choice of fluid in sepsis
DESCRIPTION
Choice of fluid in sepsis. Anders Perner Dept of Intensive Care, Rigshospitalet, University of Copenhagen Scandinavian Critical Care Trials Group www.ssai.info/research/SCCTG Intensive Care Medicine http://icmjournal.esicm.org/index.html - PowerPoint PPT PresentationTRANSCRIPT
![Page 1: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/1.jpg)
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
![Page 2: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/2.jpg)
CCM 2013;41:580ICM 2013;39:165
![Page 3: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/3.jpg)
6STRIAL
![Page 4: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/4.jpg)
Investigator-initiated & publicly-funded
6STRIAL
![Page 5: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/5.jpg)
Investigator-initiated & publicly-funded
High internal validityPre-publiced protocol and SAPFive-fold blinding100% follow-up
6STRIAL
![Page 6: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/6.jpg)
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
![Page 7: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/7.jpg)
Inclusion criteria
Adult patients in the ICUAND
Fulfil severe sepsis criteria within 24 hAND
Need for fluid resuscitation
6STRIAL
![Page 8: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/8.jpg)
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)
![Page 9: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/9.jpg)
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
![Page 10: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/10.jpg)
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
![Page 11: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/11.jpg)
Fluid volumes and balances6STRIAL
![Page 12: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/12.jpg)
180 g HES
![Page 13: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/13.jpg)
Starch increased….6STRIAL
![Page 14: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/14.jpg)
Number needed to harm….
136STRIAL
![Page 15: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/15.jpg)
6STRIAL
ICM 2013; 39: 1936
![Page 16: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/16.jpg)
Meta-analysis of HES130 vs. crystalloid/HA in sepsis
Mortality
RR 1.1 (1.0-1.2)
BMJ 2013; 346: f839
![Page 17: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/17.jpg)
Starch increased….6STRIAL
![Page 18: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/18.jpg)
ESICM 2013
6STRIALEarlier use of RRT with starch
![Page 19: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/19.jpg)
RRT and risk of death6STRIAL
NEJM 2012
![Page 20: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/20.jpg)
RRT and risk of death6STRIAL
NEJM 2012
![Page 21: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/21.jpg)
Meta-analysis of HES130 vs. crystalloid/HA in sepsis
RRT
RR 1.4 (1.1-1.7)
BMJ 2013; 346: f839
![Page 22: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/22.jpg)
Starch increased bleeding6STRIAL
ICM 2013 39(12):2126
![Page 23: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/23.jpg)
6STRIAL
P=0.001
Earlier bleeding with starch
ICM 2013 39(12):2126
![Page 24: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/24.jpg)
Bleeding and risk of death6STRIAL
ICM 2013 39(12):2126
![Page 25: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/25.jpg)
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
![Page 26: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/26.jpg)
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
![Page 27: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/27.jpg)
A ‘correct’ indication for starch?
![Page 28: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/28.jpg)
Existing data do not support ‘correct’ indication for starch
Haase et al. Critical Care 2013
![Page 29: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/29.jpg)
A safe starch dose?
![Page 30: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/30.jpg)
A safe starch dose?
Lower volume
Higher volume
Cochrane CD007594
![Page 31: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/31.jpg)
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
![Page 32: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/32.jpg)
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
![Page 33: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/33.jpg)
New data
![Page 34: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/34.jpg)
• 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
![Page 35: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/35.jpg)
![Page 36: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/36.jpg)
Primary outcome
![Page 37: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/37.jpg)
90-day mortality
![Page 38: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/38.jpg)
•High risk of bias in 3 domains
•Unblinded
•Uncertain allocation concealment
•Baseline imbalance
The CRISTAL trial JAMA Oct. 2013
![Page 39: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/39.jpg)
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
![Page 40: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/40.jpg)
CCM 2013;41:580ICM 2013;39:165
![Page 41: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/41.jpg)
CCM 2013;41:580ICM 2013;39:165
![Page 42: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/42.jpg)
Shall we use albumin in sepsis?
![Page 43: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/43.jpg)
![Page 44: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/44.jpg)
Fraud?
HES comparator / Non-septic patient
HES comparator / Non-septic patient
Kids
![Page 45: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/45.jpg)
SAFE septic pts – outcome
Finfer S. ICM 2010
![Page 46: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/46.jpg)
Multivariate analyses
Finfer S. ICM 2010
![Page 47: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/47.jpg)
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
![Page 48: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/48.jpg)
Until then.....................crystalloids for sepsis
![Page 49: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/49.jpg)
www.NEJM.org Sept 24th 2013
![Page 50: Choice of fluid in sepsis](https://reader036.vdocument.in/reader036/viewer/2022062809/568156f9550346895dc4a210/html5/thumbnails/50.jpg)
www.NEJM.org Sept 24th 2013
3 2 4 1