HEAT (acetaminophen)
Trial question
What is the role of acetaminophen in fever among critically ill patients with suspected infection?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
35.0% female
65.0% male
N = 691
691 patients (242 female, 449 male).
Inclusion criteria: patients with fever (temperature ≥ 38 °C) and known or suspected infection.
Key exclusion criteria: pregnancy, clinically significant rhabdomyolysis, moribund, requirement for ongoing use of non-steroidal anti-inflammatory drugs, AST or ALT > 5 times the ULN, or bilirubin > 2 times the ULN, or any other contraindication to 4 g acetaminophen/day.
Interventions
N=347 acetaminophen (an infusion containing 1 g of intravenous acetaminophen, every 6 hours).
N=344 placebo (an infusion of 5% dextrose in water, every 6 hours).
Primary outcome
ICU-free days to day 28
23 days
22 days
23.0 days
17.3 days
11.5 days
5.8 days
0.0 days
Acetaminophen
Placebo
No significant
difference ↔
No significant difference in ICU-free days to day 28 (23 days vs. 22 days; AD 1 days, 95% CI -0.08 to 2.08).
Secondary outcomes
No significant difference in the rate of death by 90 days (15.9% vs. 16.6%; RR 0.96, 96% CI 0.66 to 1.39).
No significant difference in length of ICU stay (4.1 days vs. 4.2 days; AD -0.1 days, 95% CI -0.7 to 0.4).
No significant difference in hospital length of stay (13.7 days vs. 13.8 days; AD -0.01 days, 95% CI -1.6 to 1.6).
Safety outcomes
No significant difference in liver dysfunction leading to discontinuation of the drug.
Conclusion
In patients with fever (temperature ≥ 38 °C) and known or suspected infection, acetaminophen was not superior to placebo with respect to a ICU-free days to day 28.
Reference
Young P, Saxena M, Bellomo R et al. Acetaminophen for Fever in Critically Ill Patients with Suspected Infection. N Engl J Med. 2015 Dec 3;373(23):2215-24.
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