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Leziunea primara

1).ocul hipovolemic
scderea absolut sau relativ a volumului sanguin
manifestri
scderea DC,TA, presarcin
reacie simpatic
tahicardie,paloare,oligurie,cianoz,hipotermie
cauzele
hemoragiile,traumatismele
Leziunea primara
2). ocul posttraumatic
pierderi sanguine
reacie hiperergic hipodinamic
sacrificare splahnic
substane vasoactive
hipoxia,anemia,tb respiratorii
sindromul inflamator localizat,generalizat
deficit de perfuzie tisular



Suferin multipl
Politraumatismele
Pacientul politraumatizat
Caracteristici:
Internat la TI ( funciile vitale)
Este preluat de echipa medical
Necesitatea unui dg precis si complet
funcional
clinic
Ordinea manevrelor
ora de aur decesul survine (Ph. Stahel sept 2006)
Pe coridor
Ascensor
La CT.


Prioritati diagnostice imediate
Situaia pulmonar
Contuzia cardiaca, hemopericard, ruptur cardiac
Cont esofag, plaman, coaste(unica, multipla, volet.)
asfixia toracica (sindr de compresiune, hernia diafragm)
Michael AJ Sawyer eMedicinek 30 iune 2006.
Complexul toraco pulmonar

Hemodinamica
Evaluarea neurologic (GCS)

Evaluare prin
Utilizarea scorurilor
APACHE II
Glasgow Coma Scale
ATLS (Advanced trauma Life Suport)
Examinarea neurologic
De trunchi cerebral
Explorri
CT scan, RMN, EEG, Poteniale evocate
Oximetria cerebral

Un remember fiziopatologic
Neurologic
Leziunea primar
Doctrina Monro Kellie.
V
cranian
= V
cerebral
+ V
sanguin
+ V
LCR

Fluxul sanguin cerebral
Presiunea de perfuzie cerebral
Presiunea intracraniana undele pulsatile ale lui Lundberg.
Edemul cerebral
Compliana cerebral
Leziunea secundar
Sindromul de ischemie reperfuzie.

Unda pulsatil normal i patologic
Patologia pulmonara
Primara;
Fr costale cu sau far insuficien vent.
Colecii pleurale hemo pneumo)
Rupturi bronice, cardiace, vasculare
Inundaia bronic
Compresiunea toracopulmonar
Hernia diafragm !!
Secundara
Infectioas (cauze atelectazia,bronhoplegia, hipoventilatia)
Contuzia pulm (reactivitatea imunologica)
ARDS
Investigatiile
Examinarea clinic
Biochimia
Hematologia
Imagistica
RX
CT scanner pe trei componente S. Shepard. 2006.
Tisular
Osos
Subdural
RMN
Ecografic
Dopler
Bronhoscopie
Cum procedm
Avem un diagnostic de etap stabilit !
Dg clinic
Dg funcional
Ce conduit adoptm?
Ordinea interveniilor
Funciile vitale

De ce dispunem ?
Terapia
Hemodinamica
Ventilatia
Protectia cerebrala
Echilibrul fluidocoagulant
Managementul anemiei.
Fizioterapia
Nutriia
Asepsia i antisepsia.
Ventilatia
Stabilizarea complexului toraco pulmonar
Asigurarea expansiunii pulmonare
Analgezia (an. locale, peridural)
Urmrirea EAB
Ventilaia : asistat sau controlat
Scopul : ventilaia plmnului deschis
Gattinoni, Pelon
Dificulti n caz de PIC ridicat
Ce modul ventilator alegem ?
Protectia cerebrala
Ne adresam penumbrei lezionale.
Resuscitarea cerebral Necesit determinarea PIC !
Doctrina Monro Kellie
V
cranian
= V
cerebral
+ V
sanguin
+ V
LCR

Asigurarea unei PPC
Terapia edemului cerebral
Drenajul venos (ridicarea capului)
Indicaii
Contraindicaii
Utilizarea barbituricelor. Coma barbituric la PIC rebel Bader HK,
Hipotermia Meiloy LH
Hipertermia accentueaza cascada enzimatica a leziunilor secundare
Terapia anticonvulsivant
Blocanii de canal de calciu (nimodipina) trial Bayer
Ind, contraindicaii
Corticoterapia
Utilizarea F VII recombinat : Pro i Con
(Advanced Bleeding Care Barcelona 2006)
Interventii chirurgicale
Cnd se intervine?
Pentru hemostaz
Pentru refacerea complexului toraco pulmonar
Fracturile deschise de membre
Rezolvarea eschilelor craniene
Evacuarea elementului de mas
Cnd?


Antibioterapia
Indicaia antibiotic
Profilactic
Curativ
Dileme:
TCC nchis necesit antibiotice ?
Profilaxia antibiotic ne scutete de infecii pulmonare?
Importana nursingului.
Antibioterapie iniial sau ntrziat
Care este spectrul nosocomialitii spitalului
Recomandare pentru spectru larg


Leziunea primara
3). ocul postcombustional
scade volumul sanguin circulant
pierderi de electrolii i ap

oc hipovolemic
SIRS infecie




MSOF
Leziunea primara
4). oc anafilactic,anafilactoid
Atg+Atc activare C

mastocite histamin

vasodilataie acut-colaps bronhospasm

DC,hipoxie,AV IRA
Stop cardiac
Leziunea primara
5). Debit cardiac mic
Cauze

cardiace extracardiace vasculare
tamponada embolia
oc cardiogen emfizem ARDS
pericardit tromboza
hipovolemia

Insuficienta cardiaca

IC=2,5
PCWP=18 mmHg
Reperfuzia
Dou etape:

Ischemia
Reperfuzia
Ischemia
Prag critic de perfuzie
Penumbra ischemica
Extractie de O2
Flux sanguin cerebral
Metabolismul celular :acumularea de xantina
Peroxidarea fosfolipidica
Inflamatia
Semne EEG,RMN cu PET

Reperfuzia Rolul oxigenului.
Reperfuzia fluxul sanguin
Sindromul de reperfuzie
Reperfuzia
biochimia sindromului
radicalii liberi
infiltraia cu polimorfonucleare
inactivarea pompei de ioni i a ATP-azei
peroxidarea lipidelor de membran(PUFA)
Microcirculaia n reperfuzie
hiperemia de reperfuzie
ischemia secundar








Sindromul de reperfuzie
tratament
blocarea intrrii Ca n celul
inhibitori de canale de Ca
terapia edemului
blocarea radicalilor liberi de O2-
allopurinol
aprotinina-xantindehidrogenaza
deferoxamina-blocheaz Fe +2
acid ascorbic
-tocoferol.
blocarea prostaglandinelor vasoactive
cu antiinflamatorii




Sepsisul
Cascada sepsisului
Infecia local
Inflamaia
Sindromul inflamator sistemic
Sepsisul
Sepsis sever
ocul septic
SDOM


Infectia
Infecia exogen sau/ endogen
Prezena
bacteriilor
virusurilor
fungilor
La nivelul unui esut
Bacteremia
Prezena microorganismelor n torentul circulator
inflamatia


Reacia enzimatic i celular la prezena
microorganismelor
polipeptidelor active
Sindromul inflamator sistemic
generalizarea rspunsului
mediatori ai inflamaiei
reacii celulare
agresiune endotelial
activarea coagulrii
activarea complementului
sepsis

SIRS care are la origine o infecie
elementele clinice
procalcitonina (PCT) un marker important
Elementele de SIRS + 4 semne
Infecia de natur
-exogen
-endogen
Sepsis sever
Prezena a cel puin dou elemente
tahicardie
polipnee
leucocitoz
febr
Prezena a dou funcii cu SDOM
hipotensiune remis prin terapie volemic
Soc septic


Tabloul de sepsis sever plus
profilul hemodinamic
hipotensiune fr hipovolemie
necesit susinere farmacologica
Incadrarea in sepsis (din 1992)

Infectie
inflamatie
SIRS Sepsis Sepsis sever Soc septic MODS
Infectie +
Reactie
Inflamatorie
localizata

Tahicardie
Polipnee
Febra
leucocitoza
Infectie+
Semne SIRS
Sepsis+

TA scazuta
Remisa
volemic+
disfunctii
de organe
Sepsis
sever cu
TA
sustinuta
inotrop
Disfunctii
multiple
de
organe
Neclaritati si confuzii
Cum diferentiem ?
Conferinta de consens din 2001
SIRS este adaugit cu
reactia neuro endocrina si de coagulare
La conceptul de sepsis se adauga
Alterarea cerebrala
Edeme semnificative
Hiperglicemia
PCR PCT
La disfunctiile din sepsis se adauga
Hipoxia, oliguria
Ileusul
Trombocitopenia
Acidoza lactica
Hiperbilirubinemia
Markeri ai sepsisului
Procalcitonina
Proteina (114 AA) imun modulatoare
Inductia
Proteina C reactiva
interleukin-1
TNF alfa
Acidul lactic

Aprecierea eficientei unui test
Sensibilitatea diagnostica a unui test
Cati sunt pozitivi din 100 bolnavi testati


Specificitatea diagnostica a unui test
Cat la % din sanatosi sunt pozitivi
Clinica
Sistemul cardiovascular
RVS scazuta, DC crescut, (status hiperdinamic)
Spatiul 3, mediatori vasoactivi, reducere metabolism
Disfunctia miocardica precoce (2-3 z) 40% in sep sever
Cauze citokinele, TNF, prostanoidele, NO, reperfuzia
Factorul de depresie miocardica,Disfunctie stg, dr
La supravituitori se constata
Scade FE si creste volumul rezidual diastolic, cu revenire
Apare dilatatia ventriculara stg.
La cei care decedeaza nu se constata aceste modificari
Reprezinta inadaptabilitatea organismului la sepsis.
39
Incidence of Severe Sepsis in Europe
2.28
3.6
11.6
13
13.2
14
30
0
10
20
30
I
n
c
i
d
e
n
c
e

(
%
)

AIDS Uterus Lung
Cancer
Colon
Cancer
Prostate
Cancer
Breast
Cancer
Severe
Sepsis
1
2
2
2
2
2
3
1
Semaille C et al. Euro Surveill 2003; 8: 57-64
2
Ferlay J et al Annals of Oncology 2007; 18: 581-592 (Cancer cases as percentage of total cancers in 2006, EU)
3
Vincent J -L et al Crit Care Med 2006; 34: 344-353 (% severe sepsis during ICU stay for EU)
40
Mortality of Severe Sepsis in ICU (Europe)

5.8
7.3
12
20.2
27-36
0
20
40
D
e
a
t
h
s

(
%
)

AIDS Prostate
Cancer
Breast
Cancer
Colon
Cancer
Lung
Cancer
Severe sepsis
in the ICU
1
3
2
2
2
2
1
Lopez AD et al Lancet 2006; 367: 1747-1757 (Deaths for AIDS/HIV worldwide, low- and middle-income countries in 2001)
2
Ferlay J et al Annals of Oncology 2007; 18: 581-592 (Cancer deaths as percentage of total cancer deaths in 2006, EU)
3
Vincent J L et al Crit Care Med 2006; 34: 344-353 (ICU mortality rate, 27% and hospital mortality rate,36% for EU)
5.3
De ce avem vasodilatatie?
Avem scaderea RVS
Vesele nu reactioneaza la vasopresoare
Cauzele sunt
Activarea canalelor ATP (Katp)
Eliberarea de NO prin NO sintetaza (declansat de citokine)
Deficienta de vasopresina
Rolul ei in
Contracararea efectului NO
Blocarea canalelor de K. (ATP)
Respiratorul
In sepsis 40% fac ALI. Suprafata pulmonara
VAP, bronhopn, genereaza ARDS
Etiologia endoteliala al sepsisului
Ventilatia mecanica, avantaj,dezavantaj
Barotrauma, volutrauma
Cascada enzimatica a barotraumei
O noua conceptia a fiziopatologiei
sepsisului.
Insuficien de
organ
Sepsis
Coagularea
Fibrinoliza
Inflamaie
Agresiune
endotelial
moarte
Homeostazia este pierdut in sepsis
PAI-1= inhibitoul activatorului de plasminogen-1;TAFI
a
= Inhibitor al fibrinolizei activabil de trombin
Carvalho and Freeman. J Crit Illness. 1994;9:51; Kidokoro et al. Shock. 1996;5:223; Vervloet et al. Semin
Thromb Hemost. 1998;24:33.
Homeostazia
Mediatori proinflamatori
Injurie endotelial
Exprimarea factorilor
tisulari
Producia de trombin
PAl-1 crescut
Crete TAFI
a

Reducerea Proteinei C
( Protein C activat
inhib PAI-1)
Cascada SIRS-sepsis

Proteina C reactiv

Cascada mediatorilor
faza moleculara

endotoxinele
macrofag
IL-1
IL-6
TNF
Cascada mediatorilor
faza moleculara

IL-1
IL-6
TNF

ficat Proteinele de
faza acuta
1 globuline
2 globuline
globuline
Cascada mediatorilor
faza moleculara

Activare complement
Proteinele de faza acuta
Complexe Atg-Atc
Factorul XII
Opsonizare
Liza celulara
Chemotactica
Anafilatoxinica
Cascada mediatorilor
faza vascular oxidativa

kalicreinogenul kalicreina
Factor XII
acidoza
bradikininogen bradikinina
Plasminogen plasmina
Activitate vasculara
coagularea- faza vascular-oxidativa
Calea extrinsec Calea intrinsec
VII
Factor tisular
VIIa
X Xa
Ca**
fosfolipid
Va
protrombin
trombin
XII XIIa
XI XIa
IX IXa
fosfolipid
VIIIa
X
Fibrinogen Fibrin
XIII
XIIIa
Fibrin stabil
Ca**
Ca**
Teoria modelului celular
Iniierea
Pe celulele purttoare de FT
Amplificarea
Activarea trombocitelor
Acumularea de cofactori
Propagarea
Generare exploziv de trombin
Polimerizarea fibrinei.
Teoria modelului celular
Iniierea
Pe celulele purttoare de FT
Amplificarea
Activarea trombocitelor
Acumularea de cofactori
Propagarea
Generare exploziv de trombin
Polimerizarea fibrinei.
Sistemul fibrinolitic
faza vascular-oxidativa

F XII
kininele Sterptochinaza urokinaza
plasminogen
plasmina
Fibrinoliza kininele complementul chemotactic
PAI-1
Lipidele biologic active
faza vascular oxidativa

fosfolipide
Acid arahidonic
Ciclooxigenare Lipooxigenare
PGE PGI2 TxA2 Leucotriene
Vasoconstrictie vasodilatatie activ. Plt Chemotactism
Proteina C activa
Role
antitrombotic
antiinflamator
profibrinolitic
moduleaza coagularea si inflamatia
un nivel plasmatic sczut n sepsis arat un cerc
vicios al coagulrii i al inflamaiei cu consecine
potenial letale
Taylor citat de T.Esmon Crit.Care 2001,5
tratament
1. Triggerul

2. Cascada enzimatic

3. Suportul mecanic i farmacologic
1. trigerul
Terapia Infeciei
etiologie exogen
etiologie endogen
Mijloace
specifice- antibioticele
intervenioniste eseniale!
Pentru pacienii cu infecii severe...
Antibioticul adecvat
(right Drug)
Doza corect
(right Dose)
Durata corect
(right Duration)
Dezescaladare
(De-
escalation)
Terapia antimicrobian
optim
principiul celor 4D

Adaptat dup J.Joseph & K.A. Rodvold, The role of carbapenems in the treatment of severe nosocomial respiratory tract infections, Expert Opin
Pharmacother.(2008) 9(4):561-575

Pentru pacienii cu infecii severe...
Antibioticul adecvat poate face diferena
p < 0,001
Adaptat dup M. Tumbarello i colab., Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum--Lactamase-
Producing Enterobacteriaceae: Importance of Inadequate Initial Antimicrobial Treatment, Antimicrobial Agents and Chemotherapy, June 2007, p.1987-
1994

...dac este administrat de la
nceput!
p < 0,001
Adaptat dup M. Tumbarello i colab., Predictors of Mortality in Patients with Bloodstream Infections Caused by Extended-Spectrum--Lactamase-
Producing Enterobacteriaceae: Importance of Inadequate Initial Antimicrobial Treatment, Antimicrobial Agents and Chemotherapy, June 2007, p.1987-
1994


1. Incepei terapia antibiotic ct mai curnd posibil i n prima or n
cazul sepsisului sever i ocului septic.

2. Utilizai antibiotice cu spectru larg.

3. Re-evaluai zilnic regimul antimicrobian pentru:
optimizarea eficacitii
prevenirea rezistenei
evitarea toxicitii
scderea costurilor

4. Limitai durata tratamentului la 7-10 zile.

5. Oprii terapia antibiotic dac sursa este ne-infecioas.
R.P. Dellinger i colab., Surviving Sepsis Campaign: International Guidelines for Menegement of Severe Sepsis and Septic Shock: 2008, Crit Care Med 2008;
36(1): 296-327.
Principii de alegere a terapiei
antibiotice adecvate
Pentru pacienii cu infecii severe...
Fiecare or conteaz!
Adaptat dup Kumar i colab, Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human
septic shock, Crit Care Med 2006 vol 34, nr6
Clasificarea infeciilor
INFECII COMUNITARE
INFECII NOSOCOMIALE
INFECII COMUNITARE
INFECII
ASOCIATE
ASISTENEI
MEDICALE
INFECII NOSOCOMIALE
Germeni
cu sensibilitate
la antibiotice
posibil pstrat
G-neg/poz
posibil
MDR ESBL
MRSA
G-neg MDR:
+
non-fermentativi:
- Pseudomonas
- Acinetobacter
A.Streinu-Cercel, Stadializarea infeciilor acute severe. Implicaii terapeutice, editorial, Terapeutic, Farmacologie i Toxicologie Clinic, an XII, vol 12, nr1/2008.
Adaptat dup M.H. Kollef i colab., Broad-Spectrum Antimicrobials and the Treatment of Serious Bacterial Infections: Getting It Right Up Front, Clin Infect
Dis 2008;

Algoritm de terapie antibiotic adecvat

Suspiciune de infecie bacterian (pneumonie nozocomial, sepsis)
Recoltarea probelor pentru cultur
Terapia antibiotic empiric:
caracteristicile pacientului
datele locale de sensibilitate bacterian
Evaluarea raspunsului clinic la 48-72 h
Antibiotic cu spectru mai redus (pe
baza antibiogramei)
Reevaluarea continurii terapiei dup
7-8 zile
Reevaluarea strii pacientului:
infecie cu germeni rezistenti,
complicaii (abces, empiem),
cauze non-infecioase (febra iatrogen)
Ameliorare clinic
Fr ameliorare clinic
Administrarea empiric a antibioticelor cu spectru larg
acoper o gam larg de patogeni potenial rezisteni:

Enterobacteriaceae productoare de ESBL
Pseudomonas aeruginosa
Acinetobacter spp.

Pentru pacienii cu infecii severe...
Terapia de Dezescaladare
R.G. Masterton i colab., The new treatment paradigm and the role of carbapenems, International Journal of Antimicrobial Agents 33(2009) 105.e1-
105.e8.
ESBL (extended spectrum beta-lactameses) = beta-lactamaze cu spectru
extins
Evaluarea riscului - Carmeli
A. Contactul cu sectorul sanitar:
1) Fr contact
2) Contact fr proceduri invazive
3) Contacte repetate cu proceduri invazive

B. Tratament AB:
1) Fr AB
2) Cu AB n antecedente

C. Caracteristicile pacientului:
1) Tnr fr comorbiditi
2) Vrstnic cu comorbiditi
3) Pacient imunodeprimat:
AIDS
BPOC
Cancer
BMT
1
2
3
2
1
1
2
3
Scor: 1,2 sau 3
A.Streinu-Cercel, Stadializarea infeciilor acute severe. Implicaii terapeutice, editorial, Terapeutic, Farmacologie i Toxicologie Clinic, an XII, vol 12, nr1/2008.
Carmeli 1
Carmeli 2
Carmeli 3
Infecii
comunitare
Amoxi/clav
FQ Levo/Moxi po
CGII/III
Macrolide
Ertapenem
Aminoglicozide
FQ Levo/Moxi po/i.v.
CGIII/IV, C-antiPs.
lactami+I. lactamaze
(Amoxi/clav SR, ES)
Linezolid/Vancomicin
Macrolide
Meronem/Imipenem
Aminoglicozide
FQ GIV Moxi iv
CGIII antiPS
CGIV:
Cefepim,
Cefpirom
Linezolid / Vancomicin
Macrolide
Infecii
asociate
ngrijirilor
medicale
Infecii
nosocomiale
Alegerea terapiei adecvate n funcie de factorii de risc
A.Streinu-Cercel, Stadializarea infeciilor acute severe. Implicaii terapeutice, editorial, Terapeutic, Farmacologie i Toxicologie Clinic, an XII, vol 12, nr1/2008.
FQ GIV fluorchinolone, generatia IV; CG II, CG III, CG IV cefalosporine generaia II sau generaia III sau generaia IV; C anti PS cefalosporine anti-
Pseudomonas.
Franta Romania Italia UK Germania
http://ecdc.europa.eu/en/activities/surveillance/EARS-
Net/database/Pages/table_reports.aspx

0
20
40
60
80
2
0
0
0
2
0
0
1
2
0
0
2
2
0
0
3
2
0
0
4
2
0
0
5
2
0
0
6
2
0
0
7
2
0
0
8
2
0
0
9
2
0
1
0
2
0
1
1
I
n
c
i
d
e
n
t
a

(
%
)
MRSA
0
5
10
15
20
25
2
0
0
0
2
0
0
1
2
0
0
2
2
0
0
3
2
0
0
4
2
0
0
5
2
0
0
6
2
0
0
7
2
0
0
8
2
0
0
9
2
0
1
0
I
n
c
i
d
e
n
t
a

(
%
)
E. coli cefalosporine gen. III
Franta Germania Italia Lituania Spania UK
Europa: cresterea rezistentei bacteriene
Adaptat dupa Silver. Clin Microbiol Rev. 2011 Jan;24(1):71-109
Antibioticele (2004): 1,6%
din totalul moleculelor
aflate in dezvoltare
1

Actual, cateva antibiotice
se afla in faza finala de
cercetare si pot combate
eficient rezistenta
bacteriana
2

1. World Health Organization and European Observatory on
Health Systems and Policies. Policies and incentives for
promoting innovation in antibiotic research. 2010;
2. Spellberg et al. Clin Infect Dis 2004;38:127986
Sulfamide
Streptomicina
Bacitracina
Nitrofurani
Cloramfenicol
Polimixina
Clortetracicline
Cefalosporine
Pleuromutilina
Eritromicina
Izoniazida
Vancomicina
Streptogramina
Cicloserina
Novobiocina
Rifampicina
Metronidazol Mupirocin
Fosfomicina
Acid fusidic
Lincomicina
Trimetoprim
Acid nalidix ic
Carbapeneme
Oxazolidina
Monobactami
Daptomicina
1910 1920 1930 1940 1950 1960 1970 1980 1990 2010 2000
Vid al descoperirilor
Salvarsan
Penicillina
Nevoia actuala: antibiotice NOI
Prevaleta MRSA in spitale
Korea
Japan
HK
Taiwan
Sri Lanka
Vietnam
Thailand
Malta
Grundmann et al. Lancet 2006;368:87485
Song et al. ANSORP surveillance (2005-2006)
Annual report of the EARS-Net 2009
Mejia et al. Braz J Infect Dis 2010;14 Suppl 2:S7986
< 1% 5-10% 10-25% 25-50% > 50% 1-5% Unknown
S. aureus: cel mai frecvent agent patogen
in inf. complicate cutanate & tes. moi
1. Sader HS et al. Int J Antimicrob Agents 2010:36:28-32;
2. Itani KM et al. Am J Infect Control 2011; 39:42-49
Izolate obtinute din 33 institutii (Belgia, Franta, Germania, Grecia, Irlanda, Italia, Polonia,
Rusia, Spania, Suedia, Elvetia, Turcia, UK, Israel)
ICCTM cu MRSA sunt asociate cu cresterea semnificativa (p=.0001) a
mortalitatii vs. ICCTM non-MRSA
2
MSSA
MRSA
22.5% 77.5%
Enterococi
9%
S. coagulazo-
negativi
8%
S. Aureus
71%
S. Viridans
1%
S. -
hemolitici
11%
71%
S. Aureus
Prevalenta MRSA in Romania: 25-50%
European Centre for Disease Control, 2013. Available at:
http://ecdc.europa.eu/en/activities/surveillance/EARS-
Net/database/Pages/maps_report.aspx (accessed January 2013)
Fara date raportate/< 10 izolate
Neincluse
Nu apar in harta:
Activitate
anti-MRSA
Zhanel GG et al. Drugs. 2009;69:80931
N
S
O
S
N
N
+
O
O
N
N
S N
N
N
O
P
O
O
O
S
C H
3
O
N
S
O
S
N
N
+
O
O
N
N
S N
N
O
S
C H
3
O
Cresterea solubilitatii
Inhibarea sintezei peretelui
celular bacterian
Stabilitate -lactamazica
C
e
f
t
a
r
o
l
i
n
a

f
o
s
a
m
i
l

(
p
r
o
d
r
o
g
)

C
e
f
t
a
r
o
l
i
n
a

(
m
e
t
a
b
o
l
i
t

a
c
t
i
v
)

H2N
ZINFORO: creata pentru a fi diferita
vs. alte cefalosporine
Factorii de risc pentru
pneumonia nozocomial

Vrsta > 65 ani
Afeciuni pulmonare organice
Tratament antibiotic anterior
Debutul tardiv al pneumoniei (>5 zile)
Ventilaia mecanic sau non-invaziv
Alte insuficiene de organ
Adaptat dup K.F. Bodmann i colab., Current Guidelines for the Treatment of Severe Pneumonia and Sepsis, Chemotherapy 2005; 51:227-233

Pentru pacienii cu risc nozocomial,
gndii-v ntotdeauna la patogenii dificili
Productorii de ESBL
Pentru patogenii Gram-negativi, producia de beta-lactamaze este cel
mai important factor care contribuie la rezistena fa de antibioticele beta-
lactamice.


Beta-lactamazele sunt enzime bacteriene care inactiveaz antibioticele
beta-lactamice prin hidroliz.


Dintre acestea, beta-lactamazele cu spectru extins (ESBL) pot hidroliza
i cauza rezisten la mai multe clase de antibiotice.


Principalii productori de ESBL sunt Escherichia coli i Klebsiella
pneumoniae.
J.D.D.Pitout, K.B.Laupland, Extended Spectrum -lactamase-producing Enterobacteriaceae: an emerging public-health concern, Lancet Infect Dis
2008; 8:159-66.
11

30

35

66

17

5

16

18

7

0

10

20

30

40

50

60

70

Cost aproximativ
(mii USD)

Durata median de
spitalizare (zile)

Mortalitate cauzat de
infecie
Mortalitate

ntrziere n iniierea terapiei
adecvate

Cazuri ESBL negative (n=99)

p < 0.001

p = 0.01

p = 0.03

Cazuri ESBL pozitive (n=99)

p < 0.001

p < 0.001

47

numr
pacieni
Consecine clinice i economice

Productorii de ESBL
. M.J.Schwaber i colab., Clinical and Economic Impact of Bacteremia with Extended-Spectrum--Lactamase-Producing Enterobacteriaceae,
Antimicrobial Agents and Chemotherapy, Apr 2006, p.1257-1262

n corelaie direct cu utilizarea cefalosporinelor de generaia a 3-
a

Utilizarea de chinolone reprezint un important factor de risc


Productorii de ESBL:
pagube colaterale
ale utilizrii antibioticelor
D.L.Paterson, Collateral Damage from Cephalosporin or Quinolone Antibiotic Therapy, Clin Inf Dis 2004; 38(Suppl 4): S341-5
Nici cefalosporinele de generaia a 3-a,
nici chinolonele, NU sunt potrivite ca
terapie antibiotic de rutin n cadrul
spitalelor
David L. Paterson
100 100
72.5
31.2
25.6
20.2
66.7
0
10
20
30
40
50
60
70
80
90
100
Meronem imipenem piperacilin/
tazobactam
ceftazidim cefepim ciprofloxacin gentamicin
s
u
s
c
e
p
t
i
b
i
l
i
t
a
t
e

(
%
)

Productorii de ESBL
E.coli
Nr total izolate = 1012
Susceptibilitatea la Meronem n Europa n
cadrul programului MYSTIC

H.Goossens, B.Grabein, Prevalence and antimicrobial susceptibility data for extended-spactrum -lactamase- and AmpC-producing Enterobacteriaceae
from MYSTIC Program in Europe and United States (1997-2004), Diagnostic Microbiology and Infectious Disease 53 (2005)257-264
Productorii de ESBL
Klebsiella spp.
Susceptibilitatea la Meronem n Europa n
cadrul programului MYSTIC

Nr total izolate = 840
H.Goossens, B.Grabein, Prevalence and antimicrobial susceptibility data for extended-spactrum -lactamase- and AmpC-producing Enterobacteriaceae
from MYSTIC Program in Europe and United States (1997-2004), Diagnostic Microbiology and Infectious Disease 53 (2005)257-264
99.1
98.2
38.6
49.1
63.6
57.5
47.5
0
20
40
60
80
100
Meronem imipenem piperacilin/tazobactam ceftazidim cefepim ciprofloxacin gentamicin
s
u
s
c
e
p
t
i
b
i
l
i
t
a
t
e

(
%
)

Susceptibilitatea la Meronem n Europa n
cadrul programului MYSTIC

Nr. de izolate =
1302
S. Unal i colab., Activity of meropenem and comparators against Pseudomonas aeruginosa and Acinetobacter spp. isolated in the MYSTIC
Program, 2002-2004, Diagn Microbiology and Inf Dis 53 (2005) 265-271
Acinetobacter baumanii
79.1
55.5
65.8
80.4
70.1
62.3
0
10
20
30
40
50
60
70
80
90
Meronem Imipenem Ceftazidim Piperacilina/
tazobactam
Ciprofloxacina Gentamicina
s
u
s
c
e
p
t
i
b
i
l
i
t
a
t
e

(
%
)

Pseudomonas aeruginosa
Susceptibilitatea la Meronem n cadrul
programului MYSTIC

Numr de izolate = 728
. P.J.Turner, MYSTIC Europe 2007: activity of meropenem and other broad-spactrum agents against nosocomial isolates, Diagnostic Microbiology and
Infectious Disease 63 (2009) 217-222
-lactamii: activitate bactericid
dependent de timp
%T>CMI=Trebuie meninut concentraia atb. mai mare dect CMI pentru o
durat de timp adecvat, n intervalul dintre administrri.
Pharmacokinetic and Pharmacodynamic properties of Meropenem, David P. Nicolau, Clinical Infectious diseases 2008;
47;S32-40
Penetrabilitate n LCR
Concluzia studiului: 40mg/kg Meronem iv atinge concentraia plasmatic i n LCR
>dect CMI 90 pentru majoritatea patogenilor implicai n meningita bacterian.
Penetration of meropenem into the cerebrospinal fluid of patients with inflamed meninges, Dagan et al,
Journal of Antimicrobial Chemotherapy 1994,;34(1):175-179
Antibioterapia
combinatii antb.
Antibioterapia
Identificarea i terapia in sepsis
Distincia ntre o etiologie infecioas i neinfecioas
Identificarea sursei de infecie
Identificarea tipului de organism
Suportul terapeutic al sursei de infecie
Selectarea tipului de antibiotic bazat pe
Sursa i locul infeciei
Suspectarea patogenului
Gradul de sensibilitate al agentului din areal.
Afectarea organic i toxicitatea potenial

Patrulaterul Shoemaker
Situatia normala
normal
0 presiune 100%
VO2
0 100%
v
o
l
u
m
I
n
d
e
x
.
c
a
r
d
patrulaterul in sepsis
volum
Index cardiac
0 presiune 100%
VO2
Resuscitarea hidrica in sepsis
Crit Care 2012 sept
Resuscitarea volemica
Normalizarea
lactat si
renuntarea la vasopresoare



Mai rapida cu cristaloide
Resuscitarea volemica
Crit Care 2012 sep
Corticoizii in sepsis
Corticoterapia in VAP si IP
Crit Care 2012 sep
Corticoterapia
Nivelul seric al biomarkerilor
Anticoagulante
Trombomodulina
Studiu f2 - rezultate
Crit Care 2013 sep
Trombofilia
Deficit ereditar al sistemului de hemostaza
Factori aditionali
Fumatul, contraceptivele orale, ateroscleroza
5-8% din populatie
Triada Virchow
Leziune endoteliala
Staza sanguina
Hipercoagulare
Cauze in sistemul arterial
venos
Deficit de metabolizare hepatica a factorilor de
coagulare
Factori de risc tromboembolic

Caracteristici pacientului

Varsta

Obezitatea

Vene varicoase

Imobilizarea

Sarcina

Trombofilia

Terapia hormonala

Antecedente de TEV
Patologii asociate (f. agravanti)

Interventii chirurgicale

Neoplazii
Afeciunile medicale acute (inclusiv acutizarea
unor afeciuni medicale cronice)
Insuficiena cardiac/ respiratorie
Infarctul miocardic acut
Bolile inflamatorii intestinale
Sindromul nefrotic

Paralizia de membre inferioare

Infectii acute severe/ sepsis

Boli mieloproliferative
Terapia anticoagulanta
Heparina sodica

Fraxiparina Arixtra

Clexanul

Fragminul
Importanta nutritiei
Crit Care 2013 sep
Candidemia
3.Suportul mecanic si farmacologic
Nutritia
NTP, NE, mixta, forarea anabolismului
Suportul adrenergic i/sau inotrop
Echilibrarea acido-bazic
Echilibrarea hidro-electrolitic
Suportul mecanic
ventilator
renal ! , hepatic ?
Terapia fluidocoagulant
Corticoterapia
Terapia sindromului anemic

121
Why is the gut so important
Inflammatory role of he gut.
The gut as a barriere
Bacterial translocation.
Nutrition and gut function
Conclusions

122
Why is the gut so important ?
The gut is vulnerable to critical illness
Splanchnic blood flow falls early in shock states
Splanchnic blood flow is restored late
The gut is a reservoir of potentially harmful
microorganisms
The gut is a crucial immune organ
The gut has frequently been postulated as the
motor of multiple organ failure
Richard Beale
123
Role of the gut
Degrading foodstuffs into nutrients.
Selective mucosal barrier.
Complex immune organ
It contains
10
12
bacteria
10
9
potentially pathogenic gram-negativ
A lot of endotoxins
S.M. Gabe. Cl. N. 2001;107-112
124
The gut and nutrition
125
The gut and immune function
Mucosal surface is the most important active
defensive barrier to infection
Intestinal tract
Respiratory tract
Genito/utinary tract
Mucosal surface is 400m
2
(200* greater than skin SA)
300 m
2
is contributed by the gut
126
Components of gut immunity
Peristalsis
Reduces pathogen adherence
Limits pathogen contact
Enhances transit time
Normal intestinal microflora
adherence of pathogens
Stimulate epithelial growth
Produce antimicrobial substances
127
Mucosal defence systems
Physical barrier
Mucous secretion
Tight junctions
GALT
Part of larger MALT
Modulates other aspect of MALT function and
surface immunity
IgA.
128
Gut-liver axis as a barrier


It acts primarily as a defence against
translocation of endotoxin.

129
Ischemia reperfusion injury
Ischemia
-oxygen delivery
-blood flow to the organ
-distribution of the flow
-oxygen extraction
-oxygen demend
Reperfusion injury
-oxygen derived
free radicals
Mucosal injury
130
Bacterial overgrowth
Broad
spectrum
antibiotics
Reduced
food intake
Impaired
intestinal
motility
Acid reducing
agents
Changes in flora composition and localisation
131
Translocation ?
Bacteria, endotoxin or cytokines ?
Occurs in other disease states
Plentiful animal evidence
Human evidence in multiple organ failure is
still unclear
Micro organisms do appear in the blood in
terminal shock
132
What is the evidence for BT?
Gut origin bacteria found in MLN
Endotoxin found in MLN or PVB
Bacterial DNA or proteins found in MLN or systemic
circulation.
Increased levels of circulating and tissue cytokines
and mediators.
Increased permeability of the gut to large molecules.
Infectious complications with gut origin organisms.
133
The gut as a proinflammatory organ.
Gut becomes pro inflammatory in shock states.
GALT releases pro inflammatory cytokines.
Alterations in gut flora can exaggerate this response.
Mesenteric microcirculation becomes priming bed
for circulating neutrophils.
Systemic consequences via the portal circulation or
the lymphatics ?
134
Lymphatic drainage ?!
Deitch E.A. at al.Surgery 2001;129:39-47

a shock model
lung permeability measured with Evans
blue increased 3-4 times
Completely prevented by pre shock
lymphatic duct ligation

135
Bacterial translocation
as a passage of bacteria through the epitelial
mocosa into the lamina propria
Berg and Garlington 1979
.and all microbial products Alexander 1990
In 59% of laparatomy-limph node culture where
positive. Only 4% for other reasons.
Deitch. Arch Surg. 1989
The most common Escherichia Coli 54%
23% septic complication.Mac Fie. Gut 1998.
136
Bacterial translocation evidences
The splanchnic perfusion is an important
determinant of intestinal integrity.
Existence of bacterial translocation.
Intestinal immune system prevents the pass.
Bacterial translocation may include postoperative
sepsis but the progression of MOF has not been
demonstrated.



137
Reasons for failure of absorbtion

Deranged motility
Reduced exocrine
Pancreatic functions
Intestinal hypoperfusion
And ischemic mucosal
damage
-gastric reflux
-aspiration
-nausea, vomiting
-abdominaldistension
-diarrhoea
-malassimilation
-etc.

138


Nutrition
139
During the per operating period
Starvation.
Energetic expenditure increases.
Energeic intake falls. !!
A lower metabolic level.
Immune competence decreases.
140
Possibilities
Total parenteral nutrition TPN

TPN + EN

Enteral nutrition EN
Importance of
Per operating nutrition.
141
TPN results in mucosal atrophy ?
The literature does not help us to answer.
In mice TPN- no atrophy Sitren JPEN 1992
TPN vs. EN with fibre free formula-no difference in int.
permeability.Reynolds, Wicks.97-94
Fibre free enriched with free glutamine-lower permeability vs
TPN.Hadfield. Am.j R.C.C.M. 95.
Nitric oxide is involved in tight junction regulation. Salzman. Am. J.
Physiol. 1995.
Difference in permeability in critical Ill patients
Harris. Int. C. M. 1992:
142
TPN results in mucosal atrophy ?
In the critically ill : mucosal atrophy,increased
permeability. Hernandez J. Cr. Care 1999.
Intestinal permeability was increased in association
with a reduction in gastric blood flow. Ohri.Gastroenterology
1994.
Increased permeability in ill patients with TPN
Carr et al. BMJ 1996.
143
The value of enteral nutrition
Intestinal barrier-Protection
-Bacterial translocation
-Septic morbidity
-Multiorgan dysfunction
-Infection rate
Stress response -
Attenuation
-stress hormone release
-mediator release
-energy expenditure
-catabolism
Substrate utilization-
Improvement
-substrate homeostasis
-visceral protein syntesis
Nutritional assesment
Substrate tolerance-
Improvement
-visceral organ integrity
-Intestinal resorbtion capacity
-gastrointestinal bleeding
- mesenteric blood flow.
144
Early postoperative E.N.
Reduces
Infectious complications
Length of stay in ICU. Beier, Cl. Ntr. 2001: 123-127
Malnutrition.
Septic morbidity.
Gut stress
Is feasible in patients with perforative peritonitis. Singh. J.Am.Coll.
Surg: 1998
A greatest barrierdisagreement amongst surgeons.
Beier R.(Denmark)