Malignant Hyperthermia Association of the United States
25 Years of Saving Lives
In 1976, Cathleen Hoefler was seventeen years old and headed for a routine tonsillectomy in Norwich, New York. But during the procedure something odd happened. Her temperature spiked, her muscles were rigid and her heartbeat too fast.
“We have to wrap this up!” her anesthesiologist said when he recognized the symptoms as a little known disorder referred to at the time as Malignant Hyperpyrexia, Malignant Hyperthermia or MH.
To save her life, Cathleen was wrapped in ice, the only treatment available then. There was also no one to consult, no hotline to call, no treatment protocol and no dantrolene, the drug to treat MH. Mortality from MH loomed at eighty percent.
Cathleen was lucky. “When I woke up, I had the sense that something had happened,” she recalls. “It was a long recovery and discouraging, and my friends and family were wondering why I was lying around tired for several days after having a tonsillectomy. I didn’t have an answer for them.”
The episode affected Cathleen’s entire family. Two years later, when her brother was in college, he developed appendicitis and had to be rushed to a hospital. Because he told doctors about his sister’s strange episode, he wasn’t given a general anesthetic, although, “He was given something,” she says. His appendectomy was excruciating.
One year later, Cathleen was looking forward to college life herself. But first she wanted to do something about a couple of cavities.
“The advice that had been given to me was ‘no anesthesia under any circumstances’” because of her previous episode during the tonsillectomy. “The dentist would not even give me a local anesthetic, because not enough was known about what could happen to me. So, in order to do the drilling, they applied a hard stream of cold water for the numbing. As a matter of fact, it worked.”
In the meantime, Cathleen was thinking, “I hope I don’t ever have a brain tumor.” In the late 1970s, there was a lack of information, but no lack of fear, about what is now known as Malignant Hyperthermia.
Little was known about this unusual syndrome at that time and much of the information was inaccurate, incomplete and not accessible except in specialized journals.
1981 - MHAUS Established
That atmosphere of uncertainty in the medical and patient communities was recognized by a patient whose nephew died from MH and who was given conflicting information about her own care. Mrs. Suellen Gallamore and her family saw that there was a desperate need to educate health care providers and patients concerning this potentially fatal, inherited disorder. She gathered other individuals whose families were affected by MH and requested that Dr. Henry Rosenberg, an anesthesiologist and research physician who had begun to explore this condition, join them in creating the Malignant Hyperthermia Association of the United States (MHAUS) in 1981.
Over the next 25 years MHAUS evolved into a model organization that promotes patient safety and helps save lives. The MHAUS Board of Directors and the physicians who became part of MHAUS adopted as a core principle that health care providers should be trained to recognize who may be at risk of MH, the signs of MH, and to understand how to treat the disorder, and how to get assistance with any of these issues. The goals were to be achieved by physicians, nurses, lay people and patients working together as members of the organization to reduce morbidity and mortality of this relatively unknown disorder.
Immediately several tools were created to get the word out. One of the first was a newsletter, The Communicator, so named because of the need to communicate what was known about MH.
Published four times or more per year, The Communicator “…became our means of getting the latest in the world of MH to the membership,” points out Dianne Daugherty, MHAUS’ Executive Director. “What makes this publication so different is that it educates our members about things they won’t get in a professional periodical or the daily newspaper. The Communicator has been instrumental in educating the medical community about drug precautions as well.” The newsletter contains articles reviewing the developments in the field, summarizes cases of MH reported to MHAUS, and answers readers’ questions.
In addition, the organization began to produce a series of brochures concerning MH, MHAUS, and how to manage the disorder. The educational information was distributed at meetings of anesthesiologists, surgeons, nurse anesthetists, and pharmacists, among other medical professionals. To this day, MHAUS exhibits at seven or more national meetings per year.
1983 – The 24/7 MH Hotline and OR Poster
But the “little association that could” didn’t stop there. Its newsletter and educational brochures worked well, but not in real time. So in 1982, MHAUS created its signature service, one that would be a primary step in an OR’s response to an MH episode, the MH Hotline, with expert consultants available 24/7. Any health care provider concerned about a possible case of MH can pick up the phone, call 1-800 MH HYPER and be in contact with an experienced anesthesiologist who has studied this syndrome in depth. Today, more than 30 such experts take turns volunteering to answer the many questions and guiding the management of MH or MH-like events.
Details of the calls are recorded without patient identifiers, and the lessons learned from these cases are shared with the hotline consultants and with the medical community through publications. Today, the MH Hotline is a lifeline for those who are confronted by an MH episode. The MH Hotline number is posted in ORs and PACUs. Each year the members of the hotline handle about one hundred cases thought to be MH.
Many hundreds of calls that do not require the expertise of the physician anesthesiologist are handled by the MHAUS office staff.
Each year MHAUS recognizes the expertise of one of its consultants with a “Partnership Award” conferred at the annual meeting of the American Society of Anesthesiologists.
At the same time the Hotline was created, the first Operating Room Poster (http://www.mhaus.org/PubData/PDFs/treatmentposter.pdf) was developed by the physician members of MHAUS who were selected to be part of a Professional Advisory Council.
The poster covers:
· Diagnosis
· Acute Phase Treatment
· Post Acute Phase Care (or Monitoring)
Over the years the poster has been revised many times as the information concerning MH has expanded. The posters are distributed at medical meetings and are provided at nominal cost otherwise. Almost every OR in the U.S. has one of the MHAUS posters on its wall.
Mid 1980s – Dantrolene Widely Used, More Education Called For
MHAUS’ efforts in the early 1980s were starting to pay off. The number of fatalities from MH were declining year by year. Hospitals began to realize that they needed to stock the life-saving drug dantrolene wherever general anesthesia was administered. For example, by 1986, ninety-three percent of all hospitals in the United States stocked Dantrolene. But with all of the new information that MHAUS was producing, a major education effort was still needed to let medical staff know about the disorder itself. This was illustrated in the case of nine-year old Kimberly Friedman in Baltimore, Maryland.
An alert senior anesthesiologist at Sinai Hospital had just read an article about the disorder, when he happened to be in the OR where Kimberly was undergoing what was supposed to be a routine tonsillectomy. When anesthesia was starting, Kimberly’s body temperature began rising, her jaw became rigid, and her heart rate was alarmingly increasing. The senior anesthesiologist, who was not involved in this case, recognized the symptoms as MH.
“He had been an anesthesiologist for 33 years, and had seen a similar case,” says Lydia Friedman, Kimberly’s mother. “Even though the surgeon wanted to continue with the procedure, the senior anesthesiologist shut everything down as soon as he saw what was going on.” “They put Kimberly on ice, and after she recovered, sent her home and asked the family to monitor her temperature for 24 hours,” recalls Lydia Friedman. “When we got home, I called my local hospital to find out more, and they knew nothing about MH.”
The Friedmans also discovered, as the Hoeflers did a decade earlier, that there was hesitancy among medical disciplines to treat family members upon the mention of MH.
“We couldn't find an oral surgeon for a procedure on Kimberly’s older sister Kelley when she was 18 in 1993, because of the possibility of MH. Even though we knew more about MH then, the oral surgeons refused us. They wanted to do procedures in their offices, but not with us."
Despite the challenges MH caused, today the Friedmans count their blessings. "Definitely my kids have angels," says Mrs. Friedman.
Meanwhile testing for susceptibility for MH was being standardized. The diagnostic test, which is still in use today, involves harvesting a small amount of muscle from a patient’s thigh and testing its response to the anesthetic halothane and to caffeine in the laboratory. The test requires attention to exacting detail and requires specialized expertise in order to assure reproducibility and accuracy. Therefore, those performing the test began to meet regularly under the auspices of MHAUS to create guidelines for using this biologic test.
Late 1980s - The MH Registry
MH morbidity and mortality was dramatically decreasing because of services like the MH Hotline and awareness efforts through MHAUS’s educational materials as well as more widespread recognition of the signs of MH. Whole chapters in anesthesia texts devoted to the signs of MH were appearing, where in the past, a scant few lines might sometimes be found. Still, an organized way to trace family histories to help researchers, anesthesiologists, and MH susceptible patients and their families know what to expect when dealing with MH was missing. The concept of a registry of patients who were evaluated for MH arose from a series of conferences that were aimed at standardizing the muscle biopsy contracture test for MH. In 1988, the North American MH Registry (www.mhreg.org) was founded at Penn State University by Marilyn Larach, MD, Senior Research Associate, Penn State University College of Medicine. (The Registry later merged with MHAUS to put MH data under one roof and encourage greater research support.) The Registry is a database of MH susceptible patients as well as patients tested for susceptiblity but found to be normal. It acquires, analyzes and disseminates clinical and laboratory information to investigators and physicians.
“Because acute MH episodes are relatively uncommon but very dangerous events, the MH Registry has performed the vital function of collecting enough of these events so that reliable descriptions of what happens and how to treat them successfully can be data driven,” says Registry Director Barbara Brandom, MD, Dept of Anesthesiology, Children’s Hospital, at the University of Pittsburgh, where the Registry is now located. “Acute MH episodes are each quite different in some respects. This is why we need to study the description of episodes and diagnostic results.”
“The Registry gives health care providers the ability to obtain specific MH information on their patients to help them plan their anesthetic and surgical procedures (including having them take place in appropriate facilities),” says Dr. Larach, the founder. “The MH Hotline consultants can also utilize these reports to help them tailor their responses to anesthetic/lifestyle management questions raised by health care providers and patients. This allows health care providers to design a safe health care management plan that is individualized to the specific needs of each patient entered into the MH Registry.”
Early 1990s - Using E-Mail to Exchange Information
With the MH Hotline, Registry, and information brochures, MHAUS found itself with a lot of valuable information shifting from researchers to physicians and back. It needed a pipeline to help coordinate the flow of information.
In 1993, ten years after the MH Hotline was developed, MHAUS took advantage of the latest in e-mail technology and created a confidential, closed listserv discussion group, initiated by Keith Ruskin, MD, Professor of Anesthesiology and Neurosurgery at the Yale University School of Medicine, with the encouragement of Dr. Rosenberg.
“The listserv discussion group gives the MH consultants instant access to each other in a way that facilitates discussion of difficult cases,” says Dr. Ruskin.
Those cases from the MH Hotline are among the daily posts and responses on the listserv. It isn’t unusual to see at least one dozen discussion group posts per day. Participants also receive a discussion group synopsis from MHAUS on a regular basis.
1990 - A Major Advance in Understanding of Malignant Hyperthermia
In 1990, as a result of several years of work to understand the genetic basis for malignant hyperthermia, work from Dr. David MacLennan’s laboratory at the University of Toronto identified a mutation in a gene that is responsible for the susceptibility to MH in the animal model for MH, i.e., certain breeds of pig. This then raised the prospect of developing a DNA-based diagnostic test for MH, which would not require a muscle biopsy, but rather a blood sample. However, it took another 14 years before a genetic test for MH susceptibility in humans was introduced since the genetic basis for MH in humans is much more complex than in the susceptible swine.
Late 1980s to Mid 1990s – MHAUS Receives Recognition as Experts
All of this progress did not go unnoticed from influential health care professionals, those representing the very anesthesia providers who would come face-to-face with MH crisis events in the OR. In 1989, the American Society of Anesthesiologists provided its first grant in support of MHAUS and the Registry. Three years later, the American Association of Nurse Anesthetists officially recognized MHAUS as representing the experts in MH. A significant symbol occurred in 1994, when an international effort involving the MH Hotline saved the life of a nine-year old girl experiencing an MH episode in Mexico.
Just two years later, statistics showed that mortality from MH was down from eighty percent in the mid 1960s, to five percent or less in the mid 1990s.
MH was rapidly becoming a misnomer. Fewer people were dying and the characteristic temperature elevation was not being seen as often since the syndrome was being treated even before body temperature could rise. Nevertheless, MHAUS was not content and continues to aim for no deaths or disabilities related to MH.
Late 1990s – Internet Presence is Born
Within a short time after the advent of the Internet, MHAUS created a web site, where it began posting all of its educational information.
Today the MHAUS web site is the centerpiece of its educational efforts, offering services such as an E-newsletter, podcast downloads, the MH Hotline Case of the Month, an educational slide show, Frequently Asked Questions, a listing of testing centers, as well as the ability to sign up for conferences and order materials like the MH procedure manuals, the new 2006 In-Service Kit, which is the latest preparedness tool for the OR and PACU, and the distribution of products such as patient ID tags.
25 Years of MHAUS Efforts Come Together in 21st Century
In 1976, Cathleen Hoefler’s case was typical. No real protocol for MH, except large doses of both ice and luck. Today, the typical MH case is handled very differently.
Shane Brossette, a nurse who suffered from an MH episode in 2000, states “MHAUS has developed a clear cut algorithm. We have it in the PACU. We have charts in the operating rooms of the Navy hospital I served at in Pensacola and my local hospital here in Lakeview, Louisiana. We have an MH cart (which contains Dantrolene, sterile water without a bacteriostatic agent to reconstitute Dantrolene, sodium bicarbonate, furosemide, dextrose, calcium chloride, regular insulin refrigerated, and antiarrhythmics.) It's visible. It’s like having a parachute, a spare tire, a go-to guide.”
Today, like Shane, Kimberly Friedman and her father wear medical identification tags specially designed by MHAUS that contains information specifically for those with MH susceptibility. The Friedmans do so because, after Kimberly’s 1987 MH episode, their susceptibility was confirmed by the diagnostic muscle biopsy test, which pointed to the father as the carrier of the MH gene. If there is an emergency like Kimberly’s sister Kelley had in 1987, Lydia Friedman feels better about her family members avoiding an MH episode.
Other new tools were added to the MHAUS armamentarium to assist in the management of MH. A detailed, customized, protocol and policy manual was developed for hospitals, ambulatory centers and office-based operating rooms. These books detail the role of nurses, doctors, technicians, even secretaries in the handling of an unexpected MH episode.
This information is constantly updated as the MHAUS Professional Advisory Council as well as the Hotline consultants meet regularly to discuss the latest in treatment, for example, which people are eligible for the genetic test and how the test should be interpreted.
At the same time, recognizing that MH is not a problem limited to the U.S., physicians and scientists in Europe, South America, Australia and Africa have also been meeting to develop treatment protocols for their countries and support research into the problem of MH. For example, the European MH Group was formed in 1980 and meets yearly with a particular focus on diagnostic testing for MH.
And because of this international interest, MHAUS has begun to translate its educational material into Spanish.
MHAUS’s educational emphasis continues to put equal emphasis on patients as well as the medical community. A Patient Liaison Committee was formed not too long ago to assist in the development of programs that are of benefit to MH families. Mrs. Friedman helps coordinate this committee, a volunteer group of patients and their families formed to educate patients and the medical community through events like patient mini-conferences. In July of 2006, the conference was held in Maryland and offered CMEs and CEUs for attendees. Attendees were brought up to date on the latest in MH treatment, including the new molecular genetics test.
"The genetics test does not take the place of the current muscle biopsy,” points out Dr. Rosenberg. “But it could identify the 50% of those at risk in an MH susceptible family. Genetic testing for identification of those at risk is the future for improving our understanding of this syndrome.”
Cathleen Hoefler, the woman who was treated with an ice wrap during her MH episode in 1976, had a heart procedure in 2001 at age 42.
“Three catheters were inserted to correct an arrhythmia, and it was a walk in the park,” she says. “I had no fear. That was because of the work of MHAUS. The things that were so terrifying in 1976 were the last things on my mind. I wasn’t anxious about it and that was kind of a miracle for me. Over the years, MH researchers found out what was going on and figured out how to solve the problem.”
“Before the heart procedure, my husband asked, ‘You told them about the MH, right?’ And I said, “It’s cool, honey.”
2006 and Beyond
After 25 years, what is there left to do? “Plenty,” says Dr. Rosenberg.
First, our goal of no mortalities from MH has not been reached. Every year we hear about a few deaths from MH. The deaths are all the more tragic because they usually affect young, apparently healthy people.
Second, the insecurity of not knowing whether a person who experienced an unusual reaction to anesthesia is really MH susceptible weighs on the minds of many. The most reliable test for MH susceptibility, the muscle biopsy, is just not applicable on a widespread basis. Clearly molecular genetic testing, which only requires a blood sample, is the future. However, much more needs to be learned as to which DNA abnormalities actually predispose to MH. At present only one-third of those with proven MH demonstrate one of the known mutations. Clearly there are many more DNA changes that are to be identified.
Third, questions often arise as to whether a patient who develops heat stroke or exercise-induced muscle breakdown is MH susceptible. If a person dies of heat stroke, there is currently no way to learn for certain if that patient was MH susceptible other than the limited genetic test. It is our vision that the molecular genetic test will provide the answers as to what situations outside the OR are risky for the susceptible patient. In addition, exciting new research has led to the creation of animal models of MH by incorporating mutations causal for MH in the animal’s genome. These animal models will help us better understand what situations predispose to MH and also to better understand the underlying defects in the syndrome.
Fourth, several muscle disorders are known to predispose patients to MH episodes. Because many muscle disorders are uncommon, it is often not clear as to whether they do predispose to the syndrome. Research is needed to understand which patients with which muscle disorders may develop MH.
Fifth, as noted, MH is not limited to the US and Canada. MH has been reported in every country and every ethnic group. The mortality from MH in other countries, especially those where dantrolene is not approved for use, is often more than 30%. There is a definite need for more education of health care professionals as well as patients as to the signs, symptoms, recognition and management of MH. This will require resources for translation and dissemination of information.
Finally, an in-depth understanding of the pathophysiology and biochemistry of MH will lead to a better understanding of the control of muscle metabolism and biochemistry in general.
In conclusion, MHAUS and the physicians, nurses, scientists, volunteers, and staff have contributed to the reduction of harm caused by this syndrome termed “the anesthesiologist’s nightmare." The progress that has been made and the lives saved over 25 years is a testimony to what a small but determined group of dedicated individuals can do to improve medical care.
