EGDT and EGDT and Inflammation Inflammation Management of Management of Sepsis Sepsis Dr. MárcioBorges Sá Coordinator of MultidisciplinarySepsis Unit Intensive Care Medicine. Hospital Son Llàtzer. Palma de Mallorca. Spain. UPDATE UPDATE-SUMMIT DE ENFERMEDADES INFECCIOSAS, Valencia, 23/03/2007 SUMMIT DE ENFERMEDADES INFECCIOSAS, Valencia, 23/03/2007 .
92
Embed
EGDT and EGDT and InflammationInflammation Management of ... Sa Borges... · EGDT and EGDT and InflammationInflammation Management of Management of SepsisSepsis ... •expresión
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
EGDT and EGDT and InflammationInflammation
Management of Management of SepsisSepsis
Dr. Márcio Borges SáCoordinator of Multidisciplinary Sepsis UnitIntensive Care Medicine.Hospital Son Llàtzer. Palma de Mallorca. Spain.
UPDATEUPDATE--SUMMIT DE ENFERMEDADES INFECCIOSAS, Valenci a, 23/03/2007SUMMIT DE ENFERMEDADES INFECCIOSAS, Valencia, 23/03 /2007 ..
Is it important EGDT?
-- Management change
- Higher incidence- Higher incidence
- Higher mortality
PIMIS PROYECT
SEPSISSEPSIS
COMPLICADA FISIOPATOLOGÍA: INTERACCIÓN COMPLEJAP
OLI
MO
RF
ISM
O G
EN
ÉT
ICO
VAR
IAB
ILIDA
D IN
TR
A e IN
TE
RP
ER
SO
NA
L
ENDOTELIO ES LA BASE FUNDAMENTALENDOTELIO ES LA BASE FUNDAMENTAL
PO
LIM
OR
FIS
MO
GE
NÉ
TIC
OVA
RIA
BILID
AD
INT
RA
e INT
ER
PE
RS
ON
AL
SEPSIS: NUEVOS y “ANTIGUOS CONCEPTOS”
• CASCADA INFLAMATORIA
• SEPSIS y SISTEMA INMUNE
• MEC. INMUNOSUPRESIÓN
1. Citoquinas: PRO/ANTI-Inflam.
2. Anergia
3. Apoptosis3. Apoptosis
4. Muerte de células sistema inmune
• SEPSIS Y COAGULACIÓN
• SEPSIS Y ENDOTELIO
• FACTORES GENÉTICOS
• HIBERNACIÓN CELULAR
• MUERTE y SEPSIS
CASCADA INFLAMATORIA
TNFIL-1IL-8IL-6 Y IL-10Radicales O2PAFProteasasProstaglandinas
TNF
IL-1
ProstaglandinasLeucotrienosBradiquininas
MICROTROMBOSIS
MECANISMOS INMUNOSUPRESIÓN
* CD4 activadas secretan Citoquinas
- Inflamatorias (Th1): TNFα; Intef.γ;
- Anti-Inflam. (Th2): IL-4; IL-10
* Anergia: no respuesta a un Ag.
Cels. T. Incapaz proliferar o secretar Cels. T. Incapaz proliferar o secretar citoquinas frente Antígenos
• Apoptosis: muerte genetic. prog.
1. Cel Necrotica: ↑ Th1
2. Cel. Apoptotica: ↑ Th2 y Anergia
• Muerte Células Inmunes
Th2 Th1
CD4
Lesión VascularActiva V y VIIIActiva XIFibronógeno: fibrinaFactor XIII: coáguloActiva Plaquetas“ Cels. EndotelialesAdhesión leucos/endot.↑Permeab. Vascular↑ citoquinas/proteasas
SEPSIS y COAGULACIÓN: TROMBINA
↑ citoquinas/proteasas↑Unión trombomodulina↑ APC y TAFI
*: Si inicio de PCA < 24 hs menor mortalidad: 22,9% vs 27,4%, p=0,01ENHANCE ↑↑↑↑ hemorragias graves que PROWESS (6,5% vs 3,5%).
ICNARCICNARC: : DrotrecoginDrotrecogin alfaalfa (activated): (activated): RealReal--life use and outcomes for the UKlife use and outcomes for the UK11
• The aims of this audit were to monitor the real-life use of DrotAA and subsequent outcomes;to undertake a rigorous, nonrandomized evaluation of the effectiveness of DrotAA, by linkingthe data on DrotAA to the ongoing outcome audit for all admissions to adult, general criticalcare units; and to compare our results with those from the PROWESS study
197 unitsinvited to participate
1:Adapted from Rowan KM et al. Crit Care. 2008,12:R58
133 unitsagreed to participate
13 unitswithdrew
or were lapsed
8 unitswere excluded
112 unitsactively participated
Recorded 1292 infusions of DrotAA
1079 admitted with severe sepsis and ≥2 organ failing (receiving DrotAA)
Primary results of matched cohort analysis on acute hospitalmortality compared with PROWESS on 28-days
ICNARC: ICNARC: DrotrecoginDrotrecogin alfaalfa (activated): (activated): RealReal--life use and outcomes for the UKlife use and outcomes for the UK 11
Individual Matching
Historic, same unit 287/609 332/609 0.008 7.4%
Contemporaneous, same unit 353/764 406/764 0.002 6.9%
Contemporaneous, non-DrotAA unit 285/666 362/666 <0.001 11.5%
DrotAA (n/N)
Control (n/N) p ARR
27
1: Adapted from Rowan KM et al. Crit Care. 2008,12:R58
0.6 0.7 0.8 0.9 1.0 1.2Relative Risk
Favors DrotAA Favors control
Propensity Matching
Contemporaneous, non-DrotAA unit 285/666 362/666 <0.001 11.5%
Contemporaneous, DrotAA unit prior to first use 422/922 486/922 0.001 6.9%
Historic, same unit 436/929 494/929 0.003 6.3%
Contemporaneous, same unit 480/1049 516/1049 0.11 3.4%
Contemporaneous, non-DrotAA unit 364/818 476/818 <0.001 13.7%
Contemporaneous, DrotAA unit prior to first use 479/1053 561/1053 <0.001 7.8%
PROWESS 210/850 259/840 0.005 6.1%
ARR: Absolute Risk Reduction
Subgroup results: acute hospital mortality for individual matching toc o n t r o l p o o l 4 . P o o l 4 i n c l u d e s p a t i e n t s f r o m acontemporaneous DrotAA unit but before the first use in that unit
ICNARC: ICNARC: DrotrecoginDrotrecogin alfaalfa (activated): (activated): RealReal--life use and outcomes for the UKlife use and outcomes for the UK 11
El 20% de los pacientes con shock séptico no tratado tienen hiperlactacidemia sin hipotensión
La importancia del shock oculto
El 50% de los pacientes resucitados del shock tienen hipoxia tisular oculta, a pesar de mantener constantes vitales normales y PVC normal (ScO2 baja, lactato elevado)
Rivers EP. Central venous oxygen saturation monitoring in the critically ill patient. Curr Opin Crit Care 2001; 7: 204-211.
58,1
74,360
70
80
90
100
Occult hypoperfusion = Shock
Lactate 0: initial
Lactate 1: 6 hs
Lactate 2: 12 hs
58,1
48,6
30,1
0
10
20
30
40
50
HypoTA Lact0 Lact1 Lact2
% LactateLactate > 2,2> 2,2
Borges M, SEIMC, 2007
OCCULT SHOCK
Relationship between MBP < 70 mmHg and mortality:-In the moment of protocol activation: 31,4%-At 6 hours: 45,7%.
Variable RR IC 95%MBP>70mmHg 1,985 (1.31-2.99)MBP<70mmHg 1,989 (1.25-3.16)
Relative risk(RR) of deaths in pts with normo or hy potensive was the same
OCCULT SHOCK
PL < 3 < 3 ≥ 3 ≥ 3 p
PL-0 20,8% 40,3% 0,002
Relationship between Plasmatic Lactate (PL) and Mortality with MBP ≥70 mmHg:
UPDATEUPDATE--SUMMIT DE ENFERMEDADES INFECCIOSAS, Valenci a, 23/03/2007SUMMIT DE ENFERMEDADES INFECCIOSAS, Valencia, 23/03 /2007 ..EGDTEGDT--InflammationInflammation
�Diagnosis -“simultaneuos” therapies�Clasical SIRS: few role�OF: main objetive�Tissue Hypoxia: Inflammation (BM)�Individualized each case/hospital
Muito obrigado!
UPDATEUPDATE--SUMMIT DE ENFERMEDADES INFECCIOSAS, Valenci a, 23/03/2007SUMMIT DE ENFERMEDADES INFECCIOSAS, Valencia, 23/03 /2007 ..EGDTEGDT--InflammationInflammation