Effect of Paracetamol (Acetaminophen) on Body Temperature in Acute Ischemic Stroke

Abstract

on Behalf of the PAPAS InvestigatorsBackground and Purpose-Body temperature is a strong predictor of outcome in acute stroke. However, it is unknown whether antipyretic treatment leads to early and clinically worthwhile reduction of body temperature in patients with acute stroke, especially when they have no fever. The main purpose of this trial was to study whether early treatment of acute ischemic stroke patients with acetaminophen (paracetamol) reduces body temperature. Methods-Seventy-five patients with acute ischemic stroke confined to the anterior circulation were randomized to treatment with either 500 mg (low dose) or 1000 mg (high dose) acetaminophen or with placebo, administered as suppositories 6 times daily during 5 days. Body temperatures were measured with a rectal electronic thermometer at the start of treatment and after 24 hours and with an infrared tympanic thermometer at 2-hour intervals during the first 24 hours and at 6-hour intervals thereafter. The primary outcome measure was rectal temperature at 24 hours after the start of treatment. Results-Treatment with high-dose acetaminophen resulted in 0.4°C lower body temperatures than placebo treatment at 24 hours (95% CI 0.1°C to 0.7°C). The mean reduction from baseline temperature with high-dose acetaminophen was 0.3°C (95% CI 0°C to 0.6°C) higher than that in placebo-treated patients. Treatment with low-dose acetaminophen did not result in lower body temperatures. After 5 days of treatment, no differences in temperature were found between the placebo and the high-or low-dose acetaminophen groups. Conclusions-Treatment with a daily dose of 6000 mg acetaminophen may result in a small, but potentially beneficial, decrease in body temperature shortly after ischemic stroke, even in normothermic and subfebrile patients. Further studies should determine whether this effect is reproducible and whether early reduction of body temperature leads to improved outcome. (Stroke. 2001;32:1607-1612.)

Stroke pathophysiology: management challenges and new treatment advances

“…In this observational study, 51% of patients taking these drugs had a good outcome compared with 38% of those not taking statins (83). Another study (18) included patients with stroke of which 18% were using statins when admitted. Better prognosis at 3 months was significantly more frequent in the statin group, indicating that these drugs may provide benefits for the long-term functional outcome when administered before the onset of cerebral ischemia.…”

“…New surface cooling devices, such as energy-transferring skin pads (48), may demonstrate a reduction in the time to target temperature and allow better temperature control. In a pilot trial (17), treatment with paracetamol at 6 grams daily, compared with placebo, led to a 0.3 ºC reduction in body temperature in normothermic patients. This temperature reduction is of potential but unproven clinical benefit.…”

Systemic Infections After Acute Stroke

“…The harmful effects of fever have been attributed to increased metabolic demands, changes in permeability of the blood-brain barrier, acidosis and an increased release of neurotransmitters [73,78]. Studies using animal models of focal and global ischemia have demonstrated that cerebral hyperthermia (over 39°C) can lead to larger infarct volume and more severe histological outcome [73,[79][80][81].…”

Management following resuscitation from cardiac arrest: Recommendations from the 2003 Rocky mountain critical care conference

“…17 Two randomized trials have evaluated acetaminophen in stroke patients and reported small decreases in core body temperature even in normothermic patients. 18,19 Acetaminophen may modestly promote hypothermia < 36.5°C or prevent hyperthermia > 37.5°C. 15 Unfortunately, the clinical significance of this effect appears small.…”

“…Multiple techniques of hypothermia induction have been published including: application of ice packs; 5 surface cooling with cooled forced-air, 4,20 or circulating water blankets; 18,19 infusion of 4°C iv fluids; [26][27][28] immersion in cold water; 29 specialized endovascular cooling devices; 21,30,31 and cardiopulmonary bypass. 32 No trials comparing hypothermia techniques in cardiac arrest patients have been published.…”