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A Systematic Review of Therapeutic Hypothermia for Adult Patients Following Traumatic Brain Injury

Watson, Hannah I., MBChB1; Shepherd, Andrew A., MBChB1; Rhodes, Jonathan K. J., PhD1,2; Andrews, Peter J. D., MD3

doi: 10.1097/CCM.0000000000003125
Neurologic Critical Care

Objectives: Therapeutic hypothermia has been of topical interest for many years and with the publication of two international, multicenter randomized controlled trials, the evidence base now needs updating. The aim of this systematic review of randomized controlled trials is to assess the efficacy of therapeutic hypothermia in adult traumatic brain injury focusing on mortality, poor outcomes, and new pneumonia.

Data Sources: The following databases were searched from January 1, 2011, to January 26, 2018: Cochrane Central Register of Controlled Trial, MEDLINE, PubMed, and EMBASE.

Study Selection: Only foreign articles published in the English language were included. Only articles that were randomized controlled trials investigating adult traumatic brain injury sustained following an acute, closed head injury were included. Two authors independently assessed at each stage.

Data Extraction: Quality was assessed using the Cochrane Collaboration’s tool for assessing the risk of bias. All extracted data were combined using the Mantel-Haenszel estimator for pooled risk ratio with 95% CIs. p value of less than 0.05 was considered statistically significant. All statistical analyses were conducted using RevMan 5 (Cochrane Collaboration, Version 5.3, Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014).

Data Synthesis: Twenty-two studies with 2,346 patients are included. Randomized controlled trials with a low risk of bias show significantly more mortality in the therapeutic hypothermia group (risk ratio, 1.37; 95% CI, 1.04–1.79; p = 0.02), whereas randomized controlled trials with a high risk of bias show the opposite with a higher mortality in the control group (risk ratio, 0.70; 95% CI, 0.60–0.82; p < 0.00001).

Conclusions: Overall, this review is in-keeping with the conclusions published by the most recent randomized controlled trials. High-quality studies show no significant difference in mortality, poor outcomes, or new pneumonia. In addition, this review shows a place for fever control in the management of traumatic brain injury.

1Departments of Anaesthesia and Critical Care, Western General Hospital, NHS Lothian, Edinburgh, United Kingdom.

2Departments of Anaesthesia and Critical Care, University of Edinburgh, Edinburgh, United Kingdom.

3The Centre for Clinical Brain Sciences, Edinburgh, United Kingdom.

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Dr. Rhodes received funding from Integra Life Science (Speakers Bureau), and he received funding from the National Health Service Research Scotland fellowship scheme. Dr. Andrews’ institution received funding from National Institute for Health Research (NIHR) Health Technology Assessment (HTA), he received funding from BARD Medical, he received support for article research from the NIHR HTA, and he received funding from NIHR, HTA project 11/01/30 Eurotherm3235 and is first author on this publication. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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