Revonto ™ (dantrolene sodium for injection)

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What is Malignant Hyperthermia (MH)?

What is Malignant Hyperthermia (MH)?

Malignant hyperthermia (MH) is a rare but potentially deadly hypermetabolic crisis that typically occurs as a complication of general anesthesia.¹ The signs, which may arise at any time during anesthesia or the early postoperative period, result from hypermetabolism in skeletal muscle, probably as a result of uncontrolled intracellular release of calcium from the sarcoplasmic reticulum.¹

In almost all cases, patients who are susceptible to MH have a defective calcium channel on the sarcoplasmic reticulum of skeletal muscle cells.¹ This defect, which is inherited as an autosomal dominant trait, has been linked to several different gene mutations.¹ The presence of these mutations can be detected only by exposure to the triggering anesthetic or by specific diagnostic testing.¹ The gold standard for determining susceptibility to MH is the caffeine-halothane contracture test, which requires a biopsy of skeletal muscle.² Genetic tests for susceptibility to MH are also being developed.²

An episode of MH can be triggered by any inhalation anesthetic except nitrous oxide; it can also be triggered by the depolarizing muscle relaxant succinylcholine (suxamethonium).¹ Note that MH has occurred in patients who had previously been exposed to the same anesthetic agents without incident.¹

Prevention of MH involves avoidance of the triggering anesthetic agents in patients with a personal or family history of MH. Dantrolene sodium for injection can be used preoperatively, and sometimes postoperatively, to prevent or attenuate the development of clinical and laboratory signs of MH in individuals judged to be susceptible to MH.³

Early recognition and prompt treatment of an MH crisis are essential for the patient's survival.4; The signs of MH include the following4:

Early metabolic signs

  • Inappropriately elevated carbon dioxide production, which is manifested as raised end-tidal
    CO on capnography or as tachypnea if the patient is breathing spontaneously
  • Increased oxygen consumption
  • Mixed metabolic and respiratory acidosis
  • Profuse sweating
  • Mottling of skin

Early cardiovascular signs

  • Inappropriate tachycardia
  • Cardiac arrhythmia (especially ectopic ventricular beats and ventricular bigemini)
  • Unstable arterial pressure

Muscle rigidity

  • Masseter spasm if succinylcholine has been used
  • Generalized muscle rigidity

Later signs

  • Hyperkalemia
  • Rapid increase in core body temperature
  • Grossly elevated blood levels of creatine phosphokinase and myoglobin
  • Dark urine (myoglobinuria)
  • Severe cardiac arrhythmia and cardiac arrest
  • Disseminated intravascular coagulation

Treatment should be started as soon as an MH crisis is suspected.4


  • Immediate discontinuation of all trigger agents
  • Administration of nontriggering anesthetic if necessary
  • Hyperventilation with 100% oxygen
  • Dantrolene sodium, administered by continuous rapid intravenous push
  • Cooling procedures until body temperature is <38.5 °C
  • Dextrose, insulin, calcium chloride, and possibly dialysis for correction of hyperkalemia
  • Hyperventilation and possibly sodium bicarbonate for management of acidosis
  • Antiarrhythmic drug treatment, if necessary
  • Diuretic and fluid therapy to maintain high urinary output

Please see full prescribing information for Revonto.


Reference List

  1. Rosenberg H, Davis M, James D, et al. Malignant hyperthermia. Orphanet J Rare Dis. 2007;2:21.
  2. Litman RS, Rosenberg H. Malignant hyperthermia: update on susceptibility testing. JAMA. 2005;293(23):2918-2924.
  3. Dantrolene sodium for injection [prescribing information]. Louisville, KY: USWM, LLC; 2008.
  4. Glahn KP, Ellis FR, Halsall PJ, et al. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group. Br J Anaesth. 2010;105(4):417-420.



Revonto is indicated, along with appropriate supportive measures, for the management of fulminant hypermetabolism of skeletal muscle characteristic of malignant hyperthermia crises in patients of all ages. It is also indicated preoperatively and sometimes postoperatively, to prevent or attenuate the development of clinical and laboratory signs of malignant hyperthermia in individuals judged to be malignant hyperthermia susceptible.

Important Safety Information

The use of Revonto in the management of malignant hyperthermia crisis is not a substitute for previously known supportive measures. These measures must be individualized, but it will usually be necessary to discontinue the suspect triggering agents, attend to increased oxygen requirements, manage the metabolic acidosis, institute cooling when necessary, monitor urinary output, and monitor for electrolyte imbalance. Patients who receive i.v. dantrolene sodium preoperatively should have vital signs monitored.

If patients judged malignant hyperthermia susceptible are administered dantrolene sodium preoperatively, anesthetic preparation must still follow a standard malignant hyperthermia susceptible regimen, including the avoidance of known triggering agents. Monitoring for early clinical and metabolic signs of malignant hyperthermia is indicated because attenuation of malignant hyperthermia, rather than prevention, is possible.

Despite initial satisfactory response to i.v. dantrolene there have been reports of fatality, which involve patients who could not be weaned from dantrolene after initial treatment. The administration of i.v. dantrolene is associated with loss of grip strength and weakness in the legs, as well as drowsiness and dizziness. There have been reports of thrombophlebitis following administration of intravenous dantrolene. Tissue necrosis secondary to extravasation has been reported. Injection site reactions (pain, erythema, swelling), commonly due to extravasation, have been reported. Fatal and non-fatal liver disorders of an idiosyncratic or hypersensitivity type may occur with dantrolene sodium therapy.

To report SUSPECTED ADVERSE REACTIONS contact US WorldMeds at 1-888-900-8796 or MEDWATCH at 1-800-FDA-1088 (1-800-332-1088)

For additional information, see full prescribing information for Revonto.