Clash of the titans: Colloids versus crystalloids

Eric A J HosteIntensive Care Unit

Ghent University HospitalBelgium

•Are we asking the correct question?

Maitland et al. N Engl J Med 2011

The FEAST studyFebrile illness, AfricaN = 3141 + 29

•Relevant question

Finfer et al SAFE TRIPS, Crit Care 2010

•Why would you choose colloids?

Fast shock reversal = survival EGDT!

Less volume< IAH/ACS

•Why would you choose colloids?

Fast shock reversal = survivalEGDT!

Less volume< IAH/ACS< ARDS

•Why would you not choose colloids?

Cost

Side effectsAcute Kidney InjuryCoagulation abnormalities …

Worse Survival

•Price (€)

•No Colloids

Survival

Acute Kidney Injury

Coagulation abnormalities

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

•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)

•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)

•Limitations of the meta-analysis

HeterogeneityCohorts: non-ICU, burns, sepsis, trauma, …Products: – Alb 4, 5, 20, 25% – HES 6, 10%, 1st, 2nd, 3rd generation– Saline, Ringer’s– …

Small studies

•The SAFE study : Albumin 4%

The SAFE study investigators N Engl J Med 2004

N = 6,997 patients

•Subgroups?

The SAFE study investigators N Engl J Med 2004

•Traumatic Brain Injury

Myburgh et al. N Engl J Med 2007

GCS 3-8N = 460 patients

No to albumin

•Severe sepsis?

Finfer et al. Intensive Care Med 2011

N = 919/1218 Yes to albumin

•EARSS: Albumin 20% in septic shock

ResultsAlbumin concentrationAll individual organ dysfunctions equalSame outcome at 28-d

No Benefit

Abstract ESICM Berlin 2011

N = 794 patients

•HES 200, 10% vs. Ringer’s

Brunkhorst et al, VISEP study. N Engl J Med 2008

N = 537 patients

•HES 200, 10% vs. Ringer’s

Brunkhorst et al, VISEP study. N Engl J Med 2008

N = 537 patients

•HES 130, 6%

Guidet et al. CRYSTMAS, abstract ESICM 2011

P = NS P = NS

PRCT, N = 130

mor

talit

y

•Summary survival

Study Colloid Survival

SAFE Albumin 4% Sepsis

EARSS Albumin 20%

VISEP HES 200, 10% >dose

CRYSTMAS HES 130, 6%

•No Colloids

Survival

Acute Kidney Injury

Coagulation abnormalities

•Acute Kidney Injury

N = 129, PRCTSevere sepsis/septic shockAKI = creat x 2 or RRT

Cittanova et al. Lancet 1996 Schortgen et al. Lancet 2004

N = 52, PRCTBrain dead kidney donors

•HES 200, 10%

P = 0.002 P = 0.001N = 537

Brunkhorst et al, VISEP study. N Engl J Med 2008

•CRYSTMAS: HES 130, 6% vs. salineHES Saline P

N 65 65Volume (mL) 1380 1708 NS

Time to HD stab (h) 11.8 14.3 NS

AKI-RIFLE 0.808

RRT 22.2% 14.7% 0.180Bleeding 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

•Albumin and AKI

SAFE study: No difference in duration of RRT

EARSS study: No difference in organ dysfunction

Spontaneous Bacterial Peritonitis: Albumin = less AKISort et al. N Engl J Med 1999

Hepatorenal syndrome: Albumin improves HRS Ortega et al. Hepatology 2002

•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

•No Colloids

Survival

Acute Kidney Injury

Coagulation abnormalities

•Coagulation tests?

Albumin SalineaPTT + 2.7 sec -0.9 secINR No

changeNo

change

Platelets

Multivariate analysis: aPTT associated with:Albumin (p=0.01) Large volume (p=0.03)

Bellomo et al. Crit Care Resusc 2009

N = 6873 units of the SAFE study group

•So,

Survival is better or worse or equalAKI is equal or more (> older HES)Coagulation abn: yes

But: What about volume & early shock reversal?

•Less volume

Catecholamines0%5%

10%15%20%25%30%35% HES Saline

Magder et al. Crit Care Med 2010

656 mL fluid/d lessLess wound infectionsLess pacing

N = 237 More need for plasma (p=0.048)

EARSS, abstract ESICM 2011

•Take home messages

Cost Crystalloid: 5 to 25 times lowerSurvival: 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

•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

•Thank You

Eric.Hoste@Ugent.be

•Relevant question

Finfer et al SAFE TRIPS, Crit Care 2010

•Acid-Base?

N = 6913 units

Bellomo et al. Crit Care Med 2006

Multivariate analysis:>3 L fluid resuscitationCl : alb>saline

•Better when albumin is low?

Finfer et al. BMJ 2006

•Acute Kidney Injury

Zarychanski et al. Open Med 2009