Impact of Fever on Outcome in Patients With Stroke and Neurologic Injury

Background and Purpose— Many studies associate fever with poor outcome in patients with neurological injury, but this relationship is blurred by divergence in populations and outcome measures. We sought to incorporate all recent scholarship addressing fever in brain-injured patients into a comprehensive meta-analysis to evaluate disparate clinical findings. Methods— We conducted a Medline search for articles since January 1, 1995 (in English with abstracts, in humans) and hand searches of references in bibliographies and review articles. Search terms covered stroke, neurological injury, thermoregulation, fever, and cooling. A total of 1139 citations were identified; we retained 39 studies with 67 tested hypotheses contrasting outcomes of fever/higher body temperature and normothermia/lower body temperature in patients with neurological injury covering 14431 subjects. A separate meta-analysis was performed for each of 7 outcome measures. Significance was evaluated with Zc developed from probability values or t values. Correlational effect size, r (es) , was calculated for each study and used to derive Cohen’s d unbiased combined effect size and relative risk. Results— Fever or higher body temperature was significantly associated with worse outcome in every measure studied. Relative risk of worse outcome with fever was: mortality, 1.5; Glasgow Outcome Scale, 1.3; Barthel Index, 1.9; modified Rankin Scale, 2.2; Canadian Stroke Scale, 1.4; intensive care length of stay, 2.8; and hospital length of stay, 3.2. Conclusions— In the pooled analyses covering 14431 patients with stroke and other brain injuries, fever is consistently associated with worse outcomes across multiple outcome measures.