What is malignant hyperthermia and how is it managed?

Malignant Hyperthermia: Definition and Management

Malignant hyperthermia is a life-threatening hypermetabolic crisis triggered by volatile anesthetic agents and succinylcholine in genetically susceptible individuals, requiring immediate cessation of triggers, aggressive dantrolene administration (2-3 mg/kg IV initially), hyperventilation with 100% oxygen, and active cooling to prevent mortality. 1

What is Malignant Hyperthermia?

Malignant hyperthermia is a pharmacogenetic disorder of skeletal muscle characterized by uncontrolled calcium release from the sarcoplasmic reticulum, leading to sustained muscle contraction and a hypermetabolic state 2. The condition has an autosomal dominant inheritance pattern with genetic prevalence estimated as high as 1:2,000 to 1:3,000 in the general population, though clinical incidence ranges from 1:10,000 to 1:250,000 anesthetics 1, 2.

Triggering Agents

The specific triggers that must be avoided include 1:

• All volatile (inhalational) anesthetic agents (halothane, sevoflurane, desflurane, isoflurane)
• Succinylcholine (depolarizing muscle relaxant)

Importantly, local anesthetics, non-depolarizing muscle relaxants, nitrous oxide, propofol, and other intravenous agents do NOT trigger MH 3.

Clinical Recognition

The earliest and most specific sign is an unexplained, progressive increase in end-tidal CO₂ (ETCO₂) despite increased minute ventilation 1, 3. This is the critical diagnostic clue that should immediately raise suspicion.

Other early signs include 1, 3:

• Tachycardia (often >100 bpm, can exceed 190 bpm)
• Masseter spasm following succinylcholine administration
• Generalized muscle rigidity (particularly concerning if occurring despite non-depolarizing neuromuscular blockade)

Later manifestations include 1:

• Hyperthermia (temperature can exceed 41°C/105.8°F, but occurs later in progression)
• Metabolic acidosis (respiratory and metabolic components)
• Hyperkalaemia (can be severe and life-threatening)
• Arrhythmias
• Rhabdomyolysis with elevated creatine kinase and myoglobinuria

A critical pitfall: hyperthermia is NOT an early sign—waiting for temperature elevation before treating will increase mortality 1, 3. Any patient can develop MH during or shortly after anesthesia with trigger agents, even if they have had previous uneventful anesthetics 1.

Immediate Crisis Management

Step 1: Eliminate Trigger Agents (Within Seconds)

Stop all volatile anesthetics and succinylcholine immediately 1, 4. The specific actions are 1, 4:

• Turn off and remove the vaporizer from the anesthetic machine
• Do not waste time changing the entire circuit or machine
• Insert activated charcoal filters on both inspiratory and expiratory limbs to rapidly adsorb residual volatile agents
• Switch to total intravenous anesthesia (TIVA) with non-triggering agents
• Hyperventilate with 100% oxygen at maximum flow (2-3 times normal minute ventilation)
• Inform the surgeon and request immediate termination or postponement of surgery
• Declare an emergency and call for help (multiple personnel needed)

Step 2: Administer Dantrolene Sodium

Dantrolene is the specific antidote and cornerstone of treatment 1, 4. The Association of Anaesthetists (2021) provides the most recent dosing guidance 1:

Initial dose: 2-3 mg/kg IV 1, 4

• Each 20 mg vial requires reconstitution with 60 mL sterile water
• Vigorous shaking for up to 5 minutes may be needed
• Administer each syringe immediately as it is prepared rather than waiting for the complete dose 1, 4
• Additional boluses of 1 mg/kg every 5 minutes until treatment goals achieved 1, 4

Treatment endpoints 1, 4:

• ETCO₂ falls below 6 kPa (45 mmHg) with normal minute ventilation
• Core temperature drops below 38.5°C
• Cardiac and respiratory systems stabilize

The maximum recommended dose of 10 mg/kg may need to be exceeded in severe cases 1. At least 36-50 ampoules should be available for an adult patient, requiring procurement from pharmacy or nearby hospitals 1, 4.

Step 3: Active Cooling Measures

Implement aggressive cooling simultaneously with dantrolene 1, 4:

• Administer 2,000-3,000 mL of chilled (4°C) 0.9% saline IV
• Surface cooling: wet cold sheets, fans, ice packs to axillae and groin
• Use any available cooling devices (cooling blankets, intravascular catheters)
• Stop cooling once temperature reaches <38.5°C to avoid overcooling

Comprehensive Monitoring and Support

Establish Invasive Monitoring

The European Malignant Hyperthermia Group recommends 1:

• Continuous core temperature monitoring
• Arterial line for blood pressure and frequent blood gas sampling
• Central venous line for fluid resuscitation and drug administration
• Urinary catheter to monitor output
• Wide-bore IV cannulas for rapid fluid administration

Laboratory Monitoring

Obtain immediate samples for 1, 4:

• Serum potassium (hyperkalaemia is life-threatening)
• Arterial blood gases (assess acidosis)
• Creatine kinase (marker of rhabdomyolysis)
• Myoglobin (serum and urine)
• Glucose
• Renal and hepatic function
• Coagulation studies

Check for compartment syndrome throughout the monitoring period 1.

Treatment of Metabolic Complications

Hyperkalaemia Management

Treat aggressively as hyperkalaemia can cause fatal arrhythmias 1, 4:

• Calcium chloride 0.1 mmol/kg IV (e.g., 7 mmol = 10 mL for 70 kg adult)
• Dextrose 50%, 50 mL with 50 IU insulin (adult dose)
• Dialysis may be required for refractory cases

Acidosis Management

Address both respiratory and metabolic components 1, 4:

• Hyperventilate to normocapnia (primary intervention)
• Sodium bicarbonate IV if pH <7.2

Arrhythmia Management

The European guidelines specify 1, 4:

• Amiodarone 300 mg IV (3 mg/kg) for adults as first-line
• Beta-blockers (propranolol/metoprolol/esmolol) if tachycardia persists
• Avoid calcium channel blockers (can interact dangerously with dantrolene)

Maintain Renal Perfusion

Prevent acute kidney injury from myoglobinuria 1, 4:

• Target urine output >2 mL/kg/hour
• Furosemide 0.5-1 mg/kg
• Mannitol 1 g/kg
• Aggressive crystalloid fluids (lactated Ringer's or 0.9% saline)

Post-Crisis Management

Monitoring Duration

Monitor the patient for a minimum of 24 hours in ICU, high-dependency unit, or recovery unit 1, 4. Recrudescence (return of MH signs) can occur, requiring continued vigilance 5.

Patient and Family Counseling

The Association of Anaesthetists emphasizes 1:

• Before hospital discharge, inform the patient and their general practitioner about the suspected MH diagnosis
• Explain implications for future anesthetics (absolute avoidance of trigger agents)
• Counsel about family implications (autosomal dominant inheritance)
• Provide written information about MH and emergency contact details

Definitive Diagnosis

It is the professional responsibility of the consultant anesthetist to make direct referral to the national MH investigation unit 1. In the UK, this is the Leeds Malignant Hyperthermia Unit; other countries have designated centers 1. Patients should undergo in vitro contracture testing (IVCT) and genetic testing when indicated 1, 2.

Preoperative Risk Assessment

Taking a personal and family history of anesthetic problems is mandatory for all patients requiring general or regional anesthesia 1. Specific red flags include:

• Family history of anesthesia-related deaths or complications
• Previous unexplained perioperative complications
• Known neuromuscular disorders (some patients with cerebral palsy and neuromuscular scoliosis may have increased risk) 6

Patients at increased risk must never be exposed to potent inhalational anesthetics or succinylchonium 1. Use total intravenous anesthesia with non-triggering agents.

Prognosis

With the availability of dantrolene and modern management protocols, mortality has decreased from 80% thirty years ago to <5% 2. However, delay in treatment significantly increases mortality and complications 1, 5. Early recognition—particularly identifying the rising ETCO₂ before hyperthermia develops—and immediate aggressive treatment are the key determinants of survival 1.