Fluid resuscitation in septic shock

Transcription

1 Fluid resuscitation in septic shock Anders Perner Dept of Intensive Care, Rigshospitalet, University of Copenhagen Scandinavian Critical Care Trials Group Intensive Care Medicine COIs - Research support from B Braun, Fresenius, CSL Behring Honoraria from Ferring, LFB University of Copenhagen

2 Fluid resuscitation in septic shock Triggers? Which fluid? How much?

3 Administer 30 ml/kg crystalloid for hypotension or lactate > 4 mm ICM 2013;39:165 CCM 2013;41:580

4 Hypotension a trigger for fluid resuscitation in sepsis? MAP > 65 associated to survival in septic shock Varpula ICM 2005; 31: 1066

5 Goal-directed fluid therapy of patients with hypotension or lactate > 4 mm Rivers et al. NEJM 2001

6 Lactate > 4 mm as trigger for fluid in sepsis? Rivers et al. NEJM 2001

7 Lower lactate trigger level? SHOCK, Vol. 38, No. 1, pp. 4-10, 2012

8 Lower lactate trigger level? 6S TRIAL

9 Fluid resuscitation in septic shock Triggers? Which fluid? How much?

10 ICM 2013;39:165 CCM 2013;41:580

11 6S TRIAL

12 Investigator-initiated & publicly-funded 6S TRIAL

13 6S TRIAL Investigator-initiated & publicly-funded High internal validity Pre-publiced protocol and SAP Five-flod blinding 100% follow-up

14 6S TRIAL Investigator-initiated & publicly-funded High internal validity Pre-publiced protocol and SAP Five-flod blinding 100% follow-up High external validity Pragmatic design 50% non-university hospitals 66% inclusion rate, simple inclusion and few exclusion criteria

15 Baseline characteristics 6S TRIAL Group Starch Ringers Numbers 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 (%)

16 Trial fluid 6S TRIAL Starch Volume, ml Ringers Volume, ml Day 1 (14 h) 1500 ( ) 1500 ( ) Day ( ) 1000 ( ) Day (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 ( ) 3000 ( )

17 Starch increased. 6S TRIAL

18 Number needed to harm. 6S TRIAL

19 6S TRIAL ICM 2013; 39: 1936

20 Meta-analysis of HES130 vs. crystalloid/ha in sepsis Mortality RR 1.1 ( ) BMJ 2013; 346: f839

21 Starch increased. 6S TRIAL Relative risk increase 1.35 ( )

22 6S TRIAL RG Müller et al ESICM 2013

23 Meta-analysis of HES130 vs. crystalloid/ha in sepsis Renal replacement therapy RR 1.4 ( ) BMJ 2013; 346: f839

24 Bleeding outcomes 6S TRIAL ICM 2013, e-pub

25 Time to bleeding 6S TRIAL P=0.001 ICM 2013, e-pub

26 New data

27 The CRISTAL trial JAMA Oct Open-label trial in 57 ICUs in 4 countries in a 9-year period ICU patients in shock Randomisation by envelopes, fixed block size of 4 Any colloid (maily HES) vs. any crystalloid (maily saline)

28 P< P<0.001

29 Primary outcome

30 90-day mortality

31 The effect of bias on mortality in HES trials in sepsis Low risk of method. bias RR 1.11 ( ), p=0.03 High risk of method. bias RR 0.49 ( ), p=0.01 Test of heterogeneity p=0.004 (BMJ 2013; 346: f839)

32 ICM 2013;39:165 CCM 2013;41:580

33 Shall we use albumin in sepsis?

34 HES comparator / Non-septic patient Fraud? Kids HES comparator / Non-septic patient Delaney et al CCM 2010

35 SAFE Albumin vs. Saline Septic pts outcome Finfer S et al. ICM 2010

36 Multivariate analyses Finfer S et al. ICM 2010

37 Shall we use albumin in sepsis? Probably not Coming trial results EARSS - 20% HA vs saline in septic shock ALBIOS - 20% HA vs saline in severe sepsis

38 Sept 24 th 2013

39 Sept 24 th 2013

40 Fluid resuscitation in septic shock Triggers? Which fluid? How much?

41 How much fluid in sepsis? Continued as long as hemodynamics improve ICM 2013;39:165 CCM 2013;41:580

42 Improved survival by resuscitation guided by MAP, CVP and ScvO 2

43 More fluid given

44 AJRCCM 2010

45 AJRCCM 2010

46 Fluid balance associated to mortality Boyd et al, CCM 2011 Secondary analysis of the VASST cohort 793 septic shock patients; highly selected 13% inclusion rate

47 Fluid balance associated to mortality + 3 L + 1 L + 5 L + 8 L Boyd et al, CCM 2011

48 Fluid volume not associated to mortality Smith & Perner, Crit Care 2012 Prospective, multicenter cohort of 163 consecutive, unselected patients with septic shock in 6 ICUs Pts divided in higher and lower fluid volume groups by the median fluid volume Subgroup analysis of pts with 3 days of shock

49 Characteristics dependent on fluid volume after the 1. and 3. day SAPS II SOFA score Lactate mmol/l ScvO 2 % Pressor dose Dialysis Death day 90 After the 1. day of shock, n=164 >4.0 L 54 (19) 11 (4) 3.4 (3.3)* 70 (14) 0.25 (0.3) 39% 46% <4.0 L 54 (22) 11 (4) 2.0 (1.6) 73 (14) 0.18 (0.2) 39% 55% After the 3. day of shock, n=95 >7.5 L 53 (21) 10 (5) 2.6 (1.7)* 74 (14) 0.16 (0.1) 38% 40%** <7.5 L 55 (13) 10 (4) 1.9 (1.8) 74 (11) 0.15 (0.1) 33% 62%

50 Characteristics dependent on fluid volume after the 1. and 3. day SAPS II SOFA score Lactate mmol/l ScvO 2 % Pressor dose Dialysis Death day 90 After the 1. day of shock, n=164 >4.0 L 54 (19) 11 (4) 3.4 (3.3)* 70 (14) 0.25 (0.3) 39% 46% <4.0 L 54 (22) 11 (4) 2.0 (1.6) 73 (14) 0.18 (0.2) 39% 55% After the 3. day of shock, n=95 >7.5 L 53 (21) 10 (5) 2.6 (1.7)* 74 (14) 0.16 (0.1) 38% 40%** <7.5 L 55 (13) 10 (4) 1.9 (1.8) 74 (11) 0.15 (0.1) 33% 62%

51 The cohort studies on fluid volumes in septic shock show.. Differing results Depend on population, disease severity, timing, design: Fluid balance vs volume? Inherent problems with confounding by indication, time-dependency, repeated exposure and competing risks

52 We give alot of non-resus fluids Day 1 6S SAFE HES Ringer Albumin Saline Trial fluid Other fluids Total, L Ratio

53 Fluid resuscitation in septic shock Hypotension or high lactate (4 mm) Give crystalloids Avoid HES Albumin? Ensure hemodynamic improvement - ScvO 2 and lactate clearence Watch cummulative fluid balance Limit non-resuscitation fluids

54 TRISS TRIAL 6S TRIAL

55 Fluid balance associated to mortality Murphy et al, Chest 2009 Retrospective, two-center cohort in US of 212 pts with septic shock AND ALI Results complex

56 Fluid balance associated to mortality Murphy et al, Chest 2009