What is the role of bromocriptine in treating central fever?

Bromocriptine for Central Fever

Bromocriptine is an effective treatment option for central fever in patients with neurological injuries when standard antipyretic measures have failed, with recent evidence showing a statistically significant temperature reduction of 0.3-0.7°C within 24-72 hours of initiation. 1

Understanding Central Fever

Central fever (also called neurogenic fever) is defined as core temperature >37.5°C driven by neurological dysregulation in the absence of sepsis or clinically significant inflammatory processes. It is relatively common in patients with brain injuries, occurring in approximately 25% of neurocritical care patients, with nearly half of fevers being non-infectious in etiology. 2

Key characteristics of central fever include:

• Rapid onset
• High temperatures (often >39°C)
• Marked temperature fluctuations
• Poor response to standard antipyretics and antibiotics
• No identifiable infectious source

Diagnostic Approach

Before diagnosing central fever, it's essential to rule out infectious causes:

• Complete infectious workup (blood cultures, urine cultures, chest imaging)
• CSF analysis if clinically appropriate and no contraindications
• Evaluation for other non-infectious causes (medications, DVT/PE)

Central fever should remain a diagnosis of exclusion. 2

Management Algorithm

1. First-line management:

   • Controlled normothermia targeting 36.0-37.5°C using automated feedback-controlled temperature management devices 2
   • Standard antipyretics (acetaminophen, NSAIDs)
   • External cooling measures (cooling blankets, ice packs)

2. If refractory to first-line measures:

   • Bromocriptine (dopamine receptor agonist)
     • Starting dose: 2.5-7.5 mg (median effective dose 7.5 mg) 1
     • Can be titrated up to 40 mg as needed 1
     • Typical duration: 5-160 days (median 13 days) 1

3. Alternative pharmacologic options:

   • Propranolol
   • Baclofen
   • Dantrolene (if NMS is suspected)

Evidence for Bromocriptine

The most recent and highest quality evidence comes from a 2023 retrospective cohort study of 33 patients with acute brain injury and suspected central fever 1:

• Temperature declined by 0.3°C at 24 hours, 0.5°C at 48 hours, and 0.7°C at 72 hours after bromocriptine initiation
• Median dose was 7.5 mg (range 2.5-40 mg)
• Median duration of treatment was 13 days (range 5-160 days)

A 2024 study of 30 patients (primarily with traumatic brain injury) showed:

• Mean temperature reduction of 0.37°C after bromocriptine initiation (p=0.005)
• Most common reason for discontinuation was resolution of fever (N=14)
• Low incidence of adverse events, with mild hepatotoxicity being most common 3

Several case reports have demonstrated successful management of intractable central fever with bromocriptine:

• A patient with thalamic hemorrhage extending to midbrain and ventricles had temperatures as high as 39.3°C that were controlled with bromocriptine 4
• A stroke patient with prolonged central hyperthermia showed reduction in fever baseline to 37°C within one week of bromocriptine initiation 5

Clinical Considerations

Monitoring

• Continuous temperature monitoring
• Regular assessment of neurological status
• Monitor for potential adverse effects:
  • Hepatotoxicity (most common)
  • Hypotension
  • Nausea/vomiting
  • Mental status changes

Duration of Treatment

• Continue until resolution of central fever
• Attempt gradual weaning once temperature has stabilized
• Be prepared for temperature fluctuations during weaning attempts 4

Importance of Treating Central Fever

Uncontrolled fever in patients with neurological injury:

• Precipitates secondary brain injury
• Is associated with worse outcomes
• Increases metabolic demand
• Can worsen intracranial pressure 2

Pitfalls and Caveats

1. Misdiagnosis: Ensure thorough infectious workup before attributing fever to central causes. Premature diagnosis can lead to missed infections and inappropriate antibiotic discontinuation.

2. Delayed treatment: Central fever should be promptly treated regardless of ICP levels, as it can worsen secondary brain injury. 2

3. Medication interactions: Bromocriptine is metabolized primarily in the liver. Use with caution in patients with hepatic impairment or those on multiple medications.

4. Monitoring requirements: Continuous temperature monitoring is essential to evaluate treatment efficacy and detect fluctuations.

5. Weaning difficulties: Abrupt discontinuation may lead to rebound hyperthermia. Consider gradual dose reduction.

Bromocriptine represents a valuable option for managing central fever when standard measures fail, with evidence supporting its efficacy and relatively favorable safety profile in the neurocritical care population.