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 Non-triggering agents Volatile gaseous inhalation anesthetics: Isoflurane Sevoflurane Desoflurane Haloflurane Enflurane Methoxyflurane Succinylcholine Suxamethonium decamethonium Propofol Ketamine Nitrous oxide All local anesthetics All narcotics Non 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

Management Based on MHAUS guidelines from 2008 Notify surgeon, discontinue agents, hyperventilate with 100% Oxygen at >10l/min, halt procedure if possible Dantrolene 2.5mg/kg IV every 5 min (1mg/kg/dose, max dose = 10 mg/kg) Repeat until control is obtained Bicarbonate 1-2 mEq/kg if blood gas values are not available for metabolic acidosis 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

Treat acidosis and hyperkalemia Don't use Ca2 channel blockers as they may cause hyperkalemia and cardiac arrest with dantrolene 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 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 Maintain anaesthesia with benzodiazepines, opioids and propofol Transfer to ICU

Quick recap of management Call for help (let surgeon know) Turn off potential triggering agents Administer dantrolene 2.5 mg/kg every five minutes Cool patient to 38C Monitor and correct blood gases, electrolytes and glucose

Sources: Wikipedia.com Toronto notes 2012 Uni-ulm.de (Malignant hyperthermia, Muscle & Nerve, January 2000)