The Effect of Paracetamol on Core Body Temperature in Acute Traumatic Brain Injury: A Randomised, Controlled Clinical Trial

PLoS One. 2015 Dec 17;10(12):e0144740. doi: 10.1371/journal.pone.0144740. eCollection 2015.

Abstract

Background: Strategies to prevent pyrexia in patients with acute neurological injury may reduce secondary neuronal damage. The aim of this study was to determine the safety and efficacy of the routine administration of 6 grams/day of intravenous paracetamol in reducing body temperature following severe traumatic brain injury, compared to placebo.

Methods: A multicentre, randomised, blind, placebo-controlled clinical trial in adult patients with traumatic brain injury (TBI). Patients were randomised to receive an intravenous infusion of either 1g of paracetamol or 0.9% sodium chloride (saline) every 4 hours for 72 hours. The primary outcome was the mean difference in core temperature during the study intervention period.

Results: Forty-one patients were included in this study: 21 were allocated to paracetamol and 20 to saline. The median (interquartile range) number of doses of study drug was 18 (17-18) in the paracetamol group and 18 (16-18) in the saline group (P = 0.85). From randomisation until 4 hours after the last dose of study treatment, there were 2798 temperature measurements (median 73 [67-76] per patient). The mean ± standard deviation temperature was 37.4±0.5°C in the paracetamol group and 37.7±0.4°C in the saline group (absolute difference -0.3°C; 95% confidence interval -0.6 to 0.0; P = 0.09). There were no significant differences in the use of physical cooling, or episodes of hypotension or hepatic abnormalities, between the two groups.

Conclusion: The routine administration of 6g/day of intravenous paracetamol did not significantly reduce core body temperature in patients with TBI.

Trial registration: Australian New Zealand Clinical Trials Registry ACTRN12609000444280.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / administration & dosage
  • Acetaminophen / therapeutic use*
  • Adult
  • Antipyretics / administration & dosage
  • Antipyretics / therapeutic use*
  • Body Temperature / drug effects*
  • Brain Injuries / drug therapy*
  • Brain Injuries / physiopathology
  • Double-Blind Method
  • Female
  • Fever / prevention & control
  • Humans
  • Infusions, Intravenous
  • Male

Substances

  • Antipyretics
  • Acetaminophen

Associated data

  • ANZCTR/ACTRN12609000444280

Grants and funding

This work was supported by: Project grant from the Australia and New Zealand College of Anaesthetists (MS JM JG JL); Unrestricted grant from the St. George Medical research Foundation (The Honda-St. George Critical Care and Trauma Fellowship) (MS JM). The funders had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; or preparation, review, and approval of the manuscript.