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Malignant Hyperthermia (MH) Laboratory

This Web page aims to provide information about Malignant Hyperthermia (MH), testing procedures to diagnose MH and treatment options. This information is intended for patients and their families.  


Dr. Joseph TobinLin Marina
Dr. Joseph Tobin
Marina Lin
Research Associate


What is it?

"Malignant" = injurious, tending to cause death
"Hyperthermia" = higher than normal temperature

Malignant Hyperthermia is a rare, inherited condition. Affected persons can experience life threatening complications ("MH crisis") when they are exposed to certain anesthetics ("trigger agents") used to put patients to sleep for surgery.

Treatment for a MH-crisis is available with a drug called dantrolene. However, effectiveness is greatest when given early.

Children of an affected person have a 50% chance to inherit this condition from their parents.

Testing for MH-susceptibility is available. This is very important in individuals who experienced a MH crisis as well as in close relatives of affected people.

Prevention is Key

If a patient is known to be MH-susceptible,
safe anesthesia agents will be used
and the risk of a MH-crisis can be avoided.


Birth of a "New" Disease

In 1960 two anesthesiologists from Australia, Drs. Denborough and Lovell, wrote about a puzzling case in a medical journal. They described the case of a young man in his twenties who was involved in a car accident and broke his leg.

In the hospital it was determined that he would need a surgical procedure to get his leg fixed. When talking to his anesthesiologist prior to the surgery, the young man was very adamant about not being "put to sleep" for this surgery because several of his close relatives had previously died under mysterious circumstances while receiving general anesthesia with ether. However, he was assured that ether would therefore not be used for his anesthesia. Rather, his anesthesiologist planned to use a just recently introduced new drug, halothane that had the reputation of being safer than ether.

Approximately 30 minutes after the patient was asleep and surgery had started, the patient was noted to be very hot to the touch, the urine was found to be of an unexplained brownish color, and blood tests revealed a severely deranged metabolism. The procedure was quickly terminated, the patient was packed in ice for his markedly increased body temperature and then observed in the intensive care unit. Fortunately, the young man survived this incident without any long-term complications.

This case report led to the recognition of the disease "Malignant Hyperthermia." Numerous researchers worked on this subject after 1960 and were able to obtain an understanding of how this condition "works" and how it can be treated.

Earlier Observations of Malignant Hyperthermia

Although the initial description of an MH crisis is credited to Drs. Denborough and Lovell (see above), it does not appear that the patient in their report was truly the very first person to experience this complication.

Armed with our current knowledge about Malignant Hyperthermia, it appears likely that similar crisis situations did in fact happen during anesthesia decades before, but at the time were likely not recognized or were attributed to other causes. The medical literature as early as the turn of the 19th century reports on "ether convulsions" under anesthesia. Since today we know that ether is one of the trigger agents that can produce an MH-crisis, these early descriptions of "ether convulsions" under anesthesia may represent in fact some form of an MH-crisis.

Unraveling MH 

What do Pigs have to do with It?

Following the initial case report by Drs. Denborough and Lovell, numerous similar episodes were reported from hospitals all over the world. However, compared with the total number of anesthetics given all over the world, this problem occurred very infrequently and therefore proved difficult to study by scientists.

In 1973, a presentation by Dr. Thomas Nelson (now emeritus faculty of our department) on the International Symposium on Malignant Hyperthermia introduced a possible solution to this problem. Striking similarities had been observed between human muscle tissue after an MH-crisis and the muscle tissue from pigs suffering from the so-called "porcine stress syndrome."

Pigs affected by this syndrome were easily affected by stress, e.g., being transported on a truck, then frequently displayed changes in metabolism similar to a MH-crisis and, finally, most of them died. Further, trigger agents produced the same chain of events in pigs. The underlying mechanism that leads to this condition in pigs appeared identical to MH, thus affording researchers with an animal model for the further study of this condition.

What is the Mechanism of Malignant Hyperthermia?

It was found very early that MH obviously represented an inherited condition and therefore could "run" in families. Affected people are usually otherwise healthy unless they were exposed certain anesthesia drugs, so-called "trigger-agents" (see below). Also, it turned out that affected individuals did not always experience problems when they first came in contact with trigger agents and that the severity of a MH-crisis could vary. In fact, some patients have had as many as 16 exposures without incidence before they developed an MH-crisis during the 17th anesthetic.

Intensive research using the pig model (see above) led to the discovery that the crucial abnormality in MH lies in abnormal calcium handling in muscle tissue when exposed to certain anesthesia drugs. In normal muscle tissue contraction is brought about by rapidly shifting calcium concentrations between the internal compartments of a muscle cell. In MH-susceptible persons one of the small channels that allows calcium movement between cell compartments functions abnormally in the presence of trigger agents. This basically leads to an overload of calcium in the wrong place and can start a cascade of events that--if left untreated--will frequently be fatal. trigger agents

Today "trigger agents" are in widespread use worldwide because they generally have excellent safety profiles and allow for safe anesthesia with the exception of MH-susceptible patients. Trigger agents currently available in the U.S. are:

  • Muscle relaxants: Succinylcholine (Suxamethonium in Canada or Britain)
  • Anesthetic gases: Halothane, Isoflurane, Enflurane, Sevoflurane, Desflurane

How is Malignant Hyperthermia Inherited?

Susceptibility to MH is inherited by a so-called autosomal-dominant mode. This means that siblings, parents and children of a MH-susceptible individual have a 50% chance of also being positive for MH. As one moves further out on the family pedigree of a susceptible person, this likelihood decreases; e.g. uncles, aunts, nephews and nieces would have a 25% chance of being positive, and in cousins this chance would be further reduced to 12.5%.

The fact that MH-susceptibility can thus "run" in families illustrates the extreme importance of informing and testing close relatives if someone in the family has been found to be susceptible

Interestingly, it has also been found that susceptible persons from different families may express slightly different forms of susceptibility. This means that, although they all are at risk to develop a MH-crisis when exposed to trigger agents, the severity of complications may vary. Genetic studies on susceptible patients have shown that the explanation for this variability lies in the fact that several different genes can be responsible for the abnormality in muscle metabolism.

If you are MH susceptible, review our MH Susceptible FAQ.


Dantrolene sodium was initially developed in the mid-70s and approved for medical use in the U.S. in 1979 by the Food & Drug Administration (FDA). Today it remains the only specific treatment available for a MH-crisis. The likelihood of fatal complications from an unsuspected MH-crisis can be very substantially reduced when dantrolene is given early through an intravenous line. Without dantrolene treatment up to 7 out of 10 patients are estimated to die from an MH-crisis; with timely treatment this number can be reduced almost to 1 out of 10. dantrium

The exact mechanism of action of dantrolene is still unclear, but it is thought to reverse the abnormal calcium regulation in muscle cells.

Dantrolene is used only in the treatment of an MH-crisis. There is no need for prophylactic treatment in MH-susceptible patients.

Testing for Malignant Hyperthermia 

Muscle Biopsy muscle biopsy

At the beginning of the 70s researchers realized that muscle tissue from susceptible humans as well as in the pig model shows an abnormal response when electrically stimulated to contract. Based on these findings a diagnostic test was developed to test whether or not an individual is susceptible to MH.

The testing procedure involves taking a small muscle biopsy (approximately 3 inches long) from the thigh while the patient is under anesthesia. Trigger agents are strictly avoided for this anesthetic in order to not put the patient at risk. Instead, non-triggering agents  (general or spinal anesthesia) are used so that even in a susceptible person no MH-crisis can be caused.  The procedure must be done on living tissue taken directly from the operating room to the laboratory.

The muscle fibers are then tested in a laboratory where they aremuscle placed in a contraction chamber and their contraction response to electrical stimulation is recorded. Further, the muscle fibers are exposed to halothane and caffeine, 2 substances known to increase contraction responses in susceptible patient. However, caffeine (or coffee) is NOT a triggering agent and will NOT cause an MH-crisis in a susceptible person. Elaborate protocols have been developed both in North America and in Europe for the interpretation of this test.

Who Should be Tested?

In general, testing for MH-susceptibility is recommended in 2 groups of patients:

  •  Anyone who experienced an MH-crisis or questionable MH-crisis during an anesthetic that involved trigger agents 
    Reason: Since other conditions can at times mimic an MH-crisis under anesthesia, it is extremely important to establish whether or not the patient is susceptible so that trigger agents will be duly avoided in future anesthetics if the test is positive for MH. Further, a negative test eliminates the need to test any relatives, e.g., siblings or children.
  • Anyone with a close relative who tested positive for MH or is very likely positive (but cannot or will not be tested)
    Reason: Anyone who is positive for MH has a 50% chance of passing this condition on to his or her children. Further, all siblings and both parents of the patient have a 50% chance of being positive.

Future Options

Since MH-susceptibility is an inherited condition, researchers are working on genetic testing methods. Genetic screening could be performed on a simple blood sample. However, since the underlying abnormality in muscle metabolism can be transferred by a number of different genes (and multiple mutations), no genetic (blood) test is yet available that could reliably test for all possible gene abnormalities.  To date, genetic screening is approximately 35% sensitive and is used for family screenings when a known (biopsy proven) MH susceptible patient wishes to assist family members.

Although hopes are still high to ultimately develop a simpler test in the future, at the present time there is no alternative to a muscle biopsy.

Life with Malignant Hyperthermia 

Safe Surgery & Anesthesia 

Individuals known to be susceptible to MH can safely undergo alternativesanesthesia for any type of surgical or dental procedure as long as trigger agents are avoided. Safe alternatives to trigger agents include a variety of drugs given through an intravenous line to induce general anesthesia, as well as a number of techniques that just numb that part of the body where the surgery is performed (e.g., spinal/epidural anesthesia, nerve blocks).

(Some of the alternative "non-triggering" drugs and techniques, e.g. spinal/epidural kit, infusion pump)


The most important thing is to inform all your health care providers and precautionsespecially your anesthesiologist if you are going to have any type of surgery. In fact, worldwide not a single patient has ever died from MH when his or her condition was previously known to the medical team and appropriate precautions were taken.

To assure that health care providers will be alerted, it is strongly recommended that all MH-susceptible persons wear a medical identification bracelet.

Copyright © 2003 Wake Forest Baptist Medical Center, Malignant Hyperthermia Laboratory. All rights reserved. Revised: November 2003.

Quick Reference

Malignant Hyperthermia

Linda Marion 336-716-7194

Department of Anesthesiology
Wake Forest School of Medicine
100 Medical Center Blvd.
Winston-Salem, NC 27157
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Malignant Hyperthermia Muscle Biopsy

This video shows a live Muslce Biopsy and Caffeine Halothane Contracture test (CHCT) performed at Wake Forest Baptist Medical Center in Winston-Salem, NC.

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