Malignant Hyperthermia Characteristics

Pathophysiology and Clinical Presentation

Malignant hyperthermia is a progressive life-threatening hypermetabolic reaction that occurs during general anesthesia in genetically susceptible individuals 1
MH is triggered specifically by exposure to potent inhalational anesthetics or suxamethonium, not merely by the stress of surgery or anesthesia 1, 2
Increased intermediary metabolism leads to increased oxygen consumption and carbon dioxide production, which manifests as increased ETCO2 in mechanically ventilated patients 3

Increased end-tidal CO2 (ETCO2) is the cardinal clinical feature and appears before temperature elevation in the typical progression of MH 3
The increased CO2 production is resistant to control by increasing minute ventilation during an MH reaction 3
Tachycardia accompanies increased carbon dioxide production due to sympathetic nervous system activation 4
Hyperthermia typically develops after the rise in ETCO2 and heart rate 3
Other clinical features include muscle rigidity, acidosis, hyperkalaemia, and rhabdomyolysis 1

Immediate treatment is essential when MH is suspected, as delay in commencing treatment is associated with increased mortality and complications 3
Dantrolene sodium is a specific antagonist for MH and should be administered at an initial dose of 2-3 mg/kg with further doses of 1 mg/kg every 5 minutes until treatment goals are reached 5
Treatment should continue until ETCO2 is <6 kPa with normal minute ventilation and core temperature is <38.5°C 5
Patients at increased risk of developing malignant hyperthermia must not be exposed to potent inhalation anesthetics or suxamethonium in future anesthetics 5

MH is rare, occurring in approximately 1:100,000 to 1:250,000 general anesthetics in the UK 2
Despite the availability of dantrolene, deaths from MH still occur with a mortality rate of approximately 4% in the UK 4
The highest reported incidence of MH occurs in pediatric populations and there is a consistently higher incidence in males compared to females 2
A history of uneventful previous anesthesia does not exclude the possibility of MH susceptibility 4

Delayed diagnosis is a major pitfall, as early recognition and treatment are critical for survival 3
Assuming a patient is not at risk due to previous uneventful anesthetics is dangerous, as patients can have multiple uneventful exposures before developing a reaction 4
Failure to have dantrolene immediately available wherever general anesthesia is administered can lead to preventable mortality 5
Misinterpreting early signs like increased ETCO2 and tachycardia as due to other causes can delay life-saving treatment 3

The American Society of Anesthesiologists acknowledges that MH susceptibility is a genetic condition that persists throughout life, and previous uneventful anesthetics do not exclude the possibility of developing MH on subsequent exposures, with a genetic prevalence of approximately 1:2000 in the general population 6
Multiple reports document patients who received several apparently uneventful anesthetics before experiencing their first MH reaction, due to reduced penetrance of MH susceptibility, meaning not every exposure to triggering agents will necessarily precipitate a crisis, even in genetically susceptible individuals 6

The European Society of Anaesthesiology identifies confirmed genetic variant pathogenic for MH susceptibility, such as RYR1, CACNA1S, STAC3 genes, as a significant risk factor for MH, along with positive in vitro contracture test, clinical myopathy with genetic etiology involving MH-related genes, history of unexplained rhabdomyolysis, idiopathic hyperCKaemia, and unexplained exertional heat illness 7

The American Heart Association recommends that if there is ANY suspicion of MH susceptibility, the patient must NEVER be exposed to triggering agents again, and absolute avoidance of all potent inhalational anesthetics and succinylcholine is necessary, with consideration of total intravenous anesthesia technique and regional anesthesia when appropriate 8

The American Society of Anesthesiologists advises that for any patient with suspected or confirmed MH susceptibility requiring anesthesia, contact the MH Unit for specialized advice before proceeding, and consider deferring non-urgent surgery until definitive diagnostic testing clarifies status, with a focus on trigger-free anesthesia and safe practice 7

The UK's National Health Service reports that despite dantrolene availability, MH mortality remains approximately 4%, highlighting the importance of early recognition and treatment, as delayed diagnosis is the major preventable cause of death 6

Malignant hyperthermia (MH) is a rare pharmacogenetic disorder that occurs in approximately 1 in 100,000 to 1 in 250,000 general anesthetic procedures. 9

A personal or family history of unexplained anesthetic complications, masseter muscle spasm, or a confirmed MH reaction should raise clinical suspicion for MH susceptibility. [9][10]
The lack of prior anesthetic complications does not exclude MH susceptibility; patients may experience multiple uneventful anesthetics before a malignant hyperthermia reaction manifests. [9][10]