IFAD 2011

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

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 (€)
1.79 2.25 4
9.5
44.7
63
0
10
20
30
40
50
60
70
Saline Hartmann Gelofusine Volulyte Alb 5% Alb 20%

8. •No Colloids
Survival
Acute Kidney Injury
Coagulation abnormalities

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

10. •Cochrane systematic review
N studies N patients RR
Albumin 23 7,754 1.01 (0.92-1.10)
HES 17 1,172 1.18 (0.96-1.44)
Gelatin 11 506 0.91 (0.49-1.72)
Dextran 9 834 1.24 (0.94-1.65)
Colloids in hypertonic 8 1238 0.88 (0.74-1.05)

12. •Cochrane systematic review
N studies N patients RR
Albumin 23 7,754 1.01 (0.92-1.10)
HES 17 1,172 1.18 (0.96-1.44)
Gelatin 11 506 0.91 (0.49-1.72)
Dextran 9 834 1.24 (0.94-1.65)
Colloids in hypertonic 8 1238 0.88 (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%, 1st, 2nd, 3rd 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 3-8N = 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
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%
0%
10%
20%
30%
40%
50%
28-d 90-dHES saline
Guidet et al. CRYSTMAS, abstract ESICM 2011
P = NS P = NS
PRCT, N = 130
mortality

22. •Summary survival
Study Colloid Survival
SAFE Albumin 4% Sepsis
EARSS Albumin 20%
VISEP HES 200, 10% >dose
CRYSTMAS HES 130, 6%

23. •No Colloids
Survival
Acute Kidney Injury
Coagulation abnormalities

24. •Acute Kidney Injury
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

25. •HES 200, 10%
0%
10%
20%
30%
40%
ARF RRT
HES Saline
P = 0.002 P = 0.001N = 537
Brunkhorst et al, VISEP study. N Engl J Med 2008

26. •CRYSTMAS: HES 130, 6% vs. saline
HES Saline P
N 65 65
Volume (mL) 1380 1708 NS
Time to HD stab (h) 11.8 14.3 NS
AKI-RIFLE 0.808
RRT 22.2% 14.7% 0.180
Bleeding NS
INR NS
Itching 3 3 NS
Death 28-d 31% 25.3% NS
Death d-90 40% 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
Study Colloid AKI
Cittanova - Kidney Donor HES 200 Yes
Schortgen - Severe sepsis HES 200 Yes
VISEP - Severe sepsis HES 130 No diff
SAFE –ICU Alb 4% No diff
EARSS – sepsis Alb 20% No diff
Cirrhosis - HRS Alb 20% Improved
Cirrhosis - SBP Alb 20% Improved

29. •No Colloids
Survival
Acute Kidney Injury
Coagulation abnormalities

30. •Coagulation tests?
Albumin Saline
aPTT + 2.7 sec -0.9 sec
INR No
change
No
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

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
0%
50%
100%
150%
200%
SAFE d1 SAFE d2 SAFE d3 SAFE d4 VISEP d1 VISEP d2-4 CRYSTMAS
Crystalloid Colloid

33. 0%
10%
20%
30%
40%
Catecholamines
HES Saline
Magder et al. Crit Care Med 2010
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
patients n Cryst Colloids Outcome
Annanne ICU 3010 >saline >HES 28-d mort
CHEST ICU 7000 Saline HES 130 90-d mort
ALBIOS Severe sepsis 1350 Any Alb>30 28-d mort
6S Severe sepsis 800 Ringer’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
Bellomo et al. Crit Care Med 2006
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