Myths Concerning Malignant Hyperthermia

Over the past many years since MH was first described, a lot has been learned about both the clinical presentations as well as the underlying problems that cause malignant hyperthermia. Of course there is much more to learn but often as new information is accumulated those ideas or clinical recommendations that were based on concepts that have been disproved remain.  In this blog I will describe ten myths related to MH that hotline consultants still hear either from callers or at national meetings. So, not necessarily in any particular order, here they are: 

1.  MH susceptibles cannot work in an environment where they might be exposed to low concentrations of volatile anesthetic gases, such as an OR, in a veterinary clinic or in a recovery room.  Even though there is a great variability in terms of sensitivity to anesthetic triggers among MH susceptibles, nevertheless the very low concentrations of trigger agents found in modern ORs are not believed to trigger MH. Support for this statement derives from 1. Studies done in susceptible MH swine have shown that low concentrations of volatile agents do not trigger MH. 2.  Several anesthesiologists and nurse anesthetists who are MH susceptible and work in the OR   have not had any problems related to MH. So, the MH susceptible need not alter his/her career plans because of concern about exposure to very low concentrations of either volatile anesthetic gases or similar hydrocarbon compounds. 

2. Even though a patient has a negative biopsy for MH by the standard caffeine /halothane contracture test, nevertheless he/she should not be exposed to trigger anesthetics. Multiple studies have demonstrated that the false negative rate on a muscle biopsy is as close to zero as can be shown statistically. One of the hardest and most challenging aspects of scientific studies especially related to biology is to conclusively prove that something does not exist. Any biologic study has a margin of error. Based on my reading and experience I (and many MH experts) believe that if a patient is tested by the muscle biopsy contracture test and found to be negative, then s/he may receive an MH trigger agent. Several studies have shown that such MH negative patients who were administered MH trigger agents did not develop MH.  One of the confounding factors related to MH is that other clinical conditions, such as sepsis and other infectious processes, can display such signs as elevated body temperature, increased carbon dioxide levels and acidosis, all signs of MH as well. 

3. MH does not occur in patients less than one year of age or older than 80 years of age. Although it is tempting to believe such statements because many studies show that the peak incidence of MH is between early teens and the forties, nevertheless there are many patients who have experienced an MH crisis at the extremes of age. Perhaps one of the reasons that MH is not observed as often at the extremes of age is that the frequency of administration of MH trigger agents is less than in patients who are between the ages of 14 to 60. Although most biopsy centers will not perform an MH biopsy on patients less than 8 years of age, the clinical diagnosis of MH in the very young has been made on many occasions.   

4.  MH susceptibles should not have outpatient surgery or must have surgery in a hospital setting. Neither of these statements is true. In a well prepared outpatient setting where equipment and drugs are immediately available, there is no contraindication to surgery on MH susceptibles, provided of course that  triggering agents are NOT used. Matter of fact, those who are known to be MH susceptible have less to fear regarding experiencing an MH crisis than the average patient, since their susceptibility is known and therefore MH trigger agents will be avoided. Of course all ASCs and outpatient surgery centers need to be prepared to manage MH and have a transfer protocol in place should MH develop. 

5.  Temperature elevation is a late sign of MH.  This statement is something reiterated in the anesthesia and MH literature. I have said it many times myself. However, a recent study of data in the North American MH Registry by Drs. Marilyn Larach, Gerald Gronert, Greg Allen, Barbara Brandom and Erik Lehman (Reference 1), has called this generalization into question.

Using the data reported over the years to the North American MH  Registry and selecting out those several hundred patients who very likely or almost certainly developed MH, they found that in roughly two thirds of the patients, significant temperature elevation was the first , second or third clinical sign of MH! The most frequent initial sign of MH was either increased in C02 levels, increased heart rate, or jaw muscle rigidity (with succinylcholine) with temperature elevation occurring often simultaneously.  

During this study they made another important observation, namely that skin liquid crystal temperature indicators were inaccurate in 10 MH cases when compared to core temperature measurement (such as the esophageal temperature). These were patients who had both skin temperature as well as central temperature monitoring.

This finding is consistent with observations in MH susceptible swine.

(See also my blog of December 2009 arguing for routine temperature monitoring during anesthesia) 

6.  It is not necessary to have 36 vials of dantrolene on hand to treat MH, since most cases respond to about 12 vials (or 240mg or roughly 3mg/kg).  The same study by Larach et al found that in 229 MH episodes a total median dose of dantrolene required to control the crisis was close to 6mg/kg, or closer to 24 vials of dantrolene. However, the amount of dantrolene needed depends on the weight of the patient. Given the obesity epidemic in the US, the reference weight for adults which was formerly 70kg or 154 pounds is no longer the case. Adults now weigh at least 20 pounds more or 175 pounds, and in many cases much more than that. Furthermore, the study found that 25% of MH cases required more than 36 vials of dantrolene.

The initial recommendation that 36 vials be on hand to treat MH was based on assumptions related to the average size patient and the upper limit of recommended dantrolene dose (10mg/kg). The obesity epidemic gives us reason to believe that 36 vials may actually be insufficient for complete treatment of MH, particularly in a rural situation where hospitals may not be close enough to provide backup supplies. 

7.  DNA testing for MH susceptibility has taken the place of muscle biopsy contracture testing. It is our fervent hope that this will be the case in the near future, but we are not there yet. The genetic basis of MH is complex. There are at least two genes associated with MH susceptibility and over 200 DNA changes that may lead to changes that cause MH. Even when the entire ryanodine gene (the gene most often linked to MH susceptibility) is sequenced, about 30% of patients do not have a mutation in the gene suspected to be linked to MH. It is tempting to prefer DNA testing to muscle biopsy testing since it only requires a blood sample.  However, the cost of such testing is not trivial and a large number of patients will not have one of the known mutations and will require a muscle biopsy to prove susceptibility or lack of susceptibility. Despite its drawbacks the   muscle biopsy contracture test is the most accurate diagnostic test for MH available so far. Therefore unless there is a very high likelihood that the patient experienced an MH episode or a family member has a proven MH episode or has had a positive genetic test, the patient should first have a muscle biopsy.  If the patient is not MH susceptible using the muscle biopsy contracture test, there is no point in doing a genetic test. If the patient is MH susceptible, then a DNA test may indicate a specific change or mutation that can be tested for in other family members.

Unfortunately, in the USA, because the muscle biopsy contracture test is expensive and many insurers will not pay for it, the number of muscle biopsies for MH has declined and there are now only about six testing centers in North America.

8.   If a patient has had one or more general anesthetics and has not had an MH episode s/he is not MH susceptible. Once again, it is well known that MH may not be manifest on every occasion during the administration of a trigger agent in an MH susceptible. This may relate to variation in sensitivity to the agents—some patients require hours of exposure prior to triggering. It is also clear that the expression of genetic characteristic may be modified by environmental factors. For example, hypothermia will delay the onset of MH in susceptible animals. In addition, so called epigenetic factors, such as other gene products and chemicals may effect the expression of a gene. Over half the patients who develop MH have had a previous general (trigger) anesthetic without problems.

9.  Patients with muscular dystrophy are at risk for MH.  Patients with Duchenne or Becker’s Muscular Dystrophy will experience life threatening elevation of serum potassium and muscle breakdown during or after anesthesia with MH triggering agents.  This is not a manifestation of MH. Dantrolene is not needed to treat these signs. Rather, the focus of the treatment should be geared toward treating the elevated potassium. Additionally, the genetic locus for Duchenne and Becker’s dystrophy is the X chromosome, while the genetic locus for MH is, in most case chromosome 19, where the ryanodine receptor gene is located. Why patients with these disorders are at risk to such problems is unknown at present.  The defective gene in these muscular dystrophies produces a modified or abnormal structural protein in muscle, while the MH gene is responsible for elaborating a calcium channel in the muscle. In both cases the potent volatile anesthetics alter the function and structure of that protein.

10.  If a patient has had signs of MH during anesthesia but survived without administration of dantrolene therefore he/she is not MH susceptible. In the study by Larach et al, (reference 1)3.3% of patients (9 patients) survived an episode of MH without sustaining complications even though they had not received dantrolene. This may have occurred because the clinician recognized the early signs of MH and discontinued trigger agents, or because the expression of MH in those patients was more benign secondary to factors such as prior cooling of the patient, low concentration of the trigger agent, etc. It should be remembered that even in the pre-dantrolene days a small percentage of patients survived an MH crisis with symptomatic treatment only. 

These are only a few of the “myths “or folklore related to MH. In future blogs I will address others.

From this information you can understand how research, not only in the laboratory, but also using databases and registries are essential for a complete understanding of MH and its variants.

MHAUS is dependent on your generosity to continue bringing you information, education and guidance in order to improve the anesthesia care of the MH patients, patients with myopathies and their families.

Your comments are always appreciated. 

 Reference

(1)     Larach MG, Gronert GA, Allen GC , Brandom BW, Lehman EB. Clinical Presentation, Treatment and Complications of Malignant Hyperthermia in North America from 1987-2006. Anesth Analg 2010;110:498-507.

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