Original Investigation | Caring for the Critically Ill Patient

Effects of Fluid Resuscitation With Colloids vs Crystalloids on Mortality in Critically Ill Patients Presenting With Hypovolemic Shock:  The CRISTAL Randomized Trial

Djillali Annane, MD, PhD1; Shidasp Siami, MD2; Samir Jaber, MD, PhD3; Claude Martin, MD, PhD4; Souheil Elatrous, MD5; Adrien Descorps Declère, MD6; Jean Charles Preiser, MD7; Hervé Outin, MD8; Gilles Troché, MD9; Claire Charpentier, MD10; Jean Louis Trouillet, MD11; Antoine Kimmoun, MD12; Xavier Forceville, MD, PhD13; Michael Darmon, MD14; Olivier Lesur, MD, PhD15; Jean Reignier, MD16; Fékri Abroug, MD17; Philippe Berger, MD18; Christophe Clec’h, MD, PhD19; Joël Cousson, MD20; Laure Thibault, MD21; Sylvie Chevret, MD, PhD22; for the CRISTAL Investigators
[+] Author Affiliations
1Raymond Poincaré Hospital, Garches, France
2CH d’Etampes, Etampes, France
3CHU Montpelier, Montpelier, France
4AP-HM Hôpital Nord, Marseille, Farnce
5EPS Taher Sfar Mahdia, Mahdia, Tunisia
6Antoine Béclère, Clamart, France
7CHU de Liège, Liège, Belgium
8CHI de Poissy St Germain, Poissy, France
9CH André Mignot, Versailles, France
10Hôpital Central, Nancy, France
11Pitié Salpêtrière, Paris, France
12Hôpital Brabois, Nancy, France
13CH de Meaux, Meaux, France
14Hôpital Saint Louis, Paris, France
15CH de Sherbrooke, Sherbrooke, Quebec, Canada
16CH de la Roche sur Yon, Roche sur Yon, France
17CHU Monastir, Monastir, Tunisia
18CH de Chalons en Champagne, Champagne, France
19Hôpital Avicenne, Bobigny, France
20CHU de Reims, Reims, France
21CH de la Réunion, Réunion Island, France
22Hôpital Saint Louis, Paris, France
JAMA. 2013;310(17):1809-1817. doi:10.1001/jama.2013.280502.
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Importance  Evidence supporting the choice of intravenous colloid vs crystalloid solutions for management of hypovolemic shock remains unclear.

Objective  To test whether use of colloids compared with crystalloids for fluid resuscitation alters mortality in patients admitted to the intensive care unit (ICU) with hypovolemic shock.

Design, Setting, and Participants  A multicenter, randomized clinical trial stratified by case mix (sepsis, trauma, or hypovolemic shock without sepsis or trauma). Therapy in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) trial was open label but outcome assessment was blinded to treatment assignment. Recruitment began in February 2003 and ended in August 2012 of 2857 sequential ICU patients treated at 57 ICUs in France, Belgium, North Africa, and Canada; follow-up ended in November 2012.

Interventions  Colloids (n = 1414; gelatins, dextrans, hydroxyethyl starches, or 4% or 20% of albumin) or crystalloids (n = 1443; isotonic or hypertonic saline or Ringer lactate solution) for all fluid interventions other than fluid maintenance throughout the ICU stay.

Main Outcomes and Measures  The primary outcome was death within 28 days. Secondary outcomes included 90-day mortality; and days alive and not receiving renal replacement therapy, mechanical ventilation, or vasopressor therapy.

Results  Within 28 days, there were 359 deaths (25.4%) in colloids group vs 390 deaths (27.0%) in crystalloids group (relative risk [RR], 0.96 [95% CI, 0.88 to 1.04]; P = .26). Within 90 days, there were 434 deaths (30.7%) in colloids group vs 493 deaths (34.2%) in crystalloids group (RR, 0.92 [95% CI, 0.86 to 0.99]; P = .03). Renal replacement therapy was used in 156 (11.0%) in colloids group vs 181 (12.5%) in crystalloids group (RR, 0.93 [95% CI, 0.83 to 1.03]; P = .19). There were more days alive without mechanical ventilation in the colloids group vs the crystalloids group by 7 days (mean: 2.1 vs 1.8 days, respectively; mean difference, 0.30 [95% CI, 0.09 to 0.48] days; P = .01) and by 28 days (mean: 14.6 vs 13.5 days; mean difference, 1.10 [95% CI, 0.14 to 2.06] days; P = .01) and alive without vasopressor therapy by 7 days (mean: 5.0 vs 4.7 days; mean difference, 0.30 [95% CI, −0.03 to 0.50] days; P = .04) and by 28 days (mean: 16.2 vs 15.2 days; mean difference, 1.04 [95% CI, −0.04 to 2.10] days; P = .03).

Conclusions and Relevance  Among ICU patients with hypovolemia, the use of colloids vs crystalloids did not result in a significant difference in 28-day mortality. 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.

Trial Registration  clinicaltrials.gov Identifier: NCT00318942

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Figure 1.
Patient Enrollment in the Colloids Versus Crystalloids for the Resuscitation of the Critically Ill (CRISTAL) Trial
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Figure 2.
Cumulative Incidence of Death Within First 28 Days After Randomization
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Figure 3.
Assessment of Treatment × Diagnosis Interaction and Death Within First 28 Days

HR indicates hazard ratio; ICU, intensive care unit. P = .70 for interaction of homogeneity of HR across the 3 strata, which was calculated using the Gail and Simon statistic test.

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Colloids versus Crystalloids in the Critically Ill

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