1. Clash of the titans: Colloids versus crystalloids Eric A J Hoste Intensive Care Unit Ghent University Hospital Belgium

2. Are we asking the correct question? Maitland et al. N Engl J Med 2011 The FEAST study Febrile illness, Africa N = 3141 + 29 The FEAST study Febrile illness, Africa N = 3141 + 29

3. Relevant question Finfer et al SAFE TRIPS, Crit Care 2010

4. Why would you choose colloids? Fast shock reversal =  survival EGDT! Less volume < IAH/ACS

5. Why would you choose colloids? Fast shock reversal =  survival EGDT! Less volume < IAH/ACS < ARDS

6. Why would you not choose colloids? Cost Side effects Acute Kidney Injury Coagulation abnormalities … Worse Survival

7. Price (€)

8. No Colloids SurvivalAcute Kidney InjuryCoagulation abnormalities

9. “The review of trials found no evidence that colloids reduce the risk of dying compared with crystalloids”

10. Cochrane systematic review N studiesN patientsRR Albumin237,7541.01 (0.92-1.10) HES171,1721.18 (0.96-1.44) Gelatin115060.91 (0.49-1.72) Dextran98341.24 (0.94-1.65) Colloids in hypertonic812380.88 (0.74-1.05)

12. Cochrane systematic review N studiesN patientsRR Albumin237,7541.01 (0.92-1.10) HES171,1721.18 (0.96-1.44) Gelatin115060.91 (0.49-1.72) Dextran98341.24 (0.94-1.65) Colloids in hypertonic812380.88 (0.74-1.05)

13. Limitations of the meta-analysis Heterogeneity Cohorts: non-ICU, burns, sepsis, trauma, … Products: – Alb 4, 5, 20, 25% – HES 6, 10%, 1 st, 2 nd, 3 rd generation – Saline, Ringer’s – … Small studies

14. The SAFE study : Albumin 4% The SAFE study investigators N Engl J Med 2004 N = 6,997 patients

15. Subgroups? The SAFE study investigators N Engl J Med 2004

16. Traumatic Brain Injury Myburgh et al. N Engl J Med 2007 GCS 3-8 N = 460 patients No to albumin

17. Severe sepsis? Finfer et al. Intensive Care Med 2011 N = 919/1218 Yes to albumin

18. EARSS: Albumin 20% in septic shock Results Albumin concentration  All individual organ dysfunctions equal Same outcome at 28-d No Benefit Abstract ESICM Berlin 2011 N = 794 patients

19. HES 200, 10% vs. Ringer’s Brunkhorst et al, VISEP study. N Engl J Med 2008 N = 537 patients

20. HES 200, 10% vs. Ringer’s Brunkhorst et al, VISEP study. N Engl J Med 2008 N = 537 patients

21. HES 130, 6% Guidet et al. CRYSTMAS, abstract ESICM 2011 P = NS PRCT, N = 130 mortality

22. Summary survival StudyColloidSurvival SAFEAlbumin 4%Sepsis EARSSAlbumin 20% VISEPHES 200, 10%>dose CRYSTMASHES 130, 6%

23. No Colloids SurvivalAcute Kidney InjuryCoagulation abnormalities

24. Acute Kidney Injury N = 129, PRCT Severe sepsis/septic shock AKI = creat x 2 or RRT N = 129, PRCT Severe sepsis/septic shock AKI = creat x 2 or RRT Cittanova et al. Lancet 1996 Schortgen et al. Lancet 2004 N = 52, PRCT Brain dead kidney donors N = 52, PRCT Brain dead kidney donors

25. HES 200, 10% P = 0.002 P = 0.001 N = 537 Brunkhorst et al, VISEP study. N Engl J Med 2008

26. CRYSTMAS: HES 130, 6% vs. saline HESSalineP N65 Volume (mL)13801708NS Time to HD stab (h)11.814.3NS AKI-RIFLE0.808 RRT22.2%14.7%0.180 BleedingNS INRNS Itching33NS Death 28-d31%25.3%NS Death d-9040%33%NS Guidet, Abstract ESICM Berlin 2011

27. Albumin and AKI SAFE study: No difference in duration of RRT EARSS study: No difference in organ dysfunction Spontaneous Bacterial Peritonitis: Albumin = less AKI Sort et al. N Engl J Med 1999 Hepatorenal syndrome: Albumin improves HRS Ortega et al. Hepatology 2002

28. Summary: AKI StudyColloidAKI Cittanova - Kidney DonorHES 200 Yes Schortgen - Severe sepsisHES 200Yes VISEP - Severe sepsisHES 130No diff SAFE –ICUAlb 4%No diff EARSS – sepsisAlb 20%No diff Cirrhosis - HRSAlb 20%Improved Cirrhosis - SBPAlb 20%Improved

29. No Colloids SurvivalAcute Kidney InjuryCoagulation abnormalities

30. Coagulation tests? AlbuminSaline aPTT+ 2.7 sec-0.9 sec INRNo change Platelets  Multivariate analysis:  aPTT associated with: Albumin (p=0.01) Large volume (p=0.03) Bellomo et al. Crit Care Resusc 2009 N = 687 3 units of the SAFE study group N = 687 3 units of the SAFE study group

31. So, Survival is better or worse or equal AKI is equal or more (> older HES) Coagulation abn: yes But: What about volume & early shock reversal?

32. Less volume

33. Magder et al. Crit Care Med 2010 656 mL fluid/d less Less wound infections Less pacing 656 mL fluid/d less Less wound infections Less pacing N = 237 More need for plasma (p=0.048) EARSS, abstract ESICM 2011

34. Take home messages Cost Crystalloid: 5 to 25 times lower Survival: equal – Alb 4%: survival  in severe sepsis – HES 200: Survival  when high volume HES 200 Side effects: – AKI: HES 200 – Coagulation ≈ volume! Don’t throw the baby out with the bad water

35. Ongoing ICU studies patientsnCrystColloidsOutcome AnnanneICU3010>saline>HES28-d mort CHESTICU7000SalineHES 13090-d mort ALBIOSSevere sepsis1350AnyAlb>3028-d mort 6SSevere sepsis800Ringer’s acetate HES 130 acetate 90-d mort/ESKD

36. Thank You Eric.Hoste@Ugent.be

37. Relevant question Finfer et al SAFE TRIPS, Crit Care 2010

38. Acid-Base? N = 691 3 units N = 691 3 units Bellomo et al. Crit Care Med 2006 Multivariate analysis: >3 L fluid resuscitation Cl  : alb>saline Multivariate analysis: >3 L fluid resuscitation Cl  : alb>saline

39. Better when albumin is low? Finfer et al. BMJ 2006

40. Acute Kidney Injury Zarychanski et al. Open Med 2009