Hypothermia for Patients Requiring Evacuation of Subdural Hematoma: A Multicenter Randomized Clinical Trial

BACKGROUND: Hypothermia is neuroprotective in some ischemia-reperfusion injuries. Ischemia-reperfusion injury may occur with traumatic subdural hematoma (SDH). This study aimed to determine whether early induction and maintenance of hypothermia in patients with acute SDH would lead to decreased ischemia-reperfusion injury and improve global neurologic outcome. METHODS: This international, multicenter randomized controlled trial enrolled adult patients with SDH requiring evacuation of hematoma within 6 h of injury. The intervention was controlled temperature management of hypothermia to 35 °C prior to dura opening followed by 33 °C for 48 h compared with normothermia (37 °C). Investigators randomly assigned patients at a 1:1 ratio between hypothermia and normothermia. Blinded evaluators assessed outcome using a 6-month Glasgow Outcome Scale Extended score. Investigators measured circulating glial fibrillary acidic protein and ubiquitin C-terminal hydrolase L1 levels. RESULTS: Independent statisticians performed an interim analysis of 31 patients to assess the predictive probability of success and the Data and Safety Monitoring Board recommended the early termination of the study because of futility. Thirty-two patients, 16 per arm, were analyzed. Favorable 6-month Glasgow Outcome Scale Extended outcomes were not statistically significantly different between hypothermia vs. normothermia groups (6 of 16, 38% vs. 4 of 16, 25%; odds ratio 1.8 [95% confidence interval 0.39 to ∞], p = .35). Plasma levels of glial fibrillary acidic protein (p = .036), but not ubiquitin C-terminal hydrolase L1 (p = .26), were lower in the patients with favorable outcome compared with those with unfavorable outcome, but differences were not identified by temperature group. Adverse events were similar between groups. CONCLUSIONS: This trial of hypothermia after acute SDH evacuation was terminated because of a low predictive probability of meeting the study objectives. There was no statistically significant difference in functional outcome identified between temperature groups.