To perform a pilot study to assess the feasibility of performing a phase III trial of therapeutic hypothermia started early and continued for at least 72 hours in children with severe traumatic brain injury.Design:
Multicenter prospective randomized controlled phase II trial.Setting:
All eight of the PICUs in Australia and New Zealand and one in Canada.Patients:
Children 1–15 years old with severe traumatic brain injury and who could be randomized within 6 hours of injury.Interventions:
The control group had strict normothermia to a temperature of 36–37°C for 72 hours. The intervention group had therapeutic hypothermia to a temperature of 32–33°C for 72 hours followed by slow rewarming at a rate compatible with maintaining intracranial pressure and cerebral perfusion pressure.Measurements and Main Results:
Of 764 children admitted to PICU with traumatic brain injury, 92 (12%) were eligible and 55 (7.2%) were recruited. There were five major protocol violations (9%): three related to recruitment and consent processes and two to incorrect temperature management. Rewarming took a median of 21.5 hours (16–35 hr) and was performed without compromise in the cerebral perfusion pressure. There was no increase in any complications, including infections, bleeding, and arrhythmias. There was no difference in outcomes 12 months after injury; in the therapeutic hypothermia group, four (17%) had a bad outcome (pediatric cerebral performance category, 4–6) and three (13%) died, whereas in the normothermia group, three (12%) had a bad outcome and one (4%) died.Conclusions:
Early therapeutic hypothermia in children with severe traumatic brain injury does not improve outcome and should not be used outside a clinical trial. Recruitment rates were lower and outcomes were better than expected. Conventional randomized controlled trials in children with severe traumatic brain injury are unlikely to be feasible. A large international trials group and alternative approaches to trial design will be required to further inform practice.