Malignant Hyperthermia

This provides an overview of malignant hyperthermia, as well as management of an MH-crisis. Preparing a trigger-free anaesthetic is covered elsewhere.

Inherited pharmacogenetic disease of skeletal muscle that:

• May be triggered by volatile anaesthetic agents or succinylcholine
  • Variable expression
  • Patient may be exposed without consequences
    Susceptible patients have had an average of 3 GAs prior to presentation.
• Causes uncontrolled muscular contraction and relaxation, leading to:
  • Hyperthermia
  • Rhabdomyolysis
    • AKI
  • Arrhythmia

#####Immediate Management{#emerg}

Prompt treatment with dantrolene and hyperventilation may obviate the need for active cooling

Priorities are to:

• Discontinue triggering agents
• Hyperventilate
• Inform surgeons and abandon operation if feasible
• Administer dantrolene
  2.5mg/kg up to 10mg/kg as needed until metabolism controlled.
• Treat hyperthermia
  Major predictor of outcome:
  • Should not distract from dantrolene
  • Should be ceased when temperature is 38°C to prevent over-cooling
  • Strategies include:
  • Non-invasive
    • Cold IV fluids
      40ml/kg of 20°C crystalloid, limited by safe fluid volume.
    • Ice-packs
    • Forced-air cooling
    • Cold-water blankets
    • Ice-water immersion
  • Invasive
    • Intravascular cooling devices
    • CPB
    • Peritoneal lavage

Epidemiology and Risk Factors

Prevalence:

• Wide range of estimates
  Probably 1:5,000 to 1:10,000.
• Incidence in anaesthesia is ~1:40,000 to 1:100:000

Pathophysiology

Defective ryanodine calcium channel gene leads to:

• Uncontrolled calcium entry into muscle
• Continuous actin-myosin interaction
  Requires massive consumption of ATP, leading to:
  • Hyperthermia and hypercarbia
  • Rhabdomyolysis

Aetiology

Cal

Clinical Manifestations

Early signs:

• Elevated CO₂
• Masseter spasm
  May be severe, and jaw may not be able to be opened.
  • Concern if:
    • Unable to open the mouth after 2 minutes
    • Difficulty opening the mouth after 4 minutes
• Tachycardia
• Arrhythmia

Developing:

• Acidosis
• Hyperthermia
• CVS instability
• Hyperkalaemia

Late:

• Cola-coloured urine
• Coaguolpathy
• Hypoxia
• Rhabdomyolysis
• Cardiac arrest

Triggers:

• Suxamethonium
  May occur alone, in the absence of volatile agent.
• Volatile anaesthetic agents
  Not nitrous oxide.
• Exercise
  Case-report level evidence that individuals suffering severe heat injury often have ryanodine receptor mutations, and should be treated as MH.

Diagnostic Approach and DDx

Key differential diagnoses:

• Inadequate anaesthesia
• Infection/sepsis
• Torniquet ischaemia
• Phaeochromocytoma
• Thyroid storm
• Cerebral ischaemia
• Anaphylaxis

Investigations

Immediate investigations:

• Blood gases
• UEC/

Confirmatory investigations: {#confirm} * In vitro contracture testing
Muscle excised under regional anaesthesia and tested with halothane and caffeine to determine response. * Genetic testing
* Limited due to the complex genetic variations

Management

Dantrolene:

• Initial dose 2.5mg/kg
• Repeat up to 10mg/kg
• Repeat doses at 1mg/kg Q4-6H whilst monitoring for recurrence

Management of Masseter Muscle Spasm

Isolated masseter spasm may be the first sign of an MH event. If it occurs:

• Patient should be observed for risk of rhabdomyolysis
  • Rhabdomyolysis without other signs of MH should be referred to a neurologist for myopathy investigation
    If no myopathies are identified, MH testing should be considered.
• No investigation is required if masseter spasm is associated with a history of a TMJ disorder

Parturient with a Parter who is MH-Susceptible

Largely theoretical concern that:

• Foetus may be MH-susceptible
• Foetus may develop MH if mother is given GA whilst pregnant

Suggested management:

• Confirmation of fathers MH status
• Use of a non-triggering anaesthetic for mother for any procedure whilst pregnant
• Recommendation of epidural analgesia for labour and delivery
  Epidural top-up should be used if GA conversion is required.
• If GA is required for caesarian:
  • Volatile should be avoided until after delivery
  • Suxamethonium may be used if required
    Very little drug will cross the placenta.

Follow-Up

After treatment of suspected MH, the patient should be referred for:

• Confirmatory investigations
• Genetic counselling
  
• Investigation of first degree relatives

Anaesthetic Considerations

• E
  • Temperature monitoring
    For all patients for GA lasting longer than 30 minutes.

Complications

Include:

• Recurrence
  Occurs in 20% of patients; 80% of which occur within 18 hours.
• Rhabdomyolysis
• Death
  Occurs in ~2-3% if treated with dantrolene.
  • Risk ↑ 10-fold if temperature monitoring is not used

Prognosis

Key Studies

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References

1. Halsall PJ, Hopkins PM. Malignant hyperthermia. BJA CEPD Reviews. 2003 Feb;3(1):5–9.