Malignant hyperthermia

- A rare complication of anaesthesia

What is it?

“It is a biochemical chain reaction response triggered by commonly used general anesthetics and the paralyzing agent succinylcholine, within the skeletal muscles of susceptible individuals” –MHAUS.org

Has autosomal dominant inheritance

Incidence of 1-5 : 100,000, < 5% mortality rate

Triggered by anesthetic drugs such as all inhalation agents (except NO) and succinylcholine (depolarising muscle relaxant)

Uncontrolled increase in intracellular Ca2 because of anomaly of ryanodine receptor which regulates Ca channels in sarcoplasmic reticulum of skeletal muscle

Clinical picture

It's onset can be immediate or hours after agent is administered

There will be increase in:

- Oxygen consumption

- ETco2 on capnograph

- Tachycardia/dysrythmia

- Tachypnia/cyanosis

- Diaphoresis

- Hypertension

- Temperature

Muscular symptoms

- Trismus (occurs in 1% of children given SCh together with halothane)

- Tender and swollen muscles due to rhabdomyolysis

- Trunk or total body rigidity

Pathophysiology

Alteration in the Ca induced ca release via the ryanodine receptor channel (RYR1) or! impairment in the ability of the sarcoplasmic reticulum to sequester calcium via the ca transporter

After trigger agent is administered, there is a sudden and prolonged release of ca which causes

- Massive muscle contraction

- Lactic acid production

- Increased body temperature

Dantrolene stops the calcium released by binding to the ryanodine receptor and blocking the opening of the channel therefore stopping the release of calcium. It has little effect on heart and smooth muscles as the ryanodine receptors differ in these tissues (RYR2).

Triggering vs safe anaesthetics

Triggering agents

Volatile gaseous inhalation anesthetics:

IsofluraneSevofluraneDesofluraneHalofluraneEnfluraneMethoxyflurane

•Succinylcholine

Suxamethoniumdecamethonium

Non-triggering agents

PropofolKetamineNitrous oxideAll local anestheticsAll narcoticsNon depolarizing muscle relaxants:

•Vecuronium

•Rocuronium

•pancuronium

Complications

Coma

DIC

Rhabdomyolysis

Myoglobinuric renal failure/hepatic dysfunction

Electrolyte abnormalities (hyperkalemia) and secondary arrhythmias

ARDS

Pulmonary edema

Can be fatal if untreated

Prevention

Check family history

Avoid trigger medication, use regional anaesthesia if possible and use clean equipment

Central body temperature and ETco2 monitoring

Used to use dantrolene as prophylaxis but not commonly used anymore

ManagementBased on MHAUS guidelines from 2008

1. Notify surgeon, discontinue agents, hyperventilate with 100% Oxygen at >10l/min, halt procedure if possible

2. Dantrolene 2.5mg/kg IV every 5 min (1mg/kg/dose, max dose = 10 mg/kg)

- Repeat until control is obtained

3. Bicarbonate 1-2 mEq/kg if blood gas values are not available for metabolic acidosis

4. Cool patient with core temp >39C

- Lavage open body cavities, stomach, bladder, rectum, apply ice to surface, imfuse cold saline IV

- Stop cooling if temp reaches 38C

1. Treat acidosis and hyperkalemia

- Don't use Ca2 channel blockers as they may cause hyperkalemia and cardiac arrest with dantrolene

2. Hyperkalemia

- Hyperventilation, bicarbonate, glucose/insulin, calcium

- Bicarbonate 1-2 mEq/kg IV, Calcium chloride 10 mg/kg or calcium gluconate 10-50 mg/kg for life threatening hyperkalemia and check glucose levels hourly

3. Observe ETco2, electrolytes, blood gases, creatine kinase, core temp, urine output/color, coagulation studies

- If CK and/or K rises more than transiently or urine output falls to less than 0.5 ml/kg/h induce diuresis to >1 ml/kg/h urine to avoid myoglobinuric renal failure

4. Maintain anaesthesia with benzodiazepines, opioids and propofol

5. Transfer to ICU

Quick recap of management

1. Call for help (let surgeon know)

2. Turn off potential triggering agents

3. Administer dantrolene 2.5 mg/kg every five minutes

4. Cool patient to 38C

5. Monitor and correct blood gases, electrolytes and glucose

Sources:

Wikipedia.com

Toronto notes 2012

Uni-ulm.de (Malignant hyperthermia, Muscle & Nerve, January 2000)