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From the Neurological Intensive Care Unit, Division of Stroke and Critical Care, Department of Neurology (A.F., M.S., J.C., D.H., K.T.K., N.D.O., R.G.K., A.P., S.A.M.), and the Department of Neurosurgery (A.P., E.S.C., S.A.M.), College of Physicians and Surgeons; and the Department of Biostatistics (M.P.), Mailman School of Public Health, Columbia University, New York, NY.
* To whom correspondence should be addressed. E-mail: sam14{at}columbia.edu.
Abstract-- Objective: To identify risk factors for refractory fever after subarachnoid hemorrhage (SAH), and to determine the impact of temperature elevation on outcome. Methods: We studied a consecutive cohort of 353 patients with SAH with a maximum daily temperature (Tmax) recorded on at least 7 days between SAH days 0 and 10. Fever (>38.3 °C) was routinely treated with acetaminophen and conventional water-circulating cooling blankets. We calculated daily Tmax above 37.0 °C, and defined extreme Tmax as daily excess above 38.3 °C. Global outcome at 90 days was evaluated with the modified Rankin Scale (mRS), instrumental activities of daily living (IADLs) with the Lawton scale, and cognitive functioning with the Telephone Interview of Cognitive Status. Mixed-effects models were used to identify predictors of Tmax, and logistic regression models to evaluate the impact of Tmax on outcome. Results: Average daily Tmax was 1.15 °C (range 0.04 to 2.74 °C). The strongest predictors of fever were poor Hunt-Hess grade and intraventricular hemorrhage (IVH) (both p < 0.001). After controlling for baseline outcome predictors, daily Tmax was associated with an increased risk of death or severe disability (mRS 
4, adjusted OR 3.0 per °C, 95% CI 1.6 to 5.8), loss of independence in IADLs (OR 2.6, 95% CI 1.2 to 5.6), and cognitive impairment (OR 2.5, 95% CI 1.2 to 5.1, all p 
0.02). These associations were even stronger when extreme Tmax was analyzed. Conclusion: Treatment-refractory fever during the first 10 days after subarachnoid hemorrhage (SAH) is predicted by poor clinical grade and intraventricular hemorrhage, and is associated with increased mortality and more functional disability and cognitive impairment among survivors. Clinical trials are needed to evaluate the impact of prophylactic fever control on outcome after SAH.
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