On May 14, 2011 MHAUS sponsored the first ever day long retreat for our hotline and professional advisory consultants. 25 consultants, including one board member (Debra Merritt), a genetic counselor associated with the University of Pittsburgh MH DNA testing center (Deanna Steele) and Dr. Albert Urwyler, head of the MH testing center in Basel, Switzerland and member of the European MH group, met in a hotel near the Chicago O’Hare airport to discuss many perplexing issues related to MH; the goal was to try and reach consensus on several important items. Although each year many hotline consultants meet at the annual meeting of the American Society of Anesthesiologists, that meeting is usually time limited because of conflicting obligations by many of the consultants. Further, even though hotline consultants often discuss problem cases on our closed internet discussion list, it is difficult to have in depth discussions in this venue.
The agenda for this meeting was developed by a committee of consultants including Drs. Cynthia Wong, Charlie Watson, Marilyn Larach, Greg Allen, Mary Theroux and me . Gloria Artist of the MHAUS staff organized the meeting and Dianne Daugherty, MHAUS Executive Director and Sharon Dirksen, MHAUS Scientific Officer were also in attendance. We plan to synthesize the discussions for review by all hotline consultants and professional advisory members, the individuals required to approve all the guidelines developed at this meeting. We realized that there were many issues that we would not have time to discuss and tried to select those that we felt were most important or were recurrent issues.
We also had no illusions that agreement would be reached on certain topics since the evidence when it comes to MH is often scanty. However we hoped that the discussions would be helpful for all consultants as they deal with calls they receive. In some cases we believed that consensus would be possible.
The topics we discussed were:
· Heat/Exercise and MH; discussion led by myself
· Genetic Testing for MH; discussion led by myself
· Dantrolene use and availability; discussion led by Dr. Cynthia Wong
· Quality Assurance; discussion led by Dr. Charlie Watson
· Syndromes related to MH; discussion led by Drs. Mary Theroux and Bob Brislin
· Anesthesia Machine preparation for the MH susceptible; discussion led by Dr. Greg Allen
· Temperature monitoring during anesthesia; discussion led by Dr. Marilyn Larach
Before beginning the meeting, we made mention that the MH hotline is now hosted by the Rocky Mountain Poison Control Center operating out of the Denver Health system. For many years, the poison control center at Upstate Medical Center in Syracuse, NY served as the host for the hotline. However due to budget cuts in NY State several poison control centers were consolidated and the one at Upstate had to assume a larger volume of calls. I wish to acknowledge the service they provided for the past 15 or so years. They are a wonderful organization and provided excellent service to MHAUS and to the community.
In a future blog, I hope to provide a bit more insight into the work of the poison control center and how beneficial such organizations are to the general community and to MHAUS. Such poison control centers are vital to the health of our communities. Unfortunately there are moves afoot in Congress to reduce funding for such services significantly.
Here is a brief synopsis of some of the highlights of the meeting. It is not meant to be inclusive; that will follow in another document.
Heat/Exercise and MH
For the topic of heat/exercise and MH, I reviewed much of the medical literature and a number of cases either in the hotline database or those with which I was familiar showing an association between MH and heat stroke, or muscle breakdown without anesthesia. Several very well researched reports show that at least some patients who develop heat stroke are found to have mutations that are known to be causal for MH. Some MH patients, perhaps as many as 1%, describe a history of heat-related problems. The issue regarding making definitive statements about MH and heat-related problems and advising MH susceptibles and their family members concerning exercise and exposure to high environmental temperatures are several. First, most heat stroke is not related to MH susceptibility. It is most often precipitated by exposure to high environmental temperature with or without exercise in patients who have no evidence of MH (witness the large number of deaths that occur in the elderly during heat waves). Second, most heat-related problems are managed by emergency medicine physicians rather than anesthesiologists. The former are not as familiar with MH and its presentation. It was therefore suggested that MHAUS should work more closely with emergency medicine organizations to better understand their experience with heat-related problems. There is potential to develop a cooperative study of patients who experience heat-related problems and determine how many might have at least a genetic predisposition to MH and how many respond to dantrolene treatment. At the present time, such a study would require resources beyond those available to MHAUS unfortunately. However, an international study with cooperation of the European MH group might be feasible, since there are many biopsy centers as well as several MH genetic centers operating in Europe.
What we do know at present is that there does not appear to be a particular MH genetic mutation that predisposes to heat problems, muscle breakdown and MH without anesthesia. This is particularly frustrating since we have some families where a child or children have died without exposure to anesthesia and upon genetic testing were found to have one of the known MH causative mutations. Advice for MH families about heat exposure and vigorous activity has to be very individualized and such patients should consult with one of the MH experts.
What we did agree on is that the paralyzing drug and MH trigger, succinylcholine, should not be used for intubation in those who present with signs of heat stroke.
The relation between heat syndromes and muscle breakdown without anesthesia is a special topic of interest for the MH community and will continue to be a focus of future discussions.
Testing for MH
The review of laboratory tests for diagnosis of MH underlined that although the most sensitive, specific diagnostic test is the muscle biopsy contracture test(halothane-caffeine contracture test, there are only a few centers in North America that are capable of performing such testing. Many centers have closed because of the expense of maintaining such a laboratory and the poor reimbursement for testing.
On the other hand, certain patients in need of diagnostic testing may benefit from a DNA or genetic test. The test requires only a blood sample, and is much less expensive than the contracture test. One of the drawbacks to the DNA test is that of the over 300 genetic variants thought to be associated with MH, only about 30 have been found to be causal for MH. Many of the others are either harmless or their significance is unknown. Although only about 30% of MH susceptibles will harbor one of the mutations know to cause MH, if a mutation is found, the diagnosis is made. However, in the absence of a mutation, no conclusion may be reached. Therefore, we generally recommend genetic counseling before a decision is made to proceed with a genetic test as well as counseling to help with test interpretation. The only center that has integrated genetic counseling into the molecular genetic testing is the one at the University of Pittsburgh. Fortunately, most of the hotline consultants are well informed about the advantages and disadvantages of the various options for testing.
Dantrolene Use & Availability
Regarding the availability and use of dantrolene, there was no debate on the need for 36 vials of dantrolene to be on hand to treat an MH crisis. There was also no debate about the need to continue dantrolene for at least 24 -36 hours or longer as determined by signs of MH after an MH crisis; i.e., titration to effect. We felt that the currently recommended dose and frequency should remain unchanged.
The consultants also agreed that the initial dose of dantrolene for treatment of an MH crisis, 2.5mg/kg, should be calculated according to the actual patient’s weight rather than lean body mass. The consultants did not feel that there should be an upper limit of dantrolene dose (currently stated in some sources as 10 mg/kg) because the syndrome can be so variable.
A consensus statement was drafted for final approval:
“Thirty six vials of dantrolene must be available for all anesthetizing locations within 10 minutes of the decision to treat for MH. Dantrolene must be available for all anesthetizing locations where MH trigger agents are used.” This is a slight modification of the current recommendation that the drug be available within five minutes because the five minute recommendation was not made based on consensus discussion and it is often not practical to have a large supply of dantrolene in every area where anesthesia is administered. For example anesthesia administration is now common in locations far from the operating rooms such as interventional radiology suites.
Dr. Larach reviewed a study that she and Dr. Barbara Brandom performed based on data in the North American MH Registry published in a recent issue of Anesthesia and Analgesia (March 2011) describing complications associated with dantrolene use. The common ones included muscle weakness, phlebitis and GI upset.
The consultants agreed that because muscle weakness sometimes accompanies dantrolene use, therefore patients should be monitored continuously following the last dose of dantrolene to assure that respiratory depression does not occur.
Our quality improvement program seeks to review the consultants’ advice in an attempt to better understand where there may be differences in opinion regarding diagnosis and/or treatment of MH. That most consultants agree with their peers’ advice is remarkable, since the consultants’ opinions are based on reports from a physician or nurse and there is no direct access to the patient.
We felt that there should, however, be better follow up with those calling the hotline. MHAUS should develop a mechanism to provide those handling an MH case with general guidance and recommendations summarizing the common issues that are encountered and discussed during hotline calls. For example a statement that outlines the pros and cons of muscle biopsy vs genetic testing and how patients may be referred for such testing could be developed.
The poison control operators are frequently helpful in obtaining information concerning the caller and how to contact him/her. We hope to work even more closely with the Rocky Mountain Poison Control Center in order to obtain important follow up information on the advice offered by the hotline consultant.
Muscle Disorders and MH
Drs. Brislin and Theroux reviewed the anesthetic management of a variety of muscle disorders that have been thought to be associated with MH but where the evidence of such an association is weak. This issue was discussed several years ago at the special symposium on MH and associated disorders at the Society of Pediatric Anesthesia. A special article was published in the journal Anesthesia and Analgesia in 2009.
Good evidence is in hand that such unusual muscle disorders such as Hypokalemic Periodic Paralysis, McArdle’s disease and Mitochondrial myopathies do not place a patient at greater risk for MH. However, for muscular dystrophy, anesthesia providers should avoid the paralyzing drug succinylcholine. There was debate concerning whether volatile anesthetics that trigger MH should be administered to patients with muscular dystrophy. Some felt strongly that, based on a few case reports, patients with muscular dystrophy may develop life threatening heart rhythm problems because potassium levels may be elevated in the presence of MH triggers.
Preparing the Anesthesia Machine for use with an MH susceptible
For many years now, the basic design of anesthesia machines did not change. MHAUS has issued recommendations for preparing the machine prior to anesthetizing an MH susceptible in order to reduce the concentration of one of the MH trigger gases that may be left in the machine. This preparation could take 10-20 minutes.
However, in recent years a new generation of anesthesia delivery machines has been developed. These machines are more complex than the older machines and allow the anesthesia provider greater flexibility in caring for the anesthetized patient particularly in relation to ventilation of the lungs. However, because of the added complexity, in order to reduce the residual amount of anesthetic remaining in the machine after use, it is necessary to take up to 90 minutes in some cases to remove trace anesthetic gases. We do not have a good idea of the lowest concentration of anesthetic gas that can trigger an MH episode in humans, but it is felt that MH susceptibles should not receive a concentration of anesthesia much above the trace amounts that may be found in the atmosphere of the operating room; a vanishingly low concentration. The 90 minute recommendation is a difficult one to follow.
Recently, an alternative to the cleansing technique has been introduced. It has been found that a small canister containing activated charcoal granules will absorb anesthetic gases and prevent even trace amounts from reaching the patient. This new device is inexpensive and disposable and may find utility in reducing anesthetic concentration during an MH crisis therefore removing a source that might delay prompt resolution of MH. Everyone was enthusiastic about the potential for activated charcoal as an adjunct to preparing the anesthesia machine, but most of the consultants would like to have more firsthand knowledge of the canisters rather than base their opinion on published literature only. It seems to me that the activated charcoal canisters will greatly simplify anesthesia machine preparation.
Temperature Monitoring During Anesthesia
This is an old but recurrent topic. MHAUS and other organizations have urged that core temperature be monitored during general anesthesia. According to a study based on data from the North American MH Registry of MHAUS, temperature elevation was found to be the earliest sign of MH in 8% of cases and the first to third sign in 64% of cases. Furthermore, the longer one delays in temperature measurement, the higher the likelihood that marked elevation of temperature will be missed and lead to significant complications.
The following consensus was reached:
“All patients undergoing general anesthesia that exceeds 30 minutes in duration should have their temperature monitored using an electronic temperature probe. Skin liquid crystal temperature sensors are not recommended as they have been found to be unreliable indicators of changing temperature during an MH event.”
The very last part of the meeting was devoted to a discussion of complex and unusual presentations of MH based on hotline calls.
All those present thought that the discussions were at a high level, focusing on issues that are either complicated or evolving. There were many other topics that could have been added to a longer meeting. The consultants felt that such a meeting should take place at least every other year.
It is a mark of the investment and dedication of our hotline consultants and professional advisory committee members that so many braved some significant weather related delays to participate in this meeting, over the weekend, no less! We hope that similar meetings will enable MHAUS to provide guidelines for the management of MH and MH-related disorders for providers of all kinds as well as for patients and their families.
Meetings such as this one are not directly supported by industry or by grants. Such support derives from the general coffers of MHAUS, but we feel that it is money well spent in pursuit of the mission of the organization to be the source of the most accurate, unbiased information and guidance for the management of MH.
We would welcome contributions to support such conferences - if you so choose, please indicate this in your donation.
Thanks for reading this essay.
Drs. Michael Adragna, Greg Allen, Kumar Belani, Robert Brislin, James Chapin, Andrew Herlich, Richard Kaplan, Tae Kim, Harvey Rosenbaum, Henry Rosenberg, John Skoog, Mary Theroux, Charles Watson, Margaret Weglinski, Cynthia Wong, Paul Allen, Paul Iaizzo, Marilyn Larach, Deanna Steele, Albert Urwyler.
Staff, Gloria Artist, Dianne Daugherty and Sharon Dirksen