Malignant hyperthermia

[BJA:CEPD Reviews 2003 Vol 3(1) "Malignant hyperthermia"]

Summary

• Consistent relationship between:
  * Increased CO2 production
  * Tachycardia
  * Hyperthermia

Epidemiology

• Incidence of MH reaction = 1 in 40,000 to 1 in 100,000
• Prevalence of genetic susceptibility = 1 in 5,000 to 1 in 10,000
• Difficult to gather data
• Factors that complicate accurate figures:
  * Apparently reduction in risk of reaction with increasing age
  * On average, susceptible patients have had 3 previous uneventful GAs
• Mortality from MH = 2-3%

 

Clinical features

• Loss of skeletal muscle cell calcium homeostasis
  --> Increased intracellular calcium concentration
  --> Muscle rigidity, hypermetabolism, rhabdomyolysis

 

High intracellular Ca2+ concentration causes:

1. Muscle rigidity
   * Due to continuous actin-myosin interaction
2. Hypermetabolism, due to:
   a. (Directly) Calcium-calmodulin complex directly stimulating glycolytic enzymes
   b. (Indirectly) Increased demand for ATP, which is consumed by myofilament interaction and Ca2+ pumps
3. Rhabdomyolysis
   * Due to excessive contractile activity and increased turnover of membrane phospholipids due to Ca2+ activation of phospholipase

 

Other features

• Hyperthermia
  * From excessive muslce contraction and metabolic stimulation
  * Body temperature may increase by more than 1 degree Celcius per 10 minutes
• Arterial oxygen desaturation
  * Oxygen delivery may not meet the demand
• Acidosis
  * From excessive production of CO2 and lactic acid
• Hyperkalaemia
  * Due to rhabdomyolysis
  * Can in turn cause cardiac arrhythmias
• Myoglobinuria
  * Due to rhabdomyolysis
  * Can in turn cause renal tubular damage and acute renal failure
• Disseminated intravascular coagulation (DIC)
  * Due to hyperthermia and necrotising tissues

Clinical presentation

Classical untreated malignant hyperthermia

Sequence of events

Early signs

• Masseter muscle spasm
• Metabolic stimulation, manifesting as:
  * Unexplained increasing CO2 production (as tachypnoea or increased EtCO2)
  * Tachycardia

Followed by...

• Unstable blood pressure
• Decline in SpO2

Late signs

• Increase in body temperature
• Generalised muscle rigidity
• Raised plasma CK
• Myoglobinuria
• Hyperkalaemia
• Cardiac arrhythmia
• Disseminated intravascular coagulation

Variability

• Sequence of events is quite consistent
• Onset time of symptoms is very variable

Other presentations

Masseter muscle spasm (MMS)

• Prior to the onset of paralysis, suxamethonium induces MMS in most people
• In patients susceptible to MH, the response is extreme
  * e.g. inability to open mouth 2 minutes after suxamethonium
  * e.g. resistance to mouth opening 4 minutes after suxamethonium
• Jaw rigidity is more pronounced in inhalation induction than IV induction
• Approximately 25% of patients referred for testing following an episode of jaw rigidity as the only feature proved to be susceptible to MH, even when the GA had continued uneventually with inhalational agents

Differential diagnosis

• Inadequate anaesthesia / analgesia
• Inappropriate breathing circuit / fresh gas flow /ventilation
• Infection / sepsis
• Tourniquet ischaemia
• Phaeochromocytoma
• Thyroid storm
• Cerebral ischaemia
• Anaphylaxis
• Other muscle diseases

Management

• Early diagnosis is important

Immediate treatment

• Removal of triggering agent
  * Discontinuation of volatile anaesthetics
  * Hyperventilation with 100% oxygen
  * Change of circuits
• Surgery should be concluded as quickly as possible while anaesthesia is maintained with IV drugs
• Active cooling
  * Cooling mattress
  * Application of ice
  * Removal of blankets
  * Need to avoid excessive cooling, which will cause peripheral vasoconstriction, preventing heat loss
• Dantrolene
  * One staff should be assigned to the preparation of dantrolene for administration
• Regular ABG and electrolyte measurements
  * Treatment of acidosis with bicarbonate
  * Treatment of hyperkalaemia with insulin and dextrose
• IV fluid
  * Maintain urine output of > 2 mL/kg/hr
  * To limit renal tubular damage

Follow-up

• Patient should be referred for confirmation of the clinical diagnosis
• Diagnosis is in vitro contracture testing (IVCT)
  * Involves testing a muscle biopsy specimen from vastus muscle, by exposure to halothane and caffeine

DNA testing

• MH susceptibility is inherited in a classic autosomal dominant fashion
• DNA testing checks 15 causative mutation in the ryanodine receptor protein (RYR1) gene
• Negative DNA testing does NOT rule out MH susceptibility
  * Muscle biopsy is still necessary
• Positive DNA testing confirms MH susceptibility

Trigger drugs and safe drugs in MH

Triggers

• Halothane
  * The most potent MH trigger
• Enflurane
• Isoflurane
• Sevoflurane
• Desflurane
• Suxamethonium

Safe drugs

• N2O
• All IV anaesthetic agents (including ketamine)
• All benzodiazepines
• All non-depolarising neuromuscular blocking drugs (NMBDs)
• All local anaesthetics (with or without vasoconstrictors)
• All analgesics, including opioids
• Neostigmine
• Atropine, glycopyrrolate
• Metoclopramide
• Droperidol