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Meta-Analysis of Therapeutic Hypothermia for Traumatic Brain Injury in Adult and Pediatric Patients*

Crompton, Ellie M. BSc; Lubomirova, Irina MBBS; Cotlarciuc, Ioana PhD; Han, Thang S. PhD; Sharma, Sapna D. MD; Sharma, Pankaj PhD

doi: 10.1097/CCM.0000000000002205
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Objective: Therapeutic hypothermia has been used to attenuate the effects of traumatic brain injuries. However, the required degree of hypothermia, length of its use, and its timing are uncertain. We undertook a comprehensive meta-analysis to quantify benefits of hypothermia therapy for traumatic brain injuries in adults and children by analyzing mortality rates, neurologic outcomes, and adverse effects.

Data Sources: Electronic databases PubMed, Google Scholar, Web of Science, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov and manual searches of studies were conducted for relevant publications up until February 2016.

Study Selection: Forty-one studies in adults (n = 3,109; age range, 18–81 yr) and eight studies in children (n = 454; age range, 3 mo to 18 yr) met eligibility criteria.

Data Extraction: Baseline patient characteristics, enrollment time, methodology of cooling, target temperature, duration of hypothermia, and rewarming protocols were extracted.

Data Synthesis: Risk ratios with 95% CIs were calculated. Compared with adults who were kept normothermic, those who underwent therapeutic hypothermia were associated with 18% reduction in mortality (risk ratio, 0.82; 95% CI, 0.70–0.96; p = 0.01) and a 35% improvement in neurologic outcome (risk ratio, 1.35; 95% CI, 1.18–1.54; p < 0.00001). The optimal management strategy for adult patients included cooling patients to a minimum of 33°C for 72 hours, followed by spontaneous, natural rewarming. In contrast, adverse outcomes were observed in children who underwent hypothermic treatment with a 66% increase in mortality (risk ratio, 1.66; 95% CI, 1.06–2.59; p = 0.03) and a marginal deterioration of neurologic outcome (risk ratio, 0.90; 95% CI, 0.80–1.01; p = 0.06).

Conclusions: Therapeutic hypothermia is likely a beneficial treatment following traumatic brain injuries in adults but cannot be recommended in children.

1Institute of Cardiovascular Research Royal Holloway University of London (ICR2UL), Egham, United Kingdom.

2Department of Medicine, Imperial College London, London, United Kingdom.

3Ashford and St Peter’s NHS Foundation Trust, Surrey, United Kingdom.

*See also p. 744.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Professor P. Sharma was a Department of Health U.K. Senior Fellow. The remaining authors have disclosed that they do not have any potential conflicts of interest.

For information regarding this article, E-mail: pankaj.sharma@rhul.ac.uk

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