Materiały źródłowe

• #1 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. […] An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. […] Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. […] The diagnosis of MH is based on clinical presentation or laboratory testing. The principal diagnostic features of MH are unexplained elevation of ETCO2 concentration, muscle rigidity, tachycardia, acidosis, hyperthermia, and hyperkalemia. The variability in the order and time of onset of signs often makes the clinical diagnosis rather difficult.

• #2 Management of malignant hyperthermia: diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4027921/

  Malignant hyperthermia is a potentially lethal inherited disorder characterized by disturbance of calcium homeostasis in skeletal muscle. […] Since the clinical presentation of malignant hyperthermia is highly variable, survival of affected patients depends largely on early recognition of the symptoms characteristic of malignant hyperthermia, and immediate action on the part of the attending anesthesiologist. Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current therapeutic guidelines, as well as adequate management of anesthesia in patients susceptible to malignant hyperthermia, are discussed in this review. […] Diagnostic testing for MH susceptibility can be indicated after an incident suspicious for MH in patients with nonspecific myopathy or persistently elevated serum creatine kinase and in families with history of MH. For about 30 years, the in vitro contracture test using halothane and caffeine has been the gold standard for determining susceptibility to MH independent of a clinical MH event. […] In summary, in vitro contracture testing and molecular genetic testing are the two approved methods for diagnosing susceptibility to MH. Both procedures require specialized testing centers and are not suitable for use as screening methods unless there is immediate suspicion of predisposition to MH.

• #3 Management of malignant hyperthermia: diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4027921/

  Malignant hyperthermia is a potentially lethal inherited disorder characterized by disturbance of calcium homeostasis in skeletal muscle. […] Since the clinical presentation of malignant hyperthermia is highly variable, survival of affected patients depends largely on early recognition of the symptoms characteristic of malignant hyperthermia, and immediate action on the part of the attending anesthesiologist. Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current therapeutic guidelines, as well as adequate management of anesthesia in patients susceptible to malignant hyperthermia, are discussed in this review. […] Diagnostic testing for MH susceptibility can be indicated after an incident suspicious for MH in patients with nonspecific myopathy or persistently elevated serum creatine kinase and in families with history of MH. For about 30 years, the in vitro contracture test using halothane and caffeine has been the gold standard for determining susceptibility to MH independent of a clinical MH event. […] In summary, in vitro contracture testing and molecular genetic testing are the two approved methods for diagnosing susceptibility to MH. Both procedures require specialized testing centers and are not suitable for use as screening methods unless there is immediate suspicion of predisposition to MH.

• #4 Malignant hyperthermia – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/malignant-hyperthermia/diagnosis-treatment/drc-20353752

  Malignant hyperthermia is diagnosed based on signs and symptoms, monitoring during and immediately after anesthesia, and lab tests to identify complications. […] Testing to find out if you’re at increased risk of malignant hyperthermia (susceptibility testing) may be recommended if you have risk factors. […] Genetic testing can identify the gene change that shows you have the genetic disorder called malignant hyperthermia susceptibility (MHS). […] In some cases, your health care provider may recommend a muscle biopsy if you’re at risk of malignant hyperthermia. […] If you’ve experienced malignant hyperthermia due to certain anesthesia drugs, exercising during excessive heat and humidity could trigger another reaction. […] Also, check with your health care provider to see if you should have genetic testing to determine if you have a genetic disorder that puts you at risk of malignant hyperthermia.

• #5 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anaesthetics or succinylcholine (suxamethonium). […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] In MH susceptible patients, this exposure may produce a clinical MH episode: a dramatic increase in metabolism, which leads to critical temperature elevation and rhabdomyolysis with potential hyperkalaemia. […] Key diagnostic factors include presence of risk factors, exposure to potent inhalation anaesthetic and/or succinylcholine (suxamethonium), susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity.

• #6 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anaesthetics or succinylcholine (suxamethonium). […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] In MH susceptible patients, this exposure may produce a clinical MH episode: a dramatic increase in metabolism, which leads to critical temperature elevation and rhabdomyolysis with potential hyperkalaemia. […] Key diagnostic factors include presence of risk factors, exposure to potent inhalation anaesthetic and/or succinylcholine (suxamethonium), susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity.

• #7 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #8 Malignant Hyperthermia – Injuries; Poisoning – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/injuries-poisoning/heat-illness/malignant-hyperthermia

  Malignant hyperthermia is a life-threatening elevation in body temperature usually resulting from a hypermetabolic response to concurrent use of a depolarizing muscle relaxant and a potent, volatile inhalational general anesthetic. Diagnosis is clinical; patients at risk can be tested for their susceptibility. […] The diagnosis is suspected by the appearance of typical symptoms and signs within 10 minutes to, occasionally, several hours after inhalational anesthesia is begun. Early diagnosis can be facilitated by prompt recognition of jaw rigidity, tachypnea, tachycardia, and increased end-tidal CO2. […] Testing for susceptibility to malignant hyperthermia is recommended for people at risk based on a family history of the disorder or a personal history of a severe or incompletely characterized previous adverse reaction to general anesthesia. The caffeine halothane contracture test (CHCT) is the most accurate. It measures the response of a muscle tissue sample to caffeine and halothane. Genetic testing is also easily available but may be limited based on the type of mutation detected.

• #9 Malignant Hyperthermia – Injuries; Poisoning – Merck Manual Professional Edition

  https://www.merckmanuals.com/professional/injuries-poisoning/heat-illness/malignant-hyperthermia

  Malignant hyperthermia is a life-threatening elevation in body temperature usually resulting from a hypermetabolic response to concurrent use of a depolarizing muscle relaxant and a potent, volatile inhalational general anesthetic. Diagnosis is clinical; patients at risk can be tested for their susceptibility. […] The diagnosis is suspected by the appearance of typical symptoms and signs within 10 minutes to, occasionally, several hours after inhalational anesthesia is begun. Early diagnosis can be facilitated by prompt recognition of jaw rigidity, tachypnea, tachycardia, and increased end-tidal CO2. […] Testing for susceptibility to malignant hyperthermia is recommended for people at risk based on a family history of the disorder or a personal history of a severe or incompletely characterized previous adverse reaction to general anesthesia. The caffeine halothane contracture test (CHCT) is the most accurate. It measures the response of a muscle tissue sample to caffeine and halothane. Genetic testing is also easily available but may be limited based on the type of mutation detected.

• #10 Malignant Hyperthermia and Related Conditions – Cancer Therapy Advisor

  https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/critical-care-medicine/malignant-hyperthermia-and-related-conditions/

  The best way to approach the diagnosis of malignant hyperthermia is through a clinical vignette, which follows: […] You and the anesthesiologist begin to discuss the possible reasons for this constellation of findings, and it is suggested that this might be malignant hyperthermia (MH). […] While not pathognomonic, the sine qua non of a full blown MH episode, however, is the mixed respiratory-metabolic acidosis in the setting of general anesthesia with volatile anesthetics, whether succinylcholine is used or not, and in the presence a rising end-tidal CO2 that cannot be controlled with increasing minute ventilation. […] There are no specific tests that can confirm MH in the acute phase. It is a constellation of findings in the setting of a general anesthetic with volatile anesthetics.

• #11 RYANODEX® | What is malignant hyperthermia (MH)?

  https://www.ryanodex.com/about-mh/

  Malignant hyperthermia (MH) is a pharmacogenetic disease that causes hypermetabolism, a fast rise in body temperature and severe muscle contractions when an affected person receives general anesthesia using volatile anesthetics or the paralytic succinylcholine. […] The signs and symptoms of MH include hypercarbia, muscle rigidity, fast-rising body temperature, tachycardia, myolysis, increased ETCO2, hyperkalemia, and acidosis. Immediate treatment with the drug dantrolene sodium usually reverses the signs of MH. […] There are multiple signs that may prompt a diagnosis of MH by anesthesia practitioners. […] Hypercarbia is often the first clinical sign of MH. Other early signs include sinus tachycardia and masseter spasm. […] Stopping the triggering agents and administering dantrolene sodium to the patient as quickly as possible are the greatest priorities in an MH crisis. […] Every delay in treatment increases the risk of further complication during an MH crisis. […] The risk of complications may increase to 30% with a 20-minute delay in treating MH from its first symptom.

• #12 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anaesthetics or succinylcholine (suxamethonium). […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] In MH susceptible patients, this exposure may produce a clinical MH episode: a dramatic increase in metabolism, which leads to critical temperature elevation and rhabdomyolysis with potential hyperkalaemia. […] Key diagnostic factors include presence of risk factors, exposure to potent inhalation anaesthetic and/or succinylcholine (suxamethonium), susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity.

• #13 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane, isoflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stressors such as vigorous exercise and heat. […] An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. […] Diagnostic testing involves the in vitro contracture response of biopsied muscle to halothane, caffeine, and in some centres ryanodine and 4-chloro-m-cresol. […] The diagnosis of MH is based on clinical presentation or laboratory testing. The principal diagnostic features of MH are unexplained elevation of ETCO2 concentration, muscle rigidity, tachycardia, acidosis, hyperthermia, and hyperkalemia. The variability in the order and time of onset of signs often makes the clinical diagnosis rather difficult.

• #14 Malignant Hyperthermia. Malignany Hyperpyrexia information

  https://patient.info/doctor/malignant-hyperthermia

  Diagnosing malignant hyperthermia […] Diagnosis is made by muscle biopsy. It involves an in vitro contracture test using a small segment of skeletal muscle. Caffeine, halothane, succinylcholine and increased potassium induce exaggerated contractions. The tests show enormous variability and each laboratory must standardise and validate its procedures. […] An increase in end-tidal carbon dioxide despite increased minute ventilation provides an early diagnostic clue. […] DNA analysis has been of increasing importance. Only a small blood sample is required to screen for an RYR1 mutation. However, DNA testing cannot be used as the sole test for malignant hyperthermia susceptibility.

• #15 Orphanet: Malignant hyperthermia of anesthesia

  https://www.orpha.net/en/disease/detail/423

  Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, to stresses such as vigorous exercise and heat. […] An early diagnostic clue is elevation of end-expired carbon dioxide. Arterial blood gas analyses reveal a combination of respiratory and metabolic acidosis with negative base excess, lactemia, hypercapnia, and hypoxemia. Diagnostic testing relies on assessing the in-vitro contracture response of biopsied muscle to halothane and caffeine. Other drugs such as ryanodine and 4-chloro-m-cresol have also been used but are not part of a standard protocol. A diagnosis of MH is given when contracture forces exceed the given threshold after exposure to these substances. […] As the sensitivity of genetic testing increases, molecular genetics will be increasing useful for identifying those at risk.

• #16 Malignant Hyperthermia Differential Diagnoses

  https://emedicine.medscape.com/article/2231150-differential

  In addition to the conditions listed in the differential diagnosis, there are a number of other conditions and circumstances that may mimic malignant hyperthermia (MH), including the following: […] Although its clinical picture is similar to that of MH, neuroleptic malignant syndrome (NMS) is caused by the central effects of drugs with dopamine antagonist properties, including antipsychotics (eg, haloperidol) and antiemetics (eg, metoclopramide and droperidol). […] Treatment consists of stopping the drug, controlling the symptoms, and administering dopamine agonists (eg, bromocriptine). Dantrolene will lower the temperature. […] A clinical grading scale to predict malignant hyperthermia susceptibility.

• #17 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  The gold standard for diagnosis of MH is currently an in vitro contracture test, which is based on contracture of muscle fibers in the presence of halothane or caffeine. […] Using the EMHG protocol, an individual is considered susceptible to MH (MHS) when both caffeine and halothane test results are positive. An individual is considered not susceptible to MH (MHN) when both tests are negative. An individual is also diagnosed as MHS when either a positive halothane or caffeine test alone is obtained and these individuals are designated MHS(h) or MHS(c). […] A clinical grading scale was developed by Larach and colleagues through an iterative Delphic process in order to assist in clinical diagnosis. […] The sensitivity of 99 % and a specificity of 94 % are obtained with the EMHG protocol while figures of 97 % sensitivity and 78 % specificity are reported for the NAMHG protocol, which provide some confidence to the results obtained.

• #18 Malignant hyperthermia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-21

  Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle that presents as a hypermetabolic response to potent volatile anesthetic gases such as halothane, sevoflurane, desflurane and the depolarizing muscle relaxant succinylcholine, and rarely, in humans, to stresses such as vigorous exercise and heat. […] Early recognition of the signs of MH, specifically elevation of end-expired carbon dioxide, provides the clinical diagnostic clues. […] The principal diagnostic features of MH are unexplained elevation of end-tidal carbon dioxide (ETCO2) concentration, muscle rigidity, tachycardia, acidosis, hyperthermia, and hyperkalemia. […] A clinical grading scale was developed by Larach and colleagues in order to assist in clinical diagnosis. […] The value of the grading scale is mainly in identifying those subjects with the most convincing episodes of MH for subsequent evaluation of the sensitivity and specificity of the diagnostic tests.

• #19 Management of malignant hyperthermia: diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4027921/

  Malignant hyperthermia is a potentially lethal inherited disorder characterized by disturbance of calcium homeostasis in skeletal muscle. […] Since the clinical presentation of malignant hyperthermia is highly variable, survival of affected patients depends largely on early recognition of the symptoms characteristic of malignant hyperthermia, and immediate action on the part of the attending anesthesiologist. Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current therapeutic guidelines, as well as adequate management of anesthesia in patients susceptible to malignant hyperthermia, are discussed in this review. […] Diagnostic testing for MH susceptibility can be indicated after an incident suspicious for MH in patients with nonspecific myopathy or persistently elevated serum creatine kinase and in families with history of MH. For about 30 years, the in vitro contracture test using halothane and caffeine has been the gold standard for determining susceptibility to MH independent of a clinical MH event. […] In summary, in vitro contracture testing and molecular genetic testing are the two approved methods for diagnosing susceptibility to MH. Both procedures require specialized testing centers and are not suitable for use as screening methods unless there is immediate suspicion of predisposition to MH.

• #20 Malignant Hyperthermia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430828/

  Malignant hyperthermia (MH) is a hereditary disorder of skeletal muscle that classically presents as a hypermetabolic response to halogenated anesthetic gasses and/or the depolarizing muscle relaxant succinylcholine. […] The gold standard in the laboratory diagnosis of malignant hyperthermia is the caffeine halothane contracture test (CHCT), although genetic testing is rapidly advancing and may one day replace the muscle biopsy. […] The CHCT involves exposing a sample of live muscle fibers to halothane and caffeine to determine the muscle response to halogenated anesthetics. […] Genetic testing for mutations of the RYR1 or other associated genetic variants associated with malignant hyperthermia is becoming increasingly more valuable as the testing improves. […] It requires a high index of suspicion of malignant hyperthermia to effect a timely and correct diagnosis and treatment. […] If signs of hypermetabolism such as metabolic and respiratory acidosis or an elevation in body temperature accompany the muscle spasm, a diagnosis of malignant hyperthermia must be considered.

• #21 Testing for MH — European Malignant Hyperthermia Group

  https://www.emhg.org/testing-for-mh

  The decision to pursue either DNA screening or muscle biopsy and IVCT in the first instance will be made on a patient-by-patient basis by the MH diagnostic centre in consultation with the patient and their health-care funder. […] Investigation of malignant hyperthermia (MH) susceptibility initially involves clinical evaluation of a patients risk based on their anaesthetic and medical history, and relevant family history. Further investigation is indicated when increased risk of susceptibility to MH cannot be excluded. The highest sensitivity for detecting susceptibility to MH is provided by pharmacological challenge tests carried out on freshly excised skeletal muscle under controlled laboratory conditions. These tests, when carried out according to the following protocol are collectively referred to as the in vitro contracture test, or IVCT. The IVCT is recommended for individuals considered to be at increased risk of MH either as a first-line test or when DNA analyses have failed to confirm the high-risk status.

• #22 How To Diagnose MH: Malignant Hyperthermia Investigation Unit, PIE, hospital education, anesthesia

  http://pie.med.utoronto.ca/MH/MH_content/diagnoseMH.html

  The most accurate diagnostic test for MH is a specific muscle biopsy from the leg. This biopsy measures the contraction of the muscle with exposure to caffeine and halothane. This test, which is called the Caffeine-Halothane Contracture test (CHCT), still remains the „gold standard” to establish MH susceptibility in patients. […] In 2005, molecular genetic testing for MH was introduced. Since DNA can be extracted from blood cells, it can be searched for genetic mutations known to cause MH. However, the genetic test yields a low sensitivity for diagnosis of MH, and in the majority of situations cannot replace CHCT. At the moment, the test is limited to specific individuals already known to be MH-susceptible and their family members.

• #23 Malignant Hyperthermia Workup: Caffeine Halothane Contracture Test, Molecular Genetic Testing

  https://emedicine.medscape.com/article/2231150-workup

  The caffeine halothane contracture test (CHCT) is the criterion standard for establishing the diagnosis of malignant hyperthermia (MH). […] A negative CHCT result is the only way to prove that a patient is not susceptible to MH. […] Molecular genetic testing (DNA testing) is less expensive and less invasive than the muscle contracture test. […] A CHCT is needed to determine MH-negative status.

• #24 Malignant Hyperthermia Diagnostic Center | Medical School

  https://med.umn.edu/vhlab/clinical

  The in vitro contracture test is performed in accordance with the guidelines provided by the North American Malignant Hyperthermia Registry, and is highly accurate for diagnosing susceptibility to malignant hyperthermia. […] The results of the contracture test are described to the patient in terms of their muscle’s sensitivity to halothane and caffeine in vitro. This test has been considered 95% accurate. […] An abnormal contracture is indicative of susceptibility to malignant hyperthermia. […] A MH diagnosis can be made with DNA analyses and family members do not need to have the muscle biopsy for confirmation. […] The muscle biopsy is performed on an outpatient basis. A muscle sample is removed from the vastus lateralis or vastus medialis (thigh) muscles using anesthesia known NOT to trigger malignant hyperthermia.

• #25 Malignant Hyperthermia Information for Patients: MH Investigation Unit, PIE, hospital education, anesthesia, CHCT, diagnosis, treatment

  http://pie.med.utoronto.ca/MH/MH_content/patientDT.html

  MH is suspected if a person has a family history of severe reactions during anesthesia. The most accurate diagnostic test for MH involves a specialized biopsy from a leg muscle. This involves surgical removal under MH-safe anesthesia of a piece of muscle, usually subjected to standardized laboratory testing. The muscle test is usually performed on an outpatient basis in two centres across Canada: Toronto General Hospital and the Ottawa Hospital, Civic Site. The muscle biopsy test remains the „gold standard” to determine MH susceptibility in individuals. […] At present, there is no simple, non-invasive test available for patients. A Canadian team, headed by Dr. David H. MacLennan at the University of Toronto, has devised a simple DNA test for pigs affected by MH. Several research teams around the world are working on ways to diagnose human MH by testing DNA from blood samples. Unfortunately, no single DNA test can be applied to the general population yet, but work is progressing in an exciting direction. Noninvasive testing of muscle using magnetic resonance imaging (MRI), is still under intense research. Several other testing methods have been studied, but have proven unreliable because of a large number of false positive and false negative results.

• #26 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  The gold standard for diagnosis of MH is currently an in vitro contracture test, which is based on contracture of muscle fibers in the presence of halothane or caffeine. […] Using the EMHG protocol, an individual is considered susceptible to MH (MHS) when both caffeine and halothane test results are positive. An individual is considered not susceptible to MH (MHN) when both tests are negative. An individual is also diagnosed as MHS when either a positive halothane or caffeine test alone is obtained and these individuals are designated MHS(h) or MHS(c). […] A clinical grading scale was developed by Larach and colleagues through an iterative Delphic process in order to assist in clinical diagnosis. […] The sensitivity of 99 % and a specificity of 94 % are obtained with the EMHG protocol while figures of 97 % sensitivity and 78 % specificity are reported for the NAMHG protocol, which provide some confidence to the results obtained.

• #27 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  The gold standard for diagnosis of MH is currently an in vitro contracture test, which is based on contracture of muscle fibers in the presence of halothane or caffeine. […] Using the EMHG protocol, an individual is considered susceptible to MH (MHS) when both caffeine and halothane test results are positive. An individual is considered not susceptible to MH (MHN) when both tests are negative. An individual is also diagnosed as MHS when either a positive halothane or caffeine test alone is obtained and these individuals are designated MHS(h) or MHS(c). […] A clinical grading scale was developed by Larach and colleagues through an iterative Delphic process in order to assist in clinical diagnosis. […] The sensitivity of 99 % and a specificity of 94 % are obtained with the EMHG protocol while figures of 97 % sensitivity and 78 % specificity are reported for the NAMHG protocol, which provide some confidence to the results obtained.

• #28 Malignant hyperthermia | MedLink Neurology

  https://www.medlink.com/articles/malignant-hyperthermia

  The only highly sensitive diagnostic test for malignant hyperthermia susceptibility is the caffeine and halothane contracture test of biopsied skeletal muscle. […] The sensitivity and specificity of the North American Malignant Hyperthermia Group Protocol has been estimated in humans to be about 97% and 78%, respectively, using a 2-component test. […] In patients who have had normal caffeine halothane contracture tests (ie, malignant hyperthermia non-susceptible), there are no reported cases of malignant hyperthermia during subsequent general anesthetics that include triggering agents. […] Although genetic testing is rapidly evolving, diagnosis of malignant hyperthermia via genetic analysis alone remains problematic due to great genetic and phenotypic heterogeneity and the high prevalence of variants of unknown significance in RYR1 and CACNA1S.

• #29 Malignant hyperthermia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-21

  The „gold standard” for diagnosis of MH is currently the in vitro contracture test (IVCT), which is based on contracture of muscle fibres in the presence of halothane or caffeine. […] DNA analysis, however, offers an alternative to the IVCT, requiring only a blood specimen, which can be sent to an accredited diagnostic laboratory. […] The identification of causative mutations suggests the widespread use of DNA testing for MH, however, this is confounded by the metabolic complexity and genetic heterogeneity of the disorder. […] In summary, because of the heterogeneity of the disorder, as well as discordance within families, a negative DNA result cannot be used to rule out MH susceptibility. […] The guidelines set down by the EMHG requires contracture testing prior to genetic testing in a family.

• #30 Malignant Hyperthermia: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17945-malignant-hyperthermia

  Malignant hyperthermia is a genetic disease that causes a life-threatening reaction to certain anesthesia medications. The disorder usually runs in families and is treatable. […] If you or your healthcare provider think you may be susceptible to malignant hyperthermia due to family history, your provider may recommend special tests and procedures to diagnose it, including: […] Caffeine halothane contracture test (CHCT). For this test, a provider takes a muscle biopsy and exposes the live muscle sample to halothane and caffeine to analyze it for a reaction to an anesthesia gas. […] Genetic testing. Genetic testing can reveal mutations in RYR1, STAC3 and CACNA1S locations on DNA. There are over 45 mutations that are recognized as diagnostic for malignant hyperthermia. […] If untreated, malignant hyperthermia is almost always fatal. The death rate is 3% to 5%, even when the condition is properly treated.

• #31 Malignant Hyperthermia Susceptibility Panel Test – PreventionGenetics

  https://www.preventiongenetics.com/testInfo?val=Malignant-Hyperthermia-Susceptibility-Panel

  Ideal MH test candidates have a family history of MH along with either a positive in vitro contracture test or a clear MH event. Testing should begin in such a family member. If a causative mutation is identified, other family members can be screened at much reduced cost. Other, less ideal candidates for testing are those with just a family history of MH or those with a MH-like event and no family history. […] Malignant Hyperthermia (MH) Susceptibility may be caused by mutations in at least three genes: RYR1, CACNA1S and STAC3. Causative mutations in RYR1 are much more common than causative mutations in the other two genes. […] Sensitivity for ideal test candidates (family history of MH plus either positive in vitro contracture test or an MH event) is approximately 60%. […] This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

• #32 Malignant hyperthermia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/malignant-hyperthermia/

  Malignant hyperthermia occurs in 1 in 5,000 to 50,000 instances in which people are given anesthetic gases. […] Susceptibility to malignant hyperthermia is probably more frequent, because many people with an increased risk of this condition are never exposed to drugs that would trigger a reaction and bring them to medical attention. […] Certain variations of the RYR1 and CACNA1S genes increase the risk of developing malignant hyperthermia. […] Mutations in the RYR1 gene account for most cases of malignant hyperthermia susceptibility, while mutations in the CACNA1S gene cause less than 1 percent of all cases of malignant hyperthermia susceptibility. […] Up to half of people with malignant hyperthermia susceptibility do not have a mutation in one of the known genes. […] Malignant hyperthermia susceptibility is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of a severe reaction to certain drugs used during surgery.

• #33 Malignant hyperthermia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/malignant-hyperthermia/

  Malignant hyperthermia occurs in 1 in 5,000 to 50,000 instances in which people are given anesthetic gases. […] Susceptibility to malignant hyperthermia is probably more frequent, because many people with an increased risk of this condition are never exposed to drugs that would trigger a reaction and bring them to medical attention. […] Certain variations of the RYR1 and CACNA1S genes increase the risk of developing malignant hyperthermia. […] Mutations in the RYR1 gene account for most cases of malignant hyperthermia susceptibility, while mutations in the CACNA1S gene cause less than 1 percent of all cases of malignant hyperthermia susceptibility. […] Up to half of people with malignant hyperthermia susceptibility do not have a mutation in one of the known genes. […] Malignant hyperthermia susceptibility is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to increase the risk of a severe reaction to certain drugs used during surgery.

• #34 Malignant Hyperthermia Susceptibility Panel Test – PreventionGenetics

  https://www.preventiongenetics.com/testInfo?val=Malignant-Hyperthermia-Susceptibility-Panel

  Ideal MH test candidates have a family history of MH along with either a positive in vitro contracture test or a clear MH event. Testing should begin in such a family member. If a causative mutation is identified, other family members can be screened at much reduced cost. Other, less ideal candidates for testing are those with just a family history of MH or those with a MH-like event and no family history. […] Malignant Hyperthermia (MH) Susceptibility may be caused by mutations in at least three genes: RYR1, CACNA1S and STAC3. Causative mutations in RYR1 are much more common than causative mutations in the other two genes. […] Sensitivity for ideal test candidates (family history of MH plus either positive in vitro contracture test or an MH event) is approximately 60%. […] This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

• #35

  https://link.springer.com/article/10.1007/s12630-018-1108-0

  The Clinical Grading Scale (CGS) a set of clinical diagnostic criteria for MH has been widely and effectively used to rank adverse reactions to anesthetics from unlikely MH to almost certain MH. […] Currently, there are two diagnostic approaches for patients potentially at increased risk of developing an MH reaction. These include molecular genetic testing and the ex vivo muscle contracture testing, i.e., the caffeine-halothane contracture test (CHCT) in North America and the in vitro contracture test (IVCT) elsewhere. […] The contracture test measures the contracture response of excised skeletal muscle strips to caffeine and halothane and is regarded as the gold standard diagnostic test for MH susceptibility. […] Genetic testing for MH has been seen as an advanced alternative to MH biopsy testing. […] In summary, due to the complex nature of MH, a negative genetic test result cannot be used to rule out a patients MH susceptibility; patients with negative genetic results should be offered contracture testing to confirm their MH-negative status.

• #36 Malignant hyperthermia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-21

  The „gold standard” for diagnosis of MH is currently the in vitro contracture test (IVCT), which is based on contracture of muscle fibres in the presence of halothane or caffeine. […] DNA analysis, however, offers an alternative to the IVCT, requiring only a blood specimen, which can be sent to an accredited diagnostic laboratory. […] The identification of causative mutations suggests the widespread use of DNA testing for MH, however, this is confounded by the metabolic complexity and genetic heterogeneity of the disorder. […] In summary, because of the heterogeneity of the disorder, as well as discordance within families, a negative DNA result cannot be used to rule out MH susceptibility. […] The guidelines set down by the EMHG requires contracture testing prior to genetic testing in a family.

• #37 Malignant Hyperthermia | Atrium Health Wake Forest Baptist

  https://www.wakehealth.edu/condition/m/malignant-hyperthermia

  Malignant hyperthermia (MH) is a rare, inherited condition that causes muscle rigidity, high fever, fast heart rate, and abnormal muscle contractions when someone with the disease receives general anesthesia. […] In general, testing for MH-susceptibility is recommended in 2 groups of patients: Anyone who experienced a MH crisis or questionable MH crisis during anesthesia that involved trigger agents. […] Tests may include: Blood clotting studies, Blood work, Genetic testing, Muscle biopsy. […] Muscle biopsy testing is advised in all children of a parent known to be MH-susceptible. Currently there are 5 biopsy and testing centers in North America and Wake Forest Baptist Health is one of them. […] Muscle biopsy and CHCT remain the gold standard test for diagnosis.

• #38 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Use to determine genetic etiology of MH susceptibility (MHS) in individuals with known or suspected clinical history of MH. […] Use to assess for MHS in healthy individuals with family history of MH. […] Episodes of MH require prompt diagnosis and treatment to reduce mortality. MH susceptibility may be assessed by functional laboratory testing (caffeine-halothane contracture test, otherwise known as in vitro contracture test) or molecular testing of MH-associated genes. […] Muscle biopsy and contracture testing is recommended for: Individuals with suspected clinical history of MH, First-degree relatives of a proband with clinical history of MH, if proband cannot be tested or causative familial variant not known, At-risk family members when the MH-causing variant is not known, Individuals with suspected personal or known family history of MHS prior to military service.

• #39 Malignant Hyperthermia | Atrium Health Wake Forest Baptist

  https://www.wakehealth.edu/condition/m/malignant-hyperthermia

  Malignant hyperthermia (MH) is a rare, inherited condition that causes muscle rigidity, high fever, fast heart rate, and abnormal muscle contractions when someone with the disease receives general anesthesia. […] In general, testing for MH-susceptibility is recommended in 2 groups of patients: Anyone who experienced a MH crisis or questionable MH crisis during anesthesia that involved trigger agents. […] Tests may include: Blood clotting studies, Blood work, Genetic testing, Muscle biopsy. […] Muscle biopsy testing is advised in all children of a parent known to be MH-susceptible. Currently there are 5 biopsy and testing centers in North America and Wake Forest Baptist Health is one of them. […] Muscle biopsy and CHCT remain the gold standard test for diagnosis.

• #40 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Use to determine genetic etiology of MH susceptibility (MHS) in individuals with known or suspected clinical history of MH. […] Use to assess for MHS in healthy individuals with family history of MH. […] Episodes of MH require prompt diagnosis and treatment to reduce mortality. MH susceptibility may be assessed by functional laboratory testing (caffeine-halothane contracture test, otherwise known as in vitro contracture test) or molecular testing of MH-associated genes. […] Muscle biopsy and contracture testing is recommended for: Individuals with suspected clinical history of MH, First-degree relatives of a proband with clinical history of MH, if proband cannot be tested or causative familial variant not known, At-risk family members when the MH-causing variant is not known, Individuals with suspected personal or known family history of MHS prior to military service.

• #41 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Use to determine genetic etiology of MH susceptibility (MHS) in individuals with known or suspected clinical history of MH. […] Use to assess for MHS in healthy individuals with family history of MH. […] Episodes of MH require prompt diagnosis and treatment to reduce mortality. MH susceptibility may be assessed by functional laboratory testing (caffeine-halothane contracture test, otherwise known as in vitro contracture test) or molecular testing of MH-associated genes. […] Muscle biopsy and contracture testing is recommended for: Individuals with suspected clinical history of MH, First-degree relatives of a proband with clinical history of MH, if proband cannot be tested or causative familial variant not known, At-risk family members when the MH-causing variant is not known, Individuals with suspected personal or known family history of MHS prior to military service.

• #42 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Use to determine genetic etiology of MH susceptibility (MHS) in individuals with known or suspected clinical history of MH. […] Use to assess for MHS in healthy individuals with family history of MH. […] Episodes of MH require prompt diagnosis and treatment to reduce mortality. MH susceptibility may be assessed by functional laboratory testing (caffeine-halothane contracture test, otherwise known as in vitro contracture test) or molecular testing of MH-associated genes. […] Muscle biopsy and contracture testing is recommended for: Individuals with suspected clinical history of MH, First-degree relatives of a proband with clinical history of MH, if proband cannot be tested or causative familial variant not known, At-risk family members when the MH-causing variant is not known, Individuals with suspected personal or known family history of MHS prior to military service.

• #43 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Use to determine genetic etiology of MH susceptibility (MHS) in individuals with known or suspected clinical history of MH. […] Use to assess for MHS in healthy individuals with family history of MH. […] Episodes of MH require prompt diagnosis and treatment to reduce mortality. MH susceptibility may be assessed by functional laboratory testing (caffeine-halothane contracture test, otherwise known as in vitro contracture test) or molecular testing of MH-associated genes. […] Muscle biopsy and contracture testing is recommended for: Individuals with suspected clinical history of MH, First-degree relatives of a proband with clinical history of MH, if proband cannot be tested or causative familial variant not known, At-risk family members when the MH-causing variant is not known, Individuals with suspected personal or known family history of MHS prior to military service.

• #44 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Use to determine genetic etiology of MH susceptibility (MHS) in individuals with known or suspected clinical history of MH. […] Use to assess for MHS in healthy individuals with family history of MH. […] Episodes of MH require prompt diagnosis and treatment to reduce mortality. MH susceptibility may be assessed by functional laboratory testing (caffeine-halothane contracture test, otherwise known as in vitro contracture test) or molecular testing of MH-associated genes. […] Muscle biopsy and contracture testing is recommended for: Individuals with suspected clinical history of MH, First-degree relatives of a proband with clinical history of MH, if proband cannot be tested or causative familial variant not known, At-risk family members when the MH-causing variant is not known, Individuals with suspected personal or known family history of MHS prior to military service.

• #45 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Use to determine genetic etiology of MH susceptibility (MHS) in individuals with known or suspected clinical history of MH. […] Use to assess for MHS in healthy individuals with family history of MH. […] Episodes of MH require prompt diagnosis and treatment to reduce mortality. MH susceptibility may be assessed by functional laboratory testing (caffeine-halothane contracture test, otherwise known as in vitro contracture test) or molecular testing of MH-associated genes. […] Muscle biopsy and contracture testing is recommended for: Individuals with suspected clinical history of MH, First-degree relatives of a proband with clinical history of MH, if proband cannot be tested or causative familial variant not known, At-risk family members when the MH-causing variant is not known, Individuals with suspected personal or known family history of MHS prior to military service.

• #46 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Molecular MHS testing is recommended for: Individuals with confirmed/suspected clinical MH event or positive contracture test, Relatives of individuals with a positive contracture test or known MHS variant. […] A clinical grading scale has been proposed to assist in determining if an adverse anesthetic event is a clinical MH event. […] The European Malignant Hyperthermia Group has released guidelines for the investigation of MH susceptibility. […] A negative result does not exclude a diagnosis of MHS. […] Diagnostic errors can occur due to rare sequence variations. […] The following may not be detected: Deletions/duplications/insertions of any size by massively parallel sequencing, Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions, Low-level somatic variants.

• #47 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Molecular MHS testing is recommended for: Individuals with confirmed/suspected clinical MH event or positive contracture test, Relatives of individuals with a positive contracture test or known MHS variant. […] A clinical grading scale has been proposed to assist in determining if an adverse anesthetic event is a clinical MH event. […] The European Malignant Hyperthermia Group has released guidelines for the investigation of MH susceptibility. […] A negative result does not exclude a diagnosis of MHS. […] Diagnostic errors can occur due to rare sequence variations. […] The following may not be detected: Deletions/duplications/insertions of any size by massively parallel sequencing, Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions, Low-level somatic variants.

• #48 Malignant Hyperthermia Panel, Sequencing | Test Fact Sheet

  https://arupconsult.com/ati/malignant-hyperthermia-panel-sequencing

  Molecular MHS testing is recommended for: Individuals with confirmed/suspected clinical MH event or positive contracture test, Relatives of individuals with a positive contracture test or known MHS variant. […] A clinical grading scale has been proposed to assist in determining if an adverse anesthetic event is a clinical MH event. […] The European Malignant Hyperthermia Group has released guidelines for the investigation of MH susceptibility. […] A negative result does not exclude a diagnosis of MHS. […] Diagnostic errors can occur due to rare sequence variations. […] The following may not be detected: Deletions/duplications/insertions of any size by massively parallel sequencing, Some variants due to technical limitations in the presence of pseudogenes, repetitive, or homologous regions, Low-level somatic variants.

• #49 General — European Malignant Hyperthermia Group

  https://www.emhg.org/diagnosis

  Malignant hyperthermia (MH) is a potentially fatal pharmacogenetic disease triggered by commonly used volatile anaesthetics and/or succinylcholine. In vitro muscle contracture testing (IVCT) is the gold standard test to establish an individual’s risk of MH susceptibility. […] The diagnostic guidelines are regularly updated by the European MH Group and published on this website. […] The usual route of entry for individuals into MH investigations follows a suspected MH crisis and referral of the patient to an MH Investigation Unit. The diagnostic procedures and genetic counselling are performed according to current knowledge. […] In 2015 the EMHG has published a revision of the guidelines for the investigation of MH susceptibility. This version of the guidelines now combines previous guidelines on in-vitro contracture testing and molecular genetic investigations.

• #50 Testing for MH — European Malignant Hyperthermia Group

  https://www.emhg.org/testing-for-mh

  The decision to pursue either DNA screening or muscle biopsy and IVCT in the first instance will be made on a patient-by-patient basis by the MH diagnostic centre in consultation with the patient and their health-care funder. […] Investigation of malignant hyperthermia (MH) susceptibility initially involves clinical evaluation of a patients risk based on their anaesthetic and medical history, and relevant family history. Further investigation is indicated when increased risk of susceptibility to MH cannot be excluded. The highest sensitivity for detecting susceptibility to MH is provided by pharmacological challenge tests carried out on freshly excised skeletal muscle under controlled laboratory conditions. These tests, when carried out according to the following protocol are collectively referred to as the in vitro contracture test, or IVCT. The IVCT is recommended for individuals considered to be at increased risk of MH either as a first-line test or when DNA analyses have failed to confirm the high-risk status.

• #51 Testing for MH — European Malignant Hyperthermia Group

  https://www.emhg.org/testing-for-mh

  The decision to pursue either DNA screening or muscle biopsy and IVCT in the first instance will be made on a patient-by-patient basis by the MH diagnostic centre in consultation with the patient and their health-care funder. […] Investigation of malignant hyperthermia (MH) susceptibility initially involves clinical evaluation of a patients risk based on their anaesthetic and medical history, and relevant family history. Further investigation is indicated when increased risk of susceptibility to MH cannot be excluded. The highest sensitivity for detecting susceptibility to MH is provided by pharmacological challenge tests carried out on freshly excised skeletal muscle under controlled laboratory conditions. These tests, when carried out according to the following protocol are collectively referred to as the in vitro contracture test, or IVCT. The IVCT is recommended for individuals considered to be at increased risk of MH either as a first-line test or when DNA analyses have failed to confirm the high-risk status.

• #52 Testing for MH — European Malignant Hyperthermia Group

  https://www.emhg.org/testing-for-mh

  The decision to pursue either DNA screening or muscle biopsy and IVCT in the first instance will be made on a patient-by-patient basis by the MH diagnostic centre in consultation with the patient and their health-care funder. […] Investigation of malignant hyperthermia (MH) susceptibility initially involves clinical evaluation of a patients risk based on their anaesthetic and medical history, and relevant family history. Further investigation is indicated when increased risk of susceptibility to MH cannot be excluded. The highest sensitivity for detecting susceptibility to MH is provided by pharmacological challenge tests carried out on freshly excised skeletal muscle under controlled laboratory conditions. These tests, when carried out according to the following protocol are collectively referred to as the in vitro contracture test, or IVCT. The IVCT is recommended for individuals considered to be at increased risk of MH either as a first-line test or when DNA analyses have failed to confirm the high-risk status.

• #53 Testing for MH — European Malignant Hyperthermia Group

  https://www.emhg.org/testing-for-mh

  The decision to pursue either DNA screening or muscle biopsy and IVCT in the first instance will be made on a patient-by-patient basis by the MH diagnostic centre in consultation with the patient and their health-care funder. […] Investigation of malignant hyperthermia (MH) susceptibility initially involves clinical evaluation of a patients risk based on their anaesthetic and medical history, and relevant family history. Further investigation is indicated when increased risk of susceptibility to MH cannot be excluded. The highest sensitivity for detecting susceptibility to MH is provided by pharmacological challenge tests carried out on freshly excised skeletal muscle under controlled laboratory conditions. These tests, when carried out according to the following protocol are collectively referred to as the in vitro contracture test, or IVCT. The IVCT is recommended for individuals considered to be at increased risk of MH either as a first-line test or when DNA analyses have failed to confirm the high-risk status.

• #54 Testing for MH — European Malignant Hyperthermia Group

  https://www.emhg.org/testing-for-mh

  The decision to pursue either DNA screening or muscle biopsy and IVCT in the first instance will be made on a patient-by-patient basis by the MH diagnostic centre in consultation with the patient and their health-care funder. […] Investigation of malignant hyperthermia (MH) susceptibility initially involves clinical evaluation of a patients risk based on their anaesthetic and medical history, and relevant family history. Further investigation is indicated when increased risk of susceptibility to MH cannot be excluded. The highest sensitivity for detecting susceptibility to MH is provided by pharmacological challenge tests carried out on freshly excised skeletal muscle under controlled laboratory conditions. These tests, when carried out according to the following protocol are collectively referred to as the in vitro contracture test, or IVCT. The IVCT is recommended for individuals considered to be at increased risk of MH either as a first-line test or when DNA analyses have failed to confirm the high-risk status.

• #55 Malignant hyperthermia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-21

  The „gold standard” for diagnosis of MH is currently the in vitro contracture test (IVCT), which is based on contracture of muscle fibres in the presence of halothane or caffeine. […] DNA analysis, however, offers an alternative to the IVCT, requiring only a blood specimen, which can be sent to an accredited diagnostic laboratory. […] The identification of causative mutations suggests the widespread use of DNA testing for MH, however, this is confounded by the metabolic complexity and genetic heterogeneity of the disorder. […] In summary, because of the heterogeneity of the disorder, as well as discordance within families, a negative DNA result cannot be used to rule out MH susceptibility. […] The guidelines set down by the EMHG requires contracture testing prior to genetic testing in a family.

• #56 Malignant hyperthermia | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/1750-1172-2-21

  The „gold standard” for diagnosis of MH is currently the in vitro contracture test (IVCT), which is based on contracture of muscle fibres in the presence of halothane or caffeine. […] DNA analysis, however, offers an alternative to the IVCT, requiring only a blood specimen, which can be sent to an accredited diagnostic laboratory. […] The identification of causative mutations suggests the widespread use of DNA testing for MH, however, this is confounded by the metabolic complexity and genetic heterogeneity of the disorder. […] In summary, because of the heterogeneity of the disorder, as well as discordance within families, a negative DNA result cannot be used to rule out MH susceptibility. […] The guidelines set down by the EMHG requires contracture testing prior to genetic testing in a family.

• #57 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  A further caveat with these tests is that the results may be difficult to interpret in a patient suffering from a myopathy other than MH such as Duchenne Muscular Dystrophy where intracellular Ca2+ is elevated at baseline. […] DNA analysis, however, offers an alternative to the IVCT, requiring only a blood specimen, which can be sent to an accredited diagnostic laboratory. To date 50 to 70 % of MH susceptibility has been linked to RYR1 with over 400 variants associated with MH being identified within this gene. […] While traditional DNA sequencing from either genomic DNA or complementary DNA prepared from muscle biopsy tissue are time consuming and laborious, the advent of massively parallel sequencing (or next generation sequencing, NGS) provides potentially cost effective, rapid and high throughput platforms for both variant discovery and diagnosis at the whole genome level. […] The EMHG has established criteria including functional studies of DNA variants to establish that the variant is clinically significant.

• #58 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  A further caveat with these tests is that the results may be difficult to interpret in a patient suffering from a myopathy other than MH such as Duchenne Muscular Dystrophy where intracellular Ca2+ is elevated at baseline. […] DNA analysis, however, offers an alternative to the IVCT, requiring only a blood specimen, which can be sent to an accredited diagnostic laboratory. To date 50 to 70 % of MH susceptibility has been linked to RYR1 with over 400 variants associated with MH being identified within this gene. […] While traditional DNA sequencing from either genomic DNA or complementary DNA prepared from muscle biopsy tissue are time consuming and laborious, the advent of massively parallel sequencing (or next generation sequencing, NGS) provides potentially cost effective, rapid and high throughput platforms for both variant discovery and diagnosis at the whole genome level. […] The EMHG has established criteria including functional studies of DNA variants to establish that the variant is clinically significant.

• #59 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  A further caveat with these tests is that the results may be difficult to interpret in a patient suffering from a myopathy other than MH such as Duchenne Muscular Dystrophy where intracellular Ca2+ is elevated at baseline. […] DNA analysis, however, offers an alternative to the IVCT, requiring only a blood specimen, which can be sent to an accredited diagnostic laboratory. To date 50 to 70 % of MH susceptibility has been linked to RYR1 with over 400 variants associated with MH being identified within this gene. […] While traditional DNA sequencing from either genomic DNA or complementary DNA prepared from muscle biopsy tissue are time consuming and laborious, the advent of massively parallel sequencing (or next generation sequencing, NGS) provides potentially cost effective, rapid and high throughput platforms for both variant discovery and diagnosis at the whole genome level. […] The EMHG has established criteria including functional studies of DNA variants to establish that the variant is clinically significant.

• #60 Recent advances in the diagnosis of malignant hyperthermia susceptibility: How confident can we be of genetic testing? | European Journal of Human Genetics

  https://www.nature.com/articles/5200964

  Malignant hyperthermia (MH) is a condition that manifests in susceptible individuals only on exposure to certain anaesthetic agents. Guidelines for the genetic diagnosis for MH susceptibility have recently been introduced by the European MH Group (EMHG). These are designed to supplement the muscle biopsy testing procedure, the in vitro contracture test (IVCT), which has been the only means of patient screening for the last 30 years and which remains the method for definitive diagnosis in suspected probands. […] Discordance observed in some families between IVCT phenotype and susceptibility locus genotype could limit the confidence in genetic diagnosis. […] Genetic testing guidelines have been recently published by the EMHG to enable DNA diagnosis of MH in supplementation to the IVCT method of patient screening in MH families. In summary, genetic testing using certain mutations in the RYR1 gene demonstrated to be causative of MH through in vitro biochemical assays, or through linkage analysis with markers flanking the RYR1 locus is now feasible. Individuals carrying a causative mutation or high-risk susceptibility haplotype are considered at risk of developing MH independent of IVCT diagnoses.

• #61 Recent advances in the diagnosis of malignant hyperthermia susceptibility: How confident can we be of genetic testing? | European Journal of Human Genetics

  https://www.nature.com/articles/5200964

  A main concern of introducing DNA diagnosis for the condition is the apparent discordance between IVCT phenotype and RYR1 genotype in certain MH-susceptible families. […] To minimise false-negative results through genetic diagnosis and formally exclude risk from MH, the accepted practice of the EMHG is to use the IVCT for the characterisation of individuals where the familial mutation, or high-risk haplotype is absent. The IVCT also remains the definitive method of diagnosis for the assessment of suspected MH probands. […] The observed discordance between RYR1 genotype and IVCT phenotype is a concern from the perspective of assigning the correct diagnosis of MH status. […] The presence or absence of a mutation can be considered more definitive in the genetic diagnosis of dominant Mendelian disorders. However, current genetic diagnostic strategies for assessing MH status are conservative in this respect because of the fact that (1) the majority of mutations associated with MH susceptibility are missense, where the pathogenicity of such mutations requires careful evaluation and (2) there is evidence that additional loci/mutations may contribute to MH susceptibility in individual families, which may account for or modify the observed IVCT response.

• #62 Recent advances in the diagnosis of malignant hyperthermia susceptibility: How confident can we be of genetic testing? | European Journal of Human Genetics

  https://www.nature.com/articles/5200964

  A main concern of introducing DNA diagnosis for the condition is the apparent discordance between IVCT phenotype and RYR1 genotype in certain MH-susceptible families. […] To minimise false-negative results through genetic diagnosis and formally exclude risk from MH, the accepted practice of the EMHG is to use the IVCT for the characterisation of individuals where the familial mutation, or high-risk haplotype is absent. The IVCT also remains the definitive method of diagnosis for the assessment of suspected MH probands. […] The observed discordance between RYR1 genotype and IVCT phenotype is a concern from the perspective of assigning the correct diagnosis of MH status. […] The presence or absence of a mutation can be considered more definitive in the genetic diagnosis of dominant Mendelian disorders. However, current genetic diagnostic strategies for assessing MH status are conservative in this respect because of the fact that (1) the majority of mutations associated with MH susceptibility are missense, where the pathogenicity of such mutations requires careful evaluation and (2) there is evidence that additional loci/mutations may contribute to MH susceptibility in individual families, which may account for or modify the observed IVCT response.

• #63 Malignant Hyperthermia Information for Patients: MH Investigation Unit, PIE, hospital education, anesthesia, CHCT, diagnosis, treatment

  http://pie.med.utoronto.ca/MH/MH_content/patientDT.html

  Once an MH crisis is suspected, treatment must begin even when the diagnosis is not yet certain, to ensure patient safety. MH can be successfully managed in virtually all cases with the immediate use of the antidote, dantrolene sodium for injection, and by implementing other life-saving measures as outlined and developed by the expert professionals associated with MHAUS. Once the crisis is over, a careful review must rule out other causes and testing for MH susceptibility may be necessary.

• #64 Malignant Hyperthermia (MH) – EMCrit Project

  https://emcrit.org/ibcc/mh/

  Malignant hyperthermia (MH) can be caused by any inhalational anesthetic, other than nitrous oxide. MH usually occurs intraoperatively or in the very early postoperative period (up to an hour after finishing anesthesia). […] Treatment must be initiated empirically, when the MH diagnosis is considered probable. The treatments are fairly benign, so it’s generally better to err on the side of treatment. […] Immediate management of MH will often be necessary before a definitive diagnosis is made. Dantrolene is very safe, so when in doubt empiric therapy should be provided without delay.

• #65 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #66 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice

  https://bestpractice.bmj.com/topics/en-gb/1053

  Other diagnostic factors include tachycardia, decreased urine output, excessive sweating with exercise, muscle cramps, and spontaneous episodes of severe muscle stiffness. […] 1st investigations to order include discontinuation of inhalation anaesthetic, exhaled carbon dioxide, oxygen consumption, venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Investigations to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #67 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #68 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #69 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #70 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #71 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #72 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #73 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #74 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #75 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #76 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #77 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #78 Malignant hyperthermia – Symptoms, diagnosis and treatment | BMJ Best Practice US

  https://bestpractice.bmj.com/topics/en-us/1053

  Malignant hyperthermia is a potentially lethal syndrome usually triggered by inhalation anesthetics or succinylcholine. […] A definitive diagnosis requires testing after the acute episode has resolved. Genetic testing may be the first test performed in selected patients; it may form part of the autopsy if MH is suspected as the cause of death. Muscle contracture testing can be used to exclude susceptibility to MH. […] Key diagnostic factors include exposure to potent inhalation anesthetic and/or succinylcholine, susceptibility to MH, previous MH episode, positive family history, increased minute ventilation, elevated core temperature, and muscle rigidity. […] 1st tests to order include discontinuation of inhalation anesthetic, exhaled carbon dioxide, oxygen consumption (inspired-expired oxygen concentration difference), venous blood gases, serum electrolytes, serum creatinine, therapeutic trial of intravenous dantrolene, creatine kinase, urinalysis, urine myoglobin, platelets, and prothrombin time. […] Tests to consider include caffeine halothane contracture test (CHCT), in vitro contracture test (IVCT), genetic testing, and screening for muscle enzyme deficiencies.

• #79 Malignant Hyperthermia in PICU—From Diagnosis to Treatment in the Light of Up-to-Date Knowledge

  https://www.mdpi.com/2227-9067/9/11/1692

  Malignant Hyperthermia (MH) is a rare, hereditary, life-threatening disease triggered by volatile anesthetics and succinylcholine. […] The most typical symptoms of MH are hypercapnia, tachycardia, hyperthermia, and muscle rigidity. […] The cornerstone of good patient outcomes is to be aware of this diagnosis and commence treatment as soon as possible. […] A 1994 consensus conference led to the formulation of a set of diagnostic criteria—according to MH clinical grading scale (CGS), commonly known as the Larach score. CGS helps predict the likelihood of an acute MH crisis. […] The key to diagnosing an MH crisis is to be aware that it can develop in anybody anytime the triggering agents are administered, or as already mentioned very rarely even without them. […] Monitoring the end-tidal CO2 and temperature is the crucial part of identifying the right diagnosis.

• #80 Malignant Hyperthermia and Related Conditions – Cancer Therapy Advisor

  https://www.cancertherapyadvisor.com/home/decision-support-in-medicine/critical-care-medicine/malignant-hyperthermia-and-related-conditions/

  The best way to approach the diagnosis of malignant hyperthermia is through a clinical vignette, which follows: […] You and the anesthesiologist begin to discuss the possible reasons for this constellation of findings, and it is suggested that this might be malignant hyperthermia (MH). […] While not pathognomonic, the sine qua non of a full blown MH episode, however, is the mixed respiratory-metabolic acidosis in the setting of general anesthesia with volatile anesthetics, whether succinylcholine is used or not, and in the presence a rising end-tidal CO2 that cannot be controlled with increasing minute ventilation. […] There are no specific tests that can confirm MH in the acute phase. It is a constellation of findings in the setting of a general anesthetic with volatile anesthetics.

• #81 Malignant Hyperthermia Differential Diagnoses

  https://emedicine.medscape.com/article/2231150-differential

  In addition to the conditions listed in the differential diagnosis, there are a number of other conditions and circumstances that may mimic malignant hyperthermia (MH), including the following: […] Although its clinical picture is similar to that of MH, neuroleptic malignant syndrome (NMS) is caused by the central effects of drugs with dopamine antagonist properties, including antipsychotics (eg, haloperidol) and antiemetics (eg, metoclopramide and droperidol). […] Treatment consists of stopping the drug, controlling the symptoms, and administering dopamine agonists (eg, bromocriptine). Dantrolene will lower the temperature. […] A clinical grading scale to predict malignant hyperthermia susceptibility.

• #82 Malignant Hyperthermia Differential Diagnoses

  https://emedicine.medscape.com/article/2231150-differential

  In addition to the conditions listed in the differential diagnosis, there are a number of other conditions and circumstances that may mimic malignant hyperthermia (MH), including the following: […] Although its clinical picture is similar to that of MH, neuroleptic malignant syndrome (NMS) is caused by the central effects of drugs with dopamine antagonist properties, including antipsychotics (eg, haloperidol) and antiemetics (eg, metoclopramide and droperidol). […] Treatment consists of stopping the drug, controlling the symptoms, and administering dopamine agonists (eg, bromocriptine). Dantrolene will lower the temperature. […] A clinical grading scale to predict malignant hyperthermia susceptibility.

• #83 Malignant hyperthermia – Diagnosis & treatment – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/malignant-hyperthermia/diagnosis-treatment/drc-20353752

  Malignant hyperthermia is diagnosed based on signs and symptoms, monitoring during and immediately after anesthesia, and lab tests to identify complications. […] Testing to find out if you’re at increased risk of malignant hyperthermia (susceptibility testing) may be recommended if you have risk factors. […] Genetic testing can identify the gene change that shows you have the genetic disorder called malignant hyperthermia susceptibility (MHS). […] In some cases, your health care provider may recommend a muscle biopsy if you’re at risk of malignant hyperthermia. […] If you’ve experienced malignant hyperthermia due to certain anesthesia drugs, exercising during excessive heat and humidity could trigger another reaction. […] Also, check with your health care provider to see if you should have genetic testing to determine if you have a genetic disorder that puts you at risk of malignant hyperthermia.

• #84 Atypical Presentation of Delayed Onset Malignant Hyperthermia: Internist Needs to Be Aware Of

  https://clinmedjournals.org/articles/iaim/international-archives-of-internal-medicine-iaim-4-029.php

  Malignant hyperthermia (MH) is a rare but potentially life threatening drug related reaction predisposed by genetic factors. […] With variability in symptoms and time of onset, definitive diagnosis of MH is challenging. […] Recognizing this may prevent the potential of a life-threatening reoccurrence of MH intraoperatively, if appropriately diagnosed. […] The classic clinical presentation of MH is in the intraoperative setting; however, delayed onset or insidious onset of malignant hyperthermia should also be recognized to prevent further progression. […] In our case, the patient presented with severe oliguria in the setting of recent surgical procedure. […] He did not present with the typical symptoms of MH of hyperthermia, hypercarbia, tachycardia, or tachypnea. […] The most likely diagnosis for our case was rhabdomyolysis induced by delayed onset MH.

• #85 Malignant hyperthermia: Diagnosis and management of acute crisis – UpToDate

  https://www.uptodate.com/contents/malignant-hyperthermia-diagnosis-and-management-of-acute-crisis/print

  Malignant hyperthermia (MH) manifests clinically as a hypermetabolic crisis when an MH-susceptible (MHS) individual is exposed to a volatile anesthetic (eg, halothane, isoflurane, sevoflurane, desflurane) or succinylcholine. […] This topic will discuss the incidence, pathophysiology, clinical manifestations, and acute management of MH. […] The incidence of MH events for a given population depends upon the prevalence of MH susceptibility and use of triggering anesthetics. […] MH episodes have been estimated to occur in the general population in 1:100,000 administered anesthetics. […] An MH event does not necessarily occur every time an MH susceptible individual is exposed to an anesthetic triggering agent.

• #86 Malignant hyperthermia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/malignant-hyperthermia/

  Malignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. […] People at increased risk of this disorder are said to have malignant hyperthermia susceptibility. […] Affected individuals may never know they have the condition unless they have a severe reaction to anesthesia during a surgical procedure or they undergo testing (for instance, if susceptibility is suspected because a family member had a severe reaction). […] Malignant hyperthermia may not occur every time anesthesia is used. […] While malignant hyperthermia often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease, multiminicore disease, and STAC3 disorder) are associated with malignant hyperthermia susceptibility.

• #87 Malignant hyperthermia: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/malignant-hyperthermia/

  Malignant hyperthermia is a severe reaction to particular anesthetic drugs that are often used during surgery and other invasive procedures. […] People at increased risk of this disorder are said to have malignant hyperthermia susceptibility. […] Affected individuals may never know they have the condition unless they have a severe reaction to anesthesia during a surgical procedure or they undergo testing (for instance, if susceptibility is suspected because a family member had a severe reaction). […] Malignant hyperthermia may not occur every time anesthesia is used. […] While malignant hyperthermia often occurs in people without other serious medical problems, certain inherited muscle diseases (including central core disease, multiminicore disease, and STAC3 disorder) are associated with malignant hyperthermia susceptibility.

• #88 Management of malignant hyperthermia: diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4027921/

  Malignant hyperthermia is a potentially lethal inherited disorder characterized by disturbance of calcium homeostasis in skeletal muscle. […] Since the clinical presentation of malignant hyperthermia is highly variable, survival of affected patients depends largely on early recognition of the symptoms characteristic of malignant hyperthermia, and immediate action on the part of the attending anesthesiologist. Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current therapeutic guidelines, as well as adequate management of anesthesia in patients susceptible to malignant hyperthermia, are discussed in this review. […] Diagnostic testing for MH susceptibility can be indicated after an incident suspicious for MH in patients with nonspecific myopathy or persistently elevated serum creatine kinase and in families with history of MH. For about 30 years, the in vitro contracture test using halothane and caffeine has been the gold standard for determining susceptibility to MH independent of a clinical MH event. […] In summary, in vitro contracture testing and molecular genetic testing are the two approved methods for diagnosing susceptibility to MH. Both procedures require specialized testing centers and are not suitable for use as screening methods unless there is immediate suspicion of predisposition to MH.

• #89 RYANODEX® | What is malignant hyperthermia (MH)?

  https://www.ryanodex.com/about-mh/

  Malignant hyperthermia (MH) is a pharmacogenetic disease that causes hypermetabolism, a fast rise in body temperature and severe muscle contractions when an affected person receives general anesthesia using volatile anesthetics or the paralytic succinylcholine. […] The signs and symptoms of MH include hypercarbia, muscle rigidity, fast-rising body temperature, tachycardia, myolysis, increased ETCO2, hyperkalemia, and acidosis. Immediate treatment with the drug dantrolene sodium usually reverses the signs of MH. […] There are multiple signs that may prompt a diagnosis of MH by anesthesia practitioners. […] Hypercarbia is often the first clinical sign of MH. Other early signs include sinus tachycardia and masseter spasm. […] Stopping the triggering agents and administering dantrolene sodium to the patient as quickly as possible are the greatest priorities in an MH crisis. […] Every delay in treatment increases the risk of further complication during an MH crisis. […] The risk of complications may increase to 30% with a 20-minute delay in treating MH from its first symptom.

• #90 RYANODEX® | What is malignant hyperthermia (MH)?

  https://www.ryanodex.com/about-mh/

  Malignant hyperthermia (MH) is a pharmacogenetic disease that causes hypermetabolism, a fast rise in body temperature and severe muscle contractions when an affected person receives general anesthesia using volatile anesthetics or the paralytic succinylcholine. […] The signs and symptoms of MH include hypercarbia, muscle rigidity, fast-rising body temperature, tachycardia, myolysis, increased ETCO2, hyperkalemia, and acidosis. Immediate treatment with the drug dantrolene sodium usually reverses the signs of MH. […] There are multiple signs that may prompt a diagnosis of MH by anesthesia practitioners. […] Hypercarbia is often the first clinical sign of MH. Other early signs include sinus tachycardia and masseter spasm. […] Stopping the triggering agents and administering dantrolene sodium to the patient as quickly as possible are the greatest priorities in an MH crisis. […] Every delay in treatment increases the risk of further complication during an MH crisis. […] The risk of complications may increase to 30% with a 20-minute delay in treating MH from its first symptom.

• #91 Malignant Hyperthermia: What It Is, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17945-malignant-hyperthermia

  Malignant hyperthermia is a genetic disease that causes a life-threatening reaction to certain anesthesia medications. The disorder usually runs in families and is treatable. […] If you or your healthcare provider think you may be susceptible to malignant hyperthermia due to family history, your provider may recommend special tests and procedures to diagnose it, including: […] Caffeine halothane contracture test (CHCT). For this test, a provider takes a muscle biopsy and exposes the live muscle sample to halothane and caffeine to analyze it for a reaction to an anesthesia gas. […] Genetic testing. Genetic testing can reveal mutations in RYR1, STAC3 and CACNA1S locations on DNA. There are over 45 mutations that are recognized as diagnostic for malignant hyperthermia. […] If untreated, malignant hyperthermia is almost always fatal. The death rate is 3% to 5%, even when the condition is properly treated.

• #92 Management of malignant hyperthermia: diagnosis and treatment

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4027921/

  Malignant hyperthermia is a potentially lethal inherited disorder characterized by disturbance of calcium homeostasis in skeletal muscle. […] Since the clinical presentation of malignant hyperthermia is highly variable, survival of affected patients depends largely on early recognition of the symptoms characteristic of malignant hyperthermia, and immediate action on the part of the attending anesthesiologist. Clinical symptoms of malignant hyperthermia, diagnostic criteria, and current therapeutic guidelines, as well as adequate management of anesthesia in patients susceptible to malignant hyperthermia, are discussed in this review. […] Diagnostic testing for MH susceptibility can be indicated after an incident suspicious for MH in patients with nonspecific myopathy or persistently elevated serum creatine kinase and in families with history of MH. For about 30 years, the in vitro contracture test using halothane and caffeine has been the gold standard for determining susceptibility to MH independent of a clinical MH event. […] In summary, in vitro contracture testing and molecular genetic testing are the two approved methods for diagnosing susceptibility to MH. Both procedures require specialized testing centers and are not suitable for use as screening methods unless there is immediate suspicion of predisposition to MH.

• #93 Malignant hyperthermia: a review | Orphanet Journal of Rare Diseases | Full Text

  https://ojrd.biomedcentral.com/articles/10.1186/s13023-015-0310-1

  A further caveat with these tests is that the results may be difficult to interpret in a patient suffering from a myopathy other than MH such as Duchenne Muscular Dystrophy where intracellular Ca2+ is elevated at baseline. […] DNA analysis, however, offers an alternative to the IVCT, requiring only a blood specimen, which can be sent to an accredited diagnostic laboratory. To date 50 to 70 % of MH susceptibility has been linked to RYR1 with over 400 variants associated with MH being identified within this gene. […] While traditional DNA sequencing from either genomic DNA or complementary DNA prepared from muscle biopsy tissue are time consuming and laborious, the advent of massively parallel sequencing (or next generation sequencing, NGS) provides potentially cost effective, rapid and high throughput platforms for both variant discovery and diagnosis at the whole genome level. […] The EMHG has established criteria including functional studies of DNA variants to establish that the variant is clinically significant.

• #94 Malignant Hyperthermia – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK430828/

  Malignant hyperthermia (MH) is a hereditary disorder of skeletal muscle that classically presents as a hypermetabolic response to halogenated anesthetic gasses and/or the depolarizing muscle relaxant succinylcholine. […] The gold standard in the laboratory diagnosis of malignant hyperthermia is the caffeine halothane contracture test (CHCT), although genetic testing is rapidly advancing and may one day replace the muscle biopsy. […] The CHCT involves exposing a sample of live muscle fibers to halothane and caffeine to determine the muscle response to halogenated anesthetics. […] Genetic testing for mutations of the RYR1 or other associated genetic variants associated with malignant hyperthermia is becoming increasingly more valuable as the testing improves. […] It requires a high index of suspicion of malignant hyperthermia to effect a timely and correct diagnosis and treatment. […] If signs of hypermetabolism such as metabolic and respiratory acidosis or an elevation in body temperature accompany the muscle spasm, a diagnosis of malignant hyperthermia must be considered.

• #95 Malignant hyperthermia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/malignant-hyperthermia/symptoms-causes/syc-20353750

  Malignant hyperthermia is a severe reaction to certain drugs used for anesthesia. […] Genetic testing can reveal whether you have an affected gene. […] If someone in your family is known to be at risk of malignant hyperthermia and you need to have anesthesia, it’s important to tell your health care provider and anesthesia specialist (anesthesiologist). […] Evaluating your risk of malignant hyperthermia allows your anesthesiologist to avoid certain anesthesia drugs.

• #96 Malignant hyperthermia – Symptoms & causes – Mayo Clinic

  https://www.mayoclinic.org/diseases-conditions/malignant-hyperthermia/symptoms-causes/syc-20353750

  Malignant hyperthermia is a severe reaction to certain drugs used for anesthesia. […] Genetic testing can reveal whether you have an affected gene. […] If someone in your family is known to be at risk of malignant hyperthermia and you need to have anesthesia, it’s important to tell your health care provider and anesthesia specialist (anesthesiologist). […] Evaluating your risk of malignant hyperthermia allows your anesthesiologist to avoid certain anesthesia drugs.

• #97 Testing for MH — European Malignant Hyperthermia Group

  https://www.emhg.org/testing-for-mh

  Clinical advice provided by the diagnostic laboratory director remains the responsibility of the individual physician. All available information should be taken into account, including clinical evaluation as well as IVCT results. Muscle histopathology, serum biochemistry and molecular genetic analysis may provide additional information. However, in general all patients with any subtype of MHS IVCT classification should be considered at risk of developing malignant hyperthermia under anaesthesia. Laboratory MHN diagnosis is good evidence that the patient is not at increased risk of developing malignant hyperthermia. An MHN tested individual cannot transmit MH risk to their offspring. […] Although an MH episode must be considered a multifactorial sequence of events, the genetic basis for MH susceptibility is largely due to mutations in the RYR1 gene. Despite several linkage and screening studies, mutations associated with MHS have been found only in RYR1 and more rarely in CACNA1S, the gene for the skeletal muscle L-type voltage-dependent Ca2+ channel (Cav1.1 or DHPR).

• #98 Malignant hyperthermia | MedLink Neurology

  https://www.medlink.com/articles/malignant-hyperthermia

  The only highly sensitive diagnostic test for malignant hyperthermia susceptibility is the caffeine and halothane contracture test of biopsied skeletal muscle. […] The sensitivity and specificity of the North American Malignant Hyperthermia Group Protocol has been estimated in humans to be about 97% and 78%, respectively, using a 2-component test. […] In patients who have had normal caffeine halothane contracture tests (ie, malignant hyperthermia non-susceptible), there are no reported cases of malignant hyperthermia during subsequent general anesthetics that include triggering agents. […] Although genetic testing is rapidly evolving, diagnosis of malignant hyperthermia via genetic analysis alone remains problematic due to great genetic and phenotypic heterogeneity and the high prevalence of variants of unknown significance in RYR1 and CACNA1S.

• #99 Testing for MH — European Malignant Hyperthermia Group

  https://www.emhg.org/testing-for-mh

  Clinical advice provided by the diagnostic laboratory director remains the responsibility of the individual physician. All available information should be taken into account, including clinical evaluation as well as IVCT results. Muscle histopathology, serum biochemistry and molecular genetic analysis may provide additional information. However, in general all patients with any subtype of MHS IVCT classification should be considered at risk of developing malignant hyperthermia under anaesthesia. Laboratory MHN diagnosis is good evidence that the patient is not at increased risk of developing malignant hyperthermia. An MHN tested individual cannot transmit MH risk to their offspring. […] Although an MH episode must be considered a multifactorial sequence of events, the genetic basis for MH susceptibility is largely due to mutations in the RYR1 gene. Despite several linkage and screening studies, mutations associated with MHS have been found only in RYR1 and more rarely in CACNA1S, the gene for the skeletal muscle L-type voltage-dependent Ca2+ channel (Cav1.1 or DHPR).

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