Effects of Intravenous Acetaminophen on Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults
Condition: Fever; Critical Illness
MeSH terms: Critical Illness
Intervention: Acetaminophen; Placebo
Intervention description: acetaminophen 1 gram/100mLs intravenously administered over 15 minutes; Normal saline placebo Normal saline 100 mLs intravenous, administered over 15 minutes
Intervention MeSH terms: Acetaminophen
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 41.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Fever; Acetaminophen; Critical Care; ICU; Febrile

Summary:

      The purpose of this study is to compare the effects of intravenous acetaminophen to placebo
      on body temperature and hemodynamic (heart rate and blood pressure) responses in febrile
      critically ill adult patients.

      There are limited data to explain the variable and unpredictable antipyretic and hemodynamic
      response to acetaminophen in febrile ICU patients. The complex pathophysiology of critically
      ill patients, co-morbid conditions, the effect of multiple pharmacologic and
      non-pharmacologic care interventions, and/or the potential interferences with absorption of
      enteral or rectal formulations may be related to variations in the antipyretic response to
      acetaminophen. It is necessary for clinicians to have a better understanding of the therapy
      response and potential adverse effects of this commonly administered medication, especially
      the recently available IV formulation, in critically ill patients. Further research of the
      antipyretic response to acetaminophen in critically ill patients is warranted to inform
      evidence-based practice guidelines for fever management. Further randomized,
      placebo-controlled studies of hemodynamic responses to IV acetaminophen are also warranted.

      Primary Hypothesis:

      There is a significant reduction in time-weighted average core body temperature over 4 hours
      after administration of IV acetaminophen compared to placebo in febrile critically ill
      patients.

      Secondary Hypotheses:

        1. There is a significant reduction in time-weighted average heart rate over 4 hours after
           administration of IV acetaminophen compared to placebo in febrile critically ill
           patients.

        2. There is a significant reduction in time-weighted mean arterial pressure over 4 hours
           after administration of IV acetaminophen compared to placebo in febrile critically ill
           patients.

      Adult patients with fever (≥ 38.3ºCentigrade/101ºFarenheit) in the intensive care unit will
      be screened for eligibility and enrolled after informed consent. Patients will be randomized
      to receive IV acetaminophen 1 gram or normal saline 100 mLs. Body temperature, heart rate,
      and blood pressure will be measured at baseline and during the 4 hours post study drug
      administration.
    

Eligibility criteria:

        Inclusion Criteria:

          -  18 years of age and older

          -  Patient in an intensive care unit

          -  Weight greater or equal to 50 kgs

          -  Fever: core body temperature greater than or equal to 38.3 degrees Celsius

          -  Clinically stable: no active resuscitation with fluids, blood products, or dose
             increases of vasoactive medications within 1 hour of study drug administration

        Exclusion Criteria:

          -  Acetaminophen hypersensitivity

          -  Acute liver failure or acute liver injury

          -  Heat stroke, malignant hyperthermia, neuroleptic malignant syndrome

          -  Therapeutic cooling, physical cooling, extracorporeal blood circuit therapies

          -  Administration of acetaminophen-containing medications, non-steroidal
             anti-inflammatory drugs, or aspirin greater than 81 mg within specified times per drug
             prior to fever presentation