"Acetaminophen for Fever in Critically Ill Patients with Suspected Infection".The New England Journal of Medicine. 2015. 373(23):2215-2224.PubMed•Full text•PDF

Contents

1Clinical Question
2Bottom Line
3Major Points
4Guidelines
5Design
6Population
6.1Inclusion Criteria
6.2Exclusion Criteria
6.3Baseline Characteristics
7Interventions
8Outcomes
8.1Primary Outcome
8.2Secondary Outcomes
9Funding
10Further Reading

Clinical Question

In critically ill patients with fever and suspected infection, does acetaminophen affect the number of ICU-free days?

Bottom Line

In critically ill patients with fever and suspected infection, early administration of acetaminophen did not affect the number of ICU-free days compared to placebo.

Major Points

Fever in ICU patients with infections is commonly treated with acetaminophen, although its utility and impacts on patient outcomes are unclear. In a randomized controlled trial, acetaminophen did not increase ICU-free days and had no significant effect on mortality or other secondary outcomes.

Guidelines

Current guidelines do not provide specific recommendations regarding the use of acetaminophen in this context.

Design

- Multicenter, double-blind, randomized, controlled trial
- N=700
- Acetaminophen (n=352) vs. Placebo (n=348)
- Setting: 23 ICUs in Australia and New Zealand
- Enrollment: February 2013 to July 2014
- Follow-Up: 90 days
- Analysis: Intention-to-treat
- Primary outcome: number of ICU-free days to day 28
- Australian New Zealand Clinical Trials Registry number: ACTRN12612000513819

Population

Inclusion Criteria
- Age ≥16 years with body temperature ≥38°C
- Known or suspected infection with antimicrobial therapy

Exclusion Criteria
- Acute brain diseases
- Liver dysfunction contraindicating acetaminophen use

Baseline Characteristics
- Demographic and clinical characteristics were similar between groups.
- Most common infection sites were lungs and abdomen.

Interventions

- Intravenous acetaminophen 1g or placebo every 6 hours

Outcomes

Primary Outcome
- ICU-free days to day 28: 23 days (acetaminophen) vs. 22 days (placebo); P=0.07

Secondary Outcomes
- 28-day mortality: 15.9% (acetaminophen) vs. 16.6% (placebo); P=0.84
- 90-day mortality: Same as 28-day mortality
- Hospital length of stay and survival time to day 90: No significant difference

Funding

- Health Research Council of New Zealand
- Australian and New Zealand Intensive Care Foundation
- Waikato Medical Research Foundation

Further Reading

Results initially published on October 5, 2015, at NEJM.org with full author affiliations and disclosure forms.

Supplementary Material
Detailed statistical analyses and additional materials included.