CRISTAL: Colloids Compared to Crystalloids in Fluid Resuscitation of Critically Ill Patients: A Multinational Randomised Controlled Trial

BACKGROUND

Fluid resuscitation is a very common treatment in the ICU, and every day a thousands of critically ill patients are treated around the world with crystalloids or colloids to correct hypovolaemia (1, 2). A wide diversity of fluids is available, and new products are coming in the very near future. In 1989, a French consensus conference recommended to abandon the use of fresh frozen plasma and to limit the use of albumin to very specific situations (e.g. contraindication to other colloids, serum protein levels below 35 g/l) (1). Crystalloids and gelatins were considered as the best solutions for fluid resuscitation in the critically ill. In 1997, as starch was increasingly used, this guidelines were updated (2). It was concluded that isotonic crystalloids are as efficacious as starch pending the amount of fluid to be administered.

Three systematic reviews of the literature provided an accurate summary of data available from randomised controlled trials evaluating human albumin (3), or comparing crystalloids to colloids in fluid resuscitation in critically ill patients (4,5). The first systematic review (3) has analysed 30 randomised trials and concluded that there is no evidence that albumin administration reduces the risk of death in critically ill patients. By contrast, this review suggested that albumin administration might increase by 6% the risk of death. In the Cochrane Injury Review Group systematic review (4), 40 randomised trials were analysed. The authors concluded that the administration of colloids might be associated with an absolute increase of 3.8% in the risk of death. The last review has analysed only 17 randomised trials as they decided to exclude studies of hypertonic saline. This review showed no significant difference in the risk of death between colloids and crystalloids or in other outcomes like prevalence of pulmonary edema and length of stay at the ICU and at the hospital (5). However, when the authors considered only the studies with a high methodological quality score, they observed a nice trend toward an increased survival rate in favour of crystalloids. They reached the same conclusions for the subset of trauma patients.

JUSTIFICATION FOR THE STUDY

It seems reasonable to abandon the use of fresh frozen plasma in fluid resuscitation in critically ill patients. There are no definite criteria to decide which of crystalloids and colloids should be preferred. It is unquestionable that, to achieve a given haemodynamic effect, the amount of crystalloids needed is almost twice the amount of colloids (1, 2). Colloids and crystalloids have different effects on a range of important physiological parameters. As most of the critically ill patients underwent one or more volume replacements, even a small increase in the risk of death (around 5%) has considerable clinical implications. The meta analyses suggested a 5% absolute risk reduction in mortality in favour of crystalloids (4, 5). The number needed to treat, an estimate which is more clinically meaningful (6), is of 20, suggesting about 1 additional death (with colloids) for every 20 patients resuscitated. Given the number of patients exposed to fluid resuscitation, about 60 additional deaths might be observed per year in a ICU,receiving 600 patients a year.