Drugs Known to Trigger Malignant Hyperthermia.

Inhaled general anesthetics
  • Ether
  • A halogenated anesthetic agent alone may trigger an episode of malignant hyperthermia.

    Halogenated agents currently in use include halothane (Fluothane®), enflurane (Ethrane®), isoflurane (Forane®), desflurane (Suprane®), and sevoflurane (Ultane®).

  • Methoxyflurane
Depolarizing muscle relaxant
  • Succinylcholine



triggered by succinylcholine and the volatile inhaled anesthetics (isoflurane, desflurane, and sevoflurane).

muscle disease, the characteristic phenotypical signs and symptoms of which most commonly appear with exposure to inhaled general anesthetics or succinylcholine (triggering agents). MH may occasionally present more than an hour after emergence from an anesthetic, and rarely may occur without exposure to known triggering agents. Most cases have been reported in young males; almost none have been reported in infants, and few have been reported in the elderly. Nevertheless, all ages and both sexes may be affected. The incidence of MH varies greatly from country to country and even among different geographic localities within the same country, reflecting varying gene pools.

Occur with exertion in hot ambient temperatures.


[Early clinical features reflect increased metabolic demand; the most important of these is the presence of a mixed metabolic and respiratory acidosis.




Malignant hyperthermia is hypermetabolicgenetic abnormality in the muscle membrane that predisposes patients to severe rhabdomyolysis and temperature dysregulation.

In many of the early reported cases, both succinylcholine and a halogenated anesthetic agent were used. However, succinylcholine is less frequently used in modern practice, and about half of the cases in the past decade were associated with volatile anesthetics as the only triggering agents.

  Nearly 50% of patients who experience an episode of MH have had at least one previous uneventful exposure to anesthesia during which they received a recognized triggering agent.

Investigations into the biochemical causes of MH reveal an uncontrolled increase in intracellular calcium in skeletal muscle. The sudden release of calcium from sarcoplasmic reticulum removes the inhibition of troponin, resulting in sustained muscle contraction. Markedly increased adenosine triphosphatase activity results in an uncontrolled increase in aerobic and anaerobic metabolism. The hypermetabolic state markedly increases oxygen consumption and CO2 production, producing severe lactic acidosis and hyperthermia.

One early focus of investigations into the mechanisms of MH has been the gene for the ryanodine (Ryr1) receptor, located on chromosome 19. Ryr1 is an ion channel responsible for calcium release from the sarcoplasmic reticulum and it plays an important role in muscle depolarization. Subsequent reports linked MH with mutations involving the sodium channel on chromosome 17. An autosomal recessive form of MH has been associated with the King-Denborough syndrome. Most patients with an episode of MH have a history of relatives with a similar episode or with an abnormal halothane-caffeine contracture test (see below). The complexity of genetic inheritance patterns in families reflects the fact that MH can be caused by mutations of one or more genes on more than one chromosome. To date genetic studies in humans have revealed at least five different chromosomes and more than 180 individual mutations associated with MH. Genetic testing, although available, currently screens for less than 20% of recognized mutations. A patient with a bona fide clinical history of MH has about a 30-50% chance of testing positive.


Content 11

Malignant hyperthermia (MH) is a rare (1:15,000 in pediatric patients and 1:40,000 adult patients).

The upper Midwest appears to have the greatest incidence of MH in the United States.1




  1. Discontinue volatile anesthetic and succinylcholine. Notify the surgeon. Call for help.

  2. Mix dantrolene sodium with sterile distilled water and administer 2.5 mg/kg intravenously as soon as possible.

  3. Administer bicarbonate for metabolic acidosis.

  4. Institute cooling measures (lavage, cooling blanket, cold intravenous solutions).

  5. Treat severe hyperkalemia with dextrose, 25–50 g intravenously, and regular insulin, 10–20 units intravenously (adult dose).

  6. Administer antiarrhythmic agents if needed despite correction of hyperkalemia and acidosis.

  7. Monitor end-tidal CO2 tension, electrolytes, blood gases, creatine kinase, serum myoglobin, core temperature, urinary output and color, and coagulation status.

  8. If necessary, consult on-call physicians at the 24-hour MHAUS hotline, 1-800-644-9737.1

1Data from the MHAUS protocol available at https://www.mhaus.org/healthcare-professionals/mhaus-recommendations/.



2. Treatment of neuroleptic malignant syndrome(???) includes dantrolene in combination with bromocriptine or levodopa.

Neuroleptic malignant syndrome is a rare and potentially lethal idiosyncratic reaction to neuroleptic medications, particularly haloperidol and fluphenazine; however, it has also been reported with the atypical neuroleptics (such as olanzapine or risperidone)

What Should be on an MH Cart?

What Should be on an MH Cart?


Therapy should be aimed at prompt administration of dantrolene, treatment of hyperkalemia, hyperventilation, and cooling to a target core temperature of no more than 38°C.

  1. Dantrolene – To treat an MH episode, an initial dose of dantrolene at 2.5 mg/kg is recommended.
  2. Two formulations now available.
    1. DANTRIUM®/REVONTO® are the older formulation, which provides 20 mg dantrolene sodium/60 mL after reconstitution in sterile water.
      1. DANTRIUM®/REVONTO® – 36 vials should be available in each institution where MH can occur, each vial to be diluted at the time of use with 60 ml sterile water, USP (without a bacteriostatic agent). There are 3 grams of mannitol in each vial of 20 mg of dantrolene (0.15 g mannitol/ 1 mg dantrolene).
    2. RYANODEX® (dantrolene sodium), is a new formulation that is an injectable suspension of dantrolene sodium providing 250 mg of dantrolene sodium/5 mL after reconstitution.
      1. RYANODEX® – 3 vials should be available in each institution where MH can occur, each to be diluted at the time of use with 5 ml of sterile water for injection, USP (without a bacteriostatic agent). There are 0.125 grams of mannitol in each vial of 250 mg of Ryanodex® (0.0005 grams mannitol/1 mg dantrolene).
  3. Sterile water for injection USP (without a bacteriostatic agent) – It is mandatory to get dantrolene sodium to its effective site, the skeletal muscle.
    1. DANTRIUM®/REVONTO® – Each 20 mg vial should be reconstituted by adding 60 ml of sterile water for injection, USP (without a bacteriostatic agent) and the vial shaken until the solution is clear. If the MH episode is proceeding rapidly, simply mix and inject. We advise that the sterile water be stored in 100 ml vials, not bags, to avoid accidental IV administration of this hypotonic solution.
    2. RYANODEX® – Each 250 mg vial should be reconstituted with 5 ml of sterile water for injection, USP (without a bacteriostatic agent) and shaken to ensure an orange-colored uniform, opaque suspension. RYANODEX® should be administered by intravenous push. Five percent dextrose injection, USP, 0.9% sodium chloride injection, USP,
      1. Other acidic solutions are NOT compatible with RYANODEX® and should not be used.
      2. The contents of the vial must be used within 6 hours after reconstitution.
  4. Sodium bicarbonate (8.4%) – 50 ml x 5
  5. Dextrose 50% – 50 ml vials x 2
  6. Calcium chloride (10%) – 10 ml vial x 2
  7. Regular insulin – 100 units/ml x 1 (refrigerated)
  8. Lidocaine* for injection (2%) – 100 mg/5 ml or 100 mg/10 ml in preloaded syringes (3). Amiodarone is also acceptable. ACLS protocols, as prescribed by the AHA, would be followed when treating all cardiac derangements caused by MH.
  9. Refrigerated cold saline solution – A minimum of 3,000 ml for IV cooling

* Lidocaine or procainamide should not be given if a wide-QRS complex arrhythmia is likely due to hyper­kalemia; this may result in asystole.

General Equipment

  1. Charcoal Filters - Two pairs of activated charcoal filters (Vapor-Clean™, Dynasthetics, Salt Lake City, UT). Attach activated charcoal filters to inspiratory and expiratory ports of the anesthesia machine to quickly reduce the concentration of gas (<5ppm) from the anesthesia machine. In this situation, even though the anesthetic gas has been discontinued when MH was first suspected, the Vapor-Clean™ filter may become saturated after one hour; therefore, a replacement set of filters should be substituted after each hour of use.
  2. Syringes – (60 ml x 5) to dilute Dantrium®/Revonto® and (5 ml x 3) for Ryanodex®
  3. Intravenous catheters – 16G, 18G, 20G, 2-inch; 22G, 1-inch; 24G, 3/4-inch (4 each) (for IV access and arterial line)
  4. Pressure Bag
  5. Disposable Cold Packs - (x 4)

Monitoring Equipment

  1. Esophageal or other core (e.g., nasopharyngeal, tympanic membrane, rectal, bladder, pulmonary artery catheter) temperature probes
  2. CVP kits (sizes appropriate to your patient population).  We recommend these are used in patients who are critically ill.
  3. Transducer kits for arterial and central venous cannulation

Nursing Supplies

  1. Large sterile Steri-Drape (for rapid drape of wound)
  2. Urine meter x 1
  3. Large clear plastic bags for ice x 4
  4. Small plastic bags for ice x 4
  5. Bucket for ice
  6. Test strips for urine hemoglobin

Laboratory Testing Supplies

  1. Syringes (3 ml) for blood gas analysis or ABG kits x 6 or point of care monitors; ISTAT with TB syringes (the point of care ISTAT device has replaced lab blood gene and electrolyte measurement).
  2. Blood specimen tubes for CK, myoglobin, SMA 19 (LDH, electrolytes, thyroid studies), PT/PTT, fibrinogen, fibrin split products; and lactate, CBC, platelets. If no immediate laboratory analysis is available, samples should be kept on ice for later analysis. This may well prove useful on retrospective review and diagnosis. Blood cultures are very useful and should be included to rule out bacteremia.
  3. Urine collection container for myoglobin level. Pigrnenturia (e.g , brown or red urine and heme positive dipstick) indicates that renal protection is mandated, when the urine is centrifuged or allowed to settled, and the sample shows clear supernatant, i.e., the coloration is due to red cells in the sample.
    1. Sodium bicarbonate (8.4%) – 50 ml x 5
    2. Dextrose 50% – 50 ml vials x 2
    3. Calcium chloride (10%) – 10 ml vial x 2
    4. Regular insulin – 100 units/ml x 1 (refrigerated)
    5. Lidocaine* for injection (2%) – 100 mg/5 ml or 100 mg/10 ml in preloaded syringes (3). Amiodarone is also acceptable. ACLS protocols, as prescribed by the AHA, would be followed when treating all cardiac derangements caused by MH.
    6. Refrigerated cold saline solution – A minimum of 3,000 ml for IV cooling 




Most people with pyelonephritis do not have complications if appropriately treated with bacteria-fighting medications called antibiotics.

In rare cases, pyelonephritis may cause permanent kidney scars, which can lead to chronic kidney disease, high blood pressure, and kidney failure. These problems usually occur in people with a structural problem in the urinary tract, kidney disease from other causes, or repeated episodes of pyelonephritis.

Infection in the kidneys may spread to the bloodstream—a serious condition called sepsis—though this is also uncommon.



Fatality rate is currently 5%.

Content 13

Content 11


A 28-year-old man presents for shoulder surgery. The patient had a documented episode of malignant hyperthermia in a previous surgery under general anesthesia. Which of the following neuromuscular blockers is contraindicated in this patient?

The correct answer is D.

Malignant hyperthermia is a life-threatening hypermetabolic disorder that is triggered by succinylcholine and the volatile inhaled anesthetics (isoflurane, desflurane, and sevoflurane). All triggering agents are contraindicated in patients with a history of malignant hyperthermia.



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