1. Malignant hyperthermia
- A rare complication of anaesthesia

2. 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

4. 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

5. 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

8. 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).

11. 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

12. Complications Coma DIC Rhabdomyolysis
Myoglobinuric renal failure/hepatic dysfunction
Electrolyte abnormalities (hyperkalemia) and secondary arrhythmias
ARDS
Pulmonary edema
Can be fatal if untreated

13. 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

14. 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

15. 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 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

16. 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

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