Crystalloids May Be Best for Initial Hypovolemia Treatment

Laurie Barclay, MD

October 09, 2013

Among intensive care unit (ICU) patients with hypovolemia, treatment with colloids vs crystalloids was associated with similar 28-day mortality, according to a multicenter, randomized clinical trial published online October 9 in JAMA.

"Although the goal is to use intravenous fluids to expand the intravascular space, fluid also moves into the extravascular space," write Djillali Annane, MD, PhD, from Raymond Poincare Hospital in Garches, France, and colleagues from the Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) investigators. "Crystalloids are thought to counteract that movement via the osmotic pressure exerted by their solutes, whereas colloids are designed to exploit oncotic pressure gradients for the same effect."

In this open-label trial with outcome assessment blinded to treatment assignment, randomization was stratified by center and by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma).

Between February 2003 and August 2012, the investigators recruited 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada. Follow-up ended in November 2012. Throughout their ICU stay, participants were assigned to receive colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance.

The main study endpoint was 28-day mortality, and secondary endpoints were 90-day mortality and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressors. In the colloid group, 359 patients (25.4%) died within 28 days compared with 390 deaths (27.0%) in the crystalloid group (relative risk [RR], 0.96; 95% confidence interval [CI], 0.88 - 1.04; P = .26).

Ninety-day mortality was 30.7% in the colloid group (434 deaths) compared with 34.2% in the crystalloid group (493 deaths; RR, 0.92; 95% CI, 0.86 - 0.99; P = .03). There was no significant difference between groups in use of renal replacement therapy (156 [11.0%] in the colloid group vs 181 [12.5%] in the crystalloid group (RR, 0.93; 95% CI, 0.83 - 1.03; P = .19).

The mean number of days alive without use of mechanical ventilation in the first 7 days was 2.1 days in the colloid group and 1.8 days in the crystalloid group (mean difference, 0.30 days; 95% CI, 0.09 - 0.48 days; P = .01), and in the first 28 days, it was 14.6 vs. 13.5 days, respectively (mean difference, 1.10 days; 95% CI, 0.14 - 2.06 days; P = .01).

The mean number of days alive without use of vasopressor therapy in the first 7 days was 5.0 vs 4.7 days, respectively (mean difference, 0.30 days; 95% CI, −0.03 to 0.50 days; P = .04), and in the first 28 days it was 16.2 vs 15.2 days, respectively (mean difference, 1.04 days; 95% CI, −0.04 to 2.10 days; P = .03).

"Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality," the study authors write. "Although 90-day mortality was lower among patients receiving colloids, this finding should be considered exploratory and requires further study before reaching conclusions about efficacy."

Findings Unlikely to Change Clinical Practice

As previously reported by Medscape Medical News, septic shock guidelines from the Surviving Sepsis Campaign note a preference for crystalloids based on cost.

"The [new] study will not change present practice for most clinicians," Alan E. Jones, MD, professor and chairman, Department of Emergency Medicine, University of Mississippi Health Care, Jackson, and lead author of the Surviving Sepsis guidelines, told Medscape Medical News. "The pertinent message, as recommended by the Surviving Sepsis campaign, remains that crystalloids are the most reasonable initial resuscitative intervention."

Compared with crystalloid salt solutions, colloid solutions containing gelatin, starch, or protein in addition to salt tend to expand blood volume more and have a longer duration of action. However, colloids may be associated with increased morbidity and mortality in critically ill patients.

"[This study] has many strengths, including being a large, prospective, multinational, randomized trial that enrolled a large number of critically ill patients and had a definitive outcome," Dr. Jones said. "Some of the limitations included the heterogeneous patient population and the fairly large number of different colloid and crystalloid preparations that were examined."

The study authors note that use of a computer-generated list of randomization using permutation blocks with allocation concealment minimized the risk for selection bias and that the absence of loss to follow-up for vital status up to 90 days postrandomization and the limited proportion of crossover minimized the risk for attrition bias.

However, the study population differs from that in other recent trials in that it included only patients presenting with hypotension and lactic acidosis. Limitations included the use of open-labeled fluids and a recruitment period of 9 years.

"The findings of potential benefit of lower 90-day mortality and more days vasopressor-free and off mechanical ventilation in the colloid group are interesting findings and should be evaluated in future studies," Dr. Jones concluded.

The French Ministry of Health, Programme Hospitalier de Recherche Clinique 2001 and 2010, funded this study. Two of the study authors having various financial disclosures with Drager Ventilation, Maquet Ventilation, and/or Sérénité-Forceville. Dr. Jones has received funding from the National Institutes of Health to study sepsis.

JAMA. Published online October 9, 2013. Full text

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