Download - Choice of fluid in sepsis
Choice of fluid in sepsis
University ofCopenhagen
Anders Perner
Dept of Intensive Care, Rigshospitalet, University of Copenhagen
Scandinavian Critical Care Trials Groupwww.ssai.info/research/SCCTG
Intensive Care Medicinehttp://icmjournal.esicm.org/index.html
COIs - Research support from B Braun, Fresenius, CSL Behring Honoraria from Ferring, LFP
CCM 2013;41:580ICM 2013;39:165
6STRIAL
Investigator-initiated & publicly-funded
6STRIAL
Investigator-initiated & publicly-funded
High internal validityPre-publiced protocol and SAPFive-fold blinding100% follow-up
6STRIAL
Investigator-initiated & publicly-funded
High internal validityPre-publiced protocol and SAPFive-fold blinding100% follow-up
High external validityPragmatic design50% non-university hospitals66% inclusion rate, simple inclusion and
few exclusion criteria
6STRIAL
Inclusion criteria
Adult patients in the ICUAND
Fulfil severe sepsis criteria within 24 hAND
Need for fluid resuscitation
6STRIAL
6STRIAL
Trial fluid# 1
Trial fluid# 2
Trial fluid# X
Masked trial fluid up till 33 ml/IBW-kg/day
Intervention
6% HES 130/0.42 in Ringer’s acetate (Tetraspan)
or
Ringer’s acetate (Sterofundin)
Baseline characteristics
StarchRingers
Numbers 398 400
Age 66 (56-75) 67 (56-76)
Time from ICU admin to rando 4 (1-13) 4 (1-13)
SAPS II 50 (40-60) 51 (39-62)
Acute kidney injury 36% 35%
Shock 84% 84%Values are medians (IQRs) or numbers (%)
6STRIAL
Trial fluid
Starch Ringers
Volume, ml Volume, ml
Day 1 (14 h) 1500 (1000-1500) 1500 (1000-1550)
Day 2 1000 (300-1500) 1000 (500-1500)
Day 3 500 (0-1000) 425 (0-500)
Day 4 0 (0-500) 0 (0-500)
Day 5 0 (0-500) 0 (0-500)
Total (90 days) 3000 (1500-5000) 3000 (1800-5500)
6STRIAL
Fluid volumes and balances6STRIAL
180 g HES
Starch increased….6STRIAL
Number needed to harm….
136STRIAL
6STRIAL
ICM 2013; 39: 1936
Meta-analysis of HES130 vs. crystalloid/HA in sepsis
Mortality
RR 1.1 (1.0-1.2)
BMJ 2013; 346: f839
Starch increased….6STRIAL
ESICM 2013
6STRIALEarlier use of RRT with starch
RRT and risk of death6STRIAL
NEJM 2012
RRT and risk of death6STRIAL
NEJM 2012
Meta-analysis of HES130 vs. crystalloid/HA in sepsis
RRT
RR 1.4 (1.1-1.7)
BMJ 2013; 346: f839
Starch increased bleeding6STRIAL
ICM 2013 39(12):2126
6STRIAL
P=0.001
Earlier bleeding with starch
ICM 2013 39(12):2126
Bleeding and risk of death6STRIAL
ICM 2013 39(12):2126
Starch Ringer’s
SF-36 P value
Physical component summary score
37 (29-48) 40 (32-51) 0.23
Mental component summary score
45 (36-55) 53 (39-60) 0.01
6STRIAL
Reduced QoL at 1-year with starch
Critical Care 2013; 17: R58
The 6S summary6STRIAL
Higest methodological standards
Tested starch in clinical practice
Included patients fairly early
Gave fluid volumes early and well within the labelled dose
Biological plausibility – Cause-and-effect
A ‘correct’ indication for starch?
Existing data do not support ‘correct’ indication for starch
Haase et al. Critical Care 2013
A safe starch dose?
A safe starch dose?
Lower volume
Higher volume
Cochrane CD007594
CHEST: HES 130/0.4 vs saline in 7,000 general ICU patients
Increased use of RRT, RBCs and SAEs with mean 500 ml of starch
Myburgh et al. NEJM 2012
Ratio
CHEST NaCl vs 6% HES130 n=7000 1.26S trial Ringer vs 6% HES130 n= 800 1.1CRYSTMAS NaCl vs 6% HES130 n= 196 1.0
Crystalloid to HES volume ratio in blinded trials
New data
• Open-label trial
• ICU patients in shock
• Randomisation by envelopes, fixed block size of 4
• Any colloid (maily HES) vs. any crystalloid (maily saline)
The CRISTAL trial JAMA Oct. 2013
Primary outcome
90-day mortality
•High risk of bias in 3 domains
•Unblinded
•Uncertain allocation concealment
•Baseline imbalance
The CRISTAL trial JAMA Oct. 2013
The effect of bias on mortality in HES trials in sepsis
RR 1.11 (1.01-1.23), p=0.03
Low risk of method. bias
High risk of method. bias
RR 0.49 (0.28-0.85), p=0.01
Test of heterogeneity p<0.01
CCM 2013;41:580ICM 2013;39:165
CCM 2013;41:580ICM 2013;39:165
Shall we use albumin in sepsis?
Fraud?
HES comparator / Non-septic patient
HES comparator / Non-septic patient
Kids
SAFE septic pts – outcome
Finfer S. ICM 2010
Multivariate analyses
Finfer S. ICM 2010
Coming trial results…
EARSS - 20% HA vs saline in septic shock
ALBIOS - 20% HA vs saline in severe sepsis
Shall we use albumin in sepsis?
Probably not
Until then.....................crystalloids for sepsis
www.NEJM.org Sept 24th 2013
www.NEJM.org Sept 24th 2013
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