What is the best approach to manage hyperpyrexia?

Management of Hyperpyrexia

The best approach to managing hyperpyrexia depends critically on the underlying etiology: for malignant hyperthermia, immediately stop all triggering agents and administer dantrolene 2-3 mg/kg IV while initiating aggressive cooling measures; for post-cardiac arrest or neurological injury, treat hyperthermia (≥37.6°C) with antipyretics and active cooling; for infection-related hyperpyrexia, use standard antipyretics with surface cooling while addressing the underlying infection. 1, 2

Immediate Recognition and Etiology Determination

The first critical step is rapid identification of the cause, as management differs fundamentally:

• Malignant hyperthermia presents with excessive CO2 production (rising end-tidal CO2 despite increased ventilation), tachycardia, and eventual muscle rigidity—temperature may rise late but rapidly if untreated 1, 3
• Infection-related hyperpyrexia (≥41.1°C/106°F) accounts for 94% of cases in hospitalized patients, with common bacteria or fungi being the most frequent causes 4
• Post-cardiac arrest hyperthermia occurs in up to 50% of patients within 48 hours and is strongly associated with poor neurological outcomes 5, 2

Malignant Hyperthermia Protocol (Highest Priority)

If malignant hyperthermia is suspected, this is a life-threatening emergency requiring immediate action:

Eliminate Triggering Agents

• Stop all volatile anesthetics and succinylcholine immediately 5, 3
• Remove the vaporizer and insert activated charcoal filters on both inspiratory and expiratory limbs of the circuit 1, 3
• Hyperventilate with 100% oxygen at maximum flow, using 2-3 times normal minute ventilation 5, 3
• Declare an emergency and call for help—multiple personnel are needed 5, 3

Dantrolene Administration (Cornerstone of Treatment)

• Administer dantrolene 2-3 mg/kg IV immediately as the initial dose 1, 3
• Reconstitute each 20 mg vial with 60 mL sterile water (requires vigorous shaking up to 5 minutes) 3
• Continue additional 1 mg/kg boluses until end-tidal CO2 falls below 6 kPa and core temperature drops below 38.5°C 3
• Maximum doses may exceed 10 mg/kg—do not hesitate to use adequate amounts 5

Aggressive Cooling Measures

• Infuse 2000-3000 mL of chilled (4°C) 0.9% saline IV 5, 2
• Apply wet, cold sheets with fans, and place ice packs in axillae and groin 5, 2
• Stop cooling once temperature falls below 38.5°C 5

Critical Monitoring

• Establish arterial line and central venous catheter for invasive monitoring 3, 2
• Monitor serum potassium, creatine kinase, myoglobin, arterial blood gases, and renal function 5, 3
• Treat hyperkalemia with calcium chloride 0.1 mmol/kg IV and dextrose 50% with insulin 5, 3
• Monitor for at least 24 hours in ICU/HDU setting 5, 3

Post-Cardiac Arrest and Neurological Injury

For patients after return of spontaneous circulation or with acute brain injury:

• Treat hyperthermia (≥37.6°C) aggressively as it is associated with worse neurological outcomes and increased mortality 5, 2
• Use antipyretics and consider active cooling in unconscious patients 5, 2
• Maintain targeted temperature management at normothermia (36-37.5°C) 2
• Avoid strict glucose control but maintain blood glucose ≤10 mmol/L (180 mg/dL) to prevent hypoglycemia 5

Infection-Related Hyperpyrexia

For hyperpyrexia secondary to infection (the most common cause):

• Administer pharmacologic antipyretics (acetaminophen or NSAIDs) 2, 6
• Apply surface cooling with cold/wet sheets and fans, or cooling blankets 2, 6
• Provide volume expansion and hemodynamic support 6
• Initiate appropriate antimicrobial therapy—infection is treatable in 90% of hyperpyrexic patients 4
• Avoid tepid sponging and ice packs directly on skin as they induce shivering and vasoconstriction 7

Acute Ischemic Stroke Context (Important Caveat)

The evidence for treating hyperthermia in acute ischemic stroke is notably weak:

• For patients with acute ischemic stroke and hyperthermia, there is insufficient evidence to recommend treating hyperthermia specifically to improve functional outcome or survival 5
• Routine prevention of hyperthermia with antipyretics in normothermic stroke patients is not recommended for improving outcomes 5
• However, treating hyperthermia for patient comfort and identifying/treating the underlying cause (infection, aspiration) remains standard of care 5

General Cooling Techniques

When active cooling is indicated:

• Use intravascular cooling with chilled IV saline (2-3 L at 4°C) 2
• Apply evaporative cooling by wetting body surface with continuous fanning 2
• Employ cooling blankets or intravascular cooling catheters if available 2
• Maintain continuous core temperature monitoring (rectal, esophageal, or bladder) 2

Complications to Monitor

• Rhabdomyolysis and acute kidney injury: Maintain high urine output >2 mL/kg/h with furosemide and mannitol 5, 2
• Compartment syndrome: Monitor limbs for swelling and measure compartmental pressures if suspected 2
• Electrolyte disturbances: Particularly hyperkalemia requiring aggressive treatment 5, 2
• Arrhythmias: Treat with amiodarone 300 mg IV or beta-blockers if tachycardia persists 5, 3

Critical Pitfalls to Avoid

• Never delay treatment while awaiting diagnostic confirmation—early intervention is critical for survival 1
• Do not assume malignant hyperthermia is ruled out because temperature has not yet risen significantly—rising end-tidal CO2 is often the first sign 1
• Avoid inadequate dantrolene dosing—use sufficient amounts and continue until clinical parameters normalize 1, 3
• Do not use tepid sponging or direct ice application as these induce counterproductive shivering and vasoconstriction 7