Fluid resuscitation in acute illness--time to reappraise the basics.

Fluid resuscitation is a fundamental intervention in the treatment of critically ill patients. However, there is little conclusive evidence to guide clinicians about the best type of resuscitation fluid; the appropriate timing, volume, and rate of fluid administration; and the optimal way to adequately monitor the efficacy and safety of fluid resuscitation in various clinical conditions.1 Although the complications associated with excessive volume of resuscitation fluid — such as pulmonary and interstitial edema — are well recognized, an emerging body of evidence suggests that the type of resuscitation fluid may adversely affect the outcomes in specific clinical conditions; for example, albumin is associated with increased mortality in patients with traumatic brain injury,2 and high-molecular-weight preparations of hydroxyethyl starch are associated with acute kidney injury in patients with severe sepsis.3 Conversely, improved outcomes associated with the use of albumin for resuscitation have been shown in children with severe malaria4 and in a subgroup of adults with severe sepsis in the Saline versus Albumin Fluid Evaluation study (SAFE; Current Controlled Trials number, ISRCTN76588266).5,6 However, these reports were not sufficiently conclusive to justify the adoption of strong clinical recommendations. The results of the Fluid Expansion as Supportive Therapy (FEAST) trial,7 reported in this issue of the Journal, are an important contribution to the literature. This remarkable, pragmatic, randomized, controlled trial, conducted in six hospitals in Kenya, Tanzania, and Uganda, assessed the effects of bolus-fluid resuscitation with albumin or saline as compared with no bolus fluid in children with febrile medical illness and impaired perfusion. Children with severe hypotension, or decompensated shock, received boluses of either albumin or saline for resuscitation. The trial centers had no access to intensive care units, and the trial included a comprehensive education program aimed at optimizing early case recognition and training in emergency pediatric life support. The primary outcome was 48-hour mortality — a relevant patient-centered outcome in regions in which the high prevalence of severe sepsis in children, often due to malaria, is associated with high early mortality.8 The trial was powered to determine a plausible absolute risk reduction in 48-hour mortality (as derived from power calculations described in the Methods section in the article) of 5 percentage points and was conducted with high standards of internal validity — excellent randomization procedures, a high rate of adherence to the protocol, concealment of the treatment assignments, a minimal loss to follow-up, the use of the intention-to-treat principle for the analyses, and performance of analyses according to prespecified subgroups. The sample size was appropriately increased from 2800 patients to 3600 patients after an interim analysis showed that the rate of death was lower than predicted in the intervention groups. However, the trial was stopped after the recruitment of 3141 patients when bolusfluid resuscitation with albumin or saline was shown to increase the absolute risk of death at 48 hours by 3.3 percentage points and the risk of death, neurologic sequelae, or both at 4 weeks by 4 percentage points. No difference in mortality was observed in patients with decompensated shock, although these patients were few in number and had significantly higher mortality. The excess mortality associated with bolus-fluid resuscitation was consistent across all prespecified subgroups, which included subgroups according to age, lactate level, base deficit, presence or ab-