Safety and Efficacy of Acetaminophen in the Intensive Care Unit.
Condition: Critical Illness; Fever
MeSH terms: Critical Illness
Intervention: Acetaminophen; Placebo
Intervention description: one-time dose of acetaminophen 650mg given via the enteral route (via the gut); one-time dose of placebo (identical capsule) given via the enteral route (via the gut)
Intervention MeSH terms: Acetaminophen
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Fever; Acetaminophen; Body Temperature Regulation; Critical Illness; Hypotension

Summary:

      The intensive care unit (ICU) team needs to know what effects acetaminophen has in critically
      ill patients. Acetaminophen is better known as Tylenol. It is the drug given to reduce fever.
      Most research that has looked at how safe and effective this drug is, has been done with
      healthy people. Those studies tell us it is safe and works well to bring down fever.

      This may not be true for the ICU patient. Some research found acetaminophen was not as good
      at reducing fever as expected in the ICU. Fever helps to fight infection so it may help
      patients get better, but it is also stressful. When you have fever, you to need more oxygen,
      and your heart beats faster. If you have a fever after brain injury, you are less likely to
      make a full recovery. In patients with brain injury, a weak heart or trouble breathing we
      should treat fever. If we can predict how well acetaminophen will reduce fever, we can decide
      if this drug is enough, or other treatments are also needed.

      If you do not have problems with your brain, heart, or lungs, it is safe to not treat fever.
      When you give this drug to treat fever, the body cools itself by sweating, and bringing hot
      blood to the skin's surface. These changes do not affect healthy people. Research suggests
      ICU patients may be at risk for sudden drop in blood pressure.

      Our study will answer 2 questions: 1) When acetaminophen is given to treat fever in ICU
      patients, are they more likely to have a drop in blood pressure? 2) How much will
      acetaminophen reduce fever in ICU patients? We will study ICU patients with a fever who can
      safely get, or not get this drug. This information will help us decide when and how to treat
      fever in the ICU.
    

Eligibility criteria:

        Generally to be considered for this study one must be critically ill, febrile, and can
        safely either receive acetaminophen or have acetaminophen withheld. Also one must not have
        conditions that would alter normal drug absorption or normal thermoregulation. Specifically
        the eligibility criteria are:

        INCLUSION CRITERIA:

          -  Adult patients (> 18 years) admitted to Intensive Care Unit at Vancouver Hospital with
             a core temperature > 38.3 °C for 2 or more consecutive hours, but not longer than 48
             hours*

          -  Continuous arterial pressure monitor in place at the time of intervention and data
             collection

          -  Patients may only participate in the study once

          -  To remain in the ICU for the entire study period (2 hours prior to drug administration
             to 4 hours post drug administration)

        EXCLUSION CRITERIA:

          -  Significant liver dysfunction

          -  Acute neurological injury

          -  Seizure disorder

          -  Cardiomyopathy, elevated cardiac enzymes indicative of an acute cardiac injury,
             electrocardiogram (ECG) changes indicative of cardiac ischemia (i.e., ST segment
             elevation/depression)

          -  Hemodynamic instability (requiring fluid boluses, or change/initiation of
             vasopressors. Patients receiving steady doses of vasopressor support may be included)

          -  Severe hypoxemia, (fraction of inspired oxygen (FiO2) requirements of more than 60% to
             maintain hemoglobin oxygen saturation (SaO2) > 90% or partial pressure of oxygen in
             the blood (PaO2) > 70)

          -  Temperature > 40.0 °C

          -  Receiving external cooling

          -  Haemodialysis, plasma exchange, or any treatment where the blood is taken out of the
             body and processed

          -  Acute thermal injury to skin (i.e., burn)

          -  Gut malabsorption (i.e., receiving < 40% required calories enterally)

          -  Receiving medications that have known antipyretic effects (acetaminophen, ibuprofen,
             steroids, etc.)

          -  Physician opposed to enrolment in the study

        NOTE: in response to very low enrollment 2 exclusion criteria were changed on Nov 5, 2015.
        These were:

          1. patients no longer needed to recieve 40% of required calories enterally, instead
             patients who were not receiving any caloric intake via the gut could be enrolled as
             long as they were still permitted to receive oral medications.

          2. patients no longer had to have acetaminophen discontinued upon enrollment. They could
             not be receiving it regularly but could still receive acetaminophen on an as needed
             (PRN) basis as long as it could be safely withheld for up to 12 hours if they
             developed a fever.