What is MH? | Testing | Patient Referral | Genetic Testing for MH | Management of Perioperative Rise in Temperature | Treatment of MH | MH Poster | MH Australia

What is MH?

Malignant Hyperthermia is a genetically heterogeneous condition with at least 3, and possibly more causative loci only one of which has so far been specifically characterised. To date, causative genetic mutations can be detected in about 20% of families with the disease, and predictive testing thus still relies on the cumbersome in vitro muscle contracture procedure. Even with this testing, and the management procedures which have been developed to deal with unexpected cases of MH, deaths are still occurring, according to an MH&MRC report on deaths associated with anaesthesia in Australia from 1990 to 1996. It is therefore important to continue the search for other genetic mutations responsible for M.H.

Testing

Both in vitro muscle contracture testing (IVCT) and chromosome analysis are performed at Royal Perth Hospital. We routinely perform IVCT according to the European MH Group protocol as well as some of the tests from the North American protocol. Genetic testing is able to identify the already known mutations and research is continuing to find other possible mutations.

IVCT requires a fresh specimen of vastus medialis approximately 3 x 1 x 1 cm. This is usually performed under femoral nerve block with minimal or no sedation required.

Patient Referral

Patients for M.H. testing should be referred to Dr Phil Nelson at the Department of Anaesthesia, Royal Perth Hospital.

Arrangements for performing the test at R.P.H. or elsewhere can be made by contacting the above departments. Research on muscle preservation with ice cooling of the sample is currently being investigated and may permit remote testing in the future.

Genetic Testing for MH

Genetic mutations in the RYR1 gene on chromosome 19 (the gene for the calcium release channel of the sarcoplasmic reticulum of skeletal muscle) have so far been identified in about 30% of families worldwide. It is likely that so far unidentified mutations account for another 20-30% of cases. Mutations in the adult muscle sodium channel alpha subunit gene (SCN4A) on chromosome 17 and the alpha subunit of the dihydropyridine receptor gene (CACL1A3) on chromosome 1 have been identified in a small number of families. We have specimens from IVCT proven cases from 20 families. Six of these families have been shown to carry known mutations in the RYR1 gene. In those families not carrying an identified mutation, cDNA from affected individuals is being analysed for new mutations segregating with the disease. Blood from MH suspects can be tested from anywhere in Australia. Enquiries should be directed to Mark Davis, Neuroscientist at mark.davis@rph.health.wa.gov.au.

Management of Perioperative Rise in Temperature

Temperature rise perioperatively may be due to:

• Infection
• Inadvertent overheating by warming devices
• Systemic inflammatory response to major trauma
• Fat embolism
• Head injury
• Spinal cord injury
• Light anaesthesia and volatile anaesthetic induced shivering
• Transfusion of mismatched or infected blood products
• Drug reactions with or during anaesthesia (neuroleptic malignant syndrome, MAO inhibitors, ACE inhibitors, SSRIs, cocaine, ecstasy, atropine, scopolamine.)
• Hyperthyroidism
• Phaeochromocytoma
• Malignant Hyperthermia

Manifestations of MH

• UNEXPECTED INCREASE IN CO2 PRODUCTION with rise in end tidal CO2 and arterial PCO2. Tachypnoea will occur in spontaneously breathing patients. The CO2 absorber may become rapidly exhausted.
• MUSCLE RIGIDITY manifesting initially as masseter muscle spasm but spreading to involve truncal and limb muscles.
• TACHYCARDIA, arrhythmias, and haemodynamic instability occur as hypercarbia, hypoxaemia, hyperkalaemia, and acidosis become significant.
• CYANOSIS, skin mottling and falling O2 saturation reflect the onset of hypoxaemia.
• HYPERTHERMIA, and sweating may be a late manifestation however core temperature may rise as rapidly as 1 degree C every 5 minutes.
• ABNORMAL LABORATORY VALUES

• Metabolic &/or respiratory acidosis.
• Hypoxia
• Hyperkalaemia
• Elevated serial blood CKs
• Myoglobinaemia and myoglobinuria

Treatment of MH

IF MALIGNANT HYPERTHERMIA IS SUSPECTED IN THEATRE

• Withdraw volatile anaesthetic agents and substitute with TIVA
• Notify the Surgeons and Nurses and terminate the surgical procedure as quickly as possible
• Check the monitors (end tidal CO2, temperature)
• Check the ECG
• Check O2 saturation
• Insert an arterial line and draw an ABG, measure K, CK
• Consider inserting a central line

IF MALIGNANT HYPERTHERMIA IS SUSPECTED IN RECOVERY ROOM

As above but also consider chest X ray, blood cultures and cranial CT depending on the clinical picture.

 IF THE DIAGNOSIS OF MALIGNANT HYPERTHERMIA IS MADE

• DECLARE AN M.H. EMERGENCY
• Call for Anaesthetic assistance
• HYPERVENTILATE with 100% O2 (3-4 x normal minute volume )
• Increase fresh gas flow to more than 10 L/min.
• Exclude the Sodalime absorber from the circuit
• If using rubber circuitry, change to a fresh set
• If using silicone or plastic hoses do not change at the expense of maintaining hyperventilation
• CALL FOR DANTROLENE SUPPLY, a sterile mixing bowl and a 1 litre bag of Water for Injection
• Assign 2 people to mix Dantrolene. This is best performed by removing the tops of the vials with a bottle opener, emptying the contents into a sterile bowl and adding water drawn up with a syringe into the bowl. Each vial must be reconstituted with 60 mL of water.
• Administer Dantrolene via a central line at an initial dose of 2.5 mg/kg over 5 min.
• Further doses of the same amount can be administered according to the response of heart rate, arterial CO2, rigidity and temperature fall at intervals of 10 min.
• After a total dose of 10 mg/kg ventilatory support may be necessary if the patient is not already ventilated.

COOLING

• Stop using any heating devices ,remove covering garments or linen where possible and reduce operating theatre temperature.
• Initiate cooling if temperature is elevated. If appropriate, administer ice cold saline via a large peripheral cannula. Pack axillae and groins with plastic bags full of crushed ice.

ARRHYTHMIAS, ACIDOSIS, AND HYPERKALEMIA.

• Hypoxia, hypercarbia, acidosis and hyperkalaemia will produce tachyarrhythmias and ectopy which are best treated with Beta blockers (Metoprolol, Esmolol) or Lignocaine or Calcium.
• Acidosis in a ventilated patient can be treated with Sodium Bicarbonate. Caution should be used in the non ventilated case. THAM, which does not produce CO2, might be preferable if it is available.
• Hyperkalaemia should be treated with an Insulin / Dextrose infusion if the rise in Potassium is rapid or ECG signs of hyperkalaemia become evident.

 RENAL FUNCTION

• Insert a urinary catheter.
• Take a sample of urine for Myoglobin assay.
• Promote a diuresis with fluids (normal saline) and Frusemide
• Extra Mannitol may be given in addition to that already in the Dantrolene (3 mg per vial)

 COAGULOPATHY

• Take a sample for coagulation studies.
• Order platelets and FFP if clinical evidence of a coagulopathy is present.

 ONGOING MANAGEMENT

• Repeat blood gas and biochemistry tests frequently.
• Evidence of ongoing rigidity, rhabdomyolysis, elevated temperature, and continued hypercarbia will necessitate further doses of Dantrolene.
• Monitor haemodynamics and urine output for signs of developing renal failure.

 ARRANGE TRANSFER TO INTENSIVE CARE

 AT A LATER DATE

• review family history if available and refer to an MH Testing Centre eg. DEPARTMENTS OF ANAESTHESIA.

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What is MH? | Testing | Patient Referral | Genetic Testing for MH | Management of Perioperative Rise in Temperature | Treatment of MH | MH Poster | MH Australia