Hypothermia Therapy after Traumatic Brain Injury in Children

TLDR

Animal studies show hypothermia improves survival and neurologic outcome after traumatic brain injury, but its effect in children with severe TBI is unknown. This multicenter, international randomized trial evaluated whether initiating hypothermia within 8 hours and maintaining it for 24 hours improves neurologic outcome and reduces mortality in children with severe TBI. Children were randomized to hypothermia (32.5 °C for 24 h) or normothermia (37.0 °C), and the primary outcome was the proportion with an unfavorable Pediatric Cerebral Performance Category score at 6 months. At 6 months, 31 % of hypothermia patients had an unfavorable outcome versus 22 % of normothermia patients (RR 1.41, 95 % CI 0.89–2.22, P = 0.14), with 21 % versus 12 % mortality (RR 1.40, 95 % CI 0.90–2.27, P = 0.06); hypotension and vasoactive agent use were higher in the hypothermia group, while ICU and hospital lengths of stay were similar, indicating hypothermia does not improve neurologic outcome and may increase mortality. Trial registered at ISRCTN77393684.

Abstract

Hypothermia therapy improves survival and the neurologic outcome in animal models of traumatic brain injury. However, the effect of hypothermia therapy on the neurologic outcome and mortality among children who have severe traumatic brain injury is unknown.In a multicenter, international trial, we randomly assigned children with severe traumatic brain injury to either hypothermia therapy (32.5 degrees C for 24 hours) ), initiated within 8 hours after injury or to normothermia (37.0 degrees C). The primary outcome was the proportion of children who had an unfavorable outcome (i.e., severe disability, persistent vegetative state, or death), as assessed on the basis of the Pediatric Cerebral Performance Category score at 6 months.A total of 225 children were randomly assigned to the hypothermia group or the normothermia group; the mean temperatures achieved in the two groups were 33.1+/-1.2 degrees C and 36.9+/-0.5 degrees C, respectively. At 6 months, 31% of the patients in the hypothermia group, as compared with 22% of the patients in the normothermia group, had an unfavorable outcome (relative risk, 1.41; 95% confidence interval [CI], 0.89 to 2.22; P=0.14). There were 23 deaths (21%) in the hypothermia group and 14 deaths (12%) in the normothermia group (relative risk, 1.40; 95% CI, 0.90 to 2.27; P=0.06). There was more hypotension (P=0.047) and more vasoactive agents were administered (P<0.001) in the hypothermia group during the rewarming period than in the normothermia group. Lengths of stay in the intensive care unit and in the hospital and other adverse events were similar in the two groups.In children with severe traumatic brain injury, hypothermia therapy that is initiated within 8 hours after injury and continued for 24 hours does not improve the neurologic outcome and may increase mortality. (Current Controlled Trials number, ISRCTN77393684 [controlled-trials.com]. ).