Systematic review of randomized controlled trials of therapeutic hypothermia as a neuroprotectant in post cardiac arrest patients

Several randomized controlled trials have suggested that mild induced hypothermia may improve neurologic outcome in comatose cardiac arrest survivors. This systematic review of randomized controlled trials was designed to determine if mild induced hypothermia improves neurologic outcome, decreases mortality, or is associated with an increased incidence of adverse events. The following databases were reviewed: Cochrane Controlled Trials Register (Issue 4, 2005), MEDLINE (January 1966 to November 2005), EMBASE (1980 to November 2005), CINAHL (1982 to November 2005) and Web of Science (1989 to November 2005). For each included study, references were reviewed and the primary author contacted to identify any additional studies. Studies that met inclusion criteria were randomized controlled trials of adult patients (>18 years of age) with primary cardiac arrest who remained comatose after return of spontaneous circulation. Patients had to be randomized to mild induced hypothermia (32 degrees C-34 degrees C) or normothermia within 24 hours of presentation. Only studies reporting pre-determined outcomes including discharge neurologic outcome, mortality or significant treatment-related adverse events were included. There were no language or publication restrictions. Four studies involving 436 patients, with 232 cooled to a core temperature of 32 degrees C-34 degrees C met inclusion criteria. Pooled data demonstrated that mild hypothermia decreased in-hospital mortality (relative ratio [RR] 0.75; 95% confidence interval [CI], 0.62-0.92) and reduced the incidence of poor neurologic outcome (RR 0.74; 95% CI, 0.62-0.84). Numbers needed to treat were 7 patients to save 1 life, and 5 patients to improve neurologic outcome. There was no evidence of treatment-limiting side effects. Therapeutically induced mild hypothermia decreases in-hospital mortality and improves neurologic outcome in comatose cardiac arrest survivors. The possibility of treatment-limiting side effects cannot be excluded.