Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

inhalation anaesthetic-induced

1st line – discontinuation of triggering agent

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ACUTE
|
inhalation anaesthetic-induced
1st line – 

discontinuation of triggering agent

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 older machines.[84][85] Traces of inhalation agent may be delivered to the patient for more than 1 hour after the anaesthetic vapouriser source is removed.

High flow rates of 100% oxygen totalling more than the minute ventilation should be administered to decrease exposure to residual gas in the workstation, and minimise a rebound effect if fresh gas flow rates are decreased;[85] otherwise, an alternative source of oxygen should be provided. Application of a charcoal filter to the inspiratory limb of the ventilating circuit eliminates inspired volatile anaesthetic rapidly.[86][87] Application of a charcoal filter to the expiratory limb is also recommended.[1]

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.

Plus – intravenous dantrolene

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ACUTE
|
inhalation anaesthetic-induced
Plus – 

intravenous dantrolene

Treatment recommended for ALL patients in selected patient group

Intravenous dantrolene should be administered as soon as the diagnosis is suspected.[1][2] Extra personnel should be called to assist in mixing and administration of dantrolene.

Lyophilised dantrolene is a newer formulation that can be much more rapidly reconstituted and administered compared with the conventional intravenous formulations. Lyophilised dantrolene vials contain insufficient mannitol to maintain diuresis; additional doses of mannitol need to be administered concurrently.

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 should be repeated until muscle tone returns to normal, the acidosis has resolved, core temperature is normal, 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. 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. 

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] 

Primary options

dantrolene: consult specialist for guidance on dose

Plus – maintenance of normothermia

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ACUTE
|
inhalation anaesthetic-induced
Plus – 

maintenance of normothermia

Treatment recommended for ALL patients in selected patient group

If the core temperature is greater than 40°C (104°F) or increasing rapidly, cold intravenous balanced salt solution, preferably without potassium, should be administered rapidly.

The patient should be uncovered to allow radiant and conductive heat loss.

Cold packs should be placed at the groin, axillae, neck, and around the head until 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]

Plus – supportive care (including fluid resuscitation and management of hyperkalaemia) + intensive care unit (ICU) admission

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ACUTE
|
inhalation anaesthetic-induced
Plus – 

supportive care (including fluid resuscitation and management of hyperkalaemia) + intensive care unit (ICU) admission

Treatment recommended for ALL patients in selected patient group

Once stabilised, all patients require ICU admission. Most patients require intubation if it is not already in place.

Fluid resuscitation should be provided. Large volumes of fluid may be needed because of translocation of fluid into oedematous muscle.

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. 

Calcium channel blockers should be avoided when managing arrhythmias in the presence of an acute MH episode.[7][93]

Core temperature, carbon dioxide production, minute ventilation, and urine output should be monitored. Cardiac failure may occur because of the need for high cardiac output to meet oxygen demands.

The decision to give bicarbonate is guided by measurements of blood pH, pCO2, and potassium measurement. 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]

Plus – consideration of bicarbonate therapy + monitoring of urine output

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ACUTE
|
inhalation anaesthetic-induced
|
with myoglobinuria and low renal output
Plus – 

consideration of bicarbonate therapy + monitoring of urine output

Treatment recommended for ALL patients in selected patient group

The presence of myoglobinuria and low urine output are signs of impending profound acute kidney injury. A serum creatine kinase level of >5000 IU/L is presumptive of serious rhabdomyolysis and myoglobinuria.[97] If these occur, administration of bicarbonate may be considered and the urine output maintained above 2 mL/kg/hour.[1] Bicarbonate therapy alkalinises the urine and may decrease the likelihood of myoglobin-mediated injury to the renal tubules.

Forced alkaline diuresis may be attempted only if: the patient has established diuresis; arterial pH <7.5; and serum bicarbonate <30 mmol/L (<30 mEq/L).[98] This treatment requires expert supervision by a specialist experienced in the care of such patients.

Consider – mannitol

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ACUTE
|
inhalation anaesthetic-induced
|
with myoglobinuria and low renal output
Consider – 

mannitol

Additional treatment recommended for SOME patients in selected patient group

Mannitol should be given if urine output remains below 2 mL/kg/hour despite adequate hydration. Although most dantrolene sodium formulations contain mannitol, continued mannitol treatment may be necessary to maintain adequate urine output.

Lyophilised dantrolene vials contain insufficient mannitol to maintain diuresis; additional doses of mannitol need to be administered concurrently.

Dose should be titrated to maintain the urine output >2 mL/kg/hour.

Mannitol should be discontinued if there is no response.

Primary options

mannitol: 0.5 to 1 g/kg intravenously initially, followed by 0.25 to 0.5 g/kg every 4-6 hours; or 0.1 g/kg/hour intravenous infusion

Plus – coagulation factors

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ACUTE
|
inhalation anaesthetic-induced
|
with disseminated intravascular coagulation
Plus – 

coagulation factors

Treatment recommended for ALL patients in selected patient group

Fresh frozen plasma (FFP) is the preferred agent. Cryoprecipitates or fibrinogen concentrates are second-line alternatives.

Blood-borne diseases of all types (hepatitis, HIV) and febrile reactions are always a risk in administration of human blood products.

Rapid infusion of platelets, FFP, cryoprecipitates, or fibrinogen concentrates may cause hypotension.

Consider – plasmapheresis

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ACUTE
|
inhalation anaesthetic-induced
|
with disseminated intravascular coagulation
Consider – 

plasmapheresis

Additional treatment recommended for SOME patients in selected patient group

Plasmapheresis may be beneficial in some patients if treatment of MH and replacement of coagulation factors produces an inadequate response.

exercise- or heat-induced

1st line – restoration of normothermia

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ACUTE
|
exercise- or heat-induced
1st line – 

restoration of normothermia

This is a very rare but potentially lethal presentation of MH, in which excessive heat production in patients susceptible to MH triggers an acute myopathy.

Patients present 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.

Consider – intravenous fluids and dantrolene

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ACUTE
|
exercise- or heat-induced
Consider – 

intravenous fluids and dantrolene

Additional treatment recommended for SOME patients in selected patient group

Treatment depends on how high the temperature is and the level of consciousness of the patient. Dantrolene should be given if the core temperature is >40°C (>104°F) and increasing. If the temperature is less than 40°C (104°F) and there is no rigidity, spraying with room temperature water or immersion in cold water may reduce core temperature adequately. If the patient is rigid and unconscious, both intravenous fluids and dantrolene should be given.

Lyophilised dantrolene is a newer formulation that can be much more rapidly reconstituted and administered compared with the conventional intravenous formulations. Lyophilised dantrolene vials contain insufficient mannitol to maintain diuresis; additional doses of mannitol need to be administered concurrently.

Cold intravenous fluids should be given to support circulatory function as well as to contribute to normothermia. Dantrolene should be given until symptoms of increased metabolism and rigidity resolve.

Primary options

dantrolene: consult specialist for guidance on dose

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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