Evaluating Different Bromocriptine Doses for Central Fever in the Intensive Care Unit Maggie Nobles, Zackery Moreo, Sam Pournezhad, Chelsea Wamsley
[email protected] Grady Health System Department of Pharmacy
Background: Central fever is a diagnosis of exclusion characterized by persistent, noninfectious hyperthermia that is unresponsive to antipyretics and antimicrobial therapy. It is commonly observed in patients with acute neurologic injury and is thought to result from disruption of hypothalamic thermoregulatory pathways. Central fever has been associated with increased metabolic demand, prolonged ICU length of stay, and worse neurologic outcomes. Bromocriptine, a dopamine-2 receptor agonist, has been used off-label for central fever due to its ability to reduce hypothalamic set point and sympathetic activity. While prior studies support its antipyretic efficacy, there is limited evidence guiding optimal dosing strategies. This study aimed to evaluate the effectiveness of different bromocriptine doses for central fever in critically ill patients with neurologic injury to inform dosing decisions and institutional practice.
Methods: This single-center, retrospective chart review was conducted at an academic safety-net hospital and included adult patients (≥18 years) admitted to the neurocritical care unit or surgical-trauma ICU between January 2023 and June 2025. Eligible patients received at least one dose of bromocriptine 2.5 mg, 5 mg, or 10 mg for suspected central fever. Patients were excluded if they had evidence of active infection, prior bromocriptine use before admission, death within 48 hours of bromocriptine initiation, or belonged to a protected population. Baseline demographic and clinical characteristics, neurologic diagnoses, and use of potential confounding therapies were collected. The primary outcome was fever resolution, defined as a temperature of ≤ 38.3°C within 2 hours of the initial bromocriptine dose, compared across initial dose groups. Secondary outcomes included sustained fever resolution at 8, 24, and 48 hours, assessed according to total daily bromocriptine dose.
Results: A total of 274 patients were screened; 47 met inclusion criteria for the primary outcome analysis. Baseline characteristics were largely similar across groups, though differences in neurologic diagnosis and ICU admission location were observed. Fever resolution within 2 hours occurred in 78.6% of patients receiving an initial dose of 2.5 mg, compared with 37.5% in the 5 mg group and 47.1% in the 10 mg group. Fever resolution within 2 hours was significantly more frequent with 2.5 mg compared with 5 mg (p=0.024), while no statistically significant differences were observed between the 2.5 mg and 10 mg groups (p=0.073) or between the 5 mg and 10 mg groups (p=0.579). Secondary outcomes were similar across total daily dose groups, with no significant differences observed in sustained fever resolution at 8, 24, or 48 hours. Duration of therapy tended to increase with higher daily doses, though this did not reach statistical significance. No differences were observed in ICU length of stay or in-hospital mortality.
Conclusion: More patients achieved fever resolution within 2 hours with the 2.5 mg dose, while no differences were observed between dose groups in sustained fever control. These findings suggest that bromocriptine’s antipyretic effect may not be dose dependent, and that lower initial dosing strategies may be reasonable for the management of central fever. Prospective studies are needed to further define optimal dosing strategies and evaluate safety outcomes.
