Hypothermia Treatment for Traumatic Brain Injury: A Systematic Review and Meta-Analysis

Abstract

In this study, we conducted an updated meta-analysis of the effects of hypothermia therapy on mortality, favorable neurologic outcome, and associated adverse effects in adults with traumatic brain injury (TBI) for use by Brain Trauma Foundation (BTF)/American Association of Neurological Surgeons (AANS) task force to develop evidence-based treatment guidelines. Our data sources relied on handsearches of four previous good-quality systematic reviews, which all conducted electronic searches of primarily MEDLINE (OVID), EMBASE, and Cochrane Library. An independent, supplemental electronic search of MEDLINE was undertaken as well (last searched June 2007). Only English-language publications of randomized controlled trials of therapeutic hypothermia in adults with TBI were selected for analysis. Two reviewers independently abstracted data on trial design, patient population, hypothermia and cointervention protocols, patient outcomes, and aspects of methodological quality. Pooled relative risks (RR) and associated 95% confidence intervals (CIs) were calculated for each outcome using random-effects models. In the current study, only 13 trials met eligibility criteria, with a total of 1339 randomized patients. Sensitivity analyses revealed that outcomes were influenced by variations in methodological quality. Consequently, main analyses were conducted based on eight trials that demonstrated the lowest potential for bias (n = 781). Reductions in risk of mortality were greatest (RR 0.51; 95% CI 0.33, 0.79) and favorable neurologic outcomes much more common (RR 1.91; 95% CI 1.28, 2.85) when hypothermia was maintained for more than 48 h. However, this evidence comes with the suggestion that the potential benefits of hypothermia may likely be offset by a significant increase in risk of pneumonia (RR 2.37; 95% CI 1.37, 4.10). In sum, the present study's updated meta-analysis supports previous findings that hypothermic therapy constitutes a beneficial treatment of TBI in specific circumstances. Accordingly, the BTF/AANS guidelines task force has issued a Level III recommendation for optional and cautious use of hypothermia for adults with TBI.

Use of Magnesium in Traumatic Brain Injury

“…87 A meta-analysis of the clinical trials has shown that hypothermia reduced mortality and improved neurological outcome, although this was offset with an increased risk of pneumonia. 88 No combination effects of magnesium and hypothermia have been reported in humans with TBI.…”

European society of intensive care medicine study of therapeutic hypothermia (32-35°C) for intracranial pressure reduction after traumatic brain injury (the Eurotherm3235Trial)

“…Previous studies have shown that therapeutic hypothermia which lasts for at least 48 hours shows a trend to reduction in mortality and improved neurological function after TBI [42]. Hypothermia is continued for as long as is necessary to reduce and maintain ICP <20 mmHg.…”

“…Six meta-analyses have been published between the years 2000 and 2008 [37-42]. These included various numbers of trials, with varying quality of randomisation and blinding procedures.…”

“…The most recent meta-analysis [42] included eight trials which studied comparable patient groups at baseline. Hypothermia was shown to reduce mortality by 20% although this was not statistically significant (RR 0.80; 95% CI 0.59-1.09).…”

“…A recent meta-analysis has shown key relationships between the duration of hypothermia treatment and speed of re-warming with patient outcome [42]. Improved patient outcome was found when hypothermia was continued for between 48 hours and 5 days and patients were re-warmed slowly (1°C/4 hours).…”