Malignant hyperthermia (MH) is a rare genetic disorder leading to disordered calcium regulation in skeletal muscles in response to suxamethonium and volatile anaesthetic agents.
MH is an autosomal dominant condition with variable penetrance. The abnormality seems to arise from an abnormality in the ryanodine receptor. This is involved in regulating calcium release from the sarcoplasmic reticulum (which normally should just be in response to depolarisation from ACh). The trigger is administration of either suxamethonium or any of the volatile anaesthetic agents. The result is uncontrolled calcium release into the muscle, leading to breakdown of the normal excitation-contraction coupling process and muscle overactivity. This leads to life threatening effects from:
Hypermetabolism due to muscle overactivity
Generalised muscle rigidity
Patients may have had anaesthetics previously with triggering agents without a reaction (indeed the average is quoted as 3).
It can be challenging to detect due to the relative non-specificity of its symptoms and its variable speed of onset. They arise from the muscle overactivity and subsequent increased metabolic demands that this puts on the body. Later, features of rhabdomyolysis may become apparent.
The most common features are:
Rising end tidal CO2 (early)
Increasing body temperature (late)
Later features may include:
Generalised muscle rigidity
The increased metabolic activity result in increased CO2 production. This will manifest itself as a rising etCO2, although a spontaneously breathing patient may show a tachypnoea instead. The increased oxygen consumption may also manifest itself (desaturation), although the administration of higher levels of FiO2 may mask this.
The increased metabolic activity will likely show itself in the cardiovascular system through a tachycardia.
An increase in body temperature is where the name of the condition arises, and can be rapid (>1 degree every 5 mins). However, it may be a later sign.
Masseter muscle spasm (MMS) is linked to MH, and refers to spasm that impedes intubation and last for 2 minutes after suxamethonium administration. About 25% of patients with MMS are subsequently shown to be MH susceptible. Most of the time MH will not immediately follow MMS and so abortion of anaesthesia/surgery should be strongly considered if possible to allow investigation. If not, avoidance of triggering agents and close observation for MH should be employed.
Immediate investigations may be needed to help look for other diagnoses and identify potential problems of MH.
Alerting the team and getting help is essential. As well as senior support, multiple people are needed to help draw up the volume of dantrolene that is usually needed (each vial only contains 20mg). The surgery will need to be finished as soon as is safely and feasibly possible.
The causative agent must be stopped - this will invariably be the volatile anaesthetic agent. The agent must be stopped, a clean circuit applied and the patient ventilated with high flow oxygen at a high FiO2 (aiming for 100%) - a ‘Water’s circuit’ or Abmu bag may be used as a temporising measure. Anaesthesia should instead be maintained with propofol.
Dantrolene is the treatment of choice for MH. It is a hydantoin derivative which acts with the muscle cell, preventing the calcium release from the sarcoplasmic reticulum that is causing sustained muscle activity. The dosing regime advised by the AAGBI is:
2.5mg/kg initial dose
Repeat doses of 1mg/kg up to maximum of 10mg/kg
The target is to halt the escalating features of metabolic overactivity (Rising CO2, tachycardia, pyrexia) Occasionally repeat doses may be needed after initial control has been achieved. It’s side effects include:
Muscle weakness (including prolongation of NDMRs)
Nausea and vomiting
Supportive Management Supportive management will be essential during the treatment with dantrolene. A significant focus on this will be cooling, but an A to E approach may be helpful to structure thinking given its common usage.
A/B An airway will need to be secured in the usual manner, but likely will already be. High flow gases are needed to aid removal of volatile agent, and FiO2 of 100% to provide adequate oxygen for the increased metabolic demand. The patient should be hyperventilated to clear the increased CO2 production and combat acidosis.
C Monitoring is essential - invasive BP measurement should be established for CVS monitoring and blood sampling. Arrhythmias may occur and should be treated, but avoiding calcium channel blockers (significant interaction). Consider hyperkalemia from rhabdomyolysis in cases of arrhythmias - treatment with calcium is still suitable.
D Anaesthesia must be maintain for ongoing surgery using propofol. Muscle relaxation using a NDMR is needed. Pain can be a problem post MH from muscle injury and should be considered.
Active cooling should be initiated, but aiming to avoid peripheral vasoconstriction which may actually impede heat loss. Options include:
Cold IV fluid
Ice packs to armpits and groin
Cold water bladder irrigation
Specific cooling devices e.g. Arctic Sun
There may be significant metabolic disturbance. Sodium bicarbonate is described in the AAGBI guidelines, but attention must be paid to ensuring adequate respiratory compensation i.e. hyperventilation.
Rhabdomyolysis can result from MH. Ensure adequate hydration and urine output (2ml/kg/hr) and consider forced alkaline diuresis.
Avoidance of precipitating MH in susceptible patients can be achieved by avoiding the triggers. This can readily be achieved by alternative anaesthetic techniques but needs careful consideration.
Regional anaesthesia has significant advantages if feasible. A ‘safe’ general anaesthetic will require a TIVA technique, and using only NDMR if needed. A ‘clean’ anaesthetic circuit is needed. This can be reasonably achieved by changing the CO2 absorber and running the ventilator for 30 mins with fresh gas flows of >10L/min
Monitoring is essential, with careful attention paid to CO2 and core temperature values. Prophylactic dantrolene is not recommended, as it shouldn’t be needed if the anaesthetic technique is done appropriately and has its own side effects.
The diagnosis will be made through referral to the specialist MH centre (in the UK this is in Leeds). Diagnosis is made through in vitro contracture testing. This requires a sample of live muscle, biopsied from the patient on site (usually vastus medialis under LA). The muscle is exposed to caffeine and halothane, resulting in contracture at lower levels than normal.
DNA testing is possible, identifying mutations of the ryanodine receptor that may make the patient vulnerable to MH. However, the link between genetic carriage and clinical expression is not clear (as can be appreciated from the fact that patients with MH can have uneventful anaesthetics)