Use of Nutrition to Prevent Stress‐induced Immunosuppression in the Pediatric Intensive Care Unit: A Clinical Trials Minefield

Abstract

utrition measures intended to prevent stressinduced, immunosuppression-related morbidity in critically ill patients are receiving increased attention. Supplements such as glutamine, arginine, ω-3 fatty acids, antioxidants, zinc, and others have become candidates for such prophylaxis. Infections, especially sepsis, which occur all too commonly, are targets of these interventions. The mechanistic foundations on which these interventions are based are largely derived from studies of highly stressed animals and from cell cultures. These studies have provided a strong rationale for several treatments, especially glutamine supplementation. Furthermore, several single-center studies as well as meta-analyses of these studies in critically ill adults reveal a significant benefit of glutamine supplementation on mortality, length of stay, and infectious morbidity. Glutamine supplementation has become standard of care in certain populations. Randomized, multicenter clinical trials using glutamine as both nutrition replacement and pharmacologic intervention, independent of nutrition needs, are ongoing in adults. In this issue of the Journal of Parenteral and Enteral Nutrition (JPEN), Carcillo and colleagues 1 propose a multicenter randomized trial of glutamine, zinc, selenium, and parenteral metoclopramide, titled prevention of Critical Illness Stress-induced Immune Suppression (CRISIS) in the pediatric intensive care unit (PICU), and present the plan for this trial. The trial is designed to determine whether this intervention prolongs the time until onset of nosocomial infection or sepsis and secondarily decreases the rate of nosocomial infection or clinical sepsis per 100 PICU days; the trial also will determine the number of antibiotic-free days, the incidence of prolonged lymphopenia, and all-cause 28-day mortality.