Clinical trial NCT01869699: Effects of Intravenous Acetaminophen on Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults
Official title: Effects of Intravenous Acetaminophen on Body Temperature and Hemodynamic Responses in Febrile Critically Ill Adults: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fever
Critical Illness
Keywords: Fever
Acetaminophen
Critical Care
ICU
Febrile
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
First posted: 2013-06-05
Enrollment: 41
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: Adult patients with fever (≥ 38.3ºCentigrade (C)/101ºFarenheit(F)) in the intensive care unit will be screened for eligibility and approached for informed consent. Enrolled patients will be stratified based on the leading etiology of their fever: either neurologic injury or infection and then randomized to receive IV acetaminophen 1 gram or normal saline 100 milliliters (mLs). Core body temperature will be measured using a zero-heat flow thermometry system (non-invasive, small disk on forehead). Patients will be monitored and data collected during the 4-hour post study drug administration period. A rescue protocol will be implemented if the temperature reaches ≥ 40 ºC during the study period and includes notification of primary team provider by the nurse and the pharmacist will contact them to inform the provider of study group (acetaminophen or placebo). The provider can decide whether to order antipyretic medication or physical cooling interventions at that time.

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

Primary outcomes:
measure: Core Body Temperature
timeFrame: Baseline to 4 hours post study drug administration
Secondary outcomes:
measure: Heart Rate
timeFrame: Baseline to 4 hours post study drug administration
measure: Systolic Blood Pressure
timeFrame: Baseline to 4 hours post study drug administration
measure: Respiratory Rate
timeFrame: Baseline to 4 hours post study drug administration
measure: 2-hour Change Over Time Core Temperature
timeFrame: 2 hours
measure: 2-hour Change Over Time Systolic Blood Pressure
timeFrame: Baseline to 2 hours
measure: 2-hour Change Over Time Heart Rate
timeFrame: Baseline to 2 hours
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Medical Center
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco Medical Center
state: California
Study officials:
affiliation: University of California, San Francisco
name: Kathleen A. Puntillo, PhD
role: PRINCIPAL_INVESTIGATOR
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