What is the appropriate management for a patient with central fever?

Management of Central Fever

Central fever should be managed by first aggressively ruling out infectious causes through systematic diagnostic workup, then treating with antipyretics (acetaminophen 1000 mg every 4-6 hours) for symptomatic relief, and reserving servo-regulated cooling devices only for refractory cases unresponsive to pharmacologic measures. 1, 2

Diagnostic Workup: Rule Out Infection First

Central fever is a diagnosis of exclusion that can only be made after infectious and inflammatory causes are eliminated. 1 Missing an infection while treating presumed central fever can be fatal. 2

Mandatory initial investigations include:

• Chest radiograph for all ICU patients with new fever, as pneumonia is the most common infectious cause 3, 1, 2
• Blood cultures (at least two sets, 60 mL total) before any antibiotic changes 1, 2
• Simultaneous central and peripheral blood cultures if a central venous catheter is present 3, 1
• CT imaging (thoracic, abdominal, or pelvic) for patients with recent surgery if fever persists without identified etiology 3, 1, 2
• Abdominal ultrasound or CT for patients with abdominal symptoms, abnormal liver function tests, or recent abdominal surgery 3

Confirming Central Fever Diagnosis

Central fever is defined as core temperature >37.5°C driven by neurological dysregulation without evidence of sepsis or clinically significant inflammatory processes. 1 It occurs most commonly after traumatic brain injury (4-37% of cases), subarachnoid hemorrhage, intracerebral hemorrhage, or ischemic stroke affecting thermoregulatory regions. 1, 4

Key distinguishing features:

• Persistent temperature elevations without cyclic pattern 1
• Absence of infectious source after thorough workup 1, 4
• Presence of CNS injury affecting hypothalamic thermoregulatory pathways 1
• Core temperature >37.5°C without sepsis criteria 1

Pharmacologic Management

First-line treatment: Acetaminophen

• Dose: 1000 mg orally every 4-6 hours (maximum 4 g/day) 1, 2
• Reduce to 2 g/day maximum in hepatic insufficiency, alcohol abuse, malnutrition, or fasting 2
• Contraindicated in acute liver failure 5
• Use for symptomatic relief and patient comfort, not merely to reduce temperature 3, 1, 5

The Society of Critical Care Medicine recommends against routine antipyretic use solely for temperature reduction in critically ill patients, as fever suppression does not improve mortality or clinical outcomes. 3, 5 However, for patients who value comfort, antipyretics are preferred over non-pharmacologic cooling methods. 3

Second-line for refractory cases: Bromocriptine

While not explicitly recommended in major guidelines, bromocriptine has been reported effective for intractable central hyperthermia unresponsive to antipyretics. 6 This should only be considered after ensuring acetaminophen is optimally dosed and infectious causes are definitively excluded. 2

Non-Pharmacologic Cooling

Servo-regulated cooling devices should be employed ONLY for refractory fevers unresponsive to pharmacologic measures, NOT as first-line therapy. 1, 2

When to use:

• Temperature exceeds 37.7°C (99.9°F) despite optimal acetaminophen dosing 2
• Set device to target 37.5°C (99.5°F) with continuous central temperature monitoring 2
• Use automated feedback-controlled devices, which are superior to antipyretics alone for severe traumatic brain injury 1

Avoid basic physical cooling methods (tepid sponging, fanning) as they cause significant discomfort, increase metabolic demand through shivering, and do not improve outcomes. 2

Temperature Monitoring

Preferred methods:

• Central temperature monitoring (pulmonary artery catheter thermistors, bladder catheters, esophageal balloon thermistors) when devices are already in place or accurate measurements are critical 3, 2, 5
• Oral or rectal temperatures when central monitoring unavailable 3, 2, 5
• Avoid unreliable methods (axillary, tympanic membrane, temporal artery, chemical dot thermometers) 3, 2, 5

Special Considerations for Intracerebral Hemorrhage

For patients with spontaneous intracerebral hemorrhage, pharmacologically treating elevated temperature may be reasonable to improve functional outcomes. 3, 1 However, therapeutic hypothermia (<35°C/95°F) to decrease peri-ICH edema has unclear benefit. 3

Target Temperature Goals

For severe traumatic brain injury:

• Target normothermia: 36.0-37.5°C 1
• Uncontrolled fever precipitates secondary brain injury through increased metabolic demands, enhanced excitatory neurotransmitter release, increased free radical production, and elevated intracranial pressure 1
• Urgent management required in acute phase when patient remains at significant risk of secondary brain injury 1

Critical Pitfalls to Avoid

• Never delay identification and treatment of underlying infection while focusing on temperature control 2, 5
• Do not add vancomycin empirically for persistent fever alone without clinical deterioration 2
• Do not switch empirical antibiotics without clinical or microbiologic indication 2
• Persistent fever alone in a hemodynamically stable patient is NOT an indication to change or add antibiotics empirically 2
• Do not confuse central fever with neuroleptic malignant syndrome, which presents with muscle rigidity, elevated creatine phosphokinase, and antipsychotic medication use 1

Hemodynamic Management in TBI Patients

When managing fever in severe TBI with tachycardia:

• Maintain systolic blood pressure >110 mmHg at all times 1
• Use vasopressors (phenylephrine, norepinephrine) if hypotension develops during tachycardia management 1
• Hypotension worsens neurological outcomes and increases mortality 1