Author Affiliations: Division of Intensive Care, Department of Medicine, The Ottawa Hospital, General Campus, University of Ottawa, Ottawa, Ontario (Dr McIntyre); University of Ottawa Centre for Transfusion Research, Clinical Epidemiology Program, Ottawa Health Research Institute, Ottawa, Ontario (Dr Fergusson); Division of Intensive Care, Department of Medicine, the Ottawa Hospital, University of Ottawa, (Dr Hébert), Chalmers Research Group, Children's Hospital of Eastern Ontario Research Institute and Departments of Pediatrics and Epidemiology & Community Medicine, University of Ottawa (Mr Moher); and Departments of Critical Care and Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario (Dr Hutchison).
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
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authors of identified studies were contacted for additional unpublished or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
McIntyre LA, Fergusson DA, Hébert PC, Moher D, Hutchison JS. Prolonged Therapeutic Hypothermia After Traumatic Brain Injury in Adults: A Systematic Review. JAMA. 2003;289(22):2992–2999. doi:10.1001/jama.289.22.2992
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