Can Prophylactic Acetaminophen Prevent Hyperthermia in Acute Stroke?: Results of the Normothermia and Stroke Outcome (NOTHOT) Pilot Clinical Trial
Objective: To explore the safety and efficacy of round-the-clock acetaminophen administration to prevent hyperthermia in acute ischemic stroke patients. Background:Fever is a frequent occurrence among stroke patients and large cohort studies have identified early fever as an independent risk factor for poor functional outcome. Conventional management is to use antipyretics only in response to the appearance of fever. A pre-emptive strategy of prophylactic antipyretic therapy has not been previously studied. Methods:Sixteen consecutive patients presenting within 24 hrs of ischemic infarction were given acetaminophen 650mg q 4 hrs for 72 hrs or until discharge. Oral temperatures were recorded q 4 hrs. Cooling blankets were ordered for T >37.60 C. These results were contrasted with a historical control cohort of 16 consecutive patients who were admitted within 24 hrs of stroke onset treated with conventional reactive antipyretic therapy. Results:In the acetaminophen group, mean age was 71.4 and 62.5% were male. Mean admission NIHSS score was 8.9. Mean time from stroke onset to first dose of acetaminophen was 12.9 hrs. Mean temperature at presentation was 36.60 C for the acetaminophen group vs. 36.40 C for controls (p=NS). 44% of the acetaminophen group developed elevated body temperature vs. 40% of controls (p=NS). Mean temperature during the first 24 hrs of treatment with acetaminophen was 36.80 C vs. 36.80C for controls. Corresponding numbers for the second and third 24-hour periods were 36.90 C for the acetaminophen group vs. 37.10 C for controls (p=0.02) and 36.90 C for the acetaminophen group vs. 36.90 C for controls. Across the 72 hr treatment period, mean temperature was 36.90 C for the acetaminophen group vs. 37.00 C for controls (p=0.05). Conclusion:This pilot trial demonstrates acetaminophen administered round the clock significantly lowers average body temperature in the first 72 hrs after ischemic stroke. A randomized controlled clinical trial is needed to determine whether acetaminophen mediated body temperature lowering results in smaller infarct volume and improved clinical outcomes.