Malignant hyperthermia

Malignant hyperthermia (MH) is a life-threatening reaction that is triggered by common medicines used during surgery. MH causes:

• A sudden increase in the body’s metabolism.
• High fever.
• A rapid and irregular heart rate.

When these reactions happen, a person may be at risk for severe complications, such as a heart attack, brain damage, internal bleeding, organ failure, or death.

A person can have tests to learn if he or she is at risk of developing MH (MH susceptible). Testing for MH susceptibility is usually done if there is a family history of MH or problems under general anesthesia.

Causes of Malignant hyperthermia

This condition is caused by a genetic defect. This defect:

• Does not allow the body to process the medicines that make you fall asleep during surgery (general anesthesia).
• Can trigger the condition when you experience severe heat and physical or emotional distress. This is rare.

What increases the risk?

You are more likely to develop this condition if:

• You have a family history of problems while under general anesthesia.
• You are male.
• You are a child or young adult.
• You have a rare condition that affects the nerves and weakens the muscles (neuromuscular disorder).

Symptoms of Malignant hyperthermia

Symptoms of this condition include:

• A rapidly increasing fever.
• A fast, irregular heart rate.
• Difficulty breathing.
• Excessive sweating, often with clamminess.
• Bluish skin.
• Stiffening muscles.
• Excessive bleeding from the nose or where a surgical cut (incision) was made.
• Blood in your urine.
• Dark brown urine.

Follow these instructions at home:

Safety

• Get tested for the MH gene if you have a family member who was diagnosed with MH.
• If you are MH susceptible or have been diagnosed with MH:
  • Tell your family members. 
  • Encourage family members to get tested for MH susceptibility.
  • Carry a wallet card, bracelet, or medical identification tag that shows you have this condition. Always keep it with you. If there is an emergency and you cannot communicate, the card will tell the health care providers not to give you medicines that can trigger the condition.
• Let all your health care providers know if:
  • You have been diagnosed with MH.
  • You have been tested for MH and are MH susceptible.
  • You have any family members with MH.
  • You have any family members who have had complications while under general anesthesia.
• If you are going to have surgery, make sure the facility is prepared to handle a MH event.

General instructions

• Drink enough fluid to keep your urine pale yellow.
• Take over-the-counter and prescription medicines only as told by your health care provider.
• Do not exercise in hot or humid weather. This may trigger an episode of MH.
• After an episode of MH:
  • Rest and gradually return to your normal activities.
  • Ask your health care provider what activities are safe for you.
• Keep all follow-up visits as told by your health care provider. This is important.

Contact a health care provider if you:

• Think you may be at risk for MH.

Get help right away if you have any of these symptoms after surgery:

• Fever.
• Muscle pain.
• Chest pain.
• Difficulty breathing.
• Dizziness.
• Irregular or fast heart beat.

Summary

• Malignant hyperthermia (MH) is a life-threatening reaction that is triggered by common medicines used during surgery.
• Get tested for the MH gene if you have a family member who was diagnosed with the condition.
• Let all health care providers who treat you know about your condition.

Interesting Facts of Malignant hyperthermia

• Malignant hyperthermia is an autosomal dominant skeletal muscle calcium channelopathy that can result in a hypermetabolic response in a susceptible person after exposure to triggering agents such as inhaled volatile anesthetics and succinylcholine
• This pharmacogenetic disorder is considered a subclinical disease because only exposure to a trigger leads to clinical manifestations
• A high degree of clinical suspicion is necessary for rapid diagnosis owing to variability in the order and onset of signs
• Principal clinical features of a crisis include unexplained hypercapnia, sustained muscle rigidity, tachycardia, and hyperthermia; hypermetabolic syndrome progresses to rhabdomyolysis in fulminant malignant hyperthermia crisis
• Early consultation with the malignant hyperthermia crisis hotline can assist in diagnostic and treatment decisions 
• Diagnosis of an acute crisis is based on clinical presentation with supporting laboratory findings; respiratory acidosis, metabolic acidosis, and hyperkalemia are common laboratory findings early in a crisis
• Confirm malignant hyperthermia susceptibility with genetic testing for RYR1 pathologic variants and/or gold standard caffeine halothane contracture test; consult genetic counselor to determine best individualized malignant hyperthermia susceptibility testing strategy
• Treatment involves discontinuing the triggering anesthetic, hyperventilation, administration of dantrolene, and aggressive supportive care
  • Malignant hyperthermia hotline is available 24 hours daily for expert assistance in managing an event 
• Complications of malignant hyperthermia include acute renal failure, compartment syndrome, cardiac dysfunction, disseminated intravascular coagulation, multiorgan failure, and death
• Prognosis depends on how rapidly crisis is identified and treated; mortality rate is less than 5% with early recognition and prompt treatment with dantrolene 
• Malignant hyperthermia crisis can be prevented by identifying malignant hyperthermia susceptibility in those at risk and avoiding triggers

Pitfalls

• Avoid delay in starting malignant hyperthermia treatment when clinical suspicion exists, owing to increased morbidity and mortality associated with treatment delays; rapidly assess and exclude other common anesthesia-related issues that result in early signs of a malignant hyperthermia episode (eg, rising end-tidal CO₂, tachycardia) and begin treatment protocol without delay 
• Do not use calcium channel blockers to treat an episode of malignant hyperthermia; calcium channel blockers are contraindicated for use in patients with malignant hyperthermia crisis, owing to risk of hyperkalemia and severe hypotension when used with dantrolene 
• Failure to monitor core temperature in patients during malignant hyperthermia crisis leads to increased risk of mortality 

Clinical Clarification

• Malignant hyperthermia is an autosomal dominant skeletal muscle calcium channelopathy that can result in a hypermetabolic response in a susceptible person after exposure to triggering agents such as inhaled volatile anesthetics and succinylcholine 
• This pharmacogenetic disorder is considered a subclinical disease because only exposure to a trigger leads to clinical manifestations 
• Principal clinical features of a crisis include unexplained hypercapnia, sustained muscle rigidity, tachycardia, and hyperthermia; hypermetabolic syndrome progresses to rhabdomyolysis in a fulminant malignant hyperthermia crisis 

Clinical Presentation

History

• History is suggestive for exposure to a trigger
  • Malignant hyperthermia episode occurs in approximately 1 in 100,000 operative cases requiring general anesthesia 
  • Rarely occurs after exposure to excessive thermal stress (eg, strenuous exercise, extreme heat) 
• Onset of first malignant hyperthermia crisis is variable
  • Event can occur during first exposure to anesthesia; however, an average of 3 procedures involving anesthesia are needed before triggering a malignant hyperthermia episode 
  • About half of all patients found to be malignant hyperthermia–susceptible have received a triggering agent without clinical findings of an adverse event 
• Presentation of crisis is highly variable
  • Timing of onset differs significantly between patients
    • Initial event manifestation can occur at any time while patient is under anesthesia; can occur immediately after induction ranging to several hours into anesthesia 
      • Mean time until first symptom is 45 to 55 minutes after exposure to triggering agent 
    • Presentation can occur in early postoperative period up to 1 hour after discontinuation of volatile agents 
  • Progression of symptom manifestation differs significantly between patients
    • Ranges from a rapid, dramatic presentation (particularly with succinylcholine use) to a more gradual progression 
  • Severity of crisis manifestations is variable 
    • Range of presentations exist from abortive courses with mild symptoms to fulminant malignant hyperthermia crisis with severe skeletal muscle hypermetabolism and rhabdomyolysis
• History of suggestive episodes under anesthesia (up to 3.3% of patients) 
  • Suggestive episodes often include spasms, rigidity, cardiac arrhythmias, hyperthermia, and/or hypotension
• History of severe exercise-induced or heat-induced malignant hyperthermia–like events (up to 7% of patients) 
  • Significant events include muscle rigidity, hyperpyrexia, and rhabdomyolysis after exercise- or heat-induced illness 
• Family history of malignant hyperthermia or death during anesthesia (approximately 6.5% of patients) 
• Family history of heat stroke (approximately 3.6% of patients) 

Physical examination

• Timing of clinical signs 
  • Earliest signs often include hypercapnia, sinus tachycardia, and masseter muscle spasm
    • Hypercapnia (92% of patients) 
      • End-tidal CO₂ level rises despite increased minute ventilation 
      • End-tidal CO₂ level greater than 55 mm Hg is often the earliest sign and is predictive for imminent malignant hyperthermia 
      • CO₂ rise is more often gradual and subtle as opposed to abrupt 
      • Results from excessive CO₂ production secondary to increased metabolism
    • Increased sympathetic tone
      • Inappropriate tachycardia (73% of patients) 
      • Diaphoresis (17.6% of patients) 
      • Mottled skin (6.3% of patients) 
      • Hypertension and unstable blood pressure 
    • Arrhythmias are very common (50%-80% of patients) 
      • Early rhythm disturbances are usually related to succinylcholine-induced rapid-onset hyperkalemia and/or increased sympathetic tone
      • Typically, supraventricular or ventricular arrhythmia
      • Most common ventricular arrhythmias include ectopic ventricular beats and ventricular bigemini 
    • Generalized muscular rigidity is very common (50%-80% of patients) 
      • Characteristically unresponsive to conventional paralytics 
      • Leads to development of rhabdomyolysis, hyperkalemia, and hyperthermia 
    • Masseter muscle rigidity (27% of patients) 
      • Inability to open mouth occurs particularly with succinylcholine-related malignant hyperthermia events
      • Development of masseter muscle rigidity can herald a malignant hyperthermia event; more commonly precedes malignant hyperthermia events in children than adults 
      • Rigidity lasting longer than 2 minutes is a suggestive sign heralding malignant hyperthermia crisis
    • Tachypnea (27.1% of patients) 
      • Occurs in spontaneously breathing patients to compensate for increasing acidosis
  • Later signs often include the following:
    • Hyperthermia (greater than 38.8°C) 
      • Can increase rapidly, often 1°C to 2°C every 5 minutes 
      • Severe hyperpyrexia with temperatures exceeding 44°C can occur 
        • Leads to marked increase in oxygen consumption, carbon dioxide production, widespread vital organ dysfunction, and disseminated intravascular coagulation
      • If treatment is started early, relevant changes in body temperature may not occur in some patients 
    • Cyanosis (9.4% of patients) 
      • Sustained increased metabolic state results in increased oxygen consumption
      • Dark blood in wound is consistent with hypoxemia 
    • Rhabdomyolysis
      • Dark, cola-colored urine (13.7% of patients) from rhabdomyolysis, resulting in myoglobinuria 
    • Acute renal failure
      • Oliguria or anuria 
  • Advanced signs include the following:
    • Excessive bleeding (2.7% of patients) from disseminated intravascular coagulation 
    • Malignant cardiac arrhythmias and cardiac arrest
    • Hypotension and circulatory failure

Causes and Risk Factors

Causes

• Malignant hyperthermia–susceptible patients have a genetic defect that results in abnormal regulatory calcium channel of skeletal muscle sarcoplasmic reticulum; this abnormality only leads to defective skeletal muscle calcium homeostasis when exposed to a trigger that allows calcium to accumulate in myoplasm 
  • Exposure to trigger causes an unopposed opening of the defective channel; result is sustained skeletal muscle contraction and hypermetabolic state (eg, hypoxemia, hypercapnia, lactic acidosis, hyperkalemia, hyperthermia) 
  • Prevalence of genetic polymorphisms associated with malignant hyperthermia susceptibility is estimated at 1 in 400 to 1 in 3000 people; known pathologic variants associated with malignant hyperthermia susceptibility include: 
    • RYR1 gene mutations (OMIM #145600) 
      • Location is chromosome band 19q13 
      • Gene product is ryanodine receptor 1, which forms regulatory channels that control calcium release from the sarcoplasmic reticulum in skeletal muscle
      • Present in up to 70% of patients 
      • 34 known causative RYR1 mutations 
    • CACNA1S (or CACNL1A3) gene mutations (OMIM #601887) 
      • Location is chromosome band 1q32 
      • Gene product of α1 subunit is L-type voltage-dependent calcium channel of the skeletal muscle 
      • Present in less than 1% of patients 
      • 2 known causative CACNA1S mutations 
    • STAC3 gene mutations (OMIM #255955) 
      • Location is chromosome band 12q13 
      • Abnormalities of STAC3 gene are rarely responsible for disease 
      • Causative in 1 isolated population in United States: myopathic members of southeastern Lumbee Indian tribe; gene is associated with disease in other myopathic people outside of United States 
  • Triggers include the following: 
    • Depolarizing neuromuscular blocker
      • Succinylcholine
    • Volatile, halogenated inhalation anesthetic agents
      • Halothane
      • Enflurane
      • Isoflurane
      • Sevoflurane
      • Desflurane
      • Ether 
    • Wake state triggers (rare)
      • Extreme physical exertion, heat, or emotional stress 

Risk factors and/or associations

Age

• Highest incidence of first crisis occurs in children and young adults 
  • Mean age at first event is 18.3 years 
  • Over half of initial events occur in children younger than 15 years 

Sex

• 2.5 to 4.5 times higher prevalence in males 

Genetics

• Autosomal dominant inheritance occurs with all known human genetic pathologic variants 
• De novo genetic mutations occur at an unknown incidence 
• Variable clinical manifestations exist among patients with the same genetic defect 
  • While causative genetic mutations have high prevalence in the general population, incidence of malignant hyperthermia events is comparatively low 
  • In general, underlying susceptibility to and severity of crisis depends on exact mutation, specific triggering agent or agents involved, dose and duration of trigger agents, absolute muscle mass, and unknown contributory factors (eg, diet, medications) 

Other risk factors/associations

• Certain disease states, myopathies, and congenital syndromes are predisposing factors for malignant hyperthermia susceptibility 
  • Masseter muscle rigidity
    • Malignant hyperthermia crisis, defined by changes in arterial blood gas, occurs in about 15% of patients after induction-related masseter muscle rigidity 
    • Muscle biopsy results indicate that up to 59% of children who develop masseter muscle rigidity are susceptible to malignant hyperthermia; coincidence of masseter muscle rigidity and malignant hyperthermia susceptibility is likely lower in adults than children 
  • Central core disease 
    • Rare, autosomal dominant, nonprogressive myopathy that presents in infancy with hypotonia and proximal muscle weakness; characterized by multiple cores on muscle biopsy
    • RYR1 mutations cause disease 
  • Multiminicore disease 
    • Rare, autosomal recessive, neuromuscular disorder that often presents in infancy or early childhood with muscular weakness; characterized by multiple minicores on muscle biopsy
    • RYR1 mutations cause disease 
  • King-Denborough syndrome 
    • Rare myopathy that presents with congenital hypotonia and dysmorphic facies; characterized by distinctive changes on muscle biopsy
    • Pathogenic variants in RYR1 gene are found in some patients with disease 
  • Hypokalemic periodic paralysis 
    • Primary heritable condition or secondary symptom of another syndrome or disease process in which patients present with episodes of paralysis with concomitant hypokalemia (potassium level below 2.5 mmol/L); occasionally, late-onset proximal myopathy develops
    • Pathologic variants in CACNA1S gene are found in most patients with disease
  • Myotonia fluctuans 
    • Rare sodium channel myopathy that presents in the first or second decade of life with fluctuating myotonia (ie, asymptomatic one day followed by severe myotonia the next day) primarily affecting limbs, extraocular muscles, and muscles of mastication and swallowing
    • SCN4A mutations are associated with disease 
  • Severe statin-induced myopathy
    • Usually presents within 12 weeks of starting treatment 
    • Symptoms include muscle pain and weakness; rarely progresses to rhabdomyolysis 
    • RYR1 gene abnormalities are present in minority of patients who develop severe statin-induced myopathy and who may be at increased risk for malignant hyperthermia susceptibility 

How is Malignant Hyperthermia diagnosed?

This condition is diagnosed based on signs and symptoms recognized by the health care team during surgery.

You may also have tests for MH and MH susceptibility. These include:

• Genetic testing.
• Removing a sample of tissue to be tested in the lab (muscle biopsy).

Talk to a genetic counselor to find out which type of test is best for you.

Primary diagnostic tools

• Do not delay symptomatic care and treatment with dantrolene while awaiting diagnostic test results in patient with suspected malignant hyperthermia episode 
• Presumptive diagnosis of malignant hyperthermia is clinical and supported by laboratory tests; laboratory tests are helpful to identify associated complications and to determine clinical score on malignant hyperthermia clinical grading scale 
  • Common initial clinical presentation includes unexplained increasing end-tidal CO₂ levels, masseter spasm, increased sympathetic tone, and generalized muscle rigidity; later signs include hyperthermia, cyanosis, rhabdomyolysis, and hyperkalemia; advanced signs include severe arrhythmias and disseminated intravascular coagulation
  • Immediately obtain ancillary testing at first clinical suspicion of malignant hyperthermia event; repeat laboratory assessments frequently until clinical manifestations of disease stabilize and crisis resolves
    • Assess for combined metabolic and respiratory acidosis using arterial blood gas analysis 
    • Measure lactate level; elevated level is an early indicator of malignant hyperthermia episode 
    • Assess serum electrolyte levels to assess for hyperkalemia 
    • Identify rhabdomyolysis with urine dipstick test result positive for blood without RBCs on urine microscopy; elevated serum creatine kinase level; and/or elevated urine or serum myoglobin levels. Rhabdomyolysis is often a later finding in the course of fulminant malignant hyperthermia 
    • Assess renal function
    • Obtain ECG to assess for signs of hyperkalemia and arrhythmia 
    • Begin monitoring hepatic function and coagulation 
  • Malignant hyperthermia hotline can help guide diagnostic process
• After resolution of suspected malignant hyperthermia event, diagnostic evaluation includes the following:
  • Malignant hyperthermia clinical grading scale
    • Determines likelihood that anesthetic event represents true manifestation of malignant hyperthermia 
    • Useful to assess need for further evaluation (eg, in vitro contracture test, genetic testing) and determine malignant hyperthermia susceptibility
  • Definitive diagnosis of malignant hyperthermia susceptibility 
    • Available tests are not universal screening tools for disease; formal testing for disease is limited to patients in whom there is substantial concern for malignant hyperthermia susceptibility (eg, incident suggestive of malignant hyperthermia crisis, unexplained perioperative rhabdomyolysis, family history of malignant hyperthermia) 
    • Positive caffeine halothane contracture test result or presence of causative mutation in the RYR1 gene is diagnostic for malignant hyperthermia susceptibility 
    • Consult a genetic counselor to determine best individualized malignant hyperthermia susceptibility testing strategy 
      • Decision of which test to perform first on proband is often based on patient and provider preference, guided by recommendations from genetic counselor and experts from Malignant Hyperthermia Association of the United States
        • Caffeine halothane contracture test is preferred gold standard, first choice testing option in proband, but limitations include cost (including travel expenses to specialized testing center) and invasive nature of testing 
        • Genetic testing is less costly and less invasive, but also has low sensitivity when evaluating a proband; some experts advocate necessity to demonstrate functional causality even with identification of known causative mutation. Identification of known pathologic variant may require follow-up with caffeine halothane contracture functional analysis because positive genetic test results in those with negative contracture test findings do rarely occur 
      • Caffeine halothane contracture test 
        • Overall sensitivity is greater than 95% and specificity is approximately 80%; positive results are followed by any genetic testing not already performed, owing to 20% false-positive rate 
        • This invasive test, performed only at a few specialized testing centers, requires surgical resection of a significant amount of viable muscle tissue 
        • Negative test result definitively excludes malignant hyperthermia susceptibility
        • Positive test result is followed by genetic testing to evaluate for pathologic variant known to predispose to malignant hyperthermia susceptibility; results are helpful to screen other family members for susceptibility
      • Genetic testing
        • Low sensitivity; not all causative mutations for malignant hyperthermia susceptibility are known
        • Noninvasive alternative to contracture test; requires a blood or buccal swab sample 
        • Limited number of accredited diagnostic laboratories exist for testing 
        • Genetic testing can be performed first, followed by caffeine halothane contracture test in patients without an identifiable causative genetic pathologic variant 
        • Presence of causative mutation in the RYR1 gene is diagnostic for malignant hyperthermia susceptibility 
        • Genetic testing is preferred for family members when causative mutation is known in proband
        • Contracture test is required to definitively confirm or exclude malignant hyperthermia susceptibility when causative gene defect is not identified 
    • In clinical practice, owing to the expense of definitive testing, scarcity of accredited laboratories, and availability of nontriggering anesthetics, when malignant hyperthermia is suspected, choose a nontriggering anesthetic

• Arterial blood gas analysis
  • Combined metabolic and respiratory acidosis are typically identified by arterial blood gas and serum bicarbonate measurements 
    • Respiratory acidosis 
      • Occurs in up to 78.6% of patients 
    • Metabolic acidosis 
      • Results from hypermetabolic state–induced lactic acidosis and cellular breakdown
      • Occurs in up to 26% of patients 
• Electrolyte level
  • Hyperkalemia with elevated potassium levels (greater than 6 mmol/L) is most common abnormality; results from muscle breakdown 
  • Other findings include hyponatremia, hyperphosphatemia, hypermagnesemia, and hyper- or hypocalcemia 
• Creatine kinase level
  • Elevated creatine kinase level is the most sensitive indicator of myocyte injury; level more than 5 times the reference range is evidence of rhabdomyolysis 
    • 3 fractionated creatine kinase isoenzymes exist: CK-MM is predominantly found in muscles, CK-MB is predominantly found in heart, and CK-BB is predominantly found in brain and kidneys 
  • Levels rise 2 to 12 hours after onset of muscle injury, peak by 24 to 72 hours, then decline gradually over 7 to 10 days 
  • Creatine kinase levels peaking higher than 10,000 to 20,000 units/L are common in patients with malignant hyperthermia–induced rhabdomyolysis 
  • Persistently elevated creatine kinase levels suggest continued muscle injury or compartment syndrome 
• Urinalysis
  • Myoglobinuria is present when dipstick result is positive for blood (ie, heme positive); significant RBCs are absent on urine microscopy
  • Negative blood result on urine dipstick excludes presence of myoglobinuria 
• Urine or serum myoglobin level
  • In clinical practice, urinalysis results positive for blood without RBCs alone provides evidence of myoglobinuria, indicating necessity for renal protective measures; occasionally urine and/or serum myoglobin levels are assessed
  • Myoglobin measurements can be quantified in blood and urine; clinical utility is limited, as serum myoglobin levels rise and fall rapidly in 1 to 6 hours in response to muscle injury 
  • Myoglobinuria is pathognomonic for rhabdomyolysis; elevated serum myoglobin level is a reliable indicator for rhabdomyolysis 
  • Urine myoglobin levels greater than 100 mg/dL cause urine discoloration (eg, tea- or cola-colored urine) 
• BUN and creatinine levels
  • Renal dysfunction is common, resulting from rhabdomyolysis 
• Lactate level
  • Inappropriately elevated lactate level often occurs in patients with subclinical stages of malignant hyperthermia crisis 
• Genetic testing
  • Indications 
    • Confirmed clinical episode of malignant hyperthermia
    • High likelihood of having experienced a malignant hyperthermia episode, as determined by biopsy center or hotline consultants, and/or likely malignant hyperthermia based on clinical grading scale
    • Children younger than 5 years or weighing less than 20 kg who have contraindication for muscle contracture testing but require testing for malignant hyperthermia susceptibility
    • Positive caffeine halothane contracture test result (to determine if pathologic variant is detectable for testing other family members)
    • Exercise-related rhabdomyolysis in the absence of known myopathy
    • Relative with known pathologic variant, positive contracture test result, or highly suspicious clinical episode suggestive of malignant hyperthermia
  • Testing for known causative gene defects includes the following:
    • RYR1 gene sequencing or targeted mutation analysis
      • Accepted as first line diagnostic tool for patients with known family history of causative RYR1 mutation 
    • Other known genetic defects associated with malignant hyperthermia susceptibility can be evaluated if common known genetic associations are not identified by RYR1 analysis 
      • CACNA1S gene sequencing
      • STAC3 gene sequencing
  • Diagnosis is confirmed by identifying known mutation that causes malignant hyperthermia 
  • False-negative rate is high (sensitivity is likely less than 50%); therefore, inability to identify causative mutation does not exclude malignant hyperthermia susceptibility, because not all patients with malignant hyperthermia susceptibility have a pathologic variant known to cause disease

• ECG
  • Assess for findings consistent with hyperkalemia 
  • Assess for supraventricular and ventricular arrhythmia

Procedures

Muscle biopsy with caffeine halothane contracture test 

General explanation

• Test measures isometric muscle contraction force in response to the RYR1 channel agonists (ie, caffeine, halothane); test is performed several months after a suspicious event
• Muscle bundle is 2 to 3 mm thick, more than 2 cm long, and is harvested from vastus lateralis or medialis for testing; specimen viability is improved with minimal use of electrical cautery and avoidance of stretching muscle during procedure 
• Regional anesthesia, using regional nerve block or neuraxial block with supplemental sedation, is required for muscle biopsy; direct muscle infiltration with local anesthetic adversely affects tissue viability 
• 2 protocols are available from European Malignant Hyperthermia Group and Malignant Hyperthermia Association of the United States 
  • Protocols differ in concentration of caffeine and halothane applied to muscle and mode of application (ie, incremental versus bolus) 

Indication

• Definite indications 
  • Patients with any of the following:
    • Suspected malignant hyperthermia episode
    • Relative with a positive contraction test result
    • Malignant hyperthermia–susceptible relative suggested by a malignant hyperthermia episode without a known causative genetic variant 
    • Severe masseter spasm and generalized muscular rigidity in setting of a triggering agent
    • Mild to moderate masseter spasm and evidence of rhabdomyolysis
• Relative indications 
  • Patients with any of the following:
    • Unexplained rhabdomyolysis after surgery
    • Isolated masseter muscle rigidity with succinylcholine
    • Exercise-related rhabdomyolysis in the absence of known myopathy
    • Patients with suspected malignant hyperthermia who desire enlistment in military service (military excludes people with malignant hyperthermia susceptibility from service)

Contraindications

• Most centers do not perform biopsies in patients younger than 5 years or weighing less than 20 kg, owing to the large amount of muscle required for testing 
• Diagnosis of neuroleptic malignant syndrome or serotonin syndrome 

Interpretation of results

• Positive test result
  • Diagnosis of malignant hyperthermia susceptibility (protocol notation MHS) is determined by contraction forces that exceed standardized thresholds 
    • European protocol notation includes MHSh status if contracture develops after halothane only
    • European protocol notation includes MHSc status if contracture develops after caffeine only
  • Although false-positive rate is high owing to low specificity of the test, patients with positive results should not receive triggering agents
• Negative test result
  • Malignant hyperthermia–negative status is determined by contraction forces that do not exceed standardized thresholds 
  • False-negative results are rare; negative test result effectively excludes malignant hyperthermia susceptibility
• Biopsy is evaluated by routine histopathology to assess for evidence of other identifiable neuromuscular disorders that elicit pathologic in vitro contracture test results 

Other diagnostic tools

Malignant hyperthermia clinical grading scale 

• Use to assess qualitative likelihood of a true malignant hyperthermia event after suspected episode triggered by anesthesia; can assist in determining need for further malignant hyperthermia susceptibility testing and risk for early postoperative recrudescence 
• Clinical score determines likelihood that an event is malignant hyperthermia 
  • Clinical parameters
    • Muscle rigidity 
      • Generalized muscular rigidity: 15 points
      • Succinylcholine-induced masseter muscle rigidity: 15 points
    • Muscle breakdown 
      • Creatine kinase level greater than 20,000 international units after anesthesia with succinylcholine use: 15 points
      • Creatine kinase level greater than 10,000 international units after anesthesia without succinylcholine use: 15 points
      • Cola-colored urine perioperatively: 10 points
      • Urine myoglobin level greater than 60 mcg/L or serum myoglobin level greater than 170 mcg/L: 5 points
      • Potassium level greater than 6 mEq/L: 3 points
    • Temperature 
      • Temperature that increases rapidly: 15 points
      • Inappropriate temperature, higher than 38.8°C: 10 points
    • Cardiac involvement 
      • Unexplained sinus tachycardia, ventricular tachycardia, or ventricular fibrillation: 3 points
    • Family history 
      • History of disease in first-degree relative: 15 points
      • History of disease in relative other than first-degree: 5 points
    • Respiratory acidosis 
      • End-tidal CO₂ level greater than 55 mm Hg or PaCO₂ level greater than 60 mm Hg with appropriately controlled ventilation: 15 points
      • End-tidal CO₂ level greater than 60 mm Hg or PaCO₂ level greater than 65 mm Hg with spontaneous breathing: 15 points
      • Inappropriate tachypnea: 10 points
    • Other 
      • Base excess greater than −8 mEq/L or pH less than 7.25: 10 points
      • Rapid reversal of signs with dantrolene therapy: 5 points
  • Scoring 
    • Use single highest score in each category and total individual category scores to determine final score, which indicates likelihood that an adverse event represents a true malignant hyperthermia crisis
    • 0 points: almost never
    • 3 to 9 points: unlikely
    • 10 to 19 points: somewhat less than likely
    • 20 to 34 points: somewhat greater than likely
    • 35 to 49 points: very likely
    • 50 points or more: almost certain

Differential Diagnosis

Most common 

• Common anesthesia-related issues
  • Early signs of malignant hyperthermia episode (eg, rising end-tidal CO₂ level, tachycardia) can be mistaken for common anesthesia-related issues, including inadequate depth of anesthesia, spontaneous breathing, insufficient ventilation, insufficient fresh gas flow, or malfunction of anesthesia machine 
  • Elevated end-tidal CO₂ levels can occur with laparoscopic surgery; patient does not have evidence of muscular rigidity 
  • Masseter muscle spasm occurs in 1 out of every 100 children when anesthesia is induced with halothane and succinylcholine; benign masseter muscle spasm is self-limited, resolving within 2 minutes 
  • Overheating with aggressive intraoperative heating measures can occur, especially in the pediatric population, and is associated with elevated temperature, tachycardia, and occasionally acidosis
  • Identify common anesthesia-related issues by improvement with rapid troubleshooting maneuvers (eg, identification of equipment failure, exclusion of obstruction of ventilation, improvement of masseter spasm in short period of time)
• Sepsis
  • Bacterial infections in the bloodstream trigger an inflammatory reaction and result in systemic symptoms (eg, elevated temperature, tachycardia, tachypnea, acidosis)
  • Patients with sepsis do not typically present with respiratory acidosis (eg, hypercapnia) or muscular signs (eg, muscular rigidity, masseter muscle spasm, rhabdomyolysis) that are common in malignant hyperthermia crisis 
  • Fever related to infection responds to antipyretics; however, hyperpyrexia associated with a malignant hyperthermia crisis does not. Development of an elevated temperature 1 hour or more after anesthesia is unlikely related to a malignant hyperthermia crisis 
  • Differentiate diseases based on clinical presentation and course of illness; confirm sepsis by positive blood culture results
• Neuroleptic malignant syndrome 
  • Hyperthermic syndrome that occurs after ingestion of antipsychotic drugs or dopamine antagonists; presenting symptom complexity and severity is highly variable 
  • Manifestation onset occurs hours to days after exposure to drug and can include muscle rigidity, hyperthermia, mental status changes, autonomic instability, acidosis, and rhabdomyolysis 
  • Differentiating features include prominent central nervous system signs with altered mental status (eg, mild drowsiness, agitation, confusion, delirium, coma), incontinence, dysphagia, and sialorrhea; muscular rigidity tends to be parkinsonian (eg, lead pipe, cogwheel) 
  • Clinical improvement with dantrolene administration does not exclude neuroleptic malignant syndrome as the cause, as dantrolene has been used to successfully treat neuroleptic malignant syndrome 
  • Neuroleptic malignant syndrome is a clinical diagnosis of exclusion; history of antipsychotic drug use or recent change in medication associated with disease, along with subtle differences in clinical presentation, differentiate diseases 
• Serotonin syndrome 
  • Hyperthermic syndrome that occurs after ingestion of serotonergic agent; manifests with a spectrum of symptoms, ranging from mild gastrointestinal distress to agitation with myoclonus, to a hyperthermic crisis with muscular rigidity and rhabdomyolysis 
  • Manifestation onset occurs shortly after addition of or increase in serotonin agonist (eg, MAOI, selective serotonin reuptake inhibitor) or addition of second serotonergic agent (eg, tramadol, dextromethorphan); many drugs, including dangerous recreational drugs (eg, MDMA [3,4-methylenedioxy-methamphetamine], cocaine, amphetamines), alter serotonin metabolism, and ingestion can result in serotonin syndrome
  • Differentiating features include prominent central nervous system signs with altered mental status (eg, confusion, agitation, brief generalized seizures, coma), hyperreflexia, nystagmus, tremor, ataxia, and mydriasis; myoclonus is a common and distinguishing feature of serotonin syndrome. Muscular rigidity tends to be symmetrical and most prominent in lower extremities
  • Serotonin syndrome is a clinical diagnosis of exclusion; history of serotonergic agent use or recent change in medication associated with disease, along with subtle differences in clinical presentation, differentiate diseases
• Toxins 
  • Several stimulant drugs (eg, MDMA [3,4-methylenedioxy-methamphetamine], cocaine, amphetamines) enhance central release of catecholamines and serotonin, as well as inhibit their reuptake and metabolism
  • Patients present with sympathomimetic findings (eg, tachycardia, diaphoresis, hyperpyrexia) that can mimic a malignant hyperthermia crisis; cocaine and MDMA can cause rhabdomyolysis
  • Differentiating features include prominent central nervous system signs with altered mental status, confusion, agitation, and possibly seizures
  • Confirm presence of stimulant drug by urine, hair, oral fluid, sweat, or blood testing methods 
• Thyroid storm 
  • Acute exaggeration of usual thyroid response; represents severe end of thyrotoxicosis spectrum and is characterized by compromised organ function
  • Presentation is very similar to malignant hyperthermia with fever, diaphoresis, tachypnea, hypercapnia, and tachyarrhythmias (eg, tachycardia; supraventricular and, rarely, ventricular arrhythmia); anesthesia or surgery can precipitate acute thyroid crisis symptoms 
  • Most patients will have history of underlying thyroid disease such as Graves disease or toxic multinodular goiter; patients may be taking or have recently taken medications to treat underlying disease (eg, thyroxine, radioactive iodine, propylthiouracil) 
  • Differentiating signs and symptoms can include prominent gastrointestinal symptoms (eg, vomiting, diarrhea, abdominal pain), central nervous system encephalopathic symptoms (eg, agitation, confusion, psychosis, coma), and enlarged thyroid on examination; serum potassium levels are usually within reference range
  • Differentiate diseases by clinical presentation with lack of muscular rigidity and distinguishing ancillary laboratory findings; diagnosis of thyroid crisis is primarily clinical with supporting abnormalities in serum thyroid profile (eg, elevated thyroid hormone levels)
• Pheochromocytoma 
  • Rare catecholamine-secreting neuroendocrine tumor arising in adrenal medulla; similar features include diaphoresis and tachycardia (ie, acute signs of catecholamine excess) that can manifest in the perioperative period
  • Many patients have germline susceptibility mutations for disease; certain hereditary syndromes are associated with an increased risk for pheochromocytoma including neurofibromatosis 1, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease 
  • Differentiating clinical features specific to pheochromocytoma include headache, severe hypertension, weight loss, and hyperglycemia
  • Differentiate by clinical presentation with absent muscular rigidity, absent respiratory acidosis, and prominent hypertension; ancillary test findings supporting pheochromocytoma include elevated 24-hour plasma-free metanephrines 
  • Confirm suspected diagnosis with CT or MRI imaging of adrenal glands; definitive diagnosis is made after tumor resection by histopathology of tumor 

Signs and symptoms of neuroleptic malignant syndrome, serotonin syndrome, and malignant hyperthermia

Clinical features	Neuroleptic malignant syndrome	Serotonin syndrome	Malignant hyperthermia
Triggering agent	Neuroleptic	Proserotonergic agent	Succinylcholine or inhaled anesthetic
Onset	Slow (hours to days)	Fast (minutes to hours)	Very fast to fact (minutes to hours)
Duration	Long (days to weeks)	Short (1-2 days)	Short (1-3 days)
Agitation	Sometimes	Yes	No
Confusion	Yes	Sometimes	Unusual
Hyperactivity	No	Yes	No
Bradykinesia/stupor	Yes	No	Unusual
Myoclonus	No	Yes	No
Shivering	No	Yes/sometimes	No
Tremor	Sometimes	Yes	No
Pupils	Mid-sized	Large	Not specific
Hyperreflexia	No	Yes (especially lower extremities)	No
Rigidity	Severe	Sometimes	Severe
Rigidity type	Extrapyramidal (leadpipe)	Pyramidal (clasp-knife)	Generalized
Hyperpyrexia	Yes	Yes	Severe
Tachypnea	Yes	Yes	Yes
Tachycardia	Yes	Yes	Yes (severe)
Hypertension	Sometimes	Yes	Sometimes
Leukocytosis	Yes	Uncommon	Not typical
Elevated creatine phosphokinase level	Severe	Mild	Severe

Citation: Data from Gillman PK: The serotonin syndrome and its treatment. J Psychopharmacol. 13(1):100-9, 1999; Gillman K: Serotonin toxicity. PsychoTropical Research website. Accessed February 14, 2018. https://psychotropical.info/serotonin-toxicity; Wappler F et al: Pathophysiological role of the serotonin system in malignant hyperthermia. Br J Anaesth. 87(5):794-8, 2001; and Malignant Hyperthermia. In: ToxED [database online]. Tampa, FL: Elsevier; 2012. http://www.toxed-ip.com/ToxEdView.aspx?id=596585#

How is Malignant Hyperthermia treated?

This condition may be treated with:

• Medicines given through an IV.
• A cooling blanket.
• Ice packs applied on the neck, armpit, and groin areas.
• Fluids given through a vein and by mouth.
• A machine to clean your blood if the kidneys are affected (dialysis).

Treatment is started as soon as the health care team recognizes MH.

Goals

• Discontinue triggering agent
• Administer dantrolene
• Treat hyperpyrexia with cooling measures
• Prevent acute kidney injury and renal failure with fluid resuscitation and urinary alkalinization
• Treat hyperkalemia, acidosis, and arrhythmia
• Monitor for complications

Disposition

Admission criteria

Criteria for ICU admission

• All patients with a suspected malignant hyperthermia event require ICU admission for treatment and monitoring 

Recommendations for specialist referral

• Malignant hyperthermia crisis requires a team of experts to guide management; team approach may include critical care, anesthesia, hematology, nephrology, neurology, toxicology, and surgical services 
• Refer patient and family to malignant hyperthermia testing center, in consultation with a genetic counselor to determine best individualized malignant hyperthermia susceptibility testing strategy (eg, caffeine halothane contracture testing, genetic testing) after resolution of an event suggestive of symptomatic malignant hyperthermia 
• Consult a neurologist experienced in evaluation and treatment of rhabdomyolysis during the diagnostic process of a malignant hyperthermia event and to assist in exclusion of other muscular conditions associated with adverse anesthetic reactions 
• Refer all patients with a suspected malignant hyperthermia event to Malignant Hyperthermia Association of the United States resources 

Treatment Options

Early recognition and prompt, aggressive treatment decrease morbidity and mortality associated with disease. Begin treatment at first clinical suspicion of disease; avoid delay in treatment in lieu of diagnostic testing 

• Initial measures include the following:
  • Discontinue triggering agent and terminate surgery as soon as possible 
    • Continue anesthesia with safe nontriggering agents (eg, IV opioids, propofol, ketamine, nondepolarizing muscle relaxants, nitrous oxide); total parenteral anesthesia is preferred 
  • Hyperventilate with 100% oxygen 
  • Additional personnel will be required to assist in management; open malignant hyperthermia cart 
    • Standardized protocols providing a checklist and a stepwise approach to management are available from the Malignant Hyperthermia Association of the United States 
    • Malignant hyperthermia hotline is available 24 hours daily for expert assistance in managing an event 
• Immediately administer dantrolene 
  • Specific pharmacotherapy for an acute malignant hyperthermia episode; partially inhibits calcium efflux from the sarcoplasmic reticulum through the ryanodine receptor 
  • Administer dantrolene until symptoms (eg, rigidity, tachycardia, pyrexia, acidosis, myoglobinemia) resolve 
  • Exceeding recommended maximum initial dose of 10 mg/kg is occasionally required; consider alternate diagnosis when maximum recommended doses are required 
  • Continue dantrolene treatment every 4 to 8 hours for 24 to 36 hours in ICU setting to prevent recrudescence 
• Treat hyperpyrexia; initiate active cooling measures in all hyperthermic patients 
  • Goal is to maintain core temperature below 40°C 
  • Terminate cooling once temperature reaches 38.5°C 
  • Monitor core body temperature 
  • First line measures (less invasive cooling methods)
    • Administer refrigerated IV fluids
      • 2000 to 3000 mL of IV saline 0.9% at 4°C 
    • Begin surface cooling 
      • Topical ice packs applied to groin, axillae, and neck 
      • Fans with forced-air or circulating-water cooling techniques
      • Wet, cold sheets
      • Portable forced-air warming/cooling unit (eg, Bair Hugger) on cool temperature setting
  • Second line invasive cooling measures
    • Rectal, peritoneal, or open cavity iced saline lavage 
      • Nasogastric lavage and bladder irrigation are contraindicated; increased risk of gastric rupture is associated with nasogastric lavage, and bladder irrigation obscures ability to closely monitor urine output 
    • Modern devices with feedback loops (eg, esophageal cooling device) maintain steady body temperature and prevent overcooling, when available 
      • Advantages include ease of application, patient safety, maintenance of target temperature, and control of decooling
  • Antipyretics are ineffective 
• Begin renal protective measures
  • Maintain urine output above 2 mL/kg/hour 
    • Administer fluid resuscitation with IV lactated Ringer solution or 0.9% saline 
    • Consider furosemide or mannitol forced diuresis
  • Consider urinary alkalinization
• Start aggressive supportive care 

Drug therapy

• Ryanodine receptor antagonist
  • Hydantoin
    • Dantrolene sodium 
      • Dantrolene Sodium Solution for injection; Adults, Adolescents, and Children: Initially, minimum 1 mg/kg rapid IV, with 2.5 mg/kg IV advocated by MHAUS; start immediately and repeat until symptoms subside. Repeat if physiologic/metabolic abnormalities recur starting with 1 mg/kg IV. Max cumulative dose: 10 mg/kg (up to 30 mg/kg). Post crisis, give 1 mg/kg IV or more PRN for 1 to 3 days if unable to give orally; MHAUS suggests 1 mg/kg IV every 4 to 6 hours or 0.25 mg/kg/hour IV for 24 hours or more.
      • IV dosage formulations available in the United States 
        • Dantrium and Revonto as a reconstituted solution
          • Each vial contains 20 mg of dantrolene sodium and 3000 mg of mannitol (to maintain tonicity); each vial is reconstituted with 60 mL of sterile water. Mixing of powder to a complete soluble state void of particulate matter is time consuming 
            • Note: sterile water for injection (without a bacteriostatic agent) must be used for reconstitution; precipitate may form if normal saline or dextrose-containing solutions are used for reconstitution 
          • Dosing example: a total of 35 vials are required to treat a 70-kg patient at 10 mg/kg (700 mg maximum cumulative); 1 staff member is dedicated to mixing the vials 
        • Ryanodex as a reconstituted suspension
          • Each vial contains 250 mg of dantrolene with 125 mg of mannitol; each vial is reconstituted with 5 mL of sterile water. Mixing takes a short period of time 
            • Note: sterile water for injection (without a bacteriostatic agent) must be used for reconstitution; precipitate may form if normal saline or dextrose-containing solutions are used for reconstitution 
          • Dosing example: a total of 3 vials are required to treat a 70-kg patient at 10 mg/kg (700 mg maximum cumulative) 
      • Avoid use of calcium channel blockers to treat an episode of malignant hyperthermia; calcium channel blockers are contraindicated for use with dantrolene, owing to risk of hyperkalemia and severe hypotension

Nondrug and supportive care

• Treat acidosis
  • Administer parenteral sodium bicarbonate in patients with pH less than 7.2 
  • Hyperventilate to normocapnia 
• Treat arrhythmias
  • Treat hyperkalemia associated with ECG changes and rapid increases in serum potassium level 
  • Cardiac arrhythmias often resolve with dantrolene administration 
  • Follow advanced life support protocols
    • Amiodarone 
    • β-blockers when tachycardia persists after amiodarone administration 
      • Options include propranolol, metoprolol, and esmolol
      • Exercise caution for precipitation or worsening of hyperkalemia with β-blocker administration
  • Calcium channel blockers are contraindicated; use with dantrolene can result in profound hypotension and hyperkalemia 
• Dialysis may be required to treat impaired renal function secondary to rhabdomyolysis or hyperkalemia 
• Counsel patient on follow-up to an event suggestive of malignant hyperthermia
  • Arrange for definitive diagnostic evaluation with genetic testing and/or in vitro contracture test
  • Advise patients to avoid potential triggers (eg, extreme overheating, extreme exertional stress, potential anesthetic triggers) until further susceptibility testing is complete; routine exercise is not restricted 
  • Consider avoidance of statin drugs owing to possible increased risk of statin-induced myopathy; exact relationship between statin-induced severe myopathy and some malignant hyperthermia–susceptible patients is not yet clearly defined 

Special populations

• Pediatric patients may require shorter dantrolene dosing intervals owing to rapid decreases in plasma concentration in children 
• Use total body water weight for dantrolene dosing in pregnant patients 

Monitoring

• Clinical monitoring during and after suspected event 
  • Monitor vital signs
    • Continuous core temperature monitoring
    • Continuous ECG
    • Continuous pulse oximetry and capnography
  • Laboratory monitoring
    • Frequent potassium, creatine kinase, arterial blood gas, and urine dipstick assessments (for myoglobinemia and myoglobinuria), and frequent glucose measurements 
    • Additional monitoring laboratory tests include serum myoglobin, lactate, and pyruvate levels; use to gauge treatment efficacy 
    • Monitor hepatic function, renal function, and coagulation status
  • Serial clinical examinations to monitor for signs of compartment syndrome
  • Monitor urine output
• Monitor patient for a minimum of 36 to 48 hours in ICU after transfer from postanesthesia care unit 

Complications and Prognosis

Complications

• Risk of complications
  • Higher in patients with higher maximum temperature elevation and delayed dantrolene administration
  • Increases by 2.9-fold with each 2°C increase in maximum temperature 
  • Increases by 1.6-fold with each 30-minute delay in dantrolene administration 
  • Nonfatal complications occur in up to 35% of patients 
• Acute complications
  • Acute renal failure (Related: Acute kidney injury)
  • Compartment syndrome
    • Muscle necrosis can result in extreme swelling, particularly of lower extremities, leading to compartment syndrome 
  • Coma or significantly depressed mental status
    • Occurs in up to 9.8% of patients 
  • Cardiac dysfunction
    • Occurs in up to 9.4% of patients 
  • Pulmonary edema
    • Occurs in up to 8.4% of patients 
  • Disseminated intravascular coagulation
    • Most frequent direct cause of death when body temperature exceeds 41°C 
    • Occurs in up to 7.2% of patients 
  • Hepatic dysfunction
    • Occurs in up to 5.6% of patients 
  • Multiorgan failure, circulatory collapse, cardiac arrhythmia, cardiac arrest, and death
    • Result from severe end-stage malignant hyperthermia 
    • Risk factors for cardiac arrest
      • Development of disseminated intravascular coagulation (50 times higher risk) 
      • Muscular body type (increased muscular mass; 19 times higher risk) 
      • Longer duration between induction and malignant hyperthermia reaction (eg, maximum increase in end-tidal CO₂ development) 
    • Risk factors for death
      • No temperature monitoring (14 times increased risk) 
      • Only skin temperature monitoring and no core temperature monitoring is used (up to 10 times higher risk) 
      • Development of disseminated intravascular coagulation (89 times higher risk) 
• Malignant hyperthermia event recrudescence
  • Occurs in up to 20% of patients; 13 hours is mean time from initial reaction to symptom recurrence 
  • Risk factors for symptom recurrence after initial improvement and stabilization 
    • Muscular body type (ie, increased muscular mass)
    • Longer duration between induction and malignant hyperthermia reaction
    • Temperature increase with initial malignant hyperthermia event
    • Malignant hyperthermia clinical grading score of 35 or greater 

Prognosis

• Prognosis depends on how rapidly malignant hyperthermia crisis is identified and how quickly treatment is started
  • Early treatment typically leads to full recovery
• Morbidity
  • Morbidity rates approach 34.8% 
  • May include prolonged muscle pain, prolonged ICU admission, neurologic injury, renal injury, and cardiac rhythm abnormalities 
  • Full recovery from fulminant event can take months 
• Mortality
  • With early recognition and treatment, mortality rate diminishes to less than 5% 
  • Without dantrolene treatment and aggressive symptomatic care, mortality rate reaches 70% 

Screening and Prevention

Screening

At-risk populations

• Screen patients who have confirmed family history of malignant hyperthermia to determine malignant hyperthermia susceptibility before exposure to any potential triggering agents 
• Consider screening patients with previous poorly explained perioperative rhabdomyolysis or with specific disease states and congenital syndromes that predispose to malignant hyperthermia susceptibility

Screening tests

• Genetic testing for known pathologic variants 
  • Preferred test to evaluate family members at risk when known malignant hyperthermia causative mutation is identified in proband

Prevention

• Perform mandatory, comprehensive, universal preoperative assessment in all patients to assess for family and personal history of malignant hyperthermia, recent history of suspicious episodes under anesthesia, and history of unexplained exertional rhabdomyolysis 
  • Careful preoperative assessment for risk of malignant hyperthermia can avoid exposure of potentially susceptible patient to triggering agents
• Avoid succinylcholine use for elective procedures in patients younger than 12 years 
  • Cautionary use of succinylcholine avoids the following:
    • Malignant hyperthermia event in patient with undiagnosed syndrome or disease associated with malignant hyperthermia
    • Hyperkalemic response in patient with undiagnosed muscular dystrophy
• Avoid use of succinylcholine in patients with any form of muscular disorder, muscular dystrophy, or myotonia; use inhalation agents with caution 
  • Avoidance of depolarizing agents and cautionary use of inhalation agents can avert an adverse anesthesia-related event in these potentially susceptible patient populations
  • Avoid triggering agents in patients with history of severe statin-induced myopathy; abnormalities in RYR1 gene are associated with severe statin-induced myopathy 
• Monitor core temperature in all patients receiving more than brief general anesthesia (ie, more than 20 minutes ) 
  • Early recognition and treatment of malignant hyperthermia event can abort fulminant progression of disease
• Avoid heat stroke in patients at potential risk for disease
  • Advise patients with suspected susceptibility to malignant hyperthermia to use caution in the following settings owing to slight increased risk of heat stroke: 
    • When exercising (avoid extreme exhaustion)
    • Hot, humid environments
• Avoid all contact with triggering substances (eg, all volatile anesthetics, succinylcholine) in patients with confirmed or suspected susceptibility to malignant hyperthermia 
  • Careful preparation of anesthetic machine, including decontamination, is required to prevent exposure to residual volatile anesthetic agents

Seek Additional Information

To learn more about the condition, contact the Malignant Hyperthermia Association of the United States.

• MHAUS website: www.mhaus.org  

Sources

Malignant Hyperthermia Association of the United States. Healthcare professionals. Malignant Hyperthermia Association of the United States website. Accessed February 9, 2018. http://www.mhaus.org/healthcare-professionals Reference