Malignant Hyperthermia

Question 1

Explain the pathophysiology relating to malignant hyperthermia

Answer 1

There is typically a mutation in the ryanodine receptor, although other calcium-controlling receptors have been implicated

Calcium is released as a normal part of skeletal muscle contraction as it binds to troponin C which facilitates actin-myosin cross linking and muscular contraction.

It is an ATP dependant process which produces both CO2 and heat

When a patient with the mutation is exposed to a trigger agent, it causes sustained release of calcium from the sarcoplasmic reticulum into the cytoplasm and results in sustained muscle activity.

This sustained contraction leads to O2/ATP depletion and hence hypoxia and lactic acidosis, in addition to the hypercapnea and hyperthermia (all of which probably contribute to the tachycardia seen in MH)

The sustained contraction also leads to muscular rigidity which may be seen clinically.

Eventually, sarcomere integrity is lost and intracellular contents leak out, causing hyperkalemia (with the associated risk of arrhythmia) and rhabdomyolysis.

Sustained acidosis, hyperthermia, and rhabdomyolysis can further lead to DIC.

The patient’s blood pressure may rise or fall in MH, either due to a rise in the sympathetic response or due to the presence of vasodilatory mediators, respectively

Question 2

What are the anaesthetic triggers of Malignant Hyperthermia

Answer 2

Suxamethonium
Volatile Anaesthetics, with more potent volatiles (e.g. halothane or isoflurane) in theory causing a more rapid onset of reaction

Question 3

What are the early clinical features of MH in an anaesthetisted patient that should result in the instigation of MH treatment

Answer 3

An unexplained and unexpected increase in heart rate

An unexplained and unexpected increase in EtCO2

An unexplained and unexpected increase in temperature

Question 4

What are the key elements of initial MH management once a suspected diagnosis has been made

Answer 4

Removal of the trigger, which would include:

removal of vaporisers,
maximum gas flow,
100% O2
hyperventilate
charcole filters
change the soda lime and breathing circuit

Patient cooling

Treatment with Dantrolene 2.5mg/kg bolus, with further 1mg/kg boluses every 5 minutes until the etCO2 is < 6kPa and core temperature is <38.5 degrees C

NB, although there is no maximum limit for dantrolene, no response after 10mg/kg has been demonstrated to have a poor outcome.

Question 5

What are later onset features of MH which may require further treatment?