Impact of fever on outcome in patients with stroke and neurologic injury: a comprehensive meta-analysis.
OBJECTIVE
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.
Greer
David M
DM
Department of Neurology, ACC 835, Massachusetts General Hospital, Boston, MA 02114, USA. dgreer@partners.org
Funk
Susan E
SE
Reaven
Nancy L
NL
Ouzounelli
Myrsini
M
Uman
Gwen C
GC
D000293:Adolescent; D000328:Adult; D001831:Body Temperature; D001930:Brain Injuries / Q000150:complications*; D002675:Child, Preschool; D005260:Female; D005334:Fever / Q000209:etiology / Q000628:therapy; D006801:Humans; D016239:MEDLINE; D008297:Male; D008875:Middle Aged; D020521:Stroke / Q000150:complications*; D016896:Treatment Outcome