Initiating Nutritional Support Before 72 Hours Is Associated With Favorable Outcome After Severe Traumatic Brain Injury in Children: A Secondary Analysis of a Randomized, Controlled Trial of Therapeutic Hypothermia

Objectives: To understand the relationship between the timing of initiation of nutritional support in children with severe traumatic brain injury and outcomes. Design: Secondary analysis of a randomized, controlled trial of therapeutic hypothermia (Pediatric Traumatic Brain Injury Consortium: Hypothermia, also known as the Cool Kids Trial (NCT 00222742). Settings: Fifteen clinical sites in the United States, Australia, and New Zealand. Subjects: Inclusion criteria included 1) age less than 18 years, 2) postresuscitation Glasgow Coma Scale less than or equal to 8, 3) Glasgow Coma Scale motor score less than 6, and 4) available to be randomized within 6 hours after injury. Exclusion criteria included normal head CT, Glasgow Coma Scale equals to 3, hypotension for greater than 10 minutes (< fifth percentile for age), uncorrectable coagulopathy, hypoxia (arterial oxygen saturation < 90% for > 30 min), pregnancy, penetrating injury, and unavailability of a parent or guardian to consent at centers without emergency waiver of consent. Interventions: Therapeutic hypothermia (32-33 degrees C for 48 hr) followed by slow rewarming for the primary study. For this analysis, the only intervention was the extraction of data regarding nutritional support from the existing database. Measurements and Main Results: Timing of initiation of nutritional support was determined and patients stratified into four groups (group 1-no nutritional support over first 7 d; group 2-nutritional support initiated < 48 hr after injury; group 3-nutritional support initiated 48 to < 72 hr after injury; group 4-nutritional support initiated 72-168 hr after injury). Outcomes were also stratified (mortality and Glasgow Outcomes Scale-Extended for Pediatrics; 1-4, 5-7, 8) at 6 and 12 months. Mixed-effects models were performed to define the relationship between nutrition and outcome. Children (n = 90, 77 randomized, 13 run-in) were enrolled (mean Glasgow Coma Scale = 5.8); the mortality rate was 13.3%. 57.8% of subjects received hypothermia Initiation of nutrition before 72 hours was associated with survival (p = 0.01), favorable 6 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.03), and favorable 12 months Glasgow Outcomes Scale-Extended for Pediatrics (p = 0.04). Specifically, groups 2 and 3 had favorable outcomes versus group 1. Conclusions: Initiation of nutritional support before 72 hours after traumatic brain injury was associated with decreased mortality and favorable outcome in this secondary analysis. Although this provides a rationale to initiate nutritional support early after traumatic brain injury, definitive studies that control for important covariates (severity of injury, clinical site, calories delivered, parenteral/enteral routes, and other factors) are needed to provide definitive evidence on the optimization of the timing of nutritional support after severe traumatic brain injury in children.