Prophylactic hypothermia for traumatic brain injury: A quantitative systematic review

Abstract

Introduction: During the past 7 years, considerable new evidence has accumulated supporting the use of prophylactic hypothermia for traumatic brain injury (TBI). Studies can be divided into 2 broad categories: studies with protocols for cooling for a short, predetermined period (e.g., 24-48 h), and those that cool for longer periods and/or terminate based on the normalization of intracranial pressure (ICP). There have been no systematic reviews of hypothermia for TBI that include this recent new evidence. Methods: This analysis followed the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and the QUORUM (quality of reporting of meta-analyses) statement. We developed a comprehensive search strategy to identify all randomized controlled trials (RCTs) comparing therapeutic hypothermia with standard management in TBI patients. We searched Embase, MEDLINE, Web of Science, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, ProceedingsFirst and PapersFirst. Additional relevant articles were identified by hand-searching conference proceedings and bibliographies. All stages of study identification and selection, quality assessment and analysis were conducted according to prospectively defined criteria. Study quality was determined by assessment of each study for the use of allocation concealment and outcome assessment blinding. Studies were divided into 2 a priori-defined subgroups for analysis based on cooling strategy: short term (≤ 48 h), and long term or goal-directed (> 48 h and/or continued until normalization of ICP). Outcomes included mortality and good neurologic outcome (defined as Glasgow Outcome Scale score of 4 or 5). Pooling of primary outcomes was completed using relative risk (RR) and reported with 95% confidence intervals (CIs). Results: Of 1709 articles, 12 studies with 1327 participants were selected for quantitative analysis. Eight of these studies cooled according to a long-term or goal-directed strategy, and 4 used a short-term strategy. Summary results demonstrated lower mortality (RR 0.73, 95% CI 0.62-0.85) and more common good neurologic outcome (RR 1.52, 95% CI 1.28-1.80). When only short-term cooling studies were analyzed, neither mortality (RR 0.98, 95% CI 0.75-1.30) nor neurologic outcome (RR 1.31, 95% CI 0.94-1.83) were improved. In 8 studies of long-term or goal-directed cooling, mortality was reduced (RR 0.62, 95% CI 0.51-0.76) and good neurologic outcome was more common (RR 1.68, 95% CI 1.44-1.96). Conclusion: The best available evidence to date supports the use of early prophylactic mild-to-moderate hypothermia in patients with severe TBI (Glasgow Coma Scale score ≤ 8) to decrease mortality and improve rates of good neurologic recovery. This treatment should be commenced as soon as possible after injury (e.g., in the emergency department after computed tomography) regardless of initial ICP, or before ICP is measured. Most studies report using a temperature of 32°-34°C. The maximal benefit occurred with a long-term or goal-directed cooling protocol, in which cooling was continued for at least 72 hours and/or until stable normalization of intracranial pressure for at least 24 hours was achieved. There is large potential for further research on this therapy in prehospital and emergency department settings.