multisystem disease patients are usually severely ill with a progressive condition and limited survival time; they may have many symptoms for which they will be receiving several drugs concurrently; and environmental and psychological factors have a variable, but potentially great effect on physical well being.3 5 All of these factors make palliative care research particularly challenging, and is one reason why relatively little systematic research had been carried out in this area. The European Association for Palliative Care (EAPC) has recognised these difficulties, but at the same time seeks to emphasise the importance of research.6 The EAPC has set up a Research Network (RN), whose main objective is to encourage and facilitate research in palliative care.7 The present project is the first empirical multicentre study organised by the RN of the EAPC. A secondary objective of the investigation was to identify a collaborative group of palliative care services across Europe with the ability to provide epidemiological and clinical data for this and future studies. The study was a cross-sectional survey, carried out in 2000, and encompassed 143 palliative care centres in 21 European countries. The project included all 15 member states (at the time of the research) of the European Union, as well as Norway, Switzerland, Iceland, Israel, Romania and Cyprus. The aims of the study were: 1)
Material and methods

Palliative care centres One national co-ordinator in each country recruited a maximum of 10 eligible centres in that country. We did not attempt to collect a representative sample of patients and centres according to strict scientific principles. However, in the countries where the national co-ordinators identified more than 10 centres, he/she was asked to identify a representative selection based upon his/her own experience and knowledge of the centres and of the range and distribution of palliative care programmes in that country. Study period The study was performed during a designated week in Autumn 2000. All patients who were actively receiving care from the palliative care programme on one specific day in the designated week were to be included. The questionnaires The survey was carried out by means of two questionnaires. One centre questionnaire to be completed for each centre/programme, and a patient questionnaire to be completed for every patient. The patient questionnaires were completed by the doctor, nurse or other health professionals who was the primary carer or who knew the medical and social details of the patient. The following information was collected.
3)
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To identify patient populations using specialist palliative care services in terms of demographic data, diagnostic groups, social circumstances and performance status in 21 different European countries. To provide detailed information on the use of strong opioid analgesics and some other key drugs by specialist palliative care services. To identify a network of palliative care services across Europe with the ability to participate in collaborative research.
In this paper, the demographics of the palliative care survey are presented together with basic patient characteristics.
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Patient data Anticipated life expectancy (on a categorical scale ranging from B/24 hours, one to six days, one week to one month, one to six months, six months to one year to /1 year), mobility (ranging from fully ambulatory, able to walk independently, but at an impaired level, needs assistance with walking, bed- or chair-bound, able to get to toilet to bed- or chair-bound, unable to get to the toilet). Centre data Type of service provided by the centre categorised as: hospice (freestanding), hospital palliative care ward (inpatient), day hospital, ambulatory service (outpatient), palliative care consultation service in a hospital, home care service, telephone consultation service (patient follow up), telephone consultation service for community doctors and nurse, and other. If more than one service was provided more than one box could be ticked off. Place of palliative care service delivery Place of palliative care delivery, categorised as: cancer hospital, general hospital, hospice, ambulatory/outpatient-based service, day care, home care (specialist
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Patient demographics and centre description in European palliative care units advisory service), home care (extended nursing care, or hospice at home) and other. More than one category could be ticked when care was delivered at several places simultaneously. Ethics Ethical approval was obtained at each centre according to national and/or regional recommendations. Statistics Descriptive statistics only are presented. Collection and organisation of the data was performed at the Unit for Applied Clinical Research, Norwegian University of Science and Technology. The statistical software SPSS for Windows v. 12 was used for all statistical analyses.
17
Patients Data were submitted on 3013 patients from 143 centres (Table 1). In most countries, with the exception of France, Ireland, Italy and Spain, the majority of the patients in this survey were female (56%), and the mean age for the total sample was 66 years (range 2 103 years) (Table 1). The majority of patients were married (54%), and the remaining were either widowed (25%), single (11%), divorced (7.5%), or living with a partner (3%).
Table 1 Patient characteristics
Age, years (mean; range) Male (66; 2 98) Female (66; 3 103)
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Marital status Single Married Unmarried with partner Widows Divorced Home circumstances Lives alone Lives with spouse who is in good health Lives with spouse who is not in good health Lives with other relative who is In good health Missing home circumstances
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No. % 1320 44 1693 56 316 10.5 1625 54 80 3 759 25 227 7.5 851 1320 317 467 58 28 44 10.5 15.5 2 2239 74 472 16 138 5 2831 94 90 3 16 0.5 15 0.5 10 0.3 43 1.5
Percent
Less than 24 hours
1 - 6 days
1 week to 1 month
1 to 6 months
6 months to 1 year
Diagnosis Cancer Neurological Respiratory Cardiac AIDS Other
Anticipated life expectancy
Figure 1 Anticipated life expectancy estimated by the health care provider (physician)
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> 1 year
Date of first referral to palliative care 2000 1999 1998
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50 40 30 20 10 0
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Results
Service characteristics The number of centres per country varied from one to 13, and the number of patients per country varied from five to 778 (Table 2). As shown in Table 2, the median number of patients per centre varied considerably from seven in Greece and the Netherlands, to 30 and 40 in Norway and the UK, respectively. Looking at the range, a substantial number of centres (48/143) had B/10 patients included in the study. The majority of the centres were either based upon a general hospital (33%), hospice (25%) or cancer hospital (8%), while a minority of the services were based upon home care (Table 3). Consequently as many as 2171 (74%) of the patients were recruited from inpatient-based services. The type of service provided per centre is presented in Table 4. In the questionnaire, it was possible to check off more than one type of service per centre. In order to give a general overview, the raw scores are expressed in Table 4. In all countries, except Cyprus, all services provided at least day hospital care and/or ambulatory
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Most patients were living with a spouse or other relative in good health (59%). Almost all the patients had cancer (94%), while some had a neurological diagnosis (3%), respiratory disease (0.5%), cardiac disease (0.5%), or AIDS (0.3%). The majority (75%) had been referred to the palliative care service during the six to seven months before the survey was performed; 16% had been referred during the year 1999, while 4% were referred before 1998. Very few patients had less than one week of expected survival (6%), the majority were expected to live one to six months, while as many as 16% were expected to live more than one year (Figure 1). The majority of the patients were fully ambulatory (27%) or able to walk independently (28%), while 21% were bed- or chair-bound unable to get to the toilet (Figure 2).
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Discussion
One of the objectives of this project was to identify a collaborative group of investigators in palliative care across Europe. The EAPC RN succeeded by recruiting 143 centres from 22 countries, and collected data on a total of 3013 patients. One reason for the successful outcome was the establishment of a data co-ordinating centre at the Palliative Medicine Unit in Trondheim, Norway. The need for such an organisation has long been recognised by other groups conducting clinical research in cancer patients, such as the EORTC, and by research funding bodies in many countries. The data collection was successful in spite of severe constraints on the budget. The national co-ordinators organised the study in their countries without any financial reimbursement from the EAPC RN. Clearly, this reflects the considerable enthusiasm generated by the project and the keenness of the palliative care services in so many countries to be involved in research. This experience contradicts the scepticism, raised by many palliative care providers, about the willingness of palliative care centres to participate in research. Several countries in Europe have identified a need for research in palliative care. For example, a recent report from the National Cancer Research Institute in the UK points out that the organisation of research is fragmented, and that the challenge is to achieve genuine collaborative work.8 In a Norwegian report, it is recommended that a Chair in Palliative Medicine should be established at all universities in the country in order to organise, regionally and
Fully ambulatory
Able to walk Needs assistance Bed or chair bound, Bed or chair independently, but with walking able to get to toilet bound, unable to at an impaired level get to toilet
Mobility
Table 2
Country
Distribution of centres, patients, gender per country and patients per centres
No. of centres No. of patients Gender per country Male (%) 29 49 36 36 37 56 37 43 39 53 40 52 20 31 39 39 40 51 42 43 43 44 Female (%) 71 51 64 64 63 44 63 57 61 47 60 48 80 69 61 60.5 60 49 58 57 57 56 No. of patients per centres Median 10 9 21 17 20 10 11 7 8 20 22 26 7 30 10 15 17 16 11 40 13 Range (min max) 2 17 1 27 15 56 8 25 3 51 2 36 2 23 2 19 1 33 8 53 14 47 6 50 4 10 20 40 8 25 2 43 6 37 5 48 6 20 5 299 1 299
Austria Belgium Cyprus Denmark Finland France Germany Greece Iceland Ireland Israel Italy Luxembourg Netherlands Norway Portugal Romania Spain Sweden Switzerland UK Total
7 10 5 5 5 13 9 8 7 8 4 10 1 6 4 3 5 10 7 6 10 143
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58 109 132 88 139 160 101 70 72 203 104 267 5 42 121 43 93 195 168 65 778 301
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Place of care delivery Place of palliative care delivery was reported for each patient and included eight categories. More than one category could be ticked when care was delivered at several places simultaneously. The majority of the patients (60%) (Figure 3) received care as an outpatient, either at a traditional clinic in an outpatient cancer hospital (12%) or in home care programmes, and received care from a specialist advisory service (24%) or extended nursing care (24%). Less than one-quarter of the patients received care in a hospice.
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services. Palliative care services within hospitals were established in most countries. It should be noted that the sample includes more hospital palliative care wards (n 0/49) than free-standing hospices (n 0/35).
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Figure 2 Mobility evaluated by the health care provider (physician)
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Patient demographics and centre description in European palliative care units 19

Table 3 Centre identication What is your centre based upon?
No. of patients (%) Cancer hospital 227 (7.5) General hospital 808 (27) Hospice 1137 (38) Ambulatory/outpatient hospital39 (1) based service Day care 7 (0.2) Home care (special advice service) 74 (2.5) Home care hospice at home 380 (13) Other 260 (9) Missing centre identification 81 (3) No. of centres (%) 12 47 36 1 1 7 17 19 3 (8) (33) (25) (0.7) (0.7) (5) (12) (13) (2)
Table 4 Type of services provided per centre

Country No. of centres Hospice (free-standing)
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Hospital palliative care ward (Inpatient) 4 1 2 3 5 7 1 3 1 3 1 2 2 2 5 1 3 3 49
nationally, education and research within this field.9 The poor evidence-base for much clinical practice in palliative care highlights the urgent need for well-conducted prospective studies, preferably randomised controlled trials.10 There is no doubt that one common recommendation is the need for national and international collaboration in order to perform large enough studies with a representative sample of patients. Recent Cochrane reviews evaluating oral morphine for cancer pain,11 and hydromorphone for acute and chronic pain,12 conclude that too many small, non-conclusive, studies have been performed, the heterogeneity of the studies is enormous, and the possibility to perform meta-analysis is limited. One interesting finding in this survey is the heterogeneity of the sample. However, it needs to be taken into consideration when the data are discussed that the
sample is not representative of centres providing care at either a national or international level. The number of centres per country and number of patients per centre varied considerably. Furthermore, palliative care was delivered in cancer hospitals and general hospitals, as well as hospices. The type of services differed somewhat between countries, however, in most countries both inpatients, consultation services and home care services were provided. Such a heterogeneity of palliative care was also found in a recent report, which assessed the development of palliative care services.13 Within the seven countries studied, UK, Sweden, Italy, Germany, Spain, Belgium and The Netherlands, the founding initiative of palliative care took place over a period of 14 years, from 1967 to 1991. The founding services varied from inpatient hospice and hospital inpatient units, to home care services and palliative care units within departments of medical oncology. In 1999, the number of inpatient hospice/palliative care units varied from 219 in the UK, to 18 in the Netherlands and three in Italy. A similar wide variation was found in the ratio of the inpatient hospice and palliative care beds to populations. In the UK, the number of beds per person was 1:17 866, in Spain 1:49 261 and in Italy 1:1 913 332. These numbers reflect, to some extent, the different periods of time during which palliative care has developed in different countries (with the UK being the longest, starting in 1967), but also differences in the way in which healthcare is organised and delivered in different countries. Another problem is related to differences between centres and/or
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Day hospital and/or ambulatory service (Outpatients) 1 3 3 3 9 6 5 3 4 2 7 1 2 4 1 1 6 3 3 8 75
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1 2 1 1 10 5 1 2 5 1 6 2 1 2 5 3 6 54
PC consultation Home care service in a service hospital
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1 5 4 4 3 6 6 5 6 3 7 1 2 3 5 5 3 69
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Austria 7 Belgium 10 Cyprus 5 Denmark 5 Finland 5 France 13 Germany 9 Greece 8 Iceland 7 Ireland 8 Israel 4 Italy 10 Luxembourg 1 Netherlands 6 Norway 4 Portugal 3 Romania 5 Spain 10 Sweden 7 Switzerland 6 UK 10 Total 143
2 2 1 4 3
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Telephone consultation service 5 5 4 3 11 7 3 2 8 1 5 4 3 2 2 8 3 2 5 83
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30 25 20
15 10 5 0
Place of palliative care delivery
countries on how the various types of facilities are defined according to the type of their actual care delivery. To our knowledge, there is no consensus internationally on this issue. Most palliative care patients reported by the participating services were not imminently dying. One of the striking, and encouraging, findings of this survey was the number of patients with an anticipated life expectancy of more than six months. Indeed, the overwhelming majority of patients had been referred at least six months prior, and had an anticipated life expectancy of more than a month. These findings reflect referral and practice patterns that are in keeping with the WHO recommendations that palliative care be started relatively early in the trajectory of incurable illness. The models of service delivery to palliative care varies considerably, with regard to the type of facility (inpatient units, hospice, day care, out patient clinics and home care services) and also the staffing. There are major national and international idiosyncrasies which have influenced the types of service which have been developed and the involvement and medical and nursing staff, social workers and rehabilitation staff. There are important differences even within individual countries in the availability of medical and paramedical staff to multidisciplinary palliative care teams. In a British survey performed in the Thames region, access to doctors was only provided in some centres, and some services describe themselves as more medically oriented, while other centres describe themselves as mostly socially oriented.14 In Spain, there are no free standing hospices, and many home care teams consist of a core team of a physician and a nurse and, frequently, a psychologist.15 During the last decade, palliative care has, in many countries, been incorporated into the public health care system with public funding.16 18
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Figure 3 Place of palliative care delivery reported by each centre, more than one alternative could be ticked
In this study, the majority of the centres were general or cancer hospitals; hospices were in a minority. This highlights the fact that, in many countries, hospices do not exist, but palliative care is still widely provided within the secondary care sector. It is not necessary to have a hospice in order to provide high quality palliative care. An encouraging finding is that palliative care seems to be embedded in many countries into the mainstream of health care delivery. On the other hand, these data may reflect recruitment bias. We did not attempt to obtain a representative sample and it is not possible to draw firm conclusions about all of the issues raised. However, the data certainly present some interesting trends which need to be followed up. Many centres reported on 10 patients. These centres are clearly very small services or presumably have very little infrastructure particularly to support research. The participation of such services in this study indicates a considerable enthusiasm to further research in palliative care. The small numbers again emphasise the need to be cautious in interpreting the data. The national co-ordinators were asked to include all palliative care programmes in their country, up to a maximum of 10 centres. In five countries, the maximum of 10 centres was reached; Belgium, France, Italy, Spain and UK. In all other countries B/10 centres were included, which may indicate either that very few palliative care programmes are developed in that country or that few are able to participate in such a study. Clearly, there remains an unmet need for specialist palliative care and the establishment of new palliative care centres in most European countries. There are major differences between countries, even in Europe, in the way in which health care is organised and delivered, and for this reason alone it would be very difficult to produce guidelines on service delivery for specialist palliative care which would be widely applicable. A Task Force of the EAPC is now systematically collecting information on how palliative care is delivered in most European countries, and another group is working on Centres of Excellence in palliative care. The aim is to improve the understanding of how palliative care is and should be delivered, and ultimately, this should lead to international definitions and standards for palliative care.7 We believe that the data from the present survey together with the work performed by the EAPC groups and the political initiatives taken in many countries, will improve the quality of palliative care and identify palliative care as a speciality in other countries than the UK. With different types of palliative care services in hospitals, or dedicated beds and/or specialist units in nursing homes/hospices at the community level and home care programmes, a comprehensive national network of
Out patients hospital service Home care: Spec. advisory service Home care: Ext. nursing care
Cancer hospitals
General hospitals
Hospice
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Patient demographics and centre description in European palliative care units services will provide care for patients, wherever their preference is for this care. Palliative care is assumed by many health care providers, politicians and the lay public to focus on terminal care, that is care of the dying patient. It is noteworthy that the population of patients included in this survey was not a sample of dying patients. There were a substantial number of patients with an anticipated life expectancy of more than six months, and only a minority was identified as dying patients. This emphasises that a palliative care approach may be applicable early in the disease trajectory, a concept incorporated in the EAPC definition of palliative care.18
21
Conclusions
This study has demonstrated a considerable enthusiasm for research in the palliative care community across Europe. However, it has also highlighted the fact that many palliative care services, whilst they may be interested in carrying out research, do not have the infrastructure to support it. It seems clear that, in terms of multicentre clinical trials, the EAPC has access to potentially very large numbers of healthcare workers who could participate in research and, thus, access to potentially large numbers of patients. The heterogeneity of the sample is evident, and this would need careful considerations for future clinical trials. We have no doubt that prospective identification of suitable patients would be possible for a particular study. The range of services encountered in the different countries highlights the need for organisational and clinical standards for palliative care which can be audited. These are already available in some countries, such as the UK, but need to be modified to make them applicable to other European countries. Finally, it is clear that palliative care services are serving a population of patients who may not necessarily be in the terminal phase of their illness. It is appropriate that the principles of palliative care be applied to the care of cancer patients, at whatever stage of their illness, when their needs demand it.
Kakas (Cyprus), L Pedersen (Denmark), E Kalso (Finland), P Poulain (France), L Radbruch (Germany), K Mystakidou (Greece), V Sigurdardottir (Iceland), T OBrien (Ireland), B Thill (Luxembourg), B Zylics (Netherlands), J Ferraz Goncalves (Portugal), L Ionescu-Ca linesti (Romania), JM Nunes (Spain), CJ Fu rst (Sweden), F Porchet, K Done (UK). Co-ordinators at clinical sites: Austria: G Forche, JP Zoidl, H Retschitzegger, M Werni-Kourik, B Stapel, C Stabel. Belgium: A Verhoeve, P Cornil, M Faignaert, T van Iersel, J Menten, K Sterckx, R Veekhoven, K Claassens, C Bieke, J Indirjian, S Michael, B Pitsillides, R Christou, N Koupi. Denmark: M Mrk, A Bonde, L Pedersen, B Enig. Finland: T Saarto, J Ha nninen, T Leino. France: B Veronique, R Duclos, L Hacpille, G Laval, MHH. Salamagne, P Vinan. Germany: M Cremer, F Nauck, G Hanekop, L Latasch, W Diemer, M Kloke, L Radbruch, C Bausewein, Harlaching, C Mu he. ller-Busch, Havelho UK: J Dale, D Alison, M Fallon, L Forman, C Sinnott, A Wilcock, C Regnard, M Nugent, K Forbes, C Higgs. Greece: K Mystakidou, E Tsiouri, A Kritikou, E Argiraki, T Christos, G Evgenia, E Kosmidou, M Tsitoura. Iceland: V Sigurdardottir, S Bjo rnsson, N Fredriksdottir, G Thorsdottir, H Helgadottir, E Hjo rleifsdottir. Ireland: L OSiorain, S Kingston, J Flemming, R McQuillan, M Kearney, S Donelly, T McCormack, T OBrien. Israel: Y Zinger, R Gassner, M Bercovitch. Italy: E Arcuri, R Bortolussi, O Corli, M Gallucci, A Gottlieb, M Maltoni, M Visentin, G Zaninetta, F Zucco. Luxembourg: B Thill. Netherlands: AJM Wolf, RJ van Boxtel, Z Zylicz, R Voskamp, J Koningswoud-ten Hove, F Baar. Norway: N Magery, S Ottesen, S Jrgensen. Portugal: F Goncalves, AL Marques Goncalves, I Galrica Neto. Romania: C Bogdan, G Popescu, M Daniela, H Cristina. Spain: JM Nunez Olarte, G Maranon, A Tuca i Rodriguez, J Porta i Sales, C Centeno Cortes, M Nabal Vicuna, J Sanz Ortiz, N Peraz de Lucas, R Rodeles del Pozo, L Azuara Rodriguez. Sweden: G Eckerdal, I Fridegren, I Underskog, CJ Fu rst, A Janson, A-M Graavgaard, M Fahlstro m. Switzerland: A. Levorato, D Anwar, S Pautex, G Gremaud, S Eychmu ller, H Gudat.
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Acknowledgements This project was organised by the Research Network Steering Committee of the EAPC. Data collection was performed at the Pain and Palliation Research Group at the Norwegian University of Science and Technology (NTNU), Trondheim, Norway. Study coordinator: K Torvik (Norway). National coordinators: R Likar (Austria), J Menten, (Belgium), J
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References
1 McQuay HJ, Moore A, Wiffen P. The principles of evidence-based medicine. In Doyle D, Hanks G, Cherny N, Calman K eds. Oxford textbook of palliative care , third edition. 2004: 119 28. 2 Hanks G, Kaasa S, Robbins M. Research in palliative care: getting started. In Doyle D, Hanks G, Cherny N, Calman K eds. Oxford textbook of palliative care , third edition. 2004: 128 38. 3 Jordhy M, Kaasa S, Fayers P, Ovreness T, Underland G, Ahlner-Elmqvist M. Challenges in palliative care
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research; recruitment, attrition and compliance: experience from a randomised controlled trial. Palliat Med 1999; 13: 299 310. Grande G, Todd C. Why are trials in palliative care so difcult? Palliat Med 2000; 14: 69 74. Cook AM, Finlay IG, Butler-Keating RJ. Recruiting into palliative care trials: lessons learnt from a feasibility study. Palliat Med 2002; 16: 163 65. Blumhuber H, Kaasa S, De Conno F. The European Association for Palliative Care. J Pain Symptom Manage 2002; 24: 124 27. Available at www. eapcnet.org Partners in Cancer Research. Supportive and palliative care research in the UK: report of the NCRI Strategic Planning Group on supportive and palliative care . National Cancer Research Institute, July 2004. Norges offentlige utredninger. Livshjelp. Behandling, pleie og omsorg for uhelbredelig syke og dende. NOU 1999:2. Kaasa S, Dale O; Pain and Palliation Research Group. Building up research in palliative care: an historical perspective and a case for the future. Clin Geriatr Med 2005; 21: 81 92. Wiffen PJ, Edwards JE, Barden J, McQuay HJM. Oral morphine for cancer pain (Review). The Cochrane Collaboration . The Cochrane Library, 2005 (Issue 1). 12 Quigley C. Hydromorphone for acute and chronic pain (Review). The Cochrane Collaboration . The Cochrane Library, 2005 (Issue 1). 13 Clark D, ten Have H, Janssens R. Common threads? Palliative Care Service developments in seven European countries. Palliat Med 2000; 14: 479 90. 14 Higginson IJ, Hearn J, Myers K, Naysmith A. Palliative day care: what do services do? Palliative Day Care Project Group. Palliat Med 2000; 14: 277 86. 15 Centeno C, Arnillas P, Hernansanz S, Flores LA, Gomez M, Lopez-Lara F. The reality of palliative care in Spain. Palliat Med 2000; 14: 387 94. 16 Jordhoy MS, Fayers P, Saltnes T, Ahlner-Elmqvist M, Jannert M, Kaasa S. A palliative-care intervention and death at home: a cluster randomised trial. Lancet 2000; 356: 888 93. 17 DL. 28 dicembre 1998 n8 450 convertito nella legge (converted in the law) n8 39/99 del 26/2/99 (programma nazionale per la realizzazione di strutture per Cure Palliative) (National Programme for the Realization of Structure of Palliative Care). 18 German Hospice Association (Bundesarbeitsgemeinschaft Hospiz). Available at www.hospiz.net/gesetze/ index.html;http://www.eapcnet.org/about/denition.html
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Desenvolvimento de Um Sistema Integrado para Avaliação Inicial Dos Doentes Oncológicos Admitidos em Cuidados Paliativos

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Desenvolvimento de um Sistema Integrado para Avaliao Inicial dos Doentes Oncolgicos admitidos em Cuidados Paliativos | 1

jos antnio saraiva ferraz gonalves

Orientador: Professor Doutor Rui Nunes Co-orientador: Dr. Nigel Sykes

Tese de candidatura ao grau de doutor apresentada Faculdade de Medicina da Universidade do Porto

Artigo 48, pargrafo 3 A Faculdade no responde pelas doutrinas expedidas na dissertao

corpo catedrtico da faculdade de medicina da universidade do porto

Para a ngela, o Daniel e o Ricardo.

Quadro 1 Quadro 2 Quadro 3 Quadro 4 Quadro 5 Quadro 6 Quadro 7 Quadro 8 Quadro 9

Quadro 10 Dados demogrficos.

a portuguese palliative care unit

Support Care Cancer (2000); 9:4-7

Support Care Cancer (2000) 9 : 47 DOI 10.1007/s005200000211

SUPPORTIVE CARE INTERNATIONAL

Jos Antnio S. Ferraz Gonalves

A Portuguese palliative care unit

Support Care Cancer (2000) 9 : 47 DOI 10.1007/s005200000211

Jos Antnio S. Ferraz Gonalves

A Portuguese palliative care unit

The first unit

The new unit

diagnosis disclosure in a portuguese oncological centre

Palliative Medicine (2001); 15:35-41

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Palliative Medicine 2001; 15: 3541

Diagnosis disclosure in a Portuguese oncological centre

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36 J Ferraz Gonalves and S Castro

mittee of the Portuguese Institute of Oncology Oporto Centre.

No. of questionnaires returned 22 12 5 6 45

Total returned (%) 49 27 11 13 100

Returned per speciality (%) 42 50 21 46

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Diagnosis disclosure in a Portuguese oncological centre 37

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J Ferraz Gonalves and S Castro

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Palliative Medicine (2005); 19:526-531

Palliative Medicine 2005; 19: 526 /531

Breaking bad news 527

alternative or complementary explanation for these observations is denial amongst patients.22

Breaking bad news 531

validation of a consciousness level scale for palliative care

Palliative Medicine (2008); 22:724

Palliative Medicine 2008; 22: 724729

Validation of a Consciousness Level Scale for Palliative Care

Consciousness Level Scale for Palliative Care

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726 F Gonalves et al. Statistical analysis

Face validity The results for face validity were as follows:

Table 1 Demographic data

Correlation between scales

Age: median of 68 years (range: 3882).

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728 F Gonalves et al.

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Consciousness Level Scale for Palliative Care Appendix

Procedures for assessment:

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avaliao da funo cognitiva

avaliao dos doentes sem alteraes cognitivas