The purpose of this study is to evaluate the antipyretic effect of bromocriptine in critically-ill patients with acute neurologic injury and fever from infectious and non-infectious etiologies.
In patients with acute neurologic injury such as subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), traumatic brain injury (TBI), subdural hematoma (SDH), and ischemic stroke, fever has been found to be an independent predictor of poor outcome including increased mortality rates, longer hospital stays, depressed level of consciousness, and worse functional outcomes. Our current antipyretic therapy of acetaminophen and sometimes nonsteroidal anti-inflammatory drugs are not very effective and external cooling requires sedatives and other medications to prevent shivering and pain. Bromocriptine is a dopamine D2 receptor agonist which acts at the hypothalamus, a specific area of the brain that regulates body temperature. Fevers of both central and infectious etiologies must be regulated through the hypothalamus and we have evidence that bromocriptine has an antipyretic effect at the hypothalamus; thus, we hypothesize that bromocriptine could be used safely and more broadly to treat all fevers in the acute setting and not just refractory central fevers in this patient population. Here, we propose to evaluate the acute antipyretic effects of bromocriptine in this critically-ill population through a pilot, open label, blinded endpoint, randomized controlled trial. In both enrolling centers, University of California, San Francisco Medical Center Parnassus (UCSF) and Zuckerberg San Francisco General Hospital, every patient who is admitted to the neurointensive care unit for an anticipated stay of greater than 48 hours with a diagnosis of subarachnoid hemorrhage (SAH), intracerebral hemorrhage (ICH), traumatic brain injury (TBI), subdural hematoma (SDH), and ischemic stroke will be screened and consented. If they have a temperature reading ≥ 38.3 ºC, the investigational pharmacy will randomize them to the control arm of acetaminophen or the intervention arm of acetaminophen and bromocriptine for 48 hours. We will continuously measure their temperature and other vitals data. Retrospectively, we will review imaging and labs ordered to work up infectious etiologies of fever. The ICU nurse will do a 5 minute assessment every shift during the 48 hour study period for side effects. The temperature data will be analyzed between the two study arms.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
47
Bromocriptine 5 mg every 4 hours PO/NG/FT
Acetaminophen 650 mg every 4 hours PO/NG/FT for 48 hours
Zuckerberg San Francisco General Hospital and Trauma Center
San Francisco, California, United States
University of California, San Francisco Medical Center - Parnassus
San Francisco, California, United States
Temperature Burden
Mean total body temperature burden above 37°C over 48 hours during which patient receives either control or intervention medication.
Time frame: over 48 hours
Incidence of Adverse Events - Symptomatic Hypotension, Nausea and Headache
Episodes of symptomatic hypotension, including decrease in supine systolic and diastolic pressures of greater than 20mm and 10mm Hg respectively with patient reported accompanying symptoms of light headedness or dizziness and incidence of nausea and headache.
Time frame: Nursing assessment at every shift during 48 hour study period after first drug administration
Total Time That Temperature is ≥ 38.3ºC
Time in minutes where the temperature is ≥ 38.3ºC during the 48 hours of control versus intervention administration.
Time frame: 48 hours
Total Time to First Temperature < 37.5ºC
Time in minutes it took after medication administration for the temperature to reach \< 37.5ºC.
Time frame: 48 hours
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.