Malignant Hyperthermia (MH): Clinical features, Diagnosis, Management

Definition: A hypermetabolic state that occurs in genetically susceptible patients on exposure to a triggering agent.

Triggering agents:

• Suxamethonium or Succinylcholine (Depolarizing skeletal muscle relaxant)
• All anesthetic volatile agents (eg. halothane)

Biochemical basis:

It is inherited as an autosomal dominant condition and caused by loss of normal Ca2+ homeostasis at some point along the excitation-contraction coupling process on exposure to triggering agents. Most likely site is the triadic junction between T tubule, involving the voltage sensor of the dihydropyridine receptor (DHPR), and sarcoplasmic reticulum (SR), involving the Ca2+ efflux channel of the ryanodine receptor (RYR1). About 60% of Malignant Hyperthermia families are linked to the RYR1 gene located on chromosome 19q.

Clinical features:

1. Core temperature increases by 2 degree celsius per hour or more, or 0.5 degree celsius every 15 minutes.
2. On exposure to a triggering agent patients undergo a sustained muscular contraction.
3. Failure to relax after suxamethonium.
4. The 1st sign may be masseter muscle spasm or inability to open the mouth after giving suxamethonium; however not all masseter spasms progress to malignant hyperthermia.
5. Tachycardia, cardiac arrhythmias and cardiovascular collapse.
6. Increased end-tidal carbon dioxide  (ETCO2) and tachypnea if the patient is breathing spontaneously.
7. Metabolic and respiratory acidosis.
8. Generalized muscular rigidity.
9. Hyperkalemia.
10. Myoglobinurea causing acute tubular necrosis.
11. Previously uneventful general anesthesia or exposure to triggers does not rule out the diagnosis.

• Signs of increased metabolism: tachycardia, dysrhythmias, increased CO2 production, metabolic acidosis, pyrexia, DIC
• Muscle signs: masseter spasm after suxamethonium, generalized muscle rigidity, hyperkalemia, high CK, myoglobinuria, renal failure

The Differential diagnoses for masseter muscles spasm (MMS) are:

1. Myotonic syndrome
2. TMJ dysfunction
3. Underdosing with suxamethonium
4. Not allowing sufficient time for suxamethonium to act before intubation
5. Increased muscle tone after suxamethonium in the presence of fever or elevated plasma catecholamine

Risk factors:

• Positive family history
• History of malignant neuroleptic syndrome
• Muscular dystrophy
• Trismus on induction (jaw rigidity)
• Arthrogryposis multiplex congenita, osteogenesis imperfecta, ongenital strabismus, central core disease

Diagnosis:

• A small piece of striated muscle biopsied from the patient is challenged in vitro with a triggering agent (halothane or caffeine).

Differential Diagnosis:

1. Inadequate anesthesia or analgesia
2. Inapprropriate breathing circuit/fresh gas flow/ventilation
3. Endocrine disorders: Pheochromocytoma, Thyrotoxicosis
4. Sepsis
5. Hypoxic encephalopathy
6. Other muscle disorders

Action:

1. Discontinue the triggering agent and end surgery if possible.
2. Give 100% oxygen.
3. Change the anesthetic machine to a vapour-free machine.
4. Maintain anesthesia with an alternative agent e.g. propofol.
5. Dantrolene 1-2 mg/kg i.v. should be given and repeated every 5 min, until the temperature and CO2 stop rising, upto a total of 10 mg/kg.
6. Treat acidosis with sodium bicarbonate 8.4%.
7. Treat hyperkalemia with insulin and glucose.
8. Lower temperature by:
   • Body surface cooling
   • Cooling blankets
   • Cool irrigation fluids
   • Extracorporeal cooling may be indicated.
9. Maintain urine output >1 ml/kg/h.
10. Admit the patient to ICU for supportive therapy, prevention of secondary complications and close monitoring for recurrence.
11. Arrange muscle biopsy testing of patient (and near relatives if diagnosis confirmed).

Anesthesia in patients with Malignant hyperthermia susceptibility:

1. Ensure dantrolene is available.
2. Use a vapour-free anesthetic machine, flushed with 100% oxygen for 5 minutes at a fresh gass flow rate of 10 litres/minute.
3. All circuits should be disposable and new.
4. The soda lime should be previously unused.
5. Regional anesthesia is safe.
6. Drugs which are considered safe include barbiturates, narcotics, nitrous oxide, propofol, benzodiazepines, non-depolarizing muscular blocking agents.
7. A total intravenous technique using propofol along with an infusion of short acting opioids is safest.

Source:

1. Churchill’s Pocketbooks Anaesthesia – Nathanson and Mahajan
2. Oxford Handbook of Anaesthesia – 2nd edition