What is Malignant Hyperthermia?
MH, also known as malignant hyperpyrexia, is a rapidly occurring chain reaction of events (a syndrome) "triggered" in susceptible
individuals by commonly used general anesthetics. These include volatile or gas anesthetics (e.g. halothane, enflurane, isoflurane,
and sevoflurane) as well as the muscle relaxant succinylcholine. The signs of MH include a great increase in body metabolism,
muscle rigidity and eventual hyperthermia which may exceed 110 degrees F. Death can result from cardiac arrest, brain damage,
internal hemorrhaging or failure of other body systems. Left untreated, the mortality of MH is nearly 80%.
Who is susceptible to MH?
MH susceptibility has an autosomal dominant inheritance. This means that children as well as the brothers and sisters of a
patient with MH susceptibility have a 50% chance of inheriting the gene for MH and hence would also be MH susceptible. Identification
of MH in affected families is important in order to deliver the safest anesthetic possible.
Those who are susceptible may be completely unaware of their 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 genetic defect linked to MH develops an MH episode
upon each exposure to the triggering anesthetics.
Unfortunately, the genetic defect for this disorder has not been completely identified so the only reliable way to identify
those at risk for MH is with a muscle biopsy known as the caffeine halothane contracture test (CHCT). The CHCT test should
be considered for all those judged to be at significant risk for MH. Your risk of developing MH is made either through a personal
and/ or family history, an episode of MH, or a previous adverse reaction to a general anesthetic suggestive of MH.
Are other anesthetics safe?
Yes, many other anesthetic drugs are safe: patients found to be MH susceptible can be anesthetized with non-triggering agents
and carefully monitored during surgical procedures.
Some examples of safe anesthetics are: nitrous oxide, local anesthetics, narcotics, propofol, thiopental, curare, and atracurium.
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, West Virginia and
Michigan.
What causes an MH episode?
Although the cause of MH is not yet known with certainty, research evidence points to a generalized derangement of metabolic
processes that regulate muscle contraction. The triggering agents cause a release of calcium from storage sites in muscle;
this leads to elevated concentrations of calcium in the muscle cells. High calcium levels increase the body’s metabolism and
in time cause the muscles to contract and become rigid. This process results in heat production (hyperthermia), acidosis,
and muscle cell breakdown.
What changes are observed during MH?
The presentation of MH may be quite varied. One or more of the following abnormal changes will raise the suspicion of MH:
unexplained increase in carbon dioxide excretion; body temperature elevation greater than 100F (in the absence of a infection);
muscle rigidity (especially after the use of drugs that ordinarily relax muscles); brown or tea colored urine after anesthesia;
unusually rapid breathing or heart rate (usually in association with temperature elevation or muscle rigidity); evidence of
muscle breakdown seen by cola colored urine as well as some other changes as indicated by certain blood tests.
How is MH treated?
MH had a mortality rate of nearly 80 percent at the time it was identified in 1960. Treatment consisted only of cooling the
patient and treating specific symptoms but not the underlying cause.
This syndrome must be identified and treated early in its course in order for there to be a successful recovery. Greater awareness
among anesthesiologists and other medical professionals has resulted in earlier diagnoses and treatment. Since 1979, the drug
dantrolene sodium (Dantrium) has been available for the treatment of MH and has contributed greatly to a dramatic decline
in death and disability.
If I've had an episode of MH, will I be likely to get it again?
To the best of our knowledge, people who have had MH are susceptible to developing it again on re-exposure to certain anesthetics
and muscle relaxants. However, some individuals have had an uneventful anesthetic use prior to the one that triggered an MH
event.
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. 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.
Those susceptible to MH should always wear or carry identification material to indicate their MH status. The Malignant Hyperthermia
Association of the United States (MHAUS) can provide identification bracelets and wallet cards at low or no 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, people known to have
MH should register their MH susceptibility with the North American MH Registry of MHAUS in Pittsburgh, PA by calling (412)-692-5464.
Who should be biopsied?
Patients who have had changes during anesthesia that raises the suspicion of MH should be biopsied. It is often suggested
that family members of MH patients be biopsied in order to determine the inheritance pattern of MH in a particular family.
The test is available at only eight medical centers in the United States.
What is the test for MH and what does it entail?
Currently there is no simple diagnostic test available for screening the general population (e.g., a blood test). The most
accurate test involves a biopsy of skeletal muscle from the thigh. The test is known as the caffeine halothane contracture
test (CHCT), is the "gold standard" for diagnosis of MH. It can be performed only in roughly 40 centers worldwide, 11 of which
are located in the United States and Canada. The patient must travel to one of these sites for testing because the test must
be completed rapidly after muscle is removed from the patient.
The CHCT entails the removal of approximately two grams of muscle (less than one-tenth of an ounce) through a two- to three-inch
incision usually from the thigh, following administration of a local (femoral nerve block), spinal, epidural, or non-triggering
general anesthetic. In young children (below the age of 6), the muscle biopsy may be done with general anesthesia using non-triggering
drugs Additionally, our patients are monitored closely and a drug of proven value in the treatment of MH, dantrolene sodium,
is available.
Generally the patient is admitted on the day of biopsy, and a general surgeon performs the procedure. Most patients are discharged
the same day. Muscle soreness and tightness can be expected for 5 to 7 days after biopsy. A follow-up visit for stitch removal
is generally not needed.
The rate and tension at which the muscle contracts after exposure to caffeine and separately to halothane in the laboratory
is then recorded electronically. Comparison of the strength of contraction (muscle tension) with previously established standards
allows determination of MH susceptibility. Muscle from MH susceptibles is more sensitive and contracts with greater sustained
force than normal muscle.
While the CHCT is the most sensitive diagnostic test for MH, it is biologic in nature and therefore suffers from inherent
individual-to-individual variability. Most experts agree that false negatives are rare to absent when the standardized North
American or European protocol has been followed. Over the past 20 years biopsy center leaders have met for standardization
of the test and interpretation of the results.
Can the muscle biopsy be performed at my local hospital?
NO. The specialized procedures and apparatus for MH testing using the CHCT method as previously described are available only
in a few places in this country. Moreover, the tests require fresh muscle and strict time compliances – there is no time available
for shipping, so the biopsy must be done in or very close to the laboratory that is properly equipped to do the testing.
How reliable is muscle biopsy in MH?
A biopsy performed at one of the designated testing centers is very reliable. There seems to be no false negatives. Conclusions
about MH susceptibility are drawn from the muscle biopsy along with the personal and family medical history.
Bottom Line: the Pros and Cons of the Muscle Biopsy
- Muscle biopsy testing for MH susceptibility will definitively answer the question of susceptibility in over 95% of patients.
If the biopsy is equivocal, we lean to calling the patient susceptible. In all cases a letter is written to the individual
and his/her physicians indicating what tests were performed, the results and their interpretation.
- If there has been clear evidence of MH clinically, biopsy may not be recommended since the diagnosis is already established.
However, it may be necessary to biopsy relatives in order to define the inheritance pattern of the disorder in a given family
(e.g. a parent whose child need surgery may elect to have the test and potentially eliminate anesthetic concerns for this
child and his siblings).
- Often patients are referred because an anesthesiologist recognizes one or more premonitory signs of MH, the anesthesia is
discontinued and surgery canceled. However, these signs are not always indicative of MH, therefore, a confirmatory diagnostic
test is needed (i.e., muscle biopsy).
- We often recommend that relatives of MH susceptibles have a CK blood test performed. An elevated testing CK level in an MH
relative indicates that there is a high probability of MH susceptibility.
- Those who chose to forego muscle biopsy can elect to obtain a Medic-Alert bracelet. This is for the person who had the suspected
episode as well as a close relative. Since MH is a problem related solely to anesthetic drug exposure, according to most experts,
these individuals consider it sufficient to alert their physicians, surgeons, and anesthesiologists to the potential risks
of MH.
- The medical care of suspected MH susceptibles will often be restricted. Certain physicians who do not feel sufficiently aware
of the implications of the disorder and are not well equipped to handle potential problems of MH may not wish to care for
the MH susceptible individual.
- Establishing the susceptibility to MH has significant medical implications for family members, since close family members
of MH susceptibles have up to a 50% chance of inheriting the disorder.
- Financial considerations: the cost of the biopsy includes:
- Hospitalization - operating room and recovery room charges: approximately $2,000.
- Physician Services involved in the care of the patient - general surgeon (to perform the biopsy), anesthesiology's, and in
some cases pediatrician or a neurologist. The total charge is usually about $2,000.
- Laboratory - The laboratory tests usually consist of charges for blood work, for pathologic review of the specimen (included
in the hospital costs), and in some for X-ray and EKG (patients over 40 years).
- Diagnostic Center - the charge for the performance of the diagnostic test is $750.
Most commercial insurance carriers will pay for these charges, as will some Blue Cross/Blue Shield plans. Please click here for more information.
Can MH-susceptible patients have surgery?
Yes! Surgery can be safely performed in MH-susceptible patients. However, non-triggering anesthetics must be used as well
as special precautions and techniques; this includes close monitoring of appropriate vital functions. After an uneventful
anesthetic, an observation period of 3-5 hours is recommended. Following discharge, they should be provided with an emergency
telephone number to contact if problems arise.
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 carbon dioxide concentration;
- Continuously monitor the patient's temperature;
- Have an MH kit or cart in the operating room 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 12-hour period immediately following surgery is also a critical
time; this includes the recovery room. In addition, MH can occur in emergency rooms, dental operatories, surgeons’ offices,
or intensive care units whenever trigger anesthetics and/or succinylcholine might be used.
Can anything other than anesthetic drugs trigger MH?
MH usually is triggered only by the anesthetic drugs already mentioned. The majority of experts in MH believe that stress
and/or high external temperatures rarely precipitate MH episodes, nor is the use of caffeinated products a potential problem.
MH susceptible patients can expect to lead normal lives other than when anesthesia is required.
Are there links between MH and other disorders?
MH has been linked to a rare muscle disorder called Central Core Disease. Additionally, patients with certain forms of muscular
dystrophy may develop life-threatening cardiac rhythm disturbances and muscle destruction on exposure to trigger 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. The changes 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. In addition, some believe that heat stroke may occur
more often in MH-susceptible individuals.
If I have MH susceptibility, what do you recommend?
At present, we recommend wearing a Medic-Alert or similar bracelet indicating MH susceptibility. Naturally, any dentist or
physician should be informed of your MH susceptibility prior to performing anesthesia or surgery of any kind. Those susceptible
to MH susceptible should be informed about their special needs regarding anesthesia and surgery.
Where can a patient or health care professional get more detailed information about MH?
The Malignant Hyperthermia Association of the United States (MHAUS) is the best source of information, educational materials,
and advice for both patients with MH susceptibility and health care professionals. If you are interested in learning more
about their functions and services, write to:
Malignant Hyperthermia Association of the United States (MHAUS)
32 S Main Street, PO Box 1069
Sherbume NY 13460-1069
607 674-7901 or 800 98MHAUS
Web site: http://www.mhaus.org
E-mail: mhaus@norwich.net
Fax-On-Demand: 800 440-9990
