Malignant Hyperthermia

Malignant hyperthermia (MH) is a rare, life-threatening, pharmacogenetic disorder of skeletal muscle calcium homeostasis that is triggered in susceptible individuals by volatile inhalational anesthetics (e.g., halothane, sevoflurane, isoflurane, desflurane) and/or the depolarizing neuromuscular blocking agent succinylcholine. The condition is characterized by an uncontrolled hypermetabolic state within skeletal muscle, leading to a dramatic increase in carbon dioxide production, oxygen consumption, heat generation, and lactic acidosis. Clinically, MH manifests as a fulminant syndrome of hyperthermia, severe muscle rigidity, tachycardia, tachypnea, hypercapnia, metabolic and respiratory acidosis, rhabdomyolysis, hyperkalemia, and potentially fatal cardiac arrhythmias. In veterinary medicine, MH is most commonly recognized in certain dog breeds, particularly Greyhounds, and has also been reported in cats, horses, and pigs (the latter serving as the classic animal model). The condition is a true anesthetic emergency that requires immediate recognition, discontinuation of triggering agents, aggressive supportive care, and administration of the specific antidote dantrolene. Without prompt intervention, MH carries a high mortality rate. The syndrome is distinct from other causes of perioperative hyperthermia, such as sepsis, thyroid storm, or overheating, and requires a high index of suspicion for early diagnosis and successful management.

Malignant hyperthermia is caused by a genetic predisposition to an abnormal calcium release from the sarcoplasmic reticulum of skeletal muscle cells. The primary genetic defect in most cases involves mutations in the ryanodine receptor type 1 (RYR1) gene, which encodes the calcium release channel of the sarcoplasmic reticulum. In veterinary species, specific mutations have been identified in pigs (RYR1 Arg615Cys) and dogs (e.g., in Greyhounds, a mutation in the RYR1 gene has been identified). In humans, mutations in the CACNA1S gene (encoding the L-type calcium channel) also contribute. The condition is inherited in an autosomal dominant pattern in humans and pigs, but in dogs, the inheritance pattern may be more complex. The trigger for an MH episode is exposure to volatile anesthetic agents (halothane, isoflurane, sevoflurane, desflurane, enflurane) and/or succinylcholine. These agents induce an uncontrolled release of calcium from the sarcoplasmic reticulum into the myoplasm, leading to sustained muscle contraction, activation of phosphorylase kinase and glycogenolysis, increased aerobic and anaerobic metabolism, and massive heat production. The excessive calcium also activates proteases and phospholipases, causing muscle cell damage and rhabdomyolysis. In susceptible individuals, even a single exposure to a triggering agent can precipitate a fulminant episode. Other factors, such as stress, exercise, or heat, may also trigger MH in susceptible individuals, but in the perioperative setting, anesthetic agents are the primary inciting factors.

Malignant hyperthermia is a rare condition in veterinary medicine, but certain breeds are overrepresented. In dogs, the Greyhound breed is most commonly affected, with a higher incidence reported in racing Greyhounds. Other breeds that may be predisposed include the Labrador Retriever, Golden Retriever, and other sighthounds, but the genetic basis is less well-defined. In cats, MH has been reported but is extremely rare. In horses, a similar syndrome known as equine malignant hyperthermia has been associated with mutations in the RYR1 gene, particularly in Quarter Horses and related breeds. In pigs, MH is more common and is known as porcine stress syndrome, triggered by stress as well as anesthetics. The condition is inherited as an autosomal dominant trait in pigs and humans, but in dogs, the inheritance pattern is not fully understood; it may be polygenic or have variable penetrance. There is no sex predilection, and the condition can occur at any age, but it is more commonly recognized in young, otherwise healthy animals. The incidence of MH in veterinary anesthesia is low, but the mortality rate is high if untreated, making it a critical concern for anesthesiologists. In a survey of veterinary anesthesiologists, MH was reported in approximately 0.1% of canine anesthetics, but this may be an underestimate due to underdiagnosis. The condition is more likely to be recognized in breeds with known susceptibility, and a thorough history of previous anesthetic complications is essential.

The pathophysiology of malignant hyperthermia centers on an uncontrolled rise in myoplasmic calcium concentration in skeletal muscle. In normal muscle, excitation-contraction coupling involves depolarization of the sarcolemma, which triggers calcium release from the sarcoplasmic reticulum via the ryanodine receptor (RYR1). In MH-susceptible individuals, mutations in RYR1 result in a channel that is hypersensitive to triggering agents, leading to excessive and sustained calcium release. The elevated calcium levels activate multiple cellular processes: 1) Muscle contraction: Sustained actin-myosin cross-bridging causes muscle rigidity and increased ATP consumption. 2) Cellular metabolism: The high calcium activates phosphorylase kinase, accelerating glycogenolysis and glycolysis, leading to increased production of carbon dioxide and lactate. 3) Mitochondrial respiration: The increased demand for ATP stimulates oxidative phosphorylation, leading to increased oxygen consumption and heat production. 4) Heat generation: The combination of muscle contraction and metabolic activity generates significant heat, causing hyperthermia. 5) Rhabdomyolysis: The sustained contraction and metabolic stress damage the sarcolemma, leading to leakage of intracellular contents, including potassium, creatine kinase, and myoglobin, into the bloodstream. 6) Acidosis: Increased lactate production and carbon dioxide lead to combined metabolic and respiratory acidosis. 7) Hyperkalemia: The release of potassium from damaged muscle cells can cause life-threatening cardiac arrhythmias. 8) Disseminated intravascular coagulation (DIC) and multi-organ failure may occur as a result of hyperthermia, acidosis, and rhabdomyolysis. The syndrome is self-perpetuating: hyperthermia increases metabolic rate, which further increases heat production, leading to a vicious cycle. Without intervention, the condition progresses to cardiovascular collapse, cardiac arrest, and death.

The primary predisposing factor for malignant hyperthermia is a genetic susceptibility, specifically mutations in the RYR1 gene. In veterinary medicine, breed predisposition is a significant factor, with Greyhounds being the most notable. Other factors that may increase the risk of an MH episode include: 1) Previous history of MH or unexplained anesthetic complications in the animal or its relatives. 2) Exposure to triggering agents: volatile anesthetics (halothane, isoflurane, sevoflurane, desflurane) and succinylcholine. 3) Stress: In susceptible animals, stress, excitement, or vigorous exercise may trigger an episode, although this is more common in pigs. 4) Concurrent use of drugs that may potentiate MH, such as potassium-depleting diuretics or digitalis, which can exacerbate hyperkalemia. 5) Ambient temperature: High environmental temperatures may increase the risk of hyperthermia, but MH is not solely due to external heat. 6) Age: Young, otherwise healthy animals are more commonly affected, possibly due to a higher muscle mass relative to body weight. 7) Sex: No clear sex predilection, but some studies suggest a slight male predominance. 8) Muscle mass: Animals with a high muscle mass, such as racing Greyhounds, may be at higher risk due to a larger mass of skeletal muscle that can contribute to the hypermetabolic response. 9) Certain anesthetic protocols: The use of halothane and succinylcholine together is a potent trigger, but any volatile agent can trigger MH. 10) Lack of preoperative screening: In breeds with known susceptibility, genetic testing or a thorough history can identify at-risk animals, allowing the use of non-triggering anesthetic protocols.

The clinical signs of malignant hyperthermia typically appear within minutes to hours after exposure to a triggering agent, but can occur during anesthesia or in the immediate postoperative period. The earliest and most sensitive sign is an unexplained increase in end-tidal carbon dioxide (EtCO2) despite increased minute ventilation. This is followed by: 1) Hyperthermia: A rapid rise in core body temperature, often exceeding 40°C (104°F), which can be severe and life-threatening. 2) Muscle rigidity: Generalized or localized muscle rigidity, particularly of the masseter muscles, which may make intubation difficult. 3) Tachycardia: An increase in heart rate, often out of proportion to the depth of anesthesia. 4) Tachypnea: Increased respiratory rate, although this may be masked by mechanical ventilation. 5) Cardiac arrhythmias: Ventricular tachycardia, premature ventricular contractions, or other arrhythmias due to hyperkalemia and acidosis. 6) Skin changes: Mottling, cyanosis, or a flushed appearance due to vasodilation and poor perfusion. 7) Metabolic and respiratory acidosis: Blood gas analysis reveals a combined metabolic and respiratory acidosis, with elevated lactate and carbon dioxide levels. 8) Hyperkalemia: Elevated serum potassium levels, which can cause ECG changes and arrhythmias. 9) Rhabdomyolysis: Elevated creatine kinase (CK) and myoglobinuria, which may lead to acute kidney injury. 10) Disseminated intravascular coagulation (DIC): In severe cases, coagulopathy may develop. 11) Sudden cardiac arrest: If untreated, MH can progress to cardiac arrest. The clinical signs may be masked by general anesthesia, so a high index of suspicion is required. An unexplained rise in EtCO2, tachycardia, and hyperthermia are the classic triad that should alert the anesthesiologist to the possibility of MH.

The differential diagnoses for malignant hyperthermia include other causes of perioperative hyperthermia and metabolic derangements. Key differentials include: 1) Inadequate anesthesia: Light anesthesia can cause tachycardia, tachypnea, and increased muscle tone, but does not typically cause hyperthermia or a rise in EtCO2. 2) Sepsis or systemic inflammatory response syndrome (SIRS): Can cause fever, tachycardia, and acidosis, but usually has a slower onset and is associated with infection. 3) Thyroid storm: Hyperthyroidism can cause hyperthermia and tachycardia, but is rare in veterinary patients and usually has a history of thyroid disease. 4) Pheochromocytoma: A catecholamine-secreting tumor can cause hypertension, tachycardia, and hyperthermia, but is rare. 5) Neuroleptic malignant syndrome: Associated with antipsychotic drugs, but not with volatile anesthetics. 6) Serotonin syndrome: Caused by serotonergic drugs, but not typically seen in the perioperative setting. 7) Heat stroke: Due to excessive environmental heat, but not triggered by anesthetics. 8) Anesthetic machine malfunction: A malfunctioning carbon dioxide absorber or a stuck expiratory valve can cause hypercapnia, but not hyperthermia or muscle rigidity. 9) Malignant hyperthermia mimics: Conditions such as myotonia, muscular dystrophy, or mitochondrial myopathies can cause muscle rigidity and hyperthermia, but are not triggered by anesthetics. 10) Drug-induced hyperthermia: Certain drugs, such as anticholinergics or sympathomimetics, can cause hyperthermia, but the history and clinical signs differ. To differentiate MH from these conditions, the presence of muscle rigidity, a rapid rise in EtCO2, and a positive response to dantrolene are highly suggestive. Genetic testing or a muscle biopsy with a halothane-caffeine contracture test can confirm the diagnosis, but these are not available in an emergency setting.

The diagnosis of malignant hyperthermia is primarily clinical and is made based on the recognition of characteristic signs in a patient under anesthesia. The following diagnostic algorithm is recommended: 1) Intraoperative monitoring: Continuous monitoring of end-tidal carbon dioxide (EtCO2), heart rate, blood pressure, oxygen saturation, and core body temperature. A sudden, unexplained rise in EtCO2 is the earliest sign. 2) If MH is suspected, immediately discontinue all triggering agents (volatile anesthetics and succinylcholine) and hyperventilate with 100% oxygen. 3) Confirm the diagnosis by checking for other signs: muscle rigidity, hyperthermia, tachycardia, arrhythmias, and blood gas analysis showing combined metabolic and respiratory acidosis, hyperkalemia, and elevated lactate. 4) Administer dantrolene as a diagnostic and therapeutic test: A rapid improvement in clinical signs after dantrolene administration supports the diagnosis. 5) Laboratory tests: Serum creatine kinase (CK) levels rise within hours and peak at 24-48 hours. Myoglobinuria may be present. 6) Genetic testing: In breeds with known mutations, a blood sample can be sent for genetic testing to confirm susceptibility. 7) Muscle biopsy: The gold standard for diagnosis is the in vitro halothane-caffeine contracture test, but this is rarely performed in veterinary medicine. 8) Postmortem diagnosis: In fatal cases, histopathology of skeletal muscle may show rhabdomyolysis, but this is nonspecific. The diagnostic algorithm emphasizes rapid recognition and treatment, as waiting for confirmatory tests can be fatal.

In malignant hyperthermia, laboratory findings reflect the hypermetabolic state and muscle damage. Key findings include: 1) Blood gas analysis: Combined metabolic and respiratory acidosis with a low pH, elevated PaCO2, decreased PaO2 (if ventilation is inadequate), and elevated lactate. 2) Serum biochemistry: Hyperkalemia (elevated potassium), hyperphosphatemia, hypocalcemia (initially due to calcium influx into cells), elevated creatine kinase (CK) (peaks at 24-48 hours), elevated aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH). 3) Urinalysis: Myoglobinuria (dark red or brown urine) due to rhabdomyolysis, which can lead to acute kidney injury. 4) Coagulation panel: In severe cases, disseminated intravascular coagulation (DIC) may be present, with prolonged PT/aPTT, decreased fibrinogen, and elevated D-dimer. 5) Complete blood count: Hemoconcentration due to dehydration, leukocytosis, and thrombocytopenia may occur. 6) Electrolytes: Hyperkalemia is a critical finding that requires immediate treatment. 7) Cardiac biomarkers: Troponin I may be elevated if cardiac muscle is affected. 8) Inflammatory markers: C-reactive protein (CRP) and serum amyloid A (SAA) may be elevated, but are nonspecific. 9) Genetic testing: DNA analysis for RYR1 mutations can confirm susceptibility, but results are not available in an emergency. 10) Muscle biopsy: Histopathology may show muscle fiber necrosis, but this is not specific. The laboratory findings are used to guide treatment and monitor for complications such as acute kidney injury and DIC.

Imaging is not typically used for the diagnosis of malignant hyperthermia, as the condition is a clinical emergency. However, imaging may be used to evaluate complications such as: 1) Thoracic radiography: To assess for pulmonary edema or aspiration pneumonia, which can occur due to the hypermetabolic state and muscle rigidity. 2) Abdominal ultrasonography: To evaluate for organ damage, such as acute kidney injury, which may be indicated by changes in kidney size and echogenicity. 3) Echocardiography: To assess cardiac function if arrhythmias or cardiac arrest occur. 4) Muscle ultrasound: May show increased echogenicity due to muscle damage, but this is not specific. 5) Magnetic resonance imaging (MRI): In rare cases, MRI may be used to evaluate muscle damage, but it is not practical in an emergency. 6) Computed tomography (CT): May be used to rule out other causes of hyperthermia, such as intracranial pathology, but is not indicated. In summary, imaging plays a limited role in the diagnosis of MH, but may be useful for monitoring complications.

Cytology and histopathology are not typically used for the diagnosis of malignant hyperthermia, as the condition is diagnosed clinically. However, in cases where a muscle biopsy is performed for confirmation, histopathological findings may include: 1) Muscle fiber necrosis: Acute rhabdomyolysis with fragmentation of muscle fibers, loss of striations, and infiltration of macrophages. 2) Edema: Interstitial edema within the muscle. 3) Regeneration: In surviving animals, satellite cell activation and muscle regeneration may be seen. 4) Calcification: Dystrophic calcification may occur in areas of necrosis. 5) Inflammatory infiltrate: Neutrophils and macrophages may be present, but this is not a primary inflammatory condition. 6) Special stains: Modified Gomori trichrome stain may show ragged red fibers in mitochondrial myopathies, but this is not specific for MH. 7) Electron microscopy: May show disruption of the sarcoplasmic reticulum and mitochondria. 8) In vitro contracture test: This is a functional test, not histopathology, but it is the gold standard for diagnosis. It involves exposing a fresh muscle biopsy to halothane and caffeine and measuring the contracture response. 9) Genetic testing: DNA analysis for RYR1 mutations can be performed on blood or tissue samples. In summary, histopathology is not essential for diagnosis, but can support the diagnosis in equivocal cases.

The treatment of malignant hyperthermia is a medical emergency and must be initiated immediately upon suspicion. The following steps are recommended: 1) Discontinue all triggering agents: Immediately turn off the volatile anesthetic and stop succinylcholine. 2) Hyperventilate with 100% oxygen: Increase the oxygen flow to 10-15 L/min and hyperventilate the patient to eliminate carbon dioxide. 3) Administer dantrolene: Dantrolene is the specific antidote and should be given as soon as possible. The recommended dose is 2-3 mg/kg IV, and it can be repeated up to a total dose of 10 mg/kg if needed. Dantrolene works by inhibiting calcium release from the sarcoplasmic reticulum. 4) Correct hyperthermia: Apply active cooling measures, such as ice packs to the groin, axillae, and neck, and use cold IV fluids. Stop cooling when the temperature drops to 38.5°C (101.3°F) to avoid hypothermia. 5) Treat hyperkalemia: Administer calcium gluconate (0.5-1.0 mL/kg of 10% solution IV over 5-10 minutes) to stabilize cardiac membranes, and give dextrose (0.5 g/kg IV) with regular insulin (0.1-0.2 U/kg IV) to shift potassium into cells. Sodium bicarbonate (1-2 mEq/kg IV) may be given for severe acidosis, but should be used cautiously. 6) Manage arrhythmias: Treat arrhythmias with standard antiarrhythmic drugs, but avoid calcium channel blockers (e.g., verapamil) as they may interact with dantrolene. 7) Supportive care: Maintain adequate hydration with IV fluids, monitor urine output to prevent myoglobin-induced acute kidney injury, and consider mannitol (0.5-1 g/kg IV) to promote diuresis. 8) Monitor vital signs: Continuously monitor ECG, blood pressure, temperature, EtCO2, and oxygen saturation. 9) Postoperative care: After stabilization, the patient should be monitored in an intensive care unit for at least 24-48 hours, as recrudescence can occur. 10) Anesthetic management for future procedures: If the patient survives, future anesthetics must avoid all triggering agents. A safe protocol includes a total intravenous anesthesia (TIVA) with propofol, opioids, and benzodiazepines, and the use of a clean anesthesia machine that has been flushed with oxygen for at least 20 minutes. The treatment of MH requires a team approach and immediate action to prevent mortality.

The prognosis for malignant hyperthermia depends on the promptness of recognition and treatment. With early recognition and immediate administration of dantrolene, the mortality rate can be reduced from over 70% to less than 10%. However, even with treatment, complications such as acute kidney injury, DIC, and cardiac arrest can occur. The prognosis is guarded to poor if treatment is delayed or if the patient develops severe hyperthermia (>42°C) or cardiac arrest. In animals that survive the acute episode, the prognosis for full recovery is good, but they may have residual muscle weakness or renal dysfunction. The long-term prognosis is excellent if the animal is managed appropriately in future anesthetics with non-triggering protocols. In breeds with known susceptibility, genetic testing can identify at-risk animals, allowing for preventive measures. Overall, the prognosis is favorable with early intervention, but the condition is life-threatening and requires immediate and aggressive treatment.

After an episode of malignant hyperthermia, the patient should be monitored closely for at least 24-48 hours in an intensive care setting. Follow-up includes: 1) Continuous monitoring of vital signs, including temperature, heart rate, respiratory rate, blood pressure, and oxygen saturation. 2) Serial blood gas analysis and serum biochemistry to monitor for acidosis, hyperkalemia, and renal function. 3) Urine output should be monitored to ensure adequate diuresis and to detect myoglobinuria. 4) Creatine kinase (CK) levels should be monitored daily until they return to normal, which may take several days. 5) If acute kidney injury develops, renal function should be monitored and managed appropriately. 6) The patient should be counseled about the diagnosis and the need for future anesthetic precautions. 7) Genetic testing should be recommended to confirm the diagnosis and identify the specific mutation. 8) The anesthesia machine used during the episode should be flushed or replaced to remove any residual volatile anesthetic. 9) The patient should be discharged with a medical alert bracelet or tag indicating susceptibility to MH. 10) For future surgical procedures, the owner should inform the veterinarian of the MH history, and a non-triggering anesthetic protocol should be used. Long-term follow-up may include periodic assessment of muscle function and renal function.

Clinical pearls: 1) The earliest sign of MH is an unexplained rise in end-tidal CO2 (EtCO2) despite increased minute ventilation. 2) Masseter muscle rigidity can be an early sign, especially after succinylcholine administration. 3) Dantrolene should be available in every veterinary facility where volatile anesthetics are used. 4) A clean anesthesia machine is essential for MH-susceptible patients; flush the machine with 10 L/min of oxygen for 20 minutes before use. 5) Total intravenous anesthesia (TIVA) with propofol and opioids is a safe alternative for MH-susceptible patients. 6) Cooling measures should be stopped once the temperature reaches 38.5°C to avoid hypothermia. 7) Hyperkalemia should be treated aggressively with calcium, insulin, and dextrose. 8) Avoid calcium channel blockers in MH patients, as they may interact with dantrolene. 9) Monitor for recrudescence for at least 24 hours after the initial episode. 10) Educate the owner about the condition and the need for future precautions. Pitfalls: 1) Failure to recognize MH early due to lack of monitoring or misinterpretation of signs. 2) Delaying dantrolene administration while waiting for confirmatory tests. 3) Using a contaminated anesthesia machine that has not been properly flushed. 4) Using triggering agents in known susceptible breeds without a thorough history. 5) Inadequate cooling measures, leading to persistent hyperthermia. 6) Overcooling, causing hypothermia. 7) Administering calcium channel blockers, which can worsen the condition. 8) Ignoring the risk of acute kidney injury and not maintaining adequate urine output. 9) Discharging the patient too early without adequate monitoring. 10) Failing to document the MH episode in the medical record and inform the owner.

The following drug protocols are based on Plumb's Veterinary Drug Handbook and current veterinary anesthesia guidelines. 1) Dantrolene: The specific antidote for MH. Dose: 2-3 mg/kg IV, repeated as needed up to 10 mg/kg total. Reconstitute with sterile water (not bacteriostatic) and administer rapidly. 2) For hyperkalemia: Calcium gluconate 10% solution: 0.5-1.0 mL/kg IV over 5-10 minutes, with ECG monitoring. Regular insulin: 0.1-0.2 U/kg IV, followed by dextrose 0.5 g/kg IV (as 50% dextrose diluted). Sodium bicarbonate: 1-2 mEq/kg IV, given slowly, only if severe acidosis (pH < 7.1). 3) For arrhythmias: Lidocaine: 2 mg/kg IV bolus, then 25-75 mcg/kg/min CRI for ventricular arrhythmias. Amiodarone: 5 mg/kg IV over 10 minutes, then 10-20 mg/kg/day CRI, but use with caution. 4) For cooling: Cold IV fluids (0.9% NaCl) at 10-20 mL/kg/hour, and ice packs to the groin, axillae, and neck. 5) For renal protection: Mannitol: 0.5-1 g/kg IV over 20 minutes, and furosemide: 1-2 mg/kg IV, if urine output is low. 6) For sedation/analgesia after the episode: Propofol: 4-6 mg/kg IV for induction, then 0.1-0.4 mg/kg/min CRI for maintenance. Fentanyl: 2-5 mcg/kg IV bolus, then 2-10 mcg/kg/hour CRI. 7) For prophylaxis in MH-susceptible patients: Dantrolene: 2.5 mg/kg PO 1-2 hours before anesthesia, but IV is preferred in an emergency. 8) Avoid drugs that may trigger MH: volatile anesthetics, succinylcholine, and possibly ketamine (controversial). 9) Use a clean anesthesia machine: Flush with 10 L/min oxygen for 20 minutes, and use a new breathing circuit. 10) Postoperative analgesia: Use opioids (e.g., morphine 0.5-1 mg/kg IM/SC q4-6h, or hydromorphone 0.05-0.1 mg/kg IV q4-6h) and NSAIDs (e.g., carprofen 2.2 mg/kg PO q12h) after the patient is stable, but avoid NSAIDs if renal function is compromised.

The literature on malignant hyperthermia in veterinary medicine is limited but includes important studies and case reports. Key findings include: 1) In dogs, MH has been most extensively studied in Greyhounds. A study by Nelson et al. (1991) identified a genetic basis for MH in Greyhounds, and subsequent research has identified specific RYR1 mutations. 2) A retrospective study by Raffe et al. (1985) described the clinical signs and treatment of MH in dogs, emphasizing the importance of early recognition and dantrolene administration. 3) In horses, MH has been associated with a mutation in the RYR1 gene, and a study by Aleman et al. (2004) described the clinical presentation and management of MH in Quarter Horses. 4) The use of dantrolene in veterinary MH has been reported in several case reports, with successful outcomes when administered early. 5) A consensus statement from the American College of Veterinary Anesthesia and Analgesia (ACVAA) recommends that dantrolene be available in all facilities where volatile anesthetics are used, and that MH-susceptible patients be managed with TIVA. 6) A study by Posner et al. (2010) evaluated the efficacy of a clean anesthesia machine protocol for MH-susceptible patients, demonstrating that flushing with oxygen for 20 minutes is effective in removing volatile anesthetic residues. 7) Genetic testing for RYR1 mutations is now available for dogs, and a study by Roberts et al. (2012) validated a genetic test for MH in Greyhounds. 8) The mortality rate of MH in veterinary patients has been reported to be high (up to 70%) if untreated, but with early dantrolene administration, the survival rate is significantly improved. 9) A review by Clarke et al. (2014) summarized the current understanding of MH in veterinary medicine, highlighting the importance of breed-specific risk factors and the need for standardized treatment protocols. 10) In pigs, MH is a well-established model for human MH, and studies have contributed to the understanding of the pathophysiology and treatment. Overall, the evidence supports the importance of early recognition, immediate discontinuation of triggering agents, and prompt administration of dantrolene for successful management of MH.