Early induction of hypothermia for evacuated intracranial hematomas: A post hoc analysis of two clinical trials

Object: The authors hypothesized that cooling before evacuation of traumatic intracranial hematomas protects the brain from reperfusion injury and, if so, further hypothesized that hypothermia induction before or soon after craniotomy should be associated with improved outcomes. Methods: The National Acute Brain Injury Study: Hypothermia I (NABIS:H I) was a randomized multicenter clinical trial of 392 patients with severe brain injury treated using normothermia or hypothermia for 48 hours with patients reaching 33°C at 8.4 ± 3 hours after injury. The National Acute Brain Injury Study: Hypothermia II (NABIS:H II) was a randomized, multicenter clinical trial of 97 patients with severe brain injury treated with normothermia or hypothermia for 48 hours with patients reaching 35°C within 2.6 ± 1.2 hours and 33°C within 4.4 ± 1.5 hours of injury. Entry and exclusion criteria, management, and outcome measures in the 2 trials were similar. Results: In NABIS:H II among the patients with evacuated intracranial hematomas, outcome was poor (severe disability, vegetative state, or death) in 5 of 15 patients in the hypothermia group and in 9 of 13 patients in the normothermia group (relative risk 0.44, 95% CI 0.22-0.88; p = 0.02). All patients randomized to hypothermia reached 35°C within 1.5 hours after surgery start and 33°C within 5.55 hours. Applying these criteria to NABIS:H I, 31 of 54 hypothermia-treated patients reached a temperature of 35°C or lower within 1.5 hours after surgery start time, and the remaining 23 patients reached 35°C at later time points. Outcome was poor in 14 (45%) of 31 patients reaching 35°C within 1.5 hours of surgery, in 14 (61%) of 23 patients reaching 35°C more than 1.5 hours of surgery, and in 35 (60%) of 58 patients in the normothermia group (relative risk 0.74, 95%, CI 0.49-1.13; p = 0.16). A meta-analysis of 46 patients with hematomas in both trials who reached 35°C within 1.5 hours of surgery start showed a significantly reduced rate of poor outcomes (41%) compared with 94 patients treated with hypothermia who did not reach 35°C within that time and patients treated at normothermia (62%, p = 0.009). Conclusions: Induction of hypothermia to 35°C before or soon after craniotomy with maintenance at 33°C for 48 hours thereafter may improve outcome of patients with hematomas and severe traumatic brain injury.