Acetaminophen for Altering Body Temperature in Acute Stroke

Abstract

Background and Purpose — Mild alterations in temperature have prominent effects on ischemic cell injury and stroke outcome. Elevated core body temperature (CBT), even if mild, may exacerbate neuronal injury and worsen outcome, whereas hypothermia is potentially neuroprotective. The antipyretic effects of acetaminophen were hypothesized to reduce CBT. Methods — This was a randomized, controlled clinical trial at 2 university hospitals. Patients were included if they had stroke within 24 hours of onset of symptoms, National Institutes of Health Stroke Scale (NIHSS) score ≥5, initial CBT <38.5°C, and white blood cell count <12 600 cells/mm 3 ; they were excluded if they had signs of infection, severe medical illness, or contraindication to acetaminophen. CBT was measured every 30 minutes. Patients were randomized to receive acetaminophen 650 mg or placebo every 4 hours for 24 hours. The primary outcome measure was mean CBT during the 24-hour study period; the secondary outcome measure was the change in NIHSS. Results — Thirty-nine patients were randomized. Baseline CBT was the same: 36.96°C for acetaminophen versus 36.95°C for placebo ( P =0.96). During the study period, CBT tended to be lower in the acetaminophen group (37.13°C versus 37.35°C), a difference of 0.22°C (95% CI, −0.08°C to 0.51°C; P =0.14). Patients given acetaminophen tended to be more often hypothermic <36.5°C (OR, 3.4; 95% CI, 0.83 to 14.2; P =0.09) and less often hyperthermic >37.5°C (OR, 0.52; 95% CI, 0.19 to 1.44; P =0.22). The change in NIHSS scores from baseline to 48 hours did not differ between the groups ( P =0.93). Conclusions — Early administration of acetaminophen (3900 mg/d) to afebrile patients with acute stroke may result in a small reduction in CBT. Acetaminophen may also modestly promote hypothermia <36.5°C or prevent hyperthermia >37.5°C. These effects are unlikely to have robust clinical impact, and alternative or additional methods are needed to achieve effective thermoregulation in stroke patients.