What are the management and treatment options for central fever in patients with a history of traumatic brain injury, stroke, or multiple sclerosis?

Neurologic Conditions and Procedures Associated with Central Fever

Definition and Core Concept

Central fever (neurogenic fever) is defined as core temperature >37.5°C driven by neurological dysregulation in the absence of sepsis or clinically significant inflammatory processes, and it represents a diagnosis of exclusion after infectious and other non-infectious causes have been ruled out. 1, 2

Primary Neurologic Conditions Associated with Central Fever

Traumatic Brain Injury (TBI)

• TBI is the most common cause of central fever, occurring in 4-37% of TBI survivors, particularly with injuries affecting the hypothalamus and thermoregulatory pathways. 2, 3
• Central fever is especially common in severe TBI with intraventricular hemorrhage, diffuse axonal injury, and brainstem involvement. 4
• Patients with decorticate or decerebrate posturing and autonomic dysfunction (tachycardia, profuse sweating) are at highest risk for developing central fever. 4

Stroke and Intracranial Hemorrhage

• Ischemic stroke affecting temperature-regulating regions (particularly hypothalamic and brainstem areas) commonly causes central fever. 2
• Subarachnoid hemorrhage has one of the highest incidences of fever in neurosurgical ICU populations, with >50% of patients developing fever. 5
• Hemorrhagic stroke (including pontine hemorrhage) is associated with fever in >50% of ICU admissions. 6, 5
• Intraventricular hemorrhage specifically increases risk of central fever development. 4

Other Neurologic Conditions

• Central nervous system infections (though these typically cause infectious rather than central fever, they are associated with >50% fever incidence). 5
• Seizure disorders requiring ICU admission have >50% incidence of fever episodes. 5
• Patients with prolonged ICU stays (>14 days) develop fever in 93% of cases compared to 15% in those staying <24 hours. 5

Procedures and Anatomic Locations Associated with Central Fever

High-Risk Surgical Procedures

• Neurosurgical procedures involving the hypothalamus or brainstem carry highest risk for central fever development. 2
• Patients admitted for cranial disease have significantly higher fever rates compared to spinal disorders (>50% versus 27%). 5

Critical Anatomic Structures

• Hypothalamic damage is the primary anatomic substrate for central fever, as this region controls thermoregulatory pathways. 2, 7
• Brainstem involvement is strongly associated with central fever, particularly with autonomic dysregulation. 7, 4

Clinical Characteristics Distinguishing Central Fever

Key Diagnostic Features

• Core temperature >37.5°C without evidence of infection or inflammatory processes. 1, 2
• Persistent temperature elevations without cyclic patterns (unlike infectious fever which typically has diurnal variation). 2
• Associated with autonomic dysfunction: tachycardia, profuse sweating, and abnormal posturing. 4
• Absence of typical infectious markers: negative cultures, no clear infectious source despite thorough workup. 1, 2

Distinguishing from Other Fever Syndromes

• Unlike neuroleptic malignant syndrome: central fever lacks muscle rigidity, elevated creatine phosphokinase, and antipsychotic medication exposure. 2
• Unlike malignant hyperthermia: central fever is not triggered by anesthetic agents and has different pathophysiology (central dysregulation versus peripheral muscle dysfunction). 2

Management Approach for Central Fever

Diagnostic Workup (Must Complete Before Diagnosis)

• Obtain chest radiograph for all ICU patients with new fever. 2, 6
• Collect at least two sets of blood cultures (60 mL total); if central line present, obtain simultaneous central and peripheral cultures. 2
• Consider CT imaging for patients with recent thoracic, abdominal, or pelvic surgery. 2
• Lumbar puncture if neurological symptoms warrant and not contraindicated. 2, 6

Temperature Control Strategy

For TBI patients with central fever, implement controlled normothermia targeting 36.0-37.5°C using automated feedback-controlled temperature management devices, as this approach prevents secondary brain injury regardless of fever source. 1, 3

Tiered Management Algorithm for TBI

Tier Zero (not ICP dependent, treat core temperature >38.0°C): 1

• Sedation, endotracheal intubation, mechanical ventilation
• Maintain CPP >60 mmHg
• SpO2 >94% and Hb >7 g/dL
• Consider EEG monitoring and seizure prophylaxis

Tier 1 (controlled normothermia 36.0-37.5°C): 1, 3

• Titrate sedation and analgesia to control ICP
• CPP 60-70 mmHg
• PaCO2 35-38 mmHg
• Consider osmotherapy and external ventricular drainage

Tier 2 (controlled normothermia 36.0-37.5°C): 1

• Individualized CPP goals
• PaCO2 32-35 mmHg
• Consider neuromuscular blocker

Tier 3 (mild hypothermia 35.0-36.0°C): 1

• Consider decompressive craniectomy
• Consider barbiturate coma

Pharmacologic Interventions

• Antipyretics (acetaminophen/NSAIDs) have limited efficacy in controlling central fever in severe TBI and should only be used as adjuncts during induction phase, not as primary management. 3, 6
• Propranolol 20-30 mg every 6 hours has been reported to reduce central fever by at least 1.5°C within 48 hours in TBI patients with autonomic dysfunction, though this is based on limited case series evidence. 4
• Dantrolene should NOT be used as first-line treatment for central fever; it is reserved for suspected neuroleptic malignant syndrome or malignant hyperthermia. 2

Temperature Monitoring Requirements

• Use central temperature monitoring (bladder catheter, esophageal thermistor, or pulmonary artery catheter) when available. 2, 6
• When central monitoring unavailable, use oral or rectal temperatures rather than axillary or tympanic measurements. 2, 6
• Continuous monitoring is preferable to intermittent measurements. 3, 6
• Maintain temperature with minimal variation (≤±0.5°C per hour, ≤1°C per 24 hours). 3, 6

Duration of Treatment

• Continue controlled normothermia for as long as the brain remains at risk of secondary brain injury, particularly during the acute phase. 3
• While some controlled pyrexia may be allowed during subacute phase, uncontrolled fever requires urgent management in acute phase. 1

Critical Clinical Pitfalls

Common Errors to Avoid

• Do not rely solely on antipyretics for temperature control in severe TBI—they are insufficient and ineffective as monotherapy. 3
• Do not delay treatment while searching for fever source; the deleterious effects of hyperthermia occur regardless of whether temperature is raised due to infection or impaired thermoregulation. 1, 6
• Do not discontinue temperature control prematurely while the brain remains at risk of secondary injury. 3
• Do not confuse central fever with neuroleptic malignant syndrome—premature treatment with dantrolene while missing an infection can worsen outcomes. 2

High-Risk Patient Populations Requiring Aggressive Management

• Patients with severe TBI with impending herniation or obliterated basal cisterns require more aggressive temperature management. 1
• Patients with low ICP and preserved intracranial compliance may tolerate less aggressive interventions, but temperature control remains important. 1
• TBI patients with seizures or high seizure risk require particularly careful fever control. 3

Pathophysiologic Rationale for Aggressive Management

Uncontrolled fever precipitates secondary brain injury through multiple mechanisms: increased brain metabolic rate of oxygen, enhanced release of excitatory neurotransmitters, increased free radical production, elevated intracranial pressure, and increased cerebral blood flow and volume. 1, 2, 3

• These deleterious effects occur regardless of whether fever is infectious or neurogenic in origin, making prompt temperature control essential even while diagnostic workup continues. 1
• Central fever is associated with increased risk of complications and unfavorable neurologic outcomes in multiple studies. 1, 3
• Brain temperature can be up to 2°C higher than systemic temperature and may vary independently based on pathology characteristics. 3