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VOLUME 175 NUMBER 4 OCTOBER, NOVEMBER, DECEMBER 2006 CONTENTS INCLUDE: Heart Failure: Elevated BNP Home
VOLUME 175 NUMBER 4 OCTOBER, NOVEMBER, DECEMBER 2006 CONTENTS INCLUDE: Heart Failure: Elevated BNP Home
VOLUME 175 NUMBER 4 OCTOBER, NOVEMBER, DECEMBER 2006 CONTENTS INCLUDE: Heart Failure: Elevated BNP Home
VOLUME 175 NUMBER 4 OCTOBER, NOVEMBER, DECEMBER 2006 CONTENTS INCLUDE: Heart Failure: Elevated BNP Home

VOLUME 175 NUMBER 4

OCTOBER, NOVEMBER, DECEMBER 2006

VOLUME 175 NUMBER 4 OCTOBER, NOVEMBER, DECEMBER 2006 CONTENTS INCLUDE: Heart Failure: Elevated BNP Home vs

CONTENTS INCLUDE:

Heart Failure: Elevated BNP Home vs Hospital Initiated Thrombolysis Structuring Diabetes Care Hypertension in Type 2 Diabetes FDG-PET Scanning : Cancer of the Oesophagus HRT: Have We Changed?

Diabetes Care Hypertension in Type 2 Diabetes FDG-PET Scanning : Cancer of the Oesophagus HRT: Have
EDITORIAL BOARD Editor-in-Chief David Bouchier-Hayes Editor Brian Sheppard Editorial Assistant Helen
EDITORIAL BOARD
EDITORIAL BOARD

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JMS Doctor Awards Editor

TN Walsh

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J Fenton

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Howell

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O’Connor

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Sreenan

 

S Tierney

EXECUTIVE OF THE ACADEMY President

FD O’Kelly

General Secretary

J O’Connor

Immediate Past President

D Bouchier-Hayes

Members

TN Walsh

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Published by The Royal Academy of Medicine in Ireland

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CONTENTS
CONTENTS

Original PaPers

5

Elevated BNP with normal systolic function in asymptomatic individuals at-risk for heart failure:

A marker of diastolic dysfunction and clinical risk

S

Karuppiah, F Graham, M Ledwidge, C Conlon, J Cahill, C O’Loughlin, J McManus, K McDonald

14

Feasibility and long term outcome of home vs hospital initiated thrombolysis

B

McAleer, MPS Varma

0

The experiences and attitudes of general practitioners and hospital staff towards pre-hospital thrombolysis in a rural community

D

Tedstone Doherty, J Dowling, P Wright, J Cuddihy

6

Low molecular weight heparin prophylaxis in day case surgery

J

Shabbir, PF Ridgway, W Shields, D Evoy, JB O’Mahony, K Mealy

30

Validation of a point of care lipid analyser using a hospital based reference laboratory

M

Carey, C Markham, P Gaffney, G Boran, V Maher

36

Lipid lowering targets are easier to attain than those for treatment of hypertension in type diabetes

M

Sherlock, D Mylotte, J Mac Mahon, KB Moore, CJ Thompson

4

Structuring diabetes care in general practices: Many improvements, remaining challenges

S

Jennings, DL Whitford, D Carey, SM Smith

48

FDG-PET scanning in the management of cancer of the oesophagus and oesophagogastric junction:

Early experience with 100 consecutive cases

V

Malik, M Keogan, C Gilham, G Duffy, N Ravi, JV Reynolds

55

Poor awareness of colorectal cancer symptoms; a preventable cause of emergency and late stage presentation

AT

Manning, R Waldron, K Barry

58

HRT: Have we changed?

O

Conlon, K McKinney

6

A review of neonatal attendances out of hours in a Dublin maternity hospital

LFA Wong, KT Lim, A Twomey, J Murphy

granD rOUnD

66

Management of spontaneous rupture of the oesophagus (Boerhaave’s syndrome): Single centre experience of 18 cases

R

Prichard, J Butt, N Al-Sariff, S Frohlich, S Murphy, B Manning, N Ravi, JV Reynolds

71

Endovascular aneurysm repair in a patient with a horseshoe kidney and impaired renal function

MS Sajid, N Ahmed, J Tibbals, G Hamilton

74

Encrusted Cystitis — An Unusual Cause of Recurrent Frank Haematuria

O

O’Sullivan, O Clyne, J Drumm

76

Comminuted fracture of the thoracic spine

JP

Cashman, FL Carty, M Ryan, K Mahalingham

79

Small bowel volvulus secondary to a mesenteric lipoma: a case report and review of the literature

AS McCoubrey, RLE Thompson

COrresPOnDenCe

81

Extensor tendon rupture of finger while playing Uileann pipe

SM Ali, DO’Farrell

8

Ultraviolet phototherapy risks in Ireland

C

Dupont

8

Repetitive transcranial magnetic stimulation: A psychiatric treatment of the future?

H O’Connell, R Goggins, PG Doyle

BOOK reVieWs

83 The Menopause: what you need to know

E V Mocanu

84 Private Practice — In the early twentieth century medical office of Dr. Richard Cabot

C S Breathnach

century medical office of Dr. Richard Cabot C S Breathnach  IRISH JOURNAL OF MEDICAL SCIENCE
PREss RELEAsE
PREss RELEAsE

PREss RELEAsE

Springer and the Royal Academy of Medicine of Ireland enter into publishing partnership

Irish Journal of Medical Science added to growing medical portfolio

London/New York, 17 November 2006

4

Springer, one of the world’s leading scientific publishers, has announced a partnership with the Royal Academy of Medicine of Ireland (RAMI) to publish their journal, the Irish Journal of Medical Science (IJMS), starting in 2007. The addition of this journal to Springer’s portfolio accentuates its growing strength in medical publishing.

Established in 1832, the Irish Journal of Medical Science is one of the first and foremost scientific journals in the Anglo-Celtic islands. With articles written by international specialists, it covers all branches of medicine and publishes papers relevant to the daily practice of the medical professional.

IJMS will be published quarterly and will contain reviews, original articles and commentaries. The Editor-in- Chief is Professor David Bouchier-Hayes,

a surgeon with a strong reputation in Ireland and internationally.

Dr. Fergus O’Kelly, President of the RAMI, said, “This

is an exciting and most important time for the Royal

Academy of Medicine of Ireland and its official organ,

the Irish Journal of Medical Science. The Executive Board of the Royal Academy is most positive about our association with Springer.” Dr. John O’Connor, General Secretary, continued, “We look forward to this partnership and the many benefits that Springer’s publishing experience will bring to the journal.”

Christiane Notarmarco, Executive Editor at Springer London, echoed their sentiments, “We are proud to be associated with such a respected and historic body as the RAMI and are delighted to be supporting their mission. Through global distribution and electronic publishing on SpringerLink, IJMS will continue to grow.”

Springer will publish the Irish Journal of Medical Science in both electronic and print formats to serve the needs of librarians and readers around the world. The journal will be available via SpringerLink,

Springer’s fully integrated, online information platform. Both Online First™, a feature where articles are published online before they appear in print, and Editorial Manager, an online peer review and author submission system, will be fully implemented for the journal. The Springer Open Choice program offers all potential IJMS authors the option of publishing their articles using the open access model once they have been accepted for publication.

access model once they have been accepted for publication. ABOUT RAMI The Royal Academy of Medicine

ABOUT RAMI

The Royal Academy of Medicine of Ireland (www.rami.ie) was formed in 1882, following an amalgamation of the four main medical societies in Ireland. At present there are over 1,200 fellows and members of the Academy representing 22 medical specialty sections. The primary role of the Academy is to provide a forum for the exchange of scientific information and to promote the academic discussions essential to scientific progress.

ABOUT SpRINgER

Springer (www.springer.com) is the second-largest publisher worldwide in the science, technology, and medicine (STM) sector and publishes on behalf of more than 300 academic associations and professional societies. Springer is part of Springer Science+Business Media, one of the world’s leading suppliers of scientific and specialist literature. The group owns 70 publishing houses, together publishing a total of 1,450 journals and more than 5,000 new books a year. The group operates in over 20 countries in Europe, the USA, and Asia, and has some 5,000 employees.

Media Contact: Joan Robinson joan.robinson@springer.com tel +49 (0) 6221 487 8130

Editorial Contact: Christiane Notarmarco christiane.notarmarco@springer.com tel +44 (0) 1483 734620

IRISH JOURNAL OF MEDICAL SCIENCE • VOLUME 175 • NUMBER 4

ELEvAtEd BNP wIth NORMAL systOLIC fuNCtION IN AsyMPtOMAtIC INdIvIduALs At-RIsk fOR hEARt fAILuRE:

A MARkER Of dIAstOLIC dysfuNCtION ANd CLINICAL RIsk

ORIGINAL PAPER
ORIGINAL PAPER

Elevated BNP with normal systolic function in asymptomatic individuals at-risk for heart failure: a marker of diastolic dysfunction and clinical risk

ABSTRACT

Background B-type natriuretic peptide (BNP) is widely accepted in the evaluation of left ventricular systolic dysfunction and heart failure. However, little is known of the implications of elevated BNP levels in individuals with preserved systolic function (PSF). Aims To investigate the drivers and clinical implications of elevated BNP levels in asymptomatic individuals with established PSF. Methods We enrolled 154 individuals who all underwent physical examination, BNP evaluation and Doppler-echocardiographic studies. They were divided into those above and below the median BNP level (50pg/ml). Results Independent predictors of higher BNP were older age, more severe left ventricular hypertrophy (LVH), reduced E/A ratio and ischaemic heart disease. Survival and multivariable analysis demonstrated more death and/or admission in those above the median BNP (HR: 4.79, p=0.007). Conclusions Elevated BNP is the strongest, independent predictor of serious adverse cardiovascular outcomes in this population and requires closer clinical follow-up.

S

F

Karuppiah,

Graham,

M Ledwidge,

C Conlon,

J Cahill,

C O’Loughlin,

J McManus,

K McDonald

Heart Failure Unit, St Vincent’s University Hospital, Dublin and *Carlton Clinic, Bray

INTRODUCTION

B-type natriuretic peptide (BNP) is a member of the family of genetically distinct natriuretic peptides, synthesized and released by cardiomyocytes in response to myocyte stretch due to volume expansion and pressure overload. 1-3 It is predominantly released from ventricular myocytes as NT-BNP (76 amino acid fragment) and BNP (32 amino acid fragment). In addition to natriuretic effects, BNP has been shown to relax vascular smooth muscle and exert anti-proliferative and antifibrotic effects. 4, 5

Increases in plasma BNP concentration have diagnostic and prognostic implications in selected populations. This was shown initially in the presence of heart failure due to left ventricular systolic dysfunction (LVSD) and subsequently in both early stage and asymptomatic LVSD. 6-14 More recently, the diagnostic and prognostic value of BNP has been underlined in a range of settings including the emergency room, 10 in heart failure due to diastolic dysfunction, 11 post-MI 12,13 and in an at-risk renal population. 14 McDonagh and colleagues were among the first to explore the value of BNP screening in

the general population, and while they found BNP to be an independent predictor of mortality, such screening programs may be limited by the low screening return and event rates. 15 Recent data from the Framingham Offspring Study support the role of BNP in predicting the risk of death, cardiovascular events, heart failure and stroke, independently of traditional risk factors. 16 Therefore, while BNP is widely accepted in the evaluation of LVSD and heart failure, there are emerging data on its prognostic benefits in the general population. 15-18 However, there has been little analysis of the drivers, and clinical implications of elevated BNP levels in a community population possessing risk factors for heart failure. The aim of this study was to investigate the prevalence, drivers, and clinical implications of elevated BNP levels in asymptomatic individuals with established cardiac risk factors for HF with proven normal systolic function.

METHODS

This was a collaborative study between St Vincents University Hospital Heart Failure Unit and a large General Practice in the South Eastern Area. The study

IRISH JOURNAL OF MEDICAL SCIENCE • VOLUME 175 • NUMBER 4

5

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ORIGINAL PAPER

was approved by the St Vincent’s University Hospital Medical Ethics Committee and conforms to the Declaration of Helsinki.

All patients >55 years of age with at least one risk factor for the development of HF were deemed suitable for enrollment: long-standing hypertension, diabetes and coronary artery disease. Patients with

a documented history of heart failure, documented

left ventricular systolic dysfunction or any individual with documented non-cardiac conditions that could significantly alter BNP levels (e.g. pulmonary hypertension, pulmonary embolism) were excluded.

Database query from an estimated general practice population of 17,000 people identified 816 individuals considered suitable for enrollment. From those identified, approximately a third of the sample were randomly selected using a computer generated protocol and invited to partake in the study (n=254). Those giving informed consent attended the General Practice to give a detailed medical history and undergo physical examination, 12-lead electrocardiography, Chest X-Ray, phlebotomy for BNP level evaluation and urinalysis. These individuals were subsequently referred to the St Vincent’s University Hospital Heart Failure Service for Doppler echocardiographic studies.

BNP levels were measured using the Triage Meter point-of-care assay (Biosite, Ca). 19, 20 Doppler echocardiographic analyses were performed using 2.5 and 3.5-MHz transducers (Hewlett-Packard Sonos 5500). Preserved left ventricular systolic function was defined as a LVEF ≥ 45% 21 Left ventricular hypertrophy (LVH) was assessed as a mean value of interventricular wall thickness and posterior wall thickness assessed at end-diastole. Values were subsequently graded as Grade 1 (mean value <11mm); Grade 2 (mean value 11-15.9mm); Grade 3 (mean value 16.0 to 19.9mm) and Grade 4 (mean value

≥ 20mm). Parameters of left ventricular diastolic

function were made using standard methods and included: peak velocities of both the early (E) and atrial (A) diastolic filling and the derived E/A ratio; E- wave deceleration time (DT); isovolumetric relaxation time (IVRT). For individuals in atrial fibrillation, five Doppler complexes were sampled for measurements of E-wave deceleration time and IVRT at an average ventricular rate of >90 beats/min. Premature or aberrant ventricular complexes were ignored and modal values were accepted as being representative of diastolic filling.

6

S Karuppiah et al

Operators and physicians interpreting echocardiography were blinded to BNP score. Individuals identified at this stage with LVSD (LVEF <45%) 21 and those with left ventricular chamber enlargement and normal ejection fraction were excluded from further analysis leaving a population with preserved systolic function (PSF).

The population was divided into two groups, those above and below the median BNP value for the total cohort. These two groups were termed ‘Elevated BNP’ (EB Group) and ‘Controls’ (C Group).

All participants were subsequently reviewed at the general practice, at a mean of 10 months following the initial analysis with regard to the primary endpoints of death and/or unplanned hospital admission for cardiovascular causes. The secondary endpoints evaluated were new diagnoses of heart failure and/or new cardiac diagnoses/events not requiring hospitalisation.

STATISTICAL ANALYSIS

Comparisons between EB and C Groups were conducted using independent sample t-tests for continuous variables and Mann-Whitney test for non-normal distributions (two-sided, α = 0.05). Chi- squared analysis was used for discrete variables. Since the BNP values are positively skewed, the univariate and multivariable analysis to determine predictors of higher BNP was carried out using log-transformed BNP values. Data are presented as the mean value ± the standard deviation (SD) for continuous variables and absolute or relative frequencies for discrete variables. Univariate and multivariable analyses were conducted using binary (or binomial) logistic regression using death and/or unplanned hospital admission as the outcome variable. The multivariable model included theoretically reasonable variables and those with univariate p-values of ≤ 0.25. The likelihood ratio test was conducted to identify independent variables with low explanatory power. In addition, the Hosmer and Leme show goodness of fit indices were compared to assess the fit of each specification of the multiple regression model. The Kaplan-Meier product limit method of survival analysis was used to generate and adjust survival curves (death and/or unplanned cardiovascular hospital admission) using the EB Group variable. People lost to follow-up or known to be still alive were censored. The Mantel-Haenszel log-rank test was used to test the equality of the survivor functions. Multivariable analysis incorporating both continuous and discrete predictors of survival was

IRISH JOURNAL OF MEDICAL SCIENCE • VOLUME 175 • NUMBER 4

ELEVATED BNP wITH NORMAL SYSTOLIC FUNCTION IN ASYMPTOMATIC INDIVIDUALS AT-RISk FOR HEART FAILURE:

A MARkER OF DIASTOLIC DYSFUNCTION AND CLINICAL RISk

FAILURE: A MARkER OF DIASTOLIC DYSFUNCTION AND CLINICAL RISk conducted using Cox Proportional Hazards regression

conducted using Cox Proportional Hazards regression statistical model. Receiver Operated Characteristic (ROC) analysis was carried out on different cutoff levels of BNP for the prediction of primary endpoints. The adequacy of these curves is assessed by comparing the Area Underneath the Curve (AUC) statistics (Area, P Value and 95% Confidence interval) and the sensitivity and specificity of selected BNP cutoffs were calculated. All analyses were carried out using SPSS Vs. 11 statistical software.

resUlts

The study schedule is outlined schematically in Figure 1. A total of six individuals were found to have LVSD (population rate 3.6% of which 1 (0.6%) had a BNP <50 pg/ml) and along with a further three individuals (two with mild symptomatic heart failure

and a third with moderate mitral regurgitation) were excluded leaving a study population of 154 (age 67.4 ± 9.7 years, 57% male, 40% history of ischaemic heart disease, 62% history of long-standing hypertension,

7% history of valvular heart disease, 10% cardiac

arrhythmia and 20% diabetes mellitus). Participants

were followed-up for an average of 282 ± 149 days.

The median BNP for the study population was 50pg/

ml and the cohort was divided into those above and

below this value. There were 79 patients (51.2%) with BNP levels above the median value (EB Group) and 75 patients (48.2%) with BNP levels below the median value (C Group). The demographic characteristics of the population are presented in Table 1. Univariate analysis demonstrated that in addition to higher BNP, individuals in the EB group were older with a more

IRISH JOURNAL OF MEDICAL SCIENCE • VOLUME 175 • NUMBER 4

ORIGINAL PAPER
ORIGINAL PAPER

Figure 1—

SCHEME OF

INDIVIDUAL

SCREENING AND

INCLUSION

7

ORIGINAL PAPER
ORIGINAL PAPER

frequent history of arrhythmia. The only difference in medications noted between the groups was in usage of digoxin, albeit in small numbers of individuals.

Doppler-echocardiographic analyses of both groups are presented in Table 2. They demonstrate longer DT and IVRT, reduced E/A ratio and higher LVH score consistent with more marked diastolic dysfunction and evidence of hypertensive heart disease in the EB Group. The differences in E:A ratio and LVH score were independent of age.

We analysed the dataset to determine the predictors of a higher BNP levels using log transformed values. Univariate results, presented in Table 3, suggest that the influencing variables are age, DT, E/A ratio, LVH and histories of ischaemia, hypertension and arrhythmia. However, multivariable analysis identified only four independent predictors of elevated BNP levels in the following order of decreasing significance: age (p<0.0001), LVH (p<0.0001), E/A ratio (p=0.026) and ischaemic heart disease (p=0.046).

During an average follow-up of 282 ± 149 days, 16.5% of individuals in the EB Group had reached the primary endpoints which comprised of four deaths (two cancer, one sudden death, one fall with neck fracture), nine emergency CV admissions (six arrhythmias, one preserved systolic function heart failure, one MI, one worsening angina). In contrast, 4% of the C Group had reached the primary endpoints comprising of one death (peri-operative for valvular heart disease) and two emergency cardiovascular admissions (unstable angina). Analysis of survival curves using death and/or unplanned cardiovascular readmission showed a significantly poorer outcome for people in the EB Group (p=0.004, Figure 2).

Univariate analysis using death and/or unplanned cardiovascular readmission as outcome measures is presented in Table 5. Multivariable analysis demonstrated that the only independent predictors of outcome were the categorical EB Group variable (p=0.032; HR: 4.0, 95% CI 1.12- 14.25) and ischaemic heart disease (p=0.046; HR: 2.9, 95% CI 1.08-8.70).

Secondary endpoints in the EB group were five diagnoses of PSF heart failure (four outpatient diagnoses and one during an emergency admission for heart failure), and three reported cardiovascular events not requiring hospitalization (two reported

8

S Karuppiah et al

requiring hospitalization (two reported 8 S Karuppiah et al Figure 2— kaplan Meier event-free (death and/or

Figure 2— kaplan Meier event-free (death and/or unplanned hosptialisation) survival curves of people with elevated BNP levels and normal systolic function (EB Group, normal EF and elevated BNP ≥50pg/ml, n=79) and Controls (C Group, normal EF low BNP <50pg/ml, n=75).

Figure 3— Receiver Operated Characteristic (ROC) curve using different BNP cutoff levels for the prediction of (primary endpoints) death and/or unplanned readmission. Sensitivities and specificities of selected cutoff levels are presented in Table 6.

symptomatic episode of atrial fibrillation and one reported incidence of angina). In the C group there were two new diagnoses of PSF heart failure and one episode of syncope not requiring hospitalization. In total, 24.1% of the individuals in the EB group had events in the follow-up period compared to the 8.0% in the C group (p=0.0004).

The utility of BNP as a predictor of primary endpoints (death and/or emergency hospital admission) was evaluated using receiver operating characteristic (ROC) curves (Figure 3). The area underneath the curve (AUC) statistics (Area 0.720, Std Error 0.49, P Value 0.002 and 95% Confidence interval 0.624 to 0.817) demonstrate that BNP is a highly significant predictor of the primary endpoints, although its overall performance as a clinical screen is somewhat limited by compromise between sensitivity and specificity. Accordingly, the sensitivity and specificity of a range of selected BNP cut-off values is presented in Table 6.

IRISH JOURNAL OF MEDICAL SCIENCE • VOLUME 175 • NUMBER 4

ELEVATED BNP wITH NORMAL SYSTOLIC FUNCTION IN ASYMPTOMATIC INDIVIDUALS AT-RISk FOR HEART FAILURE:

A MARkER OF DIASTOLIC DYSFUNCTION AND CLINICAL RISk

ORIGINAL PAPER
ORIGINAL PAPER

Table 1 DEMOGRAPHIC CHARACTERISTICS OF THE EB GROUP (N=79) AND THE C GROUP (N=75)

Variable

Total

C Group

EB Group

P

(BNP<50pg/ml)

(BNP>=50pg/mL)

Population

154

 

75

 

79

 

Age (Years)

67.4 ± 9.7

64.4

± 10.0

71.1 ± 8.29

0.00001

Gender: Male:Female

88:66

47:29

41:37

0.206

BMI (Kg/m 2 )

27

± 4

28

± 4

27

± 4

0.127

LVEF (%)

63

± 9

64

± 9

62

± 9

0.157

BNP (pg/ml)

99

± 178

23

± 14

171 ± 226

N/A

Ischaemic Heart disease (Y:N)

61:93

24:51

37:42

0.060

Valvular Heart Disease (Y:N)

11:143

3:72

 

8:71

0.211*

Diabetes (Y:N)

31:123

17:58

14:65

0.444

Hypertension (Y:N)

95:59

51:24

44:35

0.116

Arrythmia (Y:N)

15:139

2:73

13:66

0.005*

HR (BPM)

69.8

± 12.9

68.5 ± 11.3

71.0 ± 14.2

0.248

SBP (mmHg)

150 ± 22

147 ± 19

152

± 24

0.162

DBP(mmHg)

84

± 12

85

± 11

84

± 13

0.621

Pulse Pressure (mmHg)

44

± 10

43

± 9

45

± 10

0.135

Creatinine (µmol/L)

90.5

± 30.6

89.5

± 26.6

91.6±34.3

0.685

ACE Inhibitor (Y:N)

50:104

22:53

28:51

0.418

AII Antagonist (Y:N)

14:140

6:69

 

8:71

0.646

Beta Blocker (Y:N)

72:82

32:43

40:39

0.322

Calcium Antagonists (Y:N)

31:123

18:57

13:66

0.243

Nitrate (Y:N)

28:126

13:62

15:64

0.790

Alpha Blocker (Y:N)

1:153

0:75

1:78

N/A

Diuretic (Y:N)

50:104

28:47

22:57

0.209

Antiplatelet (Y:N)

70:84

34:41

36:43

0.977

Statin (Y:N)

38:116

22:53

16:63

0.191

Anti-arrythmic (Y:N)

1:153

0:75

1:78

N/A

Warfarin (Y:N)

11:143

4:71

7:72

0.535*

Digoxin (Y:N)

10:144

2:73

 

8:71

0.099*

*Fishers Exact Test used. (Y:N)=Yes:No

Table 2 DOPPLER ECHOCARDIOGRAPHIC CHARACTERISTICS OF THE EB GROUP (N=79) AND THE C GROUP (N=75)

VARIABLE

TOTAL

C GROUP (BNP<50pg/ml)

EB GROUP (BNP>=50pg/mL)

P

DT

263.01±57.04

244.81±52.45

280.29±56.13

0.00008

IVRT

92.02±39.29

84.65±35.43

99.10±41.68

0.020

E/A Ratio

1.00±0.46

1.19±0.44

0.83±0.42

0.000001

LVH Score

1.71±0.59

1.45±0.60

1.95±0.48

<0.000001

IRISH JOURNAL OF MEDICAL SCIENCE • VOLUME 175 • NUMBER 4

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S Karuppiah et al

Table 3 UNIVARIATE PREDICTORS OF HIGHER BNP LEVELS FOR THE ENTIRE STUDY COHORT AT BASELINE (N=154)

Variable

R

2

F

β (Unstandardised)

P

CI-Lwr

CI-Upr

Age

0.172

31.602

0.415

(0.057)

<0.00001

0.037

0.076

Gender: Male=1

0.002

0.278

-0.043 (-0.115)

0.599

-0.546

0.316

BMI

0.008

1.136

-0.088 (-0.027)

0.288

-0.077

-0.023

EF%

0.006

0.855

-0.075 (-0.011)

0.357

-0.035

0.013

DT

0.063

10.256

0.251

(0.006)

0.002

0.002

0.009

IVRT

0.011

1.710

0.106

(0.004)

0.193

-0.002

0.009

E/A Ratio

0.076

12.565

-0.276 (-0.792)

0.001

-1.234

-0.351

LVH

0.242

48.403

0.491

(1.099)

<0.00001

0.787

1.411

Ischaemia

0.053

8.467

0.230

(0.621)

0.004

0.199

1.043

Diabetes

0.009

1.330

-0.093 (-0.307)

0.251

-0.833

0.219

Hypertension

0.031

4.873

-0.176 (-0.479)

0.029

-0.908

-0.050

Arrhythmia

0.047

7.457

0.216

(0.964)

0.007

0.267

1.662

Creatinine

0.011

1.686

0.106

(0.005)

0.196

-0.002

0.012

Table 4 FINAL MULTIVARIABLE MODEL OF PREDICTORS OF HIGHER BNP LEVELS FOR THE ENTIRE STUDY COHORT (N=154)

Variable

R

2

 

F

β (Unstandardised)

P

CI-Lwr

CI-Upr

Age

0.391

23.908

P<0.00001

0.309

(0.042)

0.000006

0.024

0.060

LVH

   

0.389

(0.870)

<0.000001

0.575

1.165

E/A Ratio

   

-0.149 (-0.427)

0.026

-0.803

-0.052

Ischaemic

   

0.132 (0.356)

0.046

0.006

0.707

Table 5 UNIVARIATE PREDICTORS OF PRIMARY END-POINT

 

VARIABLE

 

MODEL χ2

-2LL

 

P

HR

CI-LWR

CI-UPR

Age

0.099

143.02

 

0.753

0.992

0.943

1.044

Male Gender

0.469

142.44

 

0.496

1.423

0.516

3.929

BMI

0.461

132.02

 

0.497

1.040

0.928

1.167

EF

0.072

143.04

 

0.789

0.993

0.943

1.046

EB vs C group

 

7.274

135.37

 

0.015

4.790

1.363

16.838

DT

0.002

143.12

 

0.966

1.000

0.992

1.008

IVRT

2.12

140.69

 

0.151

0.992

0.980

1.003

E/A

0.477

142.68

 

0.491

1.389

0.547

3.524

LVH

3.920

139.07

 

0.048

2.294

1.009

5.215

DD

0.309

142.81

 

0.579

1.307

0.508

3.364

Hx of Ischaemia

 

6.601

136.76

 

0.016

3.665

1.269

10.583

Hx of Diabetes

 

0.986

142.22

 

0.326

1.698

0.590

4.891

Hx of Hypertension

 

3.25

140.05

 

0.081

0.414

0.154

1.114

Hx of Arrhythmia

 

0.016

143.10

 

0.899

1.101

0.248

4.897

Creatinine

1.111

131.64

 

0.288

0.992

0.978

1.007

10

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ELEVATED BNP wITH NORMAL SYSTOLIC FUNCTION IN ASYMPTOMATIC INDIVIDUALS AT-RISk FOR HEART FAILURE:

A MARkER OF DIASTOLIC DYSFUNCTION AND CLINICAL RISk

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Table 6 SENSITIVITY AND SPECIFICITY VALUES OF DEFINED BNP THRESHOLDS FOR THE PREDICTION OF PRIMARY ENDPOINTS (DEATH AND/OR EMERGENCY HOSPITAL ADMISSION)

BNP LEVEL THRESHOLDS

SENSITIVITY (%)

SPECIFICITY (%)

BNP: ≥25 pg/ml

100

31

BNP: ≥50 pg/ml

81

52

BNP: ≥75 pg/ml

63

68

BNP: ≥100 pg/ml

44

77

BNP: ≥125 pg/ml

25

82

DisCUssiOn

These data indicate that there is a high prevalence of elevated BNP levels in asymptomatic individuals with preserved systolic function possessing risk factors for heart failure. In this cohort, elevated BNP levels are associated with older age, LVH, diastolic abnormalities and ischaemic heart disease. Furthermore, a clinically important proportion of these individuals had serious adverse event within one year of follow-up. An elevated BNP level was the strongest independent predictor of serious adverse outcome in this population.

Data from the Framingham Offspring Study have shown that elevated BNP is strongly associated with adverse outcome in the general population. 16 This observation suggests that BNP testing may be of benefit as a screening tool for occult structural and functional abnormalities of the heart, in particular, the left ventricle. 16,17,22,23

The Doppler-echocardiographic data from this study support this concept by demonstrating a close relationship between BNP and both LVH and parameters of diastolic dysfunction. Individuals in the EB Group had a significant increase in DT and IVRT and decrease in E/A ratio in comparison with the C Group. Additionally, the E/A ratio was found to be an independent predictor of elevated BNP levels in multivariable analysis. Moreover, the entire incident cases of heart failure during follow-up in the EB Group (6.25% rate) were associated with preserved systolic function.

Other studies have shown that BNP can identify individuals with asymptomatic LVSD 24, 25 although they provide no information on subsequent cardiovascular events. The data by Wang et al 16 demonstrate a high correlation between BNP levels and outcome in a community population, but give

few Doppler-echocardiographic data. Our study further develops these observations by identifying a high prevalence of diastolic abnormalities, strongly associated with elevated BNP levels, which is in turn associated with a high risk of subsequent cardiac events.

The clinical implication of identifying these at- risk individuals remains unclear. However, it likely includes the need to manage more intensively the risk factors of individuals with elevated BNP levels, paying particular attention to LVH, the strongest modifiable driver of BNP in the EB Group. This relates not solely to hypertension management, including 24-hour control of blood pressure, but also potentially to vascular compliance and myocardial fibrosis. Interestingly a lower rate of defined history of hypertension was observed in the EB Group compared to controls. However, there were no differences in blood pressures at baseline between the groups or in antihypertensive medications taken. It has been shown that BNP has anti-fibrotic properties 5 and may therefore be produced in response to an early fibrotic process. Such a process could explain the subtle abnormalities in diastolic function observed in the EB Group. In this regard, it is also of note that BNP can reduce the expression of aldosterone synthase, an enzyme involved in the production of aldosterone, a hormone closely linked to fibrosis. 27,28 Furthermore, it is of note that the most common clinical events observed in this study were arrhythmia and diastolic heart failure, both of which can be potentially explained by an accelerated fibrotic process.

There are a number of limitations to this study which warrant further comment. Firstly, although representative of a large, asymptomatic, at-risk population, these are preliminary data in a relatively small sample. The ability of BNP to reliably predict outcome in this particular population or to add

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value over conventional and newer risk stratification methods must be examined in larger studies.

Secondly, more work is needed to define optimal BNP cut-off levels depending on screening objectives, 17,22 population assessed, 22,29 and BNP assay used. 30 It is interesting to note that McDonagh et al demonstrated that a truly “normal” community population will have BNP values below 20 pg/ml, 15 Wang et al identified values above 20 pg/ml for males and 23 pg/ml for females as conferring substantial risk 16 and the present work demonstrates 100% sensitivity for subsequent serious clinical events using a cut-off of 25pg/ml. Although asymptomatic, the present study population is more selected and has a higher prevalence of cardiovascular disease than the general community populations described in the aforementioned studies and may, therefore warrant a higher screening threshold. Therefore, the BNP cut-off of 50pg/ml in this setting may offer a reasonable compromise between sensitivity and specificity in predicting subsequent serious clinical events.

Thirdly, a cut-off of LVEF <45% may have allowed for inclusion of patients with established ischaemic heart disease and mild but important degrees of LVSD. Furthermore, the error of measurement of echocardiography may also have resulted in the inclusion of some patients with LVSD.

Finally, although the observation of diastolic abnormalities and increased risk among individuals in the EB Group is made in this study, we have not clarified in detail any causative mechanism. Clearly this population requires further evaluation to identify these mechanisms of increased risk and other means of reducing this risk apart from aggressive risk factor management.

COnClUsiOns

Elevated BNP levels in the setting of preserved systolic function in asymptomatic, at-risk individuals is associated with older age, ischaemic heart disease, more severe LVH and abnormalities of diastolic function. Elevated BNP is the strongest, independent predictor of serious adverse outcome in this population. More work is required to clarify whether BNP testing may be a suitable screening tool for echocardiography and to establish its value as means of risk stratifying community populations with cardiovascular risk factors for intensive therapy and close clinical follow-up.

12

S Karuppiah et al

ACkNOwLEDGEMENTS

The authors wish to acknowledge the dedication and hard work of Tracey Reynolds in the organisation of this study.

REFERENCES

1. Chen HH, Burnett JC. The natriuretic peptides in heart failure: diagnosis and therapeutic potentials. Proc Assoc Am Physicians 1999;111:406-16

2. Cheung BMY, Kumana CR. Natriuretic peptides- relevance in cardiac disease. JAMA 1998;280:1983-4.

3. Maeda K, Takayoshi T, Wada A, Hisanaga T, Kinoshita M. Plasma Brain Natriuretic Peptide as a biochemical marker of high left ventricular end-diastolic pressure in individuals with symptomatic heart failure. Am Heart J

1998;135:825-32.

4. Clarkson PB, Wheeldon NM, McLeod C, Coutie W, Mac Donald TM. Brain natriuretic peptide: effect on left ventricular filling patterns in healthy subjects. Clin Sci

1995;88:159-164

5. Cao L, Fardner DG. Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. Hypertension

1995;25:227-234.

6. Cowie MR, Struthers AD, Wood DA et al. Value of natriuretic peptides in assessment of individuals with possible new heart failure in primary care. Lancet

1997;350:1349-1353.

7. Tsutamoto T, Wada A, Maeda K et al. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure: prognostic role of plasma brain natriuretic peptide concentration in individuals with chronic symptomatic left ventricular dysfunction. Circulation 1997;96:509-516.

8. Maeda K, Tsutamoto T, Wada A et al High levels of plasma brain natriuretic peptide and interleukin-6 after

optimised treatment for heart failure are independent risk factors for mortality. J Am Coll Cardiol 2000;36:1587-

1593.

9. Omland T, Aakvasg A, Vik-Mo EB Plasma cardiac natriuretic peptide determination as a screening test for the detection of individuals with mild left ventricular impairment. Heart 1996;76:232-237.

10. Maisel AS, Krishnashwamy P, Nowak RM et al Rapid measurement of B-Type Natriuretic Peptide in the emergency diagnosis of Heart Failure. N Eng J Med 2002; 347:161-167.

11. Maisel AS, McCord J, Nowak RM et al. Bedside B-type natriuretic peptide in the emergency diagnosis of heart failure with reduced or preserved ejection fraction. J Am Coll Cardiol 2003;41:2010-17.

12. Omland T, Ankvaang A, Bonarjee VV et al. Plasma brain natriuretic peptide as an indicator of left ventricular systolic function and long term survival post myocardial infarction: comparison with plasma atrial natriuretic peptide and NT-proatrial natriuretic peptide. Circulation

1996;93:1963-1969.

13. de Lemos JA, Morrow DA, Bentley JH et al The prognostic value of brain natriuretic peptide in individuals with acute coronary syndromes N Engl J Med 2001;345:1014-21.

IRISH JOURNAL OF MEDICAL SCIENCE • VOLUME 175 • NUMBER 4

ELEVATED BNP wITH NORMAL SYSTOLIC FUNCTION IN ASYMPTOMATIC INDIVIDUALS AT-RISk FOR HEART FAILURE:

A MARkER OF DIASTOLIC DYSFUNCTION AND CLINICAL RISk

14. Mallamaci F Zoccali C Tripepsi G et al Diagnostic potential of natriuretic peptides in dialysis individuals. Kidney Int 2001;59:1559-63.

15. McDonagh TA, Robb SD, Murdoch DR et al. Biochemical detection of left-ventricular systolic dysfunction. Lancet

1998;351:9-13.

16. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP Omland T, Wolf P and Vasan RS. Plasma Natriuretic Peptide Levels and the Risk of Cardiovascular Events and Death. N Engl J Med 2004;350:655-663.

17. Nakamura M, Endo EB, Nasu M, Arakawa N et al Value of B type natriuretic peptide measurement for heart disease screening in a Japanese population. Heart

2002;87:131-135.

18. McKie PM, Rodeheffer RJ, Cataliotti A, Martin FL, Urban LH, Mahoney DW, Jacobsen SJ, Redfield MM, Burnett JC Jr. Amino-terminal pro-B-type natriuretic peptide and B-type natriuretic peptide: biomarkers for mortality in a large community-based cohort free of heart failure. Hypertension 2006; 47 (5): 874-880.

19. Dao Q, Krishnaswamy P, Kazanegra R et al. Utility of B- Type Natriuretic Peptide in the diagnosis of congestive heart failure in an urgent care setting. J Am Coll Cardiol

2001;37:379-385.

20. Morrison LK, Harrison A, Krishnaswamy P et al Utility of a rapid B-natriuretic peptide assay in differentiating congestive heart failure from lung disease in individuals presenting with dyspnoea. J Am Coll Cardiol

2002;39:202-209.

21. Remme WJ, Swedberg K. Task Force Report. Guidelines for the diagnosis and treatment of chronic heart failure. Task Force for the Diagnosis and Treatment of Chronic Heart Failure, European Society of Cardiology. Euro Heart Journal 2001; 22: 1527-1560.

22. Struthers AD. Introducing a new role for BNP: as a general indicator of cardiac structural disease rather than a specific indicator of systolic dysfunction only. Heart 2002;87:109-10.

23. Kranelund C, Gronning B, Kober L, Hildebrandt P, Steffensen R. N-Terminal Pro-B-Type Natriuretic Peptide and Long-Term Mortality in Stable Coronary Heart Disease. New Eng J Med 2005;352:666-675.

24. Yu CM Sanderson JE Shum IO et al Diastolic dysfunction and natriuretic peptides in systolic heart failure: higher ANP and BNP levels are associated with restrictive filling pattern. Eur Heart J 1996;17:1694-702.

25. Lubien E, De Maria A, Krishnaswamy P et al. Utility of B-natriuretic peptide in detecting diastolic dysfunction:

comparison with Doppler velocity recordings. Circulation 2002;105:595-601.

26. Yamamoto K Burnett JC Jougasaki M et al Superiority of Brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and left ventricular hypertrophy. Hypertension 1996;28:988-94.

27. Tsutamoto T Wada A Maeda K et al Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodelling in individuals with congestive heart failure. J Am Coll Cardiol 2001;37:1228-1233

28. Holmes SJ, Espiner EA, Richards AM, Yandle TG, Framoton C. Renal, endocrine and haemodynamic effects of human brain natriuretic peptide in normal man. J Clin Endocrinol Metab 1993;76:91-96.

29. Redfield M, Rodeheffer MD, Jacobsen S et al. Plasma concentration of Brain Natriuretic Peptide: impact of age and gender. J Am Coll Cardiol 2002;40:976-82.

30. Wu AH, Packer M, Smith A, Bijou R, Fink D, Mair J, Wallentin L, Johnston N, Feldcamp CS, Haverstick DM, Ahnadi CE, Grant A, Despres N, Bluestein B, Ghani F. Analytical and clinical evaluation of the Bayer ADVIA Centaur automated B-type natriuretic peptide assay in patients with heart failure: a multisite study. Clin Chem.

2004;50:867-873

Correspondence to: Dr Ken McDonald, Director, Heart Failure Unit, St. Vincent’s University Hospital, Elm Park, Dublin 4, Ireland. Tel: 00353 1 2304629, Fax: 00353 1 2304639 e-mail. kenneth.mcdonald@ucd.ie

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FEASIBILITY AND LONG TERM OUTCOME OF HOME VS HOSPITAL INITIATED THROMBOLYSIS

Feasibility and long term outcome of home vs hospital initiated thrombolysis

aBstraCt

Background Thrombolytic therapy improves mortality in acute myocardial infarction especially in those who receive treatment early. Pre-hospital therapy can reduce the time to treatment. Methods Open, randomized study of patients with acute myocardial infarction of less than six hours duration in a rural community. Pre-hospital thrombolysis was administered using a mobile coronary care unit (MCCU) and all patients received IV streptokinase. Results Two-hundred and forty-eight patients were studied, 82 in the MCCU and 166 in the hospital group. The mean delay time to treatment was 136 minutes (MCCU group) and 196 minutes (hospital group) (p < 0.001). Reperfusion time was 116 minutes for the MCCU group and 118 minutes for the hospital group. Mortality at 30 days was 4.9% for the MCCU group and 15.7% for the hospital group (p = 0.014). Mortality at one year was 9.8% for the MCCU group and 23.5% for the hospital group (p = 0.009). Mortality for patients followed up to five years was 17.7% for the MCCU group and 35.2% for the hospital group (p = 0.005). There were no significant adverse events in either treatment group. Conclusion Pre-hospital thrombolysis by MCCU is feasible and allows significant reduction in the delay time to treatment initiation. There are encouraging improvements in short- and long-term survival with no apparent reduction in safety profile.

B McAleer

MPS Varma

Cardiac Unit, Erne Hospital, Enniskillen, N. Ireland

14

intrODUCtiOn

In recent years, several studies have shown that thrombolytic therapy used in acute myocardial infarction leads to a reduction in infarct size, improved left ventricular function and consequent improvement in mortality. 1-4 Much of this work, however, has been carried out in large centres serving mainly urban populations and with ready access to invasive facilities for investigation and further treatment of ischaemic heart disease. Use of pre-hospital thrombolysis is limited, but encouraging improvement in left ventricular function has been shown following its use in an urban area. 5

We have studied the feasibility and outcome of pre-hospital thrombolysis in an area that is almost entirely rural and these patients have been compared with a similar group who received thrombolysis in the coronary care unit of a district general hospital.

geOgraPHY

The study was carried out in the Erne hospital, a 212 bed district general hospital. There is a dedicated coronary care unit comprising 12 beds

and the hospital is the only acute hospital in County Fermanagh, which is located in the western part of Northern Ireland. The catchment area is over 800 square miles with communities up to 30 miles radius from the hospital. The total population is approximately 60,000. The nearest tertiary referral centre is located in Belfast, a distance of 90 miles.

Patients anD MetHODs

PATIENT ELIGIBILITY

Over a four-year period (1988-1992) all patients with a suspected acute myocardial infarction were seen by a mobile coronary care unit (MCCU). This unit was staffed by a physician (SHO level) and a senior coronary care trained nurse. Those patients whose major symptoms were of less than six hours duration were considered for thrombolysis. ECG evidence of myocardial infarction was required: ST- segment elevation of at least 1 mm in two or more standard leads and/or at least 2 mm in two or more praecordial leads.

After initial assessment by the MCCU staff, patients were randomly allocated to receive treatment with

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B Mcaleer & MpS VarMa

thrombolysis at home (administered by the MCCU staff) or alternatively to wait until transfer to the hospital coronary care unit. Randomisation was determined by using the on-call rota – one particular SHO commenced treatment at the patient’s home, whereas the other SHOs waited until arrival in the hospital CCU.

Patients were included irrespective of age, prior infarction, cardiogenic shock, pulmonary oedema, or life-threatening arrhythmias. Clinical grounds for exclusion were bleeding disorders, concurrent anticoagulant therapy, active peptic ulceration, recent stroke (<3 months ), recent surgery (<4 weeks), severe hypertension (BP>220/120 mmHg), and any patient whose life expectancy for other reasons was less than two years. The protocol was approved by the hospital ethical committee and appropriate patient consent was obtained.

PROTOCOL

Before initiation of therapy, all patients had a 12-

lead ECG performed. The time of onset of the acute symptoms was recorded. Blood samples were taken for group and hold, full blood count, prothrombin time, partial thromboplastin kaolin time, fibrinogen degradation products, total creatinine kinase (CK), and CK-MB fraction.

All patients received streptokinase infused in a dosage of 1.5 million units in 100 ml of N saline over a 30- minute period, and the time of commencement of the infusion was recorded. This was immediately followed by an IV infusion of heparin in a dosage of 1000-1500 U/hr such that the PTTK ratio was maintained at 1.5 - 3 times the baseline value. After five days of heparin therapy, oral anticoagulation was substituted, and this was continued for at least three months in the vast majority of cases. Ancillary therapy (aspirin, betablockers, ACE inhibitors, etc) was prescribed along standard post-infarct guidelines.

RECOGNITION OF REPERFUSION

In the absence of readily available facilities for coronary angiography, we used indirect evidence of reperfusion. The criteria used were:-

1. Rapid relief of chest pain and improvement in haemodynamic parameters.

2. Regression of ST-segment elevation (50% reduction in ST elevation).

3. Early CK and CK-MB peak.

4. Occurrence of specific reperfusion arrhythmias, i.e. idioventricular rhythm, ventricular fibrillation, ventricular tachycardia and ventricular ectopic beats.

POST-TREATMENT ASSESSMENT

Following treatment, cardiac enzymes were taken six-hourly for the first 24 hours and then 12-hourly for the next 48 hours. ECGs were recorded every 15 minutes for the first two hours and then hourly for six hours. Haemodynamic parameters were recorded hourly for the first 12 hours and thereafter at the usual times. Some patients (<35% in each group ) subsequently had coronary angiography performed, but this was decided on the basis of clinical criteria and in many cases there was a prolonged delay. Ejection fraction was determined by radionuclide ventriculography, but only in those patients who had coronary angiography performed. All patients were followed-up for five years.

STATISTICAL METHODS

For quantitative variables, differences in mean values were tested by double-tailed t-tests employing the 5% level to distinguish statistically significant differences. In the case of qualitative variables, standard χ2 tests of significance (again using the 5% level) were applied, except where the small number of cases in an individual cell of the contingency table necessitated the use of Fisher's exact probability test.

resUlts

During the study period 82 patients received thrombolysis via the MCCU and 166 were treated in the hospital coronary care unit. This represents 29% of all MCCU calls received in the study period. Table 1 shows the baseline characteristics of both groups and it can be seen that they are similar as regards mean age and percentage of male patients.

The numbers with a prior history of myocardial infarction are lower in the pre-hospital group but this is not a significant difference. The type of infarct sustained is similar in both groups. Although there is a higher percentage of anterior infarcts in the hospital group, this difference does not reach significance. Prior to treatment, similar numbers in each group had life-threatening arrhythmias. In most cases, these patients had ventricular fibrillation and all were successfully resuscitated before administration of lysis.

Table 2 shows the results of reperfusion data and the delay times to treatment. Delay time to treatment was defined as the difference between time of symptom onset and the time of commencement of the streptokinase infusion.

As expected, by administering thrombolytic therapy at home, we achieved a significant reduction in delay time to treatment (136 minutes vs 196 minutes), a difference

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FEASIBILITY AND LONG TERM OUTCOME OF HOME VS HOSPITAL INITIATED THROMBOLYSIS

Table 1 BASELINE CHARACTERISTICS

 

MCCU

HOSPITAL

Male (%)

76.8

 

76.5

Age (mean, years)

61.0

 

60.5

Age (range, years)

37 – 78

 

37 – 95

Previous infarction (%)

17.1

 

22.3

Anterior infarct (%)

40.2

 

41.6

Angina (%)

43.9

 

41.0

VF prior to Rx (%)

6.1

 

7.2

Table 2 DELAY TIMES / REPERFUSION DATA

 

MCCU

HOSPITAL

Delay time to Rx (mean, mins)

136

196

p < 0.0001

Distance from hospital (km)

16.1

 

15.8

Reperfusion (%)

92.7

81.3

p < 0.01

Reperfusion time (mean, mins)

116

118

p = NS

Table 3 CARDIAC ENzYME / LV FUNCTION DATA

 
 

MCCU

HOSPITAL

 

Peak CK level (mean)

2474

2128

 

Time to peak CK (hrs)

13.9

16.4

 

P < 0.01

Peak CKMB level (mean)

234

247

 

Time to peak CKMB (hrs)

12.2

14.0

P

= 0.012

Ejection fraction (%)

53

52

 

Heart failure on CXR ( %)

43

47

 

Table 4

MORTALITY DATA

 
 

MCCU

HOSPITAL

 
 

30 days

4/82 (4.9%)

26/166 (15.7%)

P

= 0.014

 

1 year

8/82 (9.8%)

39/166 (23.5%)

P

= 0.009

 

2

years

9/82 (11.0%)

46/166 (27.7%)

P

= 0.003

 

5

years

14/81 (17.3%)

58/165 (35.2%)

P

= 0.005

One patient lost to follow-up in each group.

 

16

of one hour (p < 0.0001). The mean time to reperfusion (as judged by indirect evidence) was marginally reduced in those patients treated by the mobile unit. Over 92% of those treated by the mobile unit showed indirect evidence of reperfusion, as opposed to 81% in

those treated in the hospital coronary care unit and this difference was significant (p < 0.01).

In Table 3, comparisons of LV function are shown. However, ejection fraction was determined in under

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30% of each group and was rarely determined in those who died in the acute phase. This almost certainly is the reason for the non-significant difference in the ejection fraction data. The times to peak CK and CKMB are shorter in the MCCU group reflecting the earlier reperfusion.

Mortality figures are shown in Table 4 and it can be seen there are significant differences in both short term and long term results up to five years post treatment.

There were no significant bleeding events in either treatment group, but minor bleeding episodes (bruising at venepuncture, haematuria) were noted in 16% of the MCCU group and in 15% of the hospital group. Blood transfusion was not required. One patient in the hospital treated group suffered a stroke (infarct). There were no significant allergic or hypotensive events in either group.

DISCUSSION Several large studies 1-4 have shown that thrombolytic agents can reduce mortality from acute myocardial infarction, especially when given within six hours of the onset of symptoms. The importance of early treatment is well shown in the GISSI study, 2 in which the mortality of those treated within the first hour was reduced by nearly 50%. Koren et al 5 had previously reported significant improvement in left ventricular function following the use of thrombolysis in nine patients treated by a mobile coronary care unit.

Most of these papers, however, relate to work in tertiary centres in predominantly urban areas where facilities for invasive investigation and treatment are readily available. The majority of patients with acute myocardial infarction are treated in district general hospitals and our results relate to the use of pre- hospital thrombolysis in a community served by a district general hospital. By administering the agent at the place of onset of attack by means of a mobile coronary care unit, significant reduction in delay time to treatment has been achieved, as compared to a similar group who received treatment in hospital. Reperfusion was assessed noninvasively and is high in both groups. A number of studies have shown that noninvasive markers of reperfusion, such as ST- segment changes 6 and creatinine kinase isoenzymes, 7 are useful predictors of reperfusion. However other studies 8,9 have shown that their usefulness to determine reperfusion early is questionable and

are only accurate if there is concordance of several criteriae, as is the case with our study.

Mortality is encouragingly low in both the short term and the long term for those treated in the pre- hospital phase and the difference is significantly lower than in the hospital group. Although the hospital treated group appears to have a high mortality when compared to the large studies of thrombolysis, this may be explained by the fact that patients in our study were included irrespective of age, the presence of cardiogenic shock or pulmonary oedema. A more valid comparative group might be that of MacLennan et al, 10 who used intravenous streptokinase in a group of 50 patients in a tertiary cardiac centre with similar hospital mortality rates. Recently, other studies 11-14 with pre-hospital thrombolysis have shown the feasibility of this treatment and the time gains that can be achieved. Morrison and colleagues published a meta-analysis 12 of six trials of pre-hospital thrombolysis carried out by paramedics, general practitioners or mobile intensive care units in Europe or the UK. The “call-to- needle time” was reduced by 33 to 130 minutes and short-term hospital mortality was reduced by 17%.

Because of delays in admission to hospital, less than 30% of patients with chest pain are suitable for thrombolysis. Methods of improving the percentage of patients who might benefit from this treatment have been suggested: (a) reducing the delay in the admission of patients with chest pain, primarily by encouraging such patients to contact the emergency services directly, thus bypassing the general practitioner, (b) initiation of treatment in the pre-hospital phase by ambulance crews, general practitioners, or mobile coronary care units and (c) reducing in-hospital delays such as time spent in A&E departments awaiting bedspace. Although significant reductions in delay to admission have been achieved in some areas, notably Brighton, general practitioners in general are reluctant to relinquish their role in the management of acute myocardial infarction and they would contend that they are ideally placed to institute thrombolytic therapy at home. However, Rawles 15 in a survey of GPs in the Aberdeen area has highlighted the problems that may occur should this approach be used - only 18% of GPs carried an ECG machine on call and only 30% carried a defibrillator. The vast majority stated that they were reluctant to use any drugs other than opiates or atropine in the treatment of patients with chest pain.

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FEASIBILITY AND LONG TERM OUTCOME OF HOME VS HOSPITAL INITIATED THROMBOLYSIS

18

In the Grampian Region Early Anistreplase Trial (GREAT) 16 it was shown that general practitioner use of thrombolysis was feasible and safe and resulted in a time saving of about two hours in the delay to treatment and there was an associated decline in mortality. Indeed the five-year mortality results of the GREAT study 17 are similar to our results using a mobile coronary care unit. However, some authorities, notably Julian, 18 qualify their support for GP use of thrombolytics and question whether the GP should use thrombolysis without an electrocardiogram. Even Rawles 19 in a follow-up study of the attitudes of general practitioners who had taken part in the GREAT study found that less than 20% of respondents had used thrombolysis in the previous year.

Administration of thrombolytic therapy via ambulance personnel has also been suggested, but many clinicians are still unhappy about the legal responsibilites with this approach, as well as the fact that this would almost certainly involve thrombolysis being administered without ECG evidence of infarction.

Treatment given by means of MCCU is a third alternative. Geddes 20 in a review of 20 years of pre- hospital coronary care has highlighted the benefits of using such a service at a time before thrombolysis became widely used. Enthusiasm for such units is not widespread in the UK, except for Northern Ireland. However, the trial performed by the European Myocardial Infarction Project Group 21 has shown that if the staff and equipment are available then pre- hospital thrombolysis by mobile coronary care units can reduce mortality, especially in those patients for whom the delay to hospital treatment is longest. Our study, based in a rural area where a delay to hospital treatment is invariably more than 60 minutes, suggests that a mobile coronary care unit can reduce mortality in the short and the long term.

In summary, pre-hospital thrombolysis using a mobile coronary care unit:

1. Is feasible and safe;

2. Allows significant reduction in delay time to treatment;

3. Reduces mortality in both short term and long term; Use of MCCUs should be developed further in order to optimize the number of patients who could benefit from thrombolytic therapy.

ACkNOwLEDGEMENTS

We thank the Nursing Staff at the Erne Hospital CCU for their help with this study; Dr E Turkington for the statistical analysis and Mrs JM Cecil for the preparation of the type script.

REFERENCES

1. AIMS Trial Study Group. Effect of intravenous APSAC on mortality after acute myocardial infarction: Preliminary report of a placebo-controlled trial. Lancet 1988; 1:545-549.

2. Gruppo Italiano per lo Studio della Streptochinasi nell’infarto miocardico (GISSI). Effectiveness of intravenous thrombolysis in acute myocardial infarction. Lancet 1986; 1:397-402.

3. ISIS Steering Committee. Intravenous streptokinase given within 0-4 hours of onset of myocardial infarction reduced mortality in ISIS-2. Lancet 1987; 1:502.

4. ISAM Study Group. A prospective trial of intravenous streptokinase in acute myocardial infarction (ISAM). Mortality, morbidity and infarct size at 21 days. N Engl J Med 1986; 314:1465-1471.

5. Koren G, Weiss AT, Hasin Y, et al. Prevention of myocardial damage in acute myocardial ischaemia by early treatment with intravenous streptokinase. N Engl J Med 1985; 313:1384-1389.

6. Hogg KJ, Hornung RS, Howie CA, et al. Electrocardiographic prediction of coronary artry patency after thrombolytic treatment in acute MI: Use of the ST-segment as a non-invasive marker. Br Heart J 1988; 60:275-280.

7. Tsukamoto H, Hashimoto H, Matsui Y, et al. Detection of myocardial reperfusion by analysis of serum creatine kinase isoforms. Clin Cardiol 1988; 11:287-291.

8. McCaliff MR, O’Neill W, Stack RS, et al. Failure of simple clinical measurements to predict perfusion status after intravenous thrombolysis. Ann Intern Med 1988;

108:658-662.

9. Kircher BJ, Topol E, O’Neill W, et al. Prediction of infarct coronary artery recanalisation after intravenous thrombolytic therapy. Am J Cardiol 1987; 59:513-515.

10. MacLennan BA, McMaster A, Webb SW, et al. High dose intravenous streptokinase in acute myocardial infarction - short and long term prognosis. Br Heart J 1986; 55:213-239.

11. Sauval P, Artigou JY, Cristofini P, et al. Pre-hospital thrombolysis with rcombinant tissue plasminogen activator in acute myocardial infarction (Fren). Arch Mal Coeur Vaiss 1989; 82:1957-1961.

12. Morrison LJ, Verbeek PR, McDonald AC, et al. Mortality and pre-hospital thrombolysis for acute myocardial infarction. JAMA 2000;283:2686-92.

13. Dubous-Rande JL, Herve C, Dubal-Moulin AM, et al. Pre- hospital thrombolysis in acute myocardial infarction:

Preliminary results in the Val-de-Marne department (Fren). Arch Mal Coeur Vaiss 1989; 82:1963-1966.

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B Mcaleer & MpS VarMa

14. Cazaux P, Leclercq G, Vahanian A, et al. Intravenous thrombolysis with tissue-type plasminogen activator (rt-PA) in the pre-hospital phase of acute myocardial infarction. 49 cases (Fren). Arch Mal Coeur Vaiss 1989;

82:1967-1971.

15. Rawles JM. General practitioner management of acute myocardial infarction and cardiac arrest: Relevance to hrombolytic therapy. Br Med J 1987; 295:639-640.

16. GREAT Group. Feasibility, safety, efficacy of domiciliary thrombolysis by general practitioners. BMJ 1992;

305:548-53.

17. Rawles JM. Quantification of the benefit of earlier thrombolytic therapy: five year results of the Grampian Region Early Anistreplase Trial (GREAT). Journal of the American College of Cardiology 1997. 30(5):1181-6.

18. Julian DG. Thrombolysis, the general practitioner, and the electrocardiogram. Br Heart J 1994; 72:220-221.

19. Rawles J. Attitudes of general practitioners to pre- hospital thrombolysis. BMJ 1994; 309:379-82.

20. Geddes JS. Twenty years of pre-hospital coronary care. Br Heart J 1986; 56:491-495.

21. The European Myocardial Infarction Project Group. Prehospital thrombolytic therapy in patients with suspected acute myocardial infarction. N Engl J Med 1993; 329:383-9.

Correspondence to: Dr B McAleer, Erne Hospital, Enniskillen, Co. Fermanagh BT74 6AY

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THE EXPERIENCES AND ATTITUDES OF GENERAL PRACTITIONERS AND HOSPITAL STAFF TOwARDS PRE-HOSPITAL THROMBOLYSIS IN A RURAL COMMUNITY

The experiences and attitudes of general practitioners and hospital staff towards pre- hospital thrombolysis in a rural community

aBstraCt

Background In rural areas it is impossible for eligible patients presenting with acute myocardial infarction (AMI) to receive thrombolysis within the recommended 90 minutes unless administered in the community by the general practitioner. Aims The aim of this study was to describe the attitudes of hospital staff and general practitioners towards pre-hospital administration of thrombolysis. Method General practitioners, consultant physicians and nursing staff participated in the survey. Results General practitioners were convinced of the added benefits of administration of thrombolysis in the community and believed the hospital had a role to play. Likewise the hospital staff agreed with the benefits of pre-hospital thrombolysis. However, they felt that the decision to thrombolyse patients should be made in consultation with the hospital. Conclusions Pre-hospital thrombolysis programmes must be continuously monitored and evaluated to identify important factors that may prevent wider use of thrombolytic treatment.

Tedstone

D

Doherty 1 ,

J

Dowling 2 ,

P

Wright 1 ,

J Cuddihy 1

Dept of Public Health Medicine, NSE–NWA, Bishop Street, Ballyshannon, Co Donegal 1 ; North West Immediate Care Programme 2

20

intrODUCtiOn

The Cardiovascular Health Strategy has recommended that eligible patients receive thrombolysis within 90 minutes of alerting medical or ambulance services. 1 Previous research in the Donegal area has shown a median call to needle time of 200 minutes, which clearly exceeds this guideline. 2 The aim of DARTS was to determine the feasibility of the administration of domiciliary thrombolysis by rural general practitioners. 4 Pre- hospital thrombolysis resulted in a median call to needle time of 62 minutes – a time saving of 142 minutes compared to a control group thrombolysed in the hospital (median call to needle time of 204 minutes). The report recommended that pre- hospital thrombolysis be extended to other areas where the recommended call to needle times cannot be achieved.

Few studies have assessed the general practitioners’ or hospital staff attitudes to pre-hospital thrombolysis. One study in the Grampian region concluded that general practitioners were more likely to use thrombolysis if they were encouraged to do so by the local cardiologist. 5 A follow-up of this study 6 to investigate the adoption of a

pre-hospital thrombolysis policy argued that the attitudes of hospital consultants were generally negative and that they lacked confidence in the general practitioners’ ability to read and analyse an elecrocardiogram (ECG). It was felt that this was a significant barrier to the adoption of a pre-hospital thrombolysis policy by the general practitioner as they felt that encouragement and support from local health authorities was necessary.

Given the previous findings, there is a need to examine the attitudes of general practitioners who took part in a pre-hospital thrombolysis study (DARTS) within an Irish context. If a pre-hospital thrombolysis policy is to be instigated, it is beneficial to be aware of the possible barriers to the use of thrombolytic treatment. The aim of this study sought to determine the participating general practitioners’ attitudes to pre-hospital thrombolysis following completion of DARTS. A questionnaire was designed to identify possible advantages for and barriers to the administration of pre-hospital thrombolysis in a rural community. Furthermore, the study extended previous work by investigating the attitudes of hospital staff including consultants and nursing staff.

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D teDStone Doherty et al

MetHOD

All general practitioners involved in DARTS were asked to complete a questionnaire designed to assess attitudes towards thrombolysis and problems that may be associated with administering pre- hospital thrombolysis. It contained questions relating to benefits and safety of pre-hospital thrombolysis,

education, training and support in pre-hospital thrombolysis, and confidence in the treatment of

acute myocardial infarction. All of the consultant

physicians and nursing staff of the ED and CCU were

administered questionnaires assessing the benefits and safety of pre-hospital thrombolysis.

The questionnaire relating to benefits and safety of pre-hospital thrombolysis was comprised of statements requiring participants to indicate agreement, disagreement, or neutrality. Questions relating to confidence in the administration of thrombolysis were on a five-point Likert type scale and general practitioners indicated how confident they were by circling the appropriate response from ‘not at all confident’ to ‘extremely confident’. Following completion of the questionnaires, participants were given the opportunity to elaborate on answers that they had given. The researcher recorded these responses by hand.

resUlts

RESPONSE RATE

A total of 82% (13 / 16) of the participating general practitioners completed the questionnaires. Of these, 38% (5 / 13) administered thrombolysis to patients in the community during the study period. All the consultant physicians (100%; n = 5), 54% (25 / 46) of the nursing staff from CCU and ED completed the questionnaires. Table 1, Table 2 and Table 3 show the percentage of the general practitioners’ responses to the individual questions, while Table 4 shows the percentage of the hospital staffs’ responses to the individual questions.

GENERAL BENEFITS OF THROMBOLYSIS AND EARLY ADMINISTRATION

All general practitioners (100%) were convinced of the benefits of thrombolysis in the treatment of acute myocardial infarction and were convinced of the additional benefits derived from administration in the community at the earliest opportunity. A total of 97% (29 / 30) of the hospital staff were convinced of the benefits of thrombolysis and 3% (1 / 30) remained neutral. Ninety-four per cent (28 / 30) were convinced of additional benefits from early administration in

the community. Only 3% (1 / 30) disagreed with the additional benefits of pre-hospital thrombolysis and 3% (1 / 30) remained neutral.

TIME, COST AND SAFETY

A total of 77% (10 / 13) of general practitioners felt

that administering thrombolysis in the community would result in appreciable time saving and 85% (11 / 13) felt that they could make time to give thrombolysis. The majority of the general practitioners (92%; 12 / 13) and hospital staff (97%; 29 / 30) disagreed that thrombolysis was too expensive for general practice. All the general practitioners (100%) agreed that it was not too difficult to administer in general practice and 69% (9 / 13) agreed that it was not inconvenient for use in general practice. The majority of the hospital staff also agreed that eligible patients are not too difficult to diagnose for pre-hospital thrombolysis (90%; 27 / 30). A total of 61% (8 / 30) of general practitioners and 67% (20 / 30) of the hospital staff agreed that it was safe to administer thrombolysis in the community. One general practitioner disagreed while three hospital staff disagreed and 30% (4 / 13) of the general practitioners remained neutral, as did 23% (7 / 30) of the hospital staff.

EqUIPMENT

A total of 92% (12 / 13) of the general practitioners

had an ECG machine that they could use on call and all (100%) were willing to record an ECG in cases of suspected AMI. A total of 85% (11 / 13) of the general practitioners reported being able to interpret the ECG, while two reported that they would not be able to interpret the ECG recording. A total of 77% (10 / 13) of the general practitioners always carried the thrombolytic kit while on duty. Regarding defibrillation, 92% (12 / 13) of general practitioners had access to a defibrillator while on duty and 85% (11 / 13)

agreed that they knew how to use a defibrillator.

TRAINING, EDUCATION AND SUPPORT

Table 2 shows the percentage responses from the general practitioners in each of the categories for the individual questions pertaining to training, education and support of prehospital thrombolysis. In terms of the training received prior to the initiation of DARTS, 61% (8 / 13) of the general practitioners agreed that training was sufficient. However, 62% (8 / 13) agreed that more training in pre-hospital emergency cardiac care is necessary. A total of 62%(8 / 13) agreed that training in ECG interpretation is sufficient, but 54% (7 / 13) felt that more training in the use of ECG equipment was necessary. In terms of the telemetry

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THE EXPERIENCES AND ATTITUDES OF GENERAL PRACTITIONERS AND HOSPITAL STAFF TOwARDS PRE-HOSPITAL THROMBOLYSIS IN A RURAL COMMUNITY

Table 1 GP ATTITUDES TOwARDS PREHOSPITAL THROMBOLYSIS. THE PERCENTAGE OF GENERAL PRACTITIONERS RESPONDING IN EACH OF THE CATEGORIES (N=13)

 

AGREE

DISAGREE

NEUTRAL

am convinced of the benefits of thrombolytic treatment in acute myocardial infarction

I

100

(13)

   

am convinced that there are additional benefits from giving thrombolytic treatment in the community at the earliest opportunity after symptom onset

I

100

(13)

   

From the point of view of my practice, giving thrombolytic treatment at home would not result in any appreciable time saving

15

(2)

77

(10)

8

(1)

could make time to give thrombolytic treatment to patients with an acute myocardial infarction

I

85

(11)

8

(1)

8

(1)

Thrombolytic treatment is too expensive for use in general practice

 

92

(12)

8

(1)

Thrombolytic treatment is safe for use in general practice

61

(8)

8

(1)

30

(4)

Thrombolytic treatment is too difficult for use in general practice because it needs to be given intravenously

 

100

 

Thrombolytic treatment is too inconvenient for use in general practice because you may have to travel to the hospital with the patient

8

(1)

69

(9)

23

(3)

I do not have an ECG machine that I could use on call

8

(1)

92

(12)

 

I would be willing to record an ECG in cases of suspected AMI

100

(13)

   

I could interpret an ECG in cases of suspected AMI

85

(11)

15

(2)

 

The decision to thrombolyse a patient is entirely the general

61

(8)

 

(4)

8

(1)

practitioner’s

31

The general practitioner’s decision to thrombolyse patients should be made in consultation with the hospital

23

(3)

59

(7)

23

(3)

I do not have access to a defibrillator

8

(1)

92

(12)

 

I know how to use a defibrillator

85

(11)

8

(1)

8

(1)

I always carry a defibrillator with me when on duty

92

(12)

8

(1)

 

I always carry a thrombolytic kit with me when on duty

77

(10)

15

(2)

8

(1)

am not willing to use thrombolytic treatment unless encouraged to do so by the Department of Health and Children

I

8

(1)

77

(10)

15

(2)

am not willing to use thrombolytic treatment unless encouraged to do so by the ICGP

I

 

77

(10)

23

(3)

am willing to use thrombolytic treatment if it is promoted by the drug manufacturers for use in general practice

I

8

(1)

77

(10)

15

(2)

I

am not willing to use thrombolytic treatment without further

 

(2)

 

(10)

8

(1)

training

15

77

I

am not willing to thrombolyse patients other than my own patients

 

92

(12)

8

(1)

22

to transmit the ECGs to the hospital, just over half the general practitioners (54%; 7 / 13) felt that training was sufficient. The majority (62%; 8 / 13) also felt that more training in administering thrombolysis was warranted.

RESPONSIBILITY AND SUPPORT

The majority of the general practitioners (61%; 8 / 13) felt that the decision to thrombolyse the patient was entirely the general practitioner’s and over half (59%; 7 / 13) thought that the decision should not be made in consultation with the hospital. In contrast, over half of the hospital staff felt that the

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Table 2 GENERAL PRACTITIONERS’ ATTITUDES TOwARDS TRAINING, EDUCATION AND SUPPORT. PERCENTAGE OF GENERAL PRACTITIONERS RESPONDING IN EACH OF THE CATEGORIES (N=13)

 

AGREE

DISAGREE

NEUTRAL

The training received prior to the initiation of the study was sufficient

61

(8)

15

(2)

23

(3)

I

feel that more training in prehospital emergency cardiac care is

62

(8)

23

(3)

15

(2)

necessary

     

I feel that the training in ECG interpretation was sufficient

62

(8)

30

(4)

8

(1)

I feel that more training in administering thrombolytic treatment is

62

(8)

23

(3)

15

(2)

necessary

     

I feel that more training in the use of the ECG equipment is necessary

54

(7)

38

(5)

8

(1)

I feel that the training given on ECG telemetry was sufficient

54

(7)

31

(4)

15

(2)

receive sufficient support from the project team in terms of training and education

I

54

(7)

15

(2)

30

(4)

I

feel that there is a need for a refresher course in cardiac care

77 (10)

 

23

(3)

Table 3 qUESTIONNAIRE ASSESSING THE PARTICIPATING GP’S CONFIDENCE IN THE ABILITY TO RECORD AND INTERPRET AN ECG AND TO ADMINISTER THROMBOLYTIC THERAPY. THE PERCENTAGE OF GENERAL PRACTITIONERS RESPONDING IN EACH OF THE CATEGORIES (N=13)

 

1a

 

2

3

4

 

5

My ability to record an ECG

   

8 (1)

23

(3)

69

(9)

My ability to interpret an ECG

   

46

(6)

46

(6)

8

(1)

My ability to transmit the ECG to the CCU

15

(2)

23

(3)

31

(4)

31

(4)

 

My awareness of the three indications to thrombolyse patients as outlined by DARTS

 

23

(3)

46

(6)

8 (1)

23

(3)

My knowledge of the contraindications to thrombolysis

 

8 (1)

46

(6)

23

(3)

23

(3)

My ability to administer the current thrombolytic agent

 

23

(3)

31

(4)

31

(4)

15

(2)

My ability to provide post thrombolytic Treatment

8 (1)

23

(3)

31

(4)

31

(4)

8

(1)

My ability to deal with possible adverse reactions

15

(2)

31

(4)

31

(4)

23

(3)

 

1a=not at all confident; 2=slightly confident; 3=moderately confident; 4=very confident; 5=extremely confident

decision to thrombolyse patients was not solely

the responsibility of the general practitioner (53%;

16 / 30) and that the decision to thrombolyse

patients should be made in consultation with the hospital (53%; 16 / 30). The majority of the general

practitioners did not feel that support for the

use of thrombolysis in the community from the Department of Health and Children (77%; 10 / 13), the Irish College of General Practitioners (77%; 10 / 13), or the drug manufacturers was necessary (77%;

10 / 13). Of the hospital staff, 97% (29 / 30) agreed

that general practitioners should be allowed to administer thrombolysis with sufficient training, and that the hospital had a role to play in pre-hospital thrombolysis. A total of 92% (12 / 13) of the general

practitioners were willing to thrombolyse patients other than their own and 77% (10 / 13) were willing to administer thrombolysis without further training.

CONFIDENCE IN PREHOSPITAL CARDIAC CARE TREATMENT

Table 3 shows the percentage of responses in each of the categories pertaining to confidence in the pre-hospital treatment of AMI patients. The majority (69%; 9 / 13) of the general practitioners reported that they were extremely confident in

the ability to record an ECG, while 23% (3 / 13) were very confident and 8% (1) were moderately confident. Regarding interpretation, 46% (6 / 13) were moderately confident, 46% (6 / 13) were very

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THE EXPERIENCES AND ATTITUDES OF GENERAL PRACTITIONERS AND HOSPITAL STAFF TOwARDS PRE-HOSPITAL THROMBOLYSIS IN A RURAL COMMUNITY

Table 4 TABLE SHOwING THE PROPORTION % (N) OF RESPONSES FROM HOSPITAL STAFF IN EACH OF THE CATEGORIES FOR THE INDIVIDUAL qUESTIONS (CONSULTANT PHYSICIANS N = 5; NURSING STAFF N = 25; TOTAL N=30)

 

AGREE

DISAGREE

NEUTRAL

am convinced of the benefits of thrombolytic treatment in acute myocardial infarction

I

97

(29)

 

3

(1)

am convinced that there are additional benefits from giving thrombolytic treatment in the community at the earliest opportunity after symptom onset

I

94

(28)

3

(1)

3

(1)

Thrombolytic treatment is too expensive for use in general practice

 

97

(29)

3

(1)

Thrombolytic treatment is safe for use in general practice

67

(20)

10

(3)

23

(7)

Thrombolytic treatment is too difficult for use in general practice because it is to difficult to diagnose eligible patients

 

90

(27)

10

(3)

The decision to thrombolyse a patient is entirely the general

 

(11)

 

(16)

 

(3)

practitioner’s

37

53

10

The general practitioner’s decision to thrombolyse patients should made in consultation with the hospital

53

(16)

27

(8)

20

(6)

Only certain thrombolytic treatments are suitable for use in the

67

(20)

26

(8)

 

(2)

community

7

General practitioners should be allowed to administer thrombolytic treatments with sufficient training

97

(29)

 

3

(1)

EMT’s should be allowed to administer thrombolytic treatment with sufficient training

27

(8)

63

(19)

10

(3)

The hospital has a role to play in prehospital thrombolysis

86

(26)

7

(2)

7

(2)

24

confident and one (8%) general practitioner was extremely confident. Confidence in the transmission of the ECG to the hospital showed that 15% (2 / 13) were not at all confident, 23% (3 / 13) were slightly confident, 31% (4 / 13) were moderately confident and 31% (4 / 13) were very confident. General practitioners reported that they were slightly confident (23%; 3 / 13), moderately confident (46%; 6 / 13), very confident

(23%; 3 / 13) or extremely confident (23%; 3 / 13) in their knowledge of the three indications for thrombolysis as outlined by the study protocol. Knowledge of the contraindications to thrombolysis showed that only one general practitioner reported slight confidence, 46% (6 / 13) reported moderate confidence and 23% (3

/ 13) reported very confident and extremely confident.

A total of 23% (3 / 13) of general practitioners reported

that they were slightly confident in their ability to administer the current thrombolytic agent, while 31% (4 / 13) reported moderate confidence, 31% (4 / 13) were very confident, and 15% (2 / 13) were extremely confident. Finally, a total of 15% (2 / 13) of the general practitioners were not at all confident in the ability to deal with adverse reactions to thrombolysis while 31% (4 / 13) felt slightly confident, 31% (4 / 13) felt very confident and 23% (3 / 13) felt extremely confident.

DisCUssiOn

Acknowledgement of the benefits of rapid treatment for AMI patients was presented in the Cardiovascular Health Strategy and the report recommended that eligible patients receive pre-hospital thrombolysis within 90 minutes of alerting medical help. 1 In rural areas, however, it is often impossible to achieve this guideline. DARTS was the first study in Ireland to introduce general practitioner administered thrombolysis. This study was a follow-up of general practitioners involved in DARTS and the aim was to investigate the attitudes towards pre-hospital thrombolysis of both the participating general practitioners and relevant hospital staff.

BENEFITS OF THROMBOLYSIS AND EARLY ADMINISTRATION

Responses to the questionnaire suggest that both the general practitioners and hospital staff believe in the efficacy of thrombolysis and of the added benefits of early administration. The general practitioners also felt that appreciable timesavings would be incurred if thrombolysis were to be administered in the community.

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COST, ADMINISTRATION AND SAFETY Both groups agreed that it was safe to administer thrombolysis in the community. In terms of the cost of thrombolysis, the general practitioners and hospital staff both agreed that thrombolysis is not too expensive for use in general practice. Likewise, the general practitioners did not see thrombolysis as too difficult or too inconvenient to administer. The majority of the hospital staff had confidence in the general practitioners’ ability to assess and diagnose eligible patients for thrombolysis. This is in contrast to the findings from Scotland. 6

EqUIPMENT

The possession of equipment such as an ECG and defibrillator are necessary for domiciliary thrombolysis. Practically all the general practitioners

had access to an ECG and were willing to use it in the case of suspected AMI. Likewise, all but one had access to a defibrillator. Only two of the general practitioners reported being unable to interpret an ECG and two reported being unable to use a defibrillator.

TRAINING AND EDUCATION NEEDS

Previous work has estimated that the general practitioners in this area will on average see three AMI cases per year 6 . Given the rare occurrence of AMI, continued training and education in pre- hospital cardiac care must become an integral part of any pre-hospital thrombolysis policy. The majority of the general practitioners felt that training was sufficient prior to the initiation of the project. However, it is clear that the general practitioners feel that refresher courses in pre-hospital cardiac care and in interpretation of the electrocardiogram are needed. Regarding ECG telemetry, only half the general practitioners felt that training was sufficient. Findings from the DART study 4,8 showed that none of the general practitioners made use of the facility to transmit the ECG to the hospital prior to the arrival of the patient. At the initiation of the project there was a shortage of hospital on-call staff making it difficult to obtain assistance from the hospital for diagnostic support. The general practitioners were confident in their diagnostic ability and felt that the decision to thrombolysis was entirely their own. Using the ECG telemetry especially when not competent in its use would only increase the delay to pre-hospital thrombolysis.

COnClUsiOn

These results show that the general practitioners are a willing, enthusiastic and confident group for the provision of pre-hospital thrombolysis. Furthermore, the hospital staff acknowledges the important role of general practitioners and are willing to provide support to those general practitioners who wish to provide this service. General practitioners should be supported in terms of equipment, training and education in pre-hospital thrombolysis and incentives should be offered to those who are willing to provide this service.

ACkNOwLEDGEMENTS

We wish to acknowledge and express our appreciation to the general practitioners, nursing staff and consultants for their time and enthusiasm to participate in this study.

REFERENCES

1. Cardiovascular Health Strategy Group (1999). Building Healthier Hearts. Department of Health and Children.

2. O’Neill J, Dowling J, Wright P et al. Patients presenting with acute myocardial infarction to a district general hospital: Baseline results and effect of audit. Irish Med J 2003; 96; 3.

3. GREAT Group. Feasibility, safety and efficacy of domiciliary thrombolysis by general practitioners:

Grampian region early anistreplase trial. Br Med J 1992; 305: 548 – 53.

4. North West Immediate Care Programme (2003). Donegal Area Rapid Treatment Study (DARTS): Final Report. North Western Health Board.

5. Rawles J. Attitudes of general practitioners to prehospital thrombolysis. Br Med J 1994; 309: 379

6. Rawles J, Ritchie L. Thrombolysis in peripheral general practices in Scotland: another rule of halves. Health Bull 1999; 57:1: 10 – 16.

7. Doherty D, Dowling J, Wright P, Murphy AW, Bury G, Bannan L. The potential use of prehospital thrombolysis in a rural community. Resus 2004, 61: 303 – 307.

8. Doherty D, Dowling J, Wright P, Murphy AW, Bury G, Bannan L. Prehospital thrombolysis in a rural community: A case series and clinical follow-up. Submitted to Irish Journal of Medical Sciences.

Correspondence to: Dr Donna Tedstone Doherty, Health Research Board, Third Floor, Knockmaun House, 42 - 47 Lower Mount Street, Dublin 2. Email: dtedstonedoherty@hrb.ie

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LOw MOLECULAR wEIGHT HEPARIN PROPHYLAXIS IN DAY CASE SURGERY

Low molecular weight heparin prophylaxis in day case surgery

aBstraCt

Background The role of Low molecular weight heparins (LMWH) in day case/ short-stay

surgery is unknown. To characterise the current national use of LMWH prophylaxis in specific day and

Aim

short stay surgeries. Methods A standardised anonymous postal questionnaire was sent to all consultant general surgeons in Ireland. The operations selected were herniorraphy, anorectal, varicose vein and laparoscopic cholecystectomy. Results Questionnaires were sent to 82 surgeons in 2003. There was a response rate of 68.3% (56). Fifty-four per cent of respondents said there was a protocol in place for administration of LMWH in day case surgery. Of these 41% were not confident that their protocols were being adhered. Fifty-nine per cent of all respondents said they stratified patients according to individual risk. Thirteen per cent reported occurrence of VTE post day case surgery. Conclusion This study demonstrates a heterogeneous pattern of administration of LMWH. In the absence of published validated protocols, the authors suggest a consensus day case protocol.

J Shabbir,

PF

Ridgway,

W

Shields,

D

Evoy,

JB

K Mealy

Dept of Surgery, Wexford General Hospital, Wexford

O’Mahony,

26

intrODUCtiOn

Venous thromboembolism (VTE) remains an important complication amongst surgical inpatients. Before the widespread introduction of heparin prophylaxis, as many as 25% of patients developed deep venous thrombosis (DVT). 1,2 Due to the largely silent nature of DVT, the true incidence and prevalence rates is probably substantially higher. 3 Several meta-analyses have revealed that Low Molecular Weight Heparins (LMWH) are as effective as unfractionated heparins for VTE prophylaxis in general surgical patients and have practically replaced unfractionated heparin for VTE prophylaxis as well as treatment for inpatients. 4,5

The prevalence of VTE after day case and short stay surgeries is less clear. The literature base upon which putative prophylaxis regimens may be based is largely absent. The authors identified one large study conducted in Denmark studying VTE post day case herniorrhaphy. 6

The study period was between 1982 and 1992 and documented rates of VTE were less than 1%. Intuitively, these patients should be at inherently lower risk as they tend to be a well population undergoing short duration surgery. Surprisingly, there

are no other correlative studies confirming incidence

in day case herniorrhaphy or other common short

stay procedures.

Thus as surgeons we practice in a time where most units have clear guidelines in place for their surgical inpatients, whereas for our day case or short stay patients no clear guidelines for VTE prophylaxis exist.

In the absence of higher-level evidence, the authors’

sought to elucidate a national consensus with respect to VTE prophylaxis for four specific day case and short stay procedures.

MetHODs

A standardised anonymous postal questionnaire

was utilised. The operations selected for review were day case herniorraphy, minor anorectal surgery and varicose vein surgery. Day case or overnight laparoscopic cholecystectomy was also included. The questionnaire was posted to all Consultant Surgeons on the active register in Ireland in 2003. Replies within one month of posting were included in the

sample. One postal reminder was sent to those who did not respond within four weeks.

Consultant surgeons were asked whether standardised protocols for prophylaxis against

IRISH JOURNAL OF MEDICAL SCIENCE • VOLUME 175 • NUMBER 4

J ShaBBir et al

VTE were in place and adhered to for each of the procedures. Usage and dosage, timing of LMWHs were investigated as well as attitudes toward risk stratification. Surgeons’ individual recollections of whether they had known cases of VT post day case surgery were assessed. The use of mechanical aids

such as intermittent compression or thromboembolic

event deterrent (TED) stockings was recorded.

resUlts

Questionnaires were sent to 82 general surgeons. There was an overall response rate of 68.3% (56). Sixty one per cent (50) responded within first four weeks and further 7% (6) following reminders. Fifty-four per cent of respondents said there was a protocol in place for administration of LMWH in day case surgery. Of these 41% were not confident that their protocols were being adhered to leaving 59% with working protocols (Figure 1).

Only one respondent utilised TED stockings in prophylaxis for patients undergoing laparoscopic cholecystectomy. Individual procedures investigated in this study with presence or absence of protocols are shown in (Figure 2 and Table 1). Enoxaparin and Tinzaparin were the two commonest LMWH preparations in use. Dosages ranged from low dose (20 mg Enoxaparin or 3,500 IU Tinzaparin) to high dose (40mg Enoxaparin or 4,500 IU Tinzaparin). Timing where stated, ranged from within an hour prior to surgery to greater than two hours (Table 2). Interestingly, 59% of all respondents said they stratified patients according to individual risk, although this appeared to be on an individual basis as protocols were not structured to include stratification.

In the varicose vein group, 43% have protocols in place, although 16% are not confident they are in use. The majority select low dose LMWH within an hour prior to surgery. Thirty-two per cent of day case herniae have LMWH prophylaxis, usually within one hour of surgery. Once again, high dose LMWH is only used in a small per centage. Anorectal day case surgery is rarely given prophylaxis. Working protocols are seen in 13%. Low dose LMWH is used exclusively. Day case and short stay laparoscopic cholecystectomy had the highest per centage of protocols in place (46%). Once again the commonest dosage is low dose LMWH given within one hour prior to the procedure.

Thirteen per cent of surgeons reported documented occurrence of VT post day case surgery within a

documented occurrence of VT post day case surgery within a Table 1 TIMING FOR PROPHYLAXIS (HOURS

documented occurrence of VT post day case surgery within a Table 1 TIMING FOR PROPHYLAXIS (HOURS

Table 1 TIMING FOR PROPHYLAXIS (HOURS BEFORE SURGERY)

       

NOT

%

<1

1 TO 2

>2

STATED

Varicose Veins

60

20

8

12

Hernia

50

22

6

22

Anorectal

25

25

13

37

Lap Chole

44

20

12

24

Table 2 LMwH DOSAGE REGIMEN FOR INDIVIDUAL PROCEDURES

VARICOSE

LAPAROSCOPIC

   

VEINS

CHOLECYSTECTOMY

HERNIA

ANORECTAL

LD

LD

None

None

LD

LD

None

None