WHAT IS MH? 

The sudden unexpected death of a healthy individual undergoing minor surgery is a tragedy almost beyond comprehension in this day of modern medical miracles.  Yet this still  happens to patients susceptible to  malignant hyperthermia (MH).  Even when treated properly, the syndrome known as the MH crisis can cause death.  In rare cases, survivors might be left with brain damage, failed kidneys, muscle damage or impaired function of other major organs. 

Another cause of unexpected death during or shortly after anesthesia is a sudden cardiac arrest in a young male patient with muscular dystrophy.  In some cases the patient may not be old enough to show the characteristic signs of muscle weakness.  The anesthesia care team may therefore not realize that the patient may develop a marked increase in potassium in the blood sufficient to stop the heart when anesthetized.  This phenomenon occurs with the use of drugs that "trigger MH," but the syndrome is distinct and different from MH.  Another sign of this reaction is severe muscle breakdown manifested by brown urine and kidney failure.  (See below:  Are There Links Between MH and Other Diseases?)                 

 WHAT IS MALIGNANT HYPERTHERMIA?

The MH crisis is a biochemical chain reaction response “triggered” by commonly used general anesthetics and the paralyzing agent succinylcholine within the skeletal muscles of susceptible individuals.  The general signs of the MH crisis include tachycardia (a rise in heart rate), a greatly increased body metabolism, muscle rigidity and/or fever that may exceed 110 degrees F.  Severe complications include:  cardiac arrest, brain damage, internal bleeding or failure of other body systems.  Thus, death, primarily due to a secondary cardiovascular collapse, can result.                     

 WHO IS SUSCEPTIBLE TO MH?

There has been dramatic improvement in our understanding of what causes MH and who is at risk.  Over 80 genetic defects have been associated with MH.  MH susceptibility  is inherited with an autosomal dominant inheritance pattern.  This means that children and siblings of a patient with MH susceptibility usually have a 50% chance of inheriting a gene defect for MH and hence would also be MH susceptible.  They, therefore, may develop an MH reaction upon exposure to triggers.

Nevertheless,  those who are carriers for susceptibility may be completely unaware of this risk unless they or a family member developed a life-threatening crisis during anesthesia.  It is important to know that not everyone who has a gene defect linked to MH develops  the MH crisis upon each exposure to the triggering anesthetics.  (See the section below on Testing for MH susceptibility.)

 WHAT DRUGS TRIGGER MH?

The volatile gaseous inhalation anesthetics are MH triggers:

sevoflurane
desflurane
isoflurane
halothane
enflurane
methoxyflurane

Also, succinylcholine (Anectine), the depolarizing muscle relaxant

 ARE OTHER ANESTHETICS SAFE?

Yes, all other anesthetic drugs are safe.  Some examples of safe anesthetics are:

local anesthetics
nitrous oxide
barbiturates
narcotics
propofol
benzodiazepines
ketamine
etomidate

The   non-depolarizing muscle relaxants (used to temporarily produce muscle paralysis) are also safe:

pancuronium
cisatracurium
atracurium
mivacurium
vecuronium
rocuronium

 WHAT IS THE INCIDENCE OF MH?

The exact incidence of MH is unknown.  The rate of occurrence has been estimated to be as frequent as one in 5,000 or as rare as one in 65,000 administrations of general anesthesia with triggering agents.  The incidence varies depending on the concentration of MH families in a given geographic area.  High incidence areas in the United States include Wisconsin, Nebraska, West Virginia and Michigan.

 WHAT CAUSES AN MH EPISODE?

MH-susceptible persons have a mutation that results in the presence of abnormal proteins in the muscle cells of their body.  Although normal in everyday life, when these patients are exposed to certain anesthetic agents, it causes an abnormal release of calcium inside the muscle cell, which results in a sustained muscle contraction and the abnormal increase in energy utilization and heat production.  The muscle cells eventually run out of energy, and die, and release large amounts of potassium into the bloodstream, which can lead to heart rhythm abnormalities.  The muscle pigment myoglobin is also released and may be toxic to the kidney.  Left untreated, these changes can cause cardiac arrest, kidney failure, blood coagulation problems, internal hemorrhage, brain injury, liver failure, and may be fatal.  A fuller explanation of the biochemical changes in MH may be found on the MHAUS Web site.

 HOW IS MH TREATED?

The  MH crisis must be identified and treated early in its course in order for there to be a successful outcome.  The treatment must be swift, focused and continued for many hours after an episode begins. 

Since 1979, the drug dantrolene sodium for injection (Dantrium® I.V.) has been available for the treatment of an MH crisis and has contributed greatly to a dramatic decline in deaths and/or resultant disabilities  associated with such occurrences.  It is therefore vital that all hospitals, ambulatory centers and offices where general anesthesia is administered have a full supply of dantrolene immediately available.  

In addition, the provider must have facilities to rapidly lower body temperature, measure acid –base changes in the blood, measure coagulation changes, blood electrolytes and tests for muscle breakdown.

A treatment plan must therefore be on hand and periodically rehearsed.  MHAUS can supply a detailed treatment protocol (in English and in Spanish) for facilities where general anesthesia is given.  

 HOW CAN MH BE PREVENTED?

The best way to prevent MH is through detection of those at risk prior to surgery.  Patients with a family history of MH or suggestive of MH should ensure that this information is communicated to his/her anesthesia caregiver.  Anesthesia providers routinely question patients about adverse events associated with anesthesia in the patient or his/her family.  Also, a personal history of a muscle disorder is obtained.  Patients should ensure that the facility (hospital, surgery center, office) is stocked with dantrolene in sufficient quantities for a crisis (36 vials) and that a treatment protocol is available.

MH-susceptible patients should always wear identification material to indicate their MH status.  MHAUS can provide identification tags and wallet cards at low cost.

 HOW CAN MH-SUSCEPTIBLE PATIENTS BE IDENTIFIED?

Because MH is considered a dominantly inherited disorder, all closely-related members of a family in which MH has occurred must also be considered MH susceptible and managed accordingly, unless proven otherwise.  It should be noted that those who have had previous anesthetics without problem cannot be certain they are not at risk; MH related deaths have occurred even though patients have undergone multiple prior uneventful surgeries.  Certainly any family with a history of anesthetic deaths or complications should make this known to the anesthesiologist before undergoing surgery.  Additionally, they should register their MH susceptibility with the North American MH Registry of MHAUS, Pittsburgh, PA by calling 412-692-5464 or toll free 888-274-7899.

 IS THERE A TEST FOR MH?

There is currently no simple diagnostic test available for screening the general population (e.g., a blood test).  Genetic testing is available, which is useful in identifying some patients with MH.  Since not all of the genes responsible for MH have been identified, the genetic tests are only useful in families with a suspicious history of MH.  Even if the genetic tests do not show that you have one of the genes for MH, you may still have other unidentified genes and therefore may be at risk for MH.  The MHAUS newsletter, The Communicator, keeps you up to date in these areas.  

The most accurate test (“gold standard”) that has been in use for thirty years involves a biopsy of skeletal muscle from the thigh.  It is usually reserved for those with a family history of MH or when a patient has had a previous suspicious reaction to anesthesia.  The test is available at eight  medical centers in the United States and Canada.  A list of the centers may be obtained from MHAUS or at www.mhaus.org.  More details regarding the test are available through the MHAUS Web site.

 CAN MH-SUSCEPTIBLE PATIENTS HAVE SURGERY?

Yes!  Surgery can be safely performed in the known MH-susceptible patients.  However, nontriggering anesthetics must be used as well as special precautions and techniques, including close monitoring of appropriate vital functions.  Close monitoring occurs in all anesthetics.

In surgery for a known MH-susceptible patient, the anesthesiologist should:

• Avoid the use of MH-triggering anesthetics.
• Be familiar with the signs and treatment of MH.
• Continuously monitor the patient's expired carbon dioxide concentration.
• Continuously monitor the patient's temperature (also during recovery).  Skin temperature is not reliable in this situation.
• Have an MH kit or cart within the operating room suite stocked with an adequate supply of dantrolene.

  CAN MH OCCUR OUTSIDE OF THE OPERATING ROOM?

Yes.  While most cases of MH occur during general anesthesia, the one-hour period immediately following surgery (including the recovery room) is also a critical time.  In addition, MH can occur if trigger anesthetics and/or succinylcholine are used in emergency rooms, dental surgeries, surgeons’ offices or intensive care units.

  CAN ANYTHING OTHER THAN ANESTHETIC DRUGS TRIGGER MH?

Only the anesthetic drugs already mentioned usually trigger MH.  However, recent studies have shown that a small percent of people who develop muscle breakdown following exercise only, or after heat stroke, harbor the genetic changes associated with MH susceptibility.  It is still unclear if the muscle breakdown and other changes result from these changes.  Generally we advise MHS patients to lead normal lives other than when anesthesia is required.  

  ARE THERE LINKS BETWEEN MH AND OTHER DISORDERS?

MH has been linked to two unusual inherited muscle disorders: Central Core Disease and Multi Mini Core Disease.  There is great variability in the onset and extent of muscle weakness in these conditions.  In some cases, the weakness is manifest in childhood; in others, the weakness is later in life.

Additionally, patients with certain forms of muscular dystrophy may develop life-threatening cardiac rhythm disturbances and muscle destruction on exposure to the known triggering agents for malignant hyperthermia.  The changes are felt to be related to release of potassium from the cells or to release of cellular constituents such as myoglobin.  Rapid excessive release of potassium from skeletal muscle produces cardiac arrest.  The overall clinical event may  resemble MH in many ways, but these changes are not considered “true” MH; they are due to weakened muscle membranes secondary to the muscular dystrophy. 

Some experts also believe that heat stroke may occur more often in MH-susceptible individuals.

  WHERE CAN A PATIENT OR HEALTH CARE PROFESSIONAL GET MORE DETAILED INFORMATION ABOUT MH?

In the U.S., MHAUS serves as your best source of information and educational materials for health care professionals and MH-susceptible individuals. 

Malignant Hyperthermia Association
of the United States (MHAUS)
 11 E State St, PO Box 1069
Sherburne NY 13460-1069
607-674-7901 or 800-98MHAUS
Web site:  www.mhaus.org

The North American MH Registry of MHAUS serves as your best source of patient-specific MH information. 

North American MH Registry of MHAUS
Barbara Brandom, MD, Director
U of Pittsburgh Children’s Hospital
Anesthesiology Dept, Room 7449
3705 Fifth Ave at DeSoto St
Pittsburgh PA 15213-2583
412 -692-5464 or 888-274-7899

Reliable information concerning MH also may be found at a variety of Web sites:

• www.emhg.org:  European MH Group
• www.genetests.org:  GeneTests, an NIH sponsored site from the University of Washington, Seattle
• www.orpha.net:  Orphanet, a compilation of information concerning orphan diseases

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There is still much that is not known about malignant hyperthermia.
Research is continuing.  
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