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Effects of IV Acetaminophen on Core Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults: A Randomized Controlled Trial

Schell-Chaple, Hildy M. PhD, RN, FAAN1; Liu, Kathleen D. PhD, MD2; Matthay, Michael A. MD2; Sessler, Daniel I. MD3; Puntillo, Kathleen A. PhD, RN, FAAN, FCCM4

doi: 10.1097/CCM.0000000000002340
Clinical Investigations

Objective: To determine the effects of IV acetaminophen on core body temperature, blood pressure, and heart rate in febrile critically ill patients.

Design: Randomized, double-blind, placebo-controlled clinical trial.

Setting: Three adult ICUs at a large, urban, academic medical center.

Patients: Forty critically ill adults with fever (core temperature, ≥ 38.3°C).

Intervention: An infusion of acetaminophen 1 g or saline placebo over 15 minutes.

Measurement and Main Results: Core temperature and vital signs were measured at baseline and at 5–15-minute intervals for 4 hours after infusion of study drug. The primary outcome was time-weighted average core temperature adjusted for baseline temperature. Secondary outcomes included adjusted time-weighted average heart rate, blood pressure, and respiratory rate, along with changes-over-time for each. Baseline patient characteristics were similar in those given acetaminophen and placebo. Patients given acetaminophen had an adjusted time-weighted average temperature that was 0.47°C less than those given placebo (95% CI, –0.76 to –0.18; p = 0.002). The acetaminophen group had significantly lower adjusted time-weighted average systolic blood pressure (–17 mm Hg; 95% CI, –25 to –8; p < 0.001), mean arterial pressure (–7 mm Hg; 95% CI, –12 to –1; p = 0.02), and heart rate (–6 beats/min; 95% CI, –10 to –1; p = 0.03). Changes-over-time temperature, blood pressure, and heart rate outcomes were also significantly lower at 2 hours, but not at 4 hours.

Conclusions: Among febrile critically ill adults, treatment with acetaminophen decreased temperature, blood pressure, and heart rate. IV acetaminophen thus produces modest fever reduction in critical care patients, along with clinically important reductions in blood pressure.

1University of California, San Francisco (UCSF) School of Nursing, San Francisco, CA.

2UCSF School of Medicine, San Francisco, CA.

3Department of Outcomes Research, Cleveland Clinic, Anesthesiology Institute, Cleveland, OH.

4UCSF School of Nursing, San Francisco, CA.

This work was performed at the University of California, San Francisco Medical Center, UCSF School of Nursing, and UCSF School of Medicine.

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Supported, in part, by grant from University of California, San Francisco Graduate Student Research Award supplemented investigational pharmacy costs.

Dr. Schell-Chaple received funding from University of California, San Francisco Graduate Student Research Award. Her institution received funding from Gordon and Betty Moore Foundation. Dr. Matthay’s institution received funding from GlaxoSmithKline (sepsis grant) and Amgen (acute lung injury grant experimental). He received funding from consulting from Bayer, Boehringer Ingelheim, Quark Pharmaceuticals, Incardia, Biogen, GlaxoSmithKline, Biomarck, Thesaris, and from Roche-Genentech for being Chair of a data safety monitoring board for clinical trials of asthma. Dr. Sessler’s institution received funding from Cadence, which was purchased by Mallinckrodt, which is now part of Covidien. Dr. Puntillo received funding from Elsevier publications and from Society of Critical Care Medicine. Dr. Liu has disclosed that she does not have any potential conflicts of interest.

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