What is the role of baclofen in managing central fever?

Baclofen in Central Fever

Baclofen is an effective treatment option for central fever (neurogenic hyperthermia) following severe brainstem injury, with case reports demonstrating successful temperature normalization at doses ranging from 30-60 mg/day when conventional antipyretics fail. 1, 2, 3

Mechanism and Rationale

• Baclofen, a GABA-B receptor agonist, appears to restore thermoregulatory function in patients with central fever caused by brainstem lesions affecting hypothalamic temperature control pathways 1, 3
• The exact mechanism for temperature reduction remains incompletely understood, but anecdotal evidence supports its efficacy in this indication 2

Clinical Evidence

The strongest evidence comes from multiple case reports demonstrating successful treatment:

• A 46-year-old female with pontine hemorrhage achieved temperature normalization after escalating baclofen from 30 mg/day to 60 mg/day, with body temperature dropping from a fluctuating range of 37.5-39.2°C to normal 1
• A 68-year-old female with basilar artery occlusion and refractory hyperthermia (temperatures fluctuating 35.5-40.0°C despite water-cooling blankets) achieved stable normothermia with baclofen 30 mg/day 3
• A 12-year-old post-hemispherotomy patient with fever reaching 39°C responded to baclofen titrated from 5 mg/day to 20 mg/day, remaining afebrile for 10 months 4

Dosing Strategy

Start with baclofen 30 mg/day in divided doses for adults, with gradual titration based on response:

• Initial dose: 30 mg/day (or 5 mg/day in pediatric patients) 1, 4
• Titrate upward if inadequate response, up to 60 mg/day in adults 1
• Monitor temperature response over several days before dose escalation 1, 3

Critical Safety Considerations

Abrupt discontinuation of baclofen is potentially catastrophic and must be avoided:

• Baclofen withdrawal syndrome manifests with high fever, altered mental status, hallucinations, delirium, seizures, tachycardia, rebound spasticity, and muscle rigidity 5
• Intrathecal baclofen withdrawal is life-threatening, leading to rhabdomyolysis, multiorgan failure, and death 5
• Withdrawal typically evolves over 1-3 days but may become fulminant if not recognized 5
• Even oral baclofen withdrawal can cause severe symptoms including fever, which could be confused with recurrent central fever 6

Diagnostic Prerequisites

Central fever is a diagnosis of exclusion—rule out infectious and inflammatory causes first:

• Exclude infectious sources through appropriate cultures, imaging, and laboratory workup 4
• Rule out aseptic meningitis in post-neurosurgical patients 4
• Consider central fever when hyperthermia persists despite empirical antibiotics and conventional antipyretics fail 1, 3
• The presence of severe brainstem lesions (pontine hemorrhage, basilar artery occlusion, hemispherotomy) supports the diagnosis 1, 4, 3

Common Pitfalls

• Do not abruptly discontinue baclofen once initiated, as withdrawal fever may be mistaken for treatment failure 5, 6
• Avoid premature escalation—allow adequate time (several days) to assess response at each dose level 1
• Continue baclofen perioperatively in patients already receiving it to prevent withdrawal syndrome 5
• Be aware that baclofen overdose can cause coma and respiratory depression, requiring careful dose titration 6

Alternative Considerations

While baclofen shows the most consistent evidence for central fever, other agents have been reported with significant heterogeneity in dosing and outcomes:

• Bromocriptine and propranolol have anecdotal support but lack standardized protocols 2
• The variation in underlying pathology and absence of comparative data make definitive recommendations for these alternatives difficult 2