Case 2.3 – Anaesthetic Emergencies: Malignant Hyperthermia

Category: Clinical Skills | Discipline: Anaesthesia | Setting: Operating Theatre

Case

Chandler Ackroyd a 16 year old boy has a lengthy operation for a post-nasal space angiofibroma. In the recovery room a large neck haematoma develops and he is returned to the operating room for exploration.

He is given Suxamethonium to facilitate reintubation and the wound is reopened. Over the next ½ hour his urine becomes dark reddish-black, CO₂ rises to 75mmHg and he develops multifocal VEBs on the ECG.

His temperature is measured - it is 39.5°C. Malignant Hyperthermia is diagnosed and appropriate treatment instituted.

He survives and returns to OR one week later for a planned second-stage procedure.

Questions

1. What is malignant hyperthermia (MH)? Outline the pathophysiology of MH, including changes at a cellular level?

MH is a rare pharmacogenetic disorder manifest when a susceptible individual (MHS) is exposed to a triggering agent. Characterised by:

Hypermetabolic state
Skeletal muscle rigidity
Pyrexia
Respiratory and metabolic acidosis
Hyperkalaemia
Arrhythmias
Rapid death in some cases

Incidence approx 1/60,000 with suxamethonium; 1/250,000 with volatiles. Children more common – 50% of cases <15years old.

Pathogenesis:

Involves sarcolemmal defect in skeletal muscle only, such that Ryanodine receptor when triggered leads to massive release of Ca from sarcoplasmic reticulum. ATP-dependent membrane pumps then attempt to return this Ca to the SR, leading to sustained glycolytic and aerobic metabolism. Return of Ca is incomplete, leading to sustained contraction and rigidity. Eventually oxidation and phosphorylation are uncoupled, anaerobic metabolism occurs, and severe mixed acidosis occurs.

2. What diseases are associated with MH susceptibility?

Genetic component:

Central core disease and mitochondrial myopathies - good evidence
Poor evidence for DMD and other myopathies, and for patients who have had NMS or severe heat stroke

Triggering agents include:

All Volatile anaesthetic agents
Suxamethonium
Ca-channel blockers

3. Describe the clinical presentation and describe the principles of management.

Clinical presentation:

Initially:

Rise in ET cO₂ and rapid exhaustion of soda-lime
Tachycardia
?Masseter spasm after Suxamethonium?

Leading on to:

Hyperthermia
Hyperkalaemia
Acidosis
Hypoxaemia
Later dark urine (myoglobin)
VEB's
CK rise
Death

Management:

Requires several people. First step is to suspect it.

Stop all triggers. Stop the surgery if possible.
Ventilate with high minute volumes from a non-triggering source.
Give Dantrolene 2.5mg/kg initial dose and repeat every 10-15 minutes until biochemical changes are reversed. Dantrolene is the only specific treatment and all hospitals should have access to an initial dose.
Treat arrhythmias and hyperkalaemia in conventional ways but avoid Ca-channel blockers.
Cooling with tepid sponging, fanning, cold iv fluids
Paralysis
Monitoring in ICU with management of rhabdomyolysis if necessary
Referral of patient and relatives for testing after recovery

4. Chandler's parents are very concerned that this could happen again with his next Anaesthetic. Explain the how the possible malignant hyperthermia syndrome patient can be tested and managed for subsequent anaesthetics.

Testing:

Currently in flux between IVCT and DNA testing.

IVCT very reliable – index case should certainly be confirmed this way. Open Quadriceps biopsy then test in bath with caffeine and/or Halothane and measure contraction developed.
DNA testing: Too many variants of RYR1 gene at present for reliable DNA testing – up to 20% may be missed.

Management for subsequent anaesthetics:

Avoid all triggering agents (volatile anaesthetics and suxamethonium)
Use non-triggering anaesthetic techniques (e.g., total intravenous anaesthesia with propofol)
Ensure Dantrolene is immediately available
Extended monitoring post-operatively
Patient should wear a medic-alert bracelet