What is the treatment for hyperpyrexia?

Treatment of Hyperpyrexia

Immediately stop all triggering agents, administer dantrolene 2-3 mg/kg IV for malignant hyperthermia, and initiate aggressive cooling measures with chilled IV saline and external cooling methods while treating the underlying cause. 1, 2, 3

Immediate Recognition and Initial Actions

The first priority is determining whether hyperpyrexia represents malignant hyperthermia (MH), which requires immediate specific treatment:

• Stop all volatile anesthetics and succinylcholine immediately if MH is suspected, as these are triggering agents 1, 4
• Remove the vaporizer and insert activated charcoal filters on both inspiratory and expiratory limbs of the breathing circuit 2, 4
• Hyperventilate with 100% oxygen at maximum flow (2-3 times normal minute ventilation) to reduce end-tidal CO2 1, 2, 4
• Declare an emergency and call for help, as multiple personnel will be needed 1, 4

Critical pitfall: Do not wait for temperature elevation to diagnose MH—unexplained increase in end-tidal CO2 despite increased ventilation is often the first sign, and temperature may rise late 2

Dantrolene Administration (For Malignant Hyperthermia)

Dantrolene is the specific antidote for malignant hyperthermia and must be given immediately:

• Administer an initial bolus of 2-3 mg/kg IV as rapidly as possible 1, 2, 5, 3
• Continue with additional 1 mg/kg boluses until end-tidal CO2 falls below 6 kPa (45 mmHg), core temperature drops below 38.5°C, and metabolic abnormalities resolve 1, 4
• The maximum cumulative dose may reach 10 mg/kg or higher if symptoms persist 1, 3
• Reconstitute each 20 mg vial with 60 mL sterile water (requires vigorous shaking for up to 5 minutes) and administer immediately upon preparation 4, 3
• Have at least 36-50 vials available for an adult patient, obtaining additional supplies from pharmacy or nearby hospitals 1

The FDA label confirms that dantrolene works by interfering with calcium release from the sarcoplasmic reticulum, reestablishing normal myoplasmic calcium levels 3

Aggressive Cooling Measures

Active cooling must be initiated simultaneously with dantrolene:

Intravascular Cooling

• Infuse 2000-3000 mL of chilled (4°C) 0.9% saline IV rapidly 1, 2, 5
• Consider intravascular cooling catheters if available 5

External Cooling

• Apply wet, cold sheets with continuous fanning for evaporative cooling 1, 5, 6
• Place ice packs in the axillae, groin, and neck 1, 2
• Use cooling blankets or other available cooling devices 1, 5
• Stop cooling once temperature falls below 38.5°C to avoid overcooling 1

Important note: Evaporative cooling (wet sheets with fans) is more effective than conduction methods and is the recommended approach based on military and civilian experience 6

Comprehensive Monitoring

Establish invasive monitoring immediately:

• Insert arterial line and central venous catheter for hemodynamic monitoring 1, 5, 4
• Place urinary catheter and maintain urine output >2 mL/kg/hour 1
• Monitor core temperature continuously (rectal, esophageal, or bladder) 1, 5
• Obtain arterial blood gases, serum potassium, creatine kinase, myoglobin, glucose, and coagulation studies 1, 5, 4
• Check renal and hepatic function serially 1
• Monitor for compartment syndrome by examining limbs for swelling 1, 5

Treatment of Metabolic Complications

Hyperkalemia

• Administer calcium chloride 0.1 mmol/kg IV (e.g., 7 mmol = 10 mL for 70 kg adult) 1, 4
• Give dextrose 50% (50 mL) with 50 units insulin for adults 1, 4
• Consider dialysis if refractory 1, 4

Metabolic Acidosis

• Hyperventilate to normocapnia 1, 4
• Administer sodium bicarbonate IV if pH <7.2 1, 4

Arrhythmias

• Give amiodarone 300 mg IV (3 mg/kg) for adults 1, 4
• Consider beta-blockers (propranolol/metoprolol/esmolol) if tachycardia persists 1, 4

Maintain Renal Function

• Administer furosemide 0.5-1 mg/kg 1
• Give mannitol 1 g/kg 1
• Maintain high urine output with crystalloid fluids (lactated Ringer's or 0.9% saline) 1

Context-Specific Considerations

Post-Cardiac Arrest Hyperpyrexia

• Treat hyperthermia (≥37.6°C) aggressively with antipyretics and active cooling in unconscious patients, as it is associated with worse neurological outcomes 1, 2
• Maintain blood glucose ≤10 mmol/L (180 mg/dL) but avoid strict glucose control due to hypoglycemia risk 1
• The development of hyperthermia after cardiac arrest is associated with increased mortality and poor neurological outcomes 1

Acute Ischemic Stroke

Important caveat: For stroke patients with hyperthermia, current evidence does not support treating fever specifically to improve functional outcome or survival, though antipyretics may be given for patient comfort 1

Non-MH Hyperpyrexia (Infection, Heatstroke)

• Use pharmacologic antipyretics (acetaminophen, NSAIDs) for all causes except MH 5
• For heatstroke, rapid cooling to <38.5°C is the primary treatment with external cooling methods and hemodynamic support 5
• Recognize that 94% of hyperpyrexia cases in hospitalized adults are associated with infection, often with common bacteria or fungi, and antimicrobial therapy is indicated in the majority 7

Post-Crisis Management

• Monitor in ICU or high-dependency unit for at least 24 hours after crisis resolution 1, 4
• Administer oral dantrolene 4-8 mg/kg/day in divided doses for 1-3 days following MH crisis to prevent recurrence 3
• Alternatively, use IV dantrolene postoperatively starting at 1 mg/kg when oral administration is not practical 3
• Refer patients with suspected MH and their blood relatives for specialized testing (in vitro contracture testing) and genetic counseling 1, 4
• Provide comprehensive counseling about future anesthetic management and the need to warn all blood relatives 4

Critical Pitfalls to Avoid

• Do not delay treatment while awaiting diagnostic confirmation—early intervention is critical for survival 2
• Do not fail to recognize MH because temperature has not yet risen significantly—other signs (increased ETCO2, tachycardia, rigidity) appear first 2
• Do not underdose dantrolene—continue until symptoms resolve, which may require exceeding the traditional 10 mg/kg maximum 1, 2
• Do not use acidic solutions (5% dextrose, 0.9% saline for reconstitution) with dantrolene as they are incompatible 3
• Do not implement strict glucose control in post-cardiac arrest patients as it increases hypoglycemia risk without survival benefit 1