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Prolonged Therapeutic Hypothermia After Traumatic Brain Injury in Adults A Systematic Review

Lauralyn A. McIntyre, MD; Dean A. Fergusson, MHA, PhD; Paul C. Hébert, MD, MHSc; David Moher, MSc; James S. Hutchison, MD
JAMA. 2003;289(22):2992-2999. doi:10.1001/jama.289.22.2992.
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Published online

Context The benefits of therapeutic hypothermia as a treatment for traumatic brain injury (TBI) remain unclear.

Objective To explore the effects of depth, duration, and rate of rewarming after discontinuation of hypothermia on mortality and neurologic outcome in adults after TBI.

Data Sources An electronic search of MEDLINE (OVID), EMBASE, Current Contents, the Cochrane library and a hand search of key journals were performed. Corresponding authors of identified studies were contacted for additional unpublished or ongoing clinical trials.

Study Selection All randomized controlled trials of therapeutic hypothermia for at least 24 hours vs normothermia in adults with TBI.

Data Extraction Demographic and clinical data, hypothermia interventions and cointerventions, mortality and neurologic outcomes, and methodological quality were abstracted by 2 independent reviewers.

Data Synthesis Twelve trials met eligibility criteria and were included in the analysis. We also performed subanalyses by different hypothermia interventions (ie, depth, duration, and rapidity of rewarming after hypothermia) and methodological quality. Therapeutic hypothermia was associated with a 19% reduction in the risk of death (95% confidence interval [CI], 0.69-0.96) and a 22% reduction in the risk of poor neurologic outcome (95% CI, 0.63-0.98) compared with normothermia. Hypothermia longer than 48 hours was associated with a reduction in the risks of death and of poor neurologic outcome (relative risk [RR], 0.70; 95% CI, 0.56-0.87 and RR, 0.65; 95% CI, 0.48-0.89, respectively) compared with normothermia. Hypothermia to a target temperature between 32°C and 33°C, a duration of 24 hours, and rewarming within 24 hours were all associated with reduced risks of poor neurologic outcome compared with normothermia. Assessment of methodological quality did not reveal evidence of bias.

Conclusions Therapeutic hypothermia may reduce the risks of mortality and poor neurologic outcome in adults with TBI. Outcomes were influenced, however, by depth and duration of hypothermia as well as rate of rewarming (≤24 hours) after discontinuation of hypothermia. Nonetheless, the evidence is not yet sufficient to recommend routine use of therapeutic hypothermia for TBI outside of research settings.

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Figure 1. Study Selection Process
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RCTs indicates randomized controlled trials.
Figure 2. Mortality in Therapeutic Hypothermia
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Figure 3. Mortality According to Different Hypothermia Interventions
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Figure 4. Poor Neurologic Outcome for Therapeutic Hypothermia*
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*Poor neurologic outcome is defined as severe disability or vegetative state or death according the Glasgow Outcome Scale score.
Figure 5. Poor Neurologic Outcome According to Different Hypothermia Interventions*
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*Poor neurologic outcome is defined as severe disability or vegetative state or death according the Glasgow Outcome Scale score.



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