How does impaired thermoregulation in a patient with a history of neurological conditions or brain injuries contribute to central fever?

Thermoregulation and Central Fever in Brain Injury

How Normal Thermoregulation Works

The hypothalamus serves as the body's thermostat, maintaining core temperature around 37°C through a balance of heat production and heat loss mechanisms. 1 When the hypothalamus detects temperature changes, it triggers responses like shivering (to generate heat) or sweating and vasodilation (to dissipate heat). 2

How Brain Injury Disrupts Thermoregulation

Central fever occurs when direct damage to the hypothalamus and its thermoregulatory pathways causes neurological dysregulation of temperature control, resulting in core temperatures >37.5°C without any infection or inflammatory process present. 1 This is fundamentally different from typical fever—the brain's temperature control center itself is broken, not responding to an infection. 3

Key Mechanisms of Disruption:

• Direct hypothalamic damage from traumatic brain injury, stroke, or other neurological insults destroys the temperature-regulating centers 1
• The injured brain loses its ability to properly sense and respond to temperature changes, leading to persistent, non-cyclic temperature elevations 4
• Unlike infectious fevers that spike and resolve in patterns, central fever presents as sustained elevation without the typical daily cycling 4

Why Central Fever Causes Secondary Brain Injury

Once central fever develops, it creates a vicious cycle that worsens brain injury through multiple harmful mechanisms, regardless of whether the fever originated from infection or neurological dysregulation. 3

Specific Pathways of Harm:

• Increased metabolic demands: The feverish brain requires more oxygen and glucose when it's already struggling from injury 1, 5
• Enhanced excitatory neurotransmitter release: Elevated temperature increases glutamate and other damaging chemicals 1
• Increased free radical production: Heat accelerates oxidative stress that kills neurons 1
• Elevated intracranial pressure: Fever increases cerebral blood flow and brain volume, raising pressure inside the skull 3, 5
• Higher brain metabolic rate of oxygen and altered CO2 control: These physiological derangements compound the injury 3

Clinical Significance in Neurological Patients

Central fever is remarkably common in traumatic brain injury, occurring in 4-37% of TBI survivors, and is consistently associated with increased complications and unfavorable outcomes. 1 The 2024 ESICM/NACCS consensus guidelines achieved 100% agreement that uncontrolled fever can precipitate secondary brain injury in severe TBI patients. 3

Critical Distinction from Other Conditions:

• Central fever must be differentiated from neuroleptic malignant syndrome, which presents with muscle rigidity, elevated creatine phosphokinase, and association with antipsychotic medications—features absent in central fever 1
• However, this differentiation should not delay treatment, as the harmful effects on the injured brain occur regardless of fever source 3

Management Approach

Controlled normothermia targeting 36.0-37.5°C should be initiated reactively when fever is detected in sedated and ventilated severe TBI patients, using automated feedback-controlled temperature management devices rather than relying on antipyretics alone. 3, 5

Why Aggressive Temperature Control Matters:

• Antipyretics like acetaminophen or NSAIDs have limited efficacy in severe TBI and should only serve as adjuncts during induction, not primary management 3, 5
• Temperature control must be precise: maintain variations ≤±0.5°C per hour and ≤1°C per 24-hour period 3, 5
• Continue normothermia for as long as the brain remains at risk of secondary injury, particularly during the acute phase 3, 5
• Brain temperature can be up to 2°C higher than systemic temperature and may vary independently, making central monitoring (bladder, esophageal, or brain temperature probes) essential over peripheral methods 5

Common Pitfall:

The most critical error is undertreatment—studies show that despite guidelines, only 31% of fever events in TBI patients receive documented nursing intervention, and patients are more likely to reach dangerously high temperatures (>40°C) than to maintain normothermia. 6 This gap between evidence and practice persists even though we know fever worsens outcomes. 6