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Meta-Analysis
. 2017 Sep 21;9(9):CD001048.
doi: 10.1002/14651858.CD001048.pub5.

Hypothermia for traumatic brain injury

Sharon R Lewis  1 , David Jw Evans, Andrew R Butler, Oliver J Schofield-Robinson, Phil Alderson
Affiliations
Meta-Analysis

Hypothermia for traumatic brain injury

Sharon R Lewis et al. Cochrane Database Syst Rev. .

Abstract

Background: Hypothermia has been used in the treatment of brain injury for many years. Encouraging results from small trials and laboratory studies led to renewed interest in the area and some larger trials.

Objectives: To determine the effect of mild hypothermia for traumatic brain injury (TBI) on mortality, long-term functional outcomes and complications.

Search methods: We ran and incorporated studies from database searches to 21 March 2016. We searched the Cochrane Injuries Group's Specialised Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase Classic+Embase (OvidSP), PubMed, ISI Web of science (SCI-EXPANDED, SSCI, CPCI-S & CPSI-SSH), clinical trials registers, and screened reference lists. We also re-ran these searches pre-publication in June 2017; the result from this search is presented in 'Studies awaiting classification'.

Selection criteria: We included randomised controlled trials of participants with closed TBI requiring hospitalisation who were treated with hypothermia to a maximum of 35 ºC for at least 12 consecutive hours. Treatment with hypothermia was compared to maintenance with normothermia (36.5 to 38 ºC).

Data collection and analysis: Two review authors assessed data on mortality, unfavourable outcomes according to the Glasgow Outcome Scale, and pneumonia.

Main results: We included 37 eligible trials with a total of 3110 randomised participants; nine of these were new studies since the last update (2009) and five studies had been previously excluded but were re-assessed and included during the 2017 update. We identified two ongoing studies from searches of clinical trials registers and database searches and two studies await classification.Studies included both adults and children with TBI. Most studies commenced treatment immediately on admission to hospital or after craniotomies and all treatment was maintained for at least 24 hours. Thirty-three studies reported data for mortality, 31 studies reported data for unfavourable outcomes (death, vegetative state or severe disability), and 14 studies reported pneumonia. Visual inspection of the results for these outcomes showed inconsistencies among studies, with differences in the direction of effect, and we did not pool these data for meta-analysis. We considered duration of hypothermia therapy and the length of follow-up in collected data for these subgroups; differences in study data remained such that we did not perform meta-analysis.Studies were generally poorly reported and we were unable to assess risk of bias adequately. Heterogeneity was evident both in the trial designs and participant inclusion. Inconsistencies in results may be explained by heterogeneity among study participants or bias introduced by individual study methodology but we did not explore this in detail in subgroup or sensitivity analyses. We used the GRADE approach to judge the quality of the evidence for each outcome and downgraded the evidence for mortality and unfavourable outcome to very low. We downgraded the evidence for the pneumonia outcome to low.

Authors' conclusions: Despite a large number studies, there remains no high-quality evidence that hypothermia is beneficial in the treatment of people with TBI. Further research, which is methodologically robust, is required in this field to establish the effect of hypothermia for people with TBI.

PubMed Disclaimer

Conflict of interest statement

Phil Alderson: None known

Sharon R Lewis: None known

David JW Evans: None known

Andrew R Butler: None known

Oliver J Schofield‐Robinson: None known

Figures

1
1
Study flow diagram.
2
2
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all 37 included studies.
3
3
Risk of bias summary: review authors' judgements about each risk of bias item for each included study. Note: blank spaces in risk of bias table indicate that the relevant outcome was not reported by study authors
4
4
Funnel plot of comparison 1: Therapeutic cooling versus no cooling, outcome: 1.1 Mortality.
1.1
1.1. Analysis
Comparison 1 Therapeutic cooling versus no cooling, Outcome 1 Mortality.
1.2
1.2. Analysis
Comparison 1 Therapeutic cooling versus no cooling, Outcome 2 Unfavourable outcome.
1.3
1.3. Analysis
Comparison 1 Therapeutic cooling versus no cooling, Outcome 3 Pneumonia.
2.1
2.1. Analysis
Comparison 2 Therapeutic cooling versus no cooling: by duration, Outcome 1 Mortality.
2.2
2.2. Analysis
Comparison 2 Therapeutic cooling versus no cooling: by duration, Outcome 2 Unfavourable outcome.
2.3
2.3. Analysis
Comparison 2 Therapeutic cooling versus no cooling: by duration, Outcome 3 Pneumonia.
3.1
3.1. Analysis
Comparison 3 Therapeutic cooling versus no cooling: by length of follow‐up, Outcome 1 Mortality.
3.2
3.2. Analysis
Comparison 3 Therapeutic cooling versus no cooling: by length of follow‐up, Outcome 2 Unfavourable outcome.
See this image and copyright information in PMC

Update of

References

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References to studies excluded from this review

ACTRN12615001119583p {published data only}
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Gál 2012 {published data only}
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