Tests
1st tests to order
discontinuation of inhalation anesthetic
Test
If there is a high index of suspicion that the patient has developed MH as a result of inhalation anesthetic, then in the first instance the inhaled anesthetic should be discontinued as soon as possible. High flow rates of oxygen and air (totaling more than the minute ventilation) should be administered to prevent rebreathing of the exhaled anesthetic agent.
This provides supportive evidence that the inhalation anesthetic was the cause, and a therapeutic trial of dantrolene should be considered.
Result
partial resolution of hypercapnia, tachycardia, and muscle rigidity
exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference)
venous blood gases
Test
This test is easily performed with point-of-care devices on a few drops of blood and should be repeated every 15 to 30 minutes until the patient is stabilized. Blood should be taken from the central venous catheter if feasible.
Findings suggestive of MH include pCO2 >55 mmHg (7.33 kPa), pH <7.25, and a base excess more negative than -8 mEq/L.
Muscle produces excess lactate during a fulminant episode of MH. However, metabolic acidosis may not be seen early in an episode of MH.
These tests are not specific for MH.
Result
hypercapnia (i.e., respiratory with metabolic acidosis)
serum electrolytes
Test
A serum potassium >6 mEq/L is suggestive of MH.[55]
The increase can be due to muscle destruction, acidemia, or acute kidney injury.
Result
hyperkalemia
serum creatinine
Test
Renal function may decline as a result of rhabdomyolysis, and should be monitored regularly.
Result
normal or elevated
therapeutic trial of intravenous dantrolene
Test
Resolution of symptoms following administration of dantrolene provides supportive evidence of an MH episode, but is not diagnostic.[7]
Dantrolene has nonspecific effects to decrease intracellular calcium and metabolism in muscle. It can therefore decrease acidosis, heart rate, and temperature in patients who do not have susceptibility to MH.[72]
Result
resolution of all symptoms
creatine kinase
Test
Elevations in creatine kinase are caused by rhabdomyolysis.
Should be measured at the time of an episode of MH and daily until it is normal.[55]
The first creatine kinase measurement should be obtained from blood taken prior to the first dose of dantrolene, if feasible.
If creatine kinase is markedly elevated and there have been minimal signs of increased metabolism, structural myopathies, such as dystrophinopathy, or enzyme defects, such as carnitine palmitoyltransferase (CPT) deficiency, may be present.[73]
Creatine kinase may not be elevated immediately and can peak 24 to 36 hours after the episode. Creatine kinase is not used to guide therapy. However, decreasing creatine kinase is usually observed after adequate treatment of MH with dantrolene.
Some families susceptible to MH have chronically elevated creatine kinase.
Ideally blood should be drawn without using a tight tourniquet.
Result
>20,000 IU after anesthesia that included succinylcholine or >10,000 IU without exposure to succinylcholine
urinalysis
Test
Dipstick testing is nonspecific and will change color in the presence of hemoglobin, red blood cells (RBCs), or myoglobin. If positive, urine should be sent for microscopic and chemical analysis to look for RBCs and to measure hemoglobin and myoglobin. Absence of RBCs with positive dipstick suggests myoglobinuria.
Result
positive for blood
urine myoglobin
Test
This test should be performed whenever there is suspicion of MH, underlying occult myopathy, or muscle injury, or if urinalysis is positive for blood.
Result
urine myoglobin >60 micrograms/L
platelets
Test
Measures of coagulation function, including platelet count, should be performed as an initial test in all patients.
Disseminated intravascular coagulation, leading to excessive bleeding, may be a complicating feature as MH progresses.
Result
normal or decreased
prothrombin time
Test
Should be measured in all patients.
Disseminated intravascular coagulation, leading to excessive bleeding, may be a complicating feature as MH progresses.[1]
Result
normal or increased
Tests to consider
caffeine halothane contracture test (CHCT)
Test
The test involves minor surgery for muscle biopsy and must be performed at an MH diagnostic testing center, according to the protocol developed by the North American Malignant Hyperthermia Group (NAMHG).[7]
Used to confirm or definitively exclude susceptibility to MH.[74]
The sensitivity is 97% and the specificity 78%.[74] The positive and negative predictive values depend on the prior probability of the patient being susceptible, which is established by the personal and family anesthetic and medical history.
If the test is negative, susceptibility is excluded and other causes must be considered.
Result
a contracture threshold ≥0.5 g with 3% halothane or ≥0.2 g with 2 mM caffeine
in vitro contracture test (IVCT)
Test
The test, as developed by the European Malignant Hyperthermia Group (EMHG),[56] involves minor surgery and must be performed at an MH Diagnostic Testing Center.
Used to confirm or definitively exclude susceptibility to MH.[74]
If an increased contracture threshold occurs only on exposure to one drug the diagnosis of MH equivocal is made. For clinical purposes equivocal patients are treated as if they are susceptible to MH.[56][75]
The sensitivity is 99% and the specificity 94% for the 2-component test.[75]
The positive and negative predictive values depend on the prior probability of the patient being susceptible, which is established by the personal and family anesthetic and medical history.
If the test is negative, susceptibility is excluded and other causes must be considered.
Result
a contracture threshold >0.2 g on exposure to 0.44 mmol/L halothane and 2 mM caffeine or lower drug concentrations
genetic testing
Test
Required in all patients diagnosed with MH susceptibility by CHCT or IVCT to facilitate evaluation of relatives.[63]
Can be carried out in blood or muscle samples.
Tests for mutations in RYR1, the gene implicated in the majority of patients. UK Genetic Testing Network: testing criteria Opens in new window[68] Defects in the alpha-1 subunit of the dihydropyridine receptor (CACNA1S) have also been identified as causative for MH.[23]
This test should also be ordered as part of an autopsy when MH is suspected as the cause of death.
There can be discordance between genetic testing and muscle contracture testing results.[7][60]
If there are existing genetic test results, do not order a duplicate test unless there is uncertainty about the existing result, e.g., the result is inconsistent with the patient’s clinical presentation or the test methodology has changed.[65]
Result
identification of a known MH causative mutation or discovery of new mutations
screen for muscle enzyme deficiencies
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