Approach
The main goal of treatment is to normalise metabolism, prevent or reverse hyperthermia, and prevent rhabdomyolysis. The mainstay of treatment includes discontinuation of the trigger agent, dantrolene therapy, and restoration of a normal core temperature.[1] The patient should be stabilised in the operating room and transferred to the intensive care unit (ICU) for continued monitoring and treatment. Some patients may experience MH in the recovery room as opposed to the operating room. Treatment is the same as that in the operating room, with the exception that there may be times when it is not necessary to insert an endotracheal tube. Complications due to critical heat injury, such as disseminated intravascular coagulation and cerebral oedema, and complications due to rhabdomyolysis, such as hyperkalaemic cardiac arrest and myoglobinuric acute kidney injury, should be anticipated. Haematologists and nephrologists should be consulted as indicated.
Initial management of MH triggered by inhalation anaesthetics
Inhalation anaesthetics must be stopped.[1][2] Succinylcholine (suxamethonium) exacerbates the condition, and must not be used to treat the muscle rigidity. The time taken for the trigger agent to be eliminated depends on the time of exposure. Modern anaesthesia workstations have a larger reservoir of inhalation anaesthetic than the older machines.[84][85] Traces of inhalation agent may be delivered to the patient for more than 1 hour after the anaesthetic vaporiser source is removed. Activated charcoal filters placed at the patient's airway circuit connection reliably eliminate volatile anaesthetic delivery during an acute MH crisis.[86][87] Manufacturers recommend that a charcoal filter be placed on both the inspiratory and the expiratory limb of the circuit.[1] In addition, high flow rates of 100% oxygen should be administered to decrease exposure to residual gas in the workstation, and minimise a rebound effect if fresh gas flow rates are decreased; otherwise, an alternative source of oxygen should be provided.[85] All modern anaesthesia machines with carbon dioxide absorbers in use can be made non-rebreathing by increasing the total fresh gas flow to higher than the patient’s minute ventilation (volume of gas ventilated in 1 minute). Exhaled carbon dioxide and minute ventilation should be monitored. Minute ventilation should be increased (two to three times normal, as physiology allows) to control respiratory acidosis.
Intravenous dantrolene must be started as soon as the diagnosis is suspected.[1][2] Dantrolene produces muscle weakness, so equipment to place an endotracheal tube must be available when dantrolene is given by rapid intravenous administration. The Malignant Hyperthermia Association of the United States (MHAUS) recommends that initial dosing of dantrolene should be repeated until muscle tone returns to normal, the acidosis has resolved, and the heart rate is normal.[88] The Association of Anaesthetists (in Great Britain and Ireland) specifies that dantrolene should be given until the ETCO₂ is less than 45mmHg (6 kPa) with normal minute ventilation and the core temperature is < 38.5°C (101.3°F).[1] When these goals have been achieved, guidelines from MHAUS and the Association of Anaesthetists (in Great Britain and Ireland) differ in their recommendations on ongoing dantrolene dosing. See "Continued management in ICU" below. If resolution of muscle rigidity and the hypermetabolic state has not been achieved after a total dantrolene dose of 10 mg/kg, alternative diagnoses should be reconsidered.
In the absence of intravenous dantrolene, suspected MH has been aborted with dantrolene administration via a nasogastric tube.[89]
If the core temperature is greater than 40°C (104°F) or increasing rapidly, it is necessary to institute emergency measures to reduce temperature.[1] Cold intravenous balanced salt solution, preferably without potassium, should be administered rapidly. The patient should be uncovered to allow radiant and conductive heat loss. Forced air cooling can be used to speed these processes. Cold packs should be placed at the groin, axillae, neck, and around the head until the core temperature decreases to 38°C (100.4°F).[88] Cooling should be discontinued once core temperature is decreased to 38°C (100.4°F), to prevent overcorrection and iatrogenic hypothermia.[1][90] Peritoneal lavage is effective and can be utilised if the peritoneal cavity has already been surgically accessed. Gastric lavage is not effective or safe, and is not recommended.[90]
Large volumes of fluid may be needed because of translocation of fluid into oedematous muscle. Blood pH, pCO₂, and potassium measurement should guide administration of bicarbonate. A low threshold for the administration of sodium bicarbonate should be considered as low pH values are associated with a poor outcome in MH.[1] Intravenous bicarbonate and glucose with insulin may be needed to treat hyperkalaemia. If there is evidence of significant hyperkalaemia (potassium > 5.9mmol/L, or developing ECG changes), intravenous calcium may be needed.[91] Hyperventilation may also help by reducing the acidosis. Hyperkalaemia may lead to cardiac arrhythmias and cardiac arrest, requiring cardiac resuscitation in addition to extreme measures such as continuous veno-venous haemofiltration in cases of severe rhabdomyolysis.[92] Calcium channel blockers should be avoided when managing arrhythmias in the presence of an acute MH episode.[7][93] Cardiac failure may occur because of the need for high cardiac output to meet oxygen demands.
If the triggering anaesthetic is given in an ambulatory surgical center (ASC), then the patient will need to be transferred to a receiving hospital.[2] Intravenous dantrolene should be initiated pending transfer since the likelihood of significant MH complications doubles for every 30 minute delay in dantrolene administration.[2][6] An emergent MH transfer plan should be initiated at this point and acute MH management should continue while awaiting (and during) hospital transfer.[2]
Continued management in ICU
There is a high risk of recurrence within the first 24 hours after initial treatment exceeding 30% in those with muscular body types.[94] For patients who respond to acute treatment with dantrolene, MHAUS recommends continuing dantrolene therapy at a reduced dose (either by intermittent bolus or infusion) in the ICU for at least 24 hours to prevent recurrence.[90] Guidance from the Association of Anaesthetists (in Great Britain and Ireland) suggests a different approach, only delivering further dantrolene therapy if recurrent MH develops.[1] The treatment team must monitor closely for any rebound increase in ETCO₂, temperature, or heart rate, particularly if following the latter strategy.
Administration of cold intravenous fluids and placement of cold packs at the groin, axillae, neck, and head should be continued if core temperature is greater than 38°C (100.4°F).
The presence of myoglobinuria and low urine output are signs of impending acute kidney injury. If these occur, bicarbonate should be given and sufficient intravenous fluid to maintain the urine output above 2 mL/kg/hour.[1] Bicarbonate therapy alkalinises the urine and may decrease the likelihood of myoglobin-mediated injury to the renal tubules. If urine output continues to fall despite good hydration, mannitol should be administered. Phlebitis is noted in about 10% of patients after administration of the intravenous dantrolene formulation, which contains mannitol.[95] The North American Malignant Hyperthermia Registry Opens in new window It is not known if it is the mannitol in the dantrolene or the dantrolene itself that is more responsible for phlebitis.
Disseminated intravascular coagulation (DIC) should be treated as in other patients with heat injury. Replacement of coagulation factors is usual. Plasmapheresis may be helpful. Consultation with an expert in coagulation should be sought to guide further drug therapy if required. DIC and profound acute kidney injury commonly contribute to death from fulminant MH. Complications are more likely in older patients and in those who received inhalation anaesthetics for a longer interval of time before treatment with dantrolene.[95]
Any patient who develops myoglobinuria should be monitored for the development of compartment syndrome. Creatine kinase levels may not peak for up to 24 hours after an MH event and so the principal means of monitoring for compartment syndrome is clinical.[1] Awake patients may report pain. In the sedated patient, regular assessment of the limbs is indicated for swelling, muscle softness and peripheral pulses.[1] Peripheral oxygen saturation should be noted. If there is any suspicion that compartment syndrome has developed, the compartmental pressures should be measured.[1]
Management of exercise- or heat-induced rhabdomyolysis
This is a very rare but potentially lethal presentation of MH, in which excessive heat production in patients susceptible to MH triggers acute rhabdomyolysis.[12][70] It presents with muscle stiffness and dark urine following vigorous exercise or a heat-related illness. Symptoms usually resolve when core temperature is restored. Restoration of core temperature is usually achieved by rest in a cool environment and increased oral fluid intake. Intravenous fluids and dantrolene may be required, but this is unusual. These patients are at an increased risk of MH if exposed to inhalation anaesthetics or succinylcholine (suxamethonium); exposure to these agents should be avoided.[36]
Management of chronic myopathy
There is no curative treatment for the chronic myopathy that may be noted in patients susceptible to MH. However, some MH-susceptible individuals reported benefit from low dose dantrolene taken orally.[35][96] The myopathy is usually sub-clinical, manifesting with a chronic elevation of creatine kinase. These patients may prefer to avoid hot environments. Central core disease may be diagnosed by histopathology in MH patients with myopathic symptoms.
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