The results of the CRISTAL study were published today online in JAMA, which is freely accessible at the hyperlink below:

The CRISTAL Randomized Trial

The Quick Rundown (Not a full study/article critique)

The CRISTAL trial (Colloids Versus Crystalloids for the Resuscitation of the Critically Ill......seriously? Who came up with this acronym, Tom Cruise?) was a multicenter, randomized, open label, assessment blinded, clinical trial, stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma), comparing colloids (n = 1,414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) with crystalloids (n = 1,443; isotonic or hypertonic saline or Ringer's lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay.

This study took place at 57 ICUs across 3 continents (NA, Africa, Europe) from February 2003 to August 2012. It was designed to detect a 5% absolute difference in mortality at 28 days but was terminated based on a predefined stopping rule after 2857 of the planned 3010 patients had been enrolled.

Fluids used

•  Crystalloids included isotonic and hypertonic solutions that are also categorized into nonbuffered (eg, isotonic saline) and buffered solutions (eg, Ringer lactate, acetate, maleate)
•  Colloids included hypooncotic (eg, gelatins, 4% or 5% of albumin) and hyperoncotic (eg, dextrans, hydroxyethyl starches, and 20% or 25% of albumin) solutions

Major results

1. no difference in
   • 28 day mortality (colloids 25.4% versus crystalloids 27.0%, RR 0.96, 95% CI 0.88 - 1.04, P=0.26)
   • renal replacement therapy use (colloids 11.0% versus crystalloids 12.5%, RR 0.93, 95% CI 0.83 to 1.03, P=0.19)
2. improved outcomes with colloid therapy
   • reduced 90 day mortality (30.7% versus 34.2%; RR 0.92, 95% CI 0.86 - 0.99; P=0.03)
   • more days alive without mechanical ventilation
     • by day 7 (mean: 2.1 versus 1.8 days; mean difference 0.30, 95% CI 0.09 to 0.48 days, P=0.01)
     • by day 28 (mean: 14.6 versus 13.5 days; mean difference, 1.10, 95% CI 0.14 to 2.06 days; P=0.01)
   • more days alive without vasopressor therapy
     • by day 7 (mean: 5.0 vs 4.7 days; mean difference 0.30, 95% CI −0.03 to 0.50 days; P=0.04) 
     • by day 28 day (mean: 16.2 vs 15.2 days; mean difference 1.04, 95% CI −0.04 to 2.10 days; P=0.03)

Points to ponder:

• Patients treated with colloids received significantly less fluid than those treated with crystalloids. There is evidence showing that positive fluid balance in sepsis is associated with a worse outcome
• What about chloride poisoning.  Can the renals handle all of the chloride? 
• Mortality at 90 days was not the primary goal of this study.  Ideally it would be as for people 28 days can be a short time. 90 days would likely have been a more ideal cutoff.

This study continues to challenge the crystalloid vs colloid debate but does not give much in the way of support for either side.  We know that albumin has been shown to not worsen outcome in the SAFE trial, HES was condemned in the 6S trial and showed no difference in mortality but higher rate of AKI in the CHEST trial.  This makes it tough to interpret the results of CRISTAL but at least does not continue the hate parade against hydroxyethyl starch.

At least if things don't pan out for CRISTAL she can at least get TAFI's contact from Dan to see if there are any openings in her line of work.

*TWERK*

STEPS TO SELECTING A COLLOID VS A CRYSTALLOID

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Select references

1. Myburgh JA, Finfer S, Bellomo R, et al; CHEST Investigators; Australian and New Zealand Intensive Care Society Clinical Trials Group. Hydroxyethyl starch or saline for fluid resuscitation in intensive care. N Engl J Med. 2012;367(20):1901-1911.

2. Perner A, Haase N, Guttormsen AB, et al. Hydroxyethyl starch 130/0.42 versus Ringer's acetate in severe sepsis (6S). N Engl J Med. 2012;367(2):124-134.

3. Finfer S, Bellomo R, Boyce N, French J, Myburgh J, Norton R; SAFE Study Investigators. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. N Engl J Med. 2004;350(22):2247-2256.

4. Yunos NM, Bellomo R, Hegarty C, et al. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012;308(15):1566-1572