As the calendar year comes to a close, I would like to take a few minutes of your time to highlight some of the activities and programs that MHAUS has either introduced or amplified over the past year and point out some of the scientific advances related to MH and MH related disorders.
2013 ended with a scientific conference in Toronto hosted by the director of the MH Investigation unit at the University of Toronto, and now a member of the Board of Directors of MHAUS, Dr. Sheila Riazi. The conference focused on disorders related to the primary gene that is associated with MH, the ryanodine receptor gene, also called RYR 1. I mention the conference because a fine summary of the conference was published in November 2014 in Canadian Journal of Anesthesia. Thanks are due to Dr. Riazi for her hard work on getting all the information collated and summarized as well as the organizing committee headed by the Chair of our Professional Advisory Council, Bob Dirksen. The publication will serve as a reference for all those interested in MH.
2014 saw the publication, on line, of a guide related to diagnostic testing for MH. The “Roadmap” was put together with the collaboration of MH experts, genetics experts, patients and was shepherded through completion by Dianne Daugherty, our excellent executive director. The roadmap provides concrete information concerning the various testing options and their pros and cons.
Also introduced in 2014 was a new program and concept for MHAUS called the “MH Prep Check”. The concept is to provide expert advice for a facility in preparing for an MH crisis. The way it works is that a facility will request one of our MH hotline consultants be present during an actual MH drill at their facility. She/he visits to observe the preparation for the drill, view the drill, and comment on the areas that worked well and those that could be improved. The “Prep Check” concept had been discussed by the Board of MHAUS, the staff and some of the consultants for a while, but final implementation occurred because of the hard work of Dianne Daugherty. We also benefitted from a very generous grant to develop and begin implementation of the program by the family of Anita and Don Kaufman, MD, long time generous supporters of MHAUS. I participated in one of the prep check sessions at a nearby hospital. I was impressed by the commitment of the OR team, anesthesia and nursing staff to make sure they were well prepared for an MH emergency.
In addition to Dr. Riazi, several other people were added to the Board of MHAUS. Kathy and Curt Keller are the parents of a young man who died from an MH-related event. They and their family have been working hard to raise awareness and funds for MHAUS. Dr. Riazi, as mentioned already, is in charge of the University of Toronto MH diagnostic unit and is engaged in both basic science and clinical research on MH and MH genetics.
Perhaps the biggest news of the year relative to the care of the MH patient, was the approval by the FDA in July of 2014 of a new formulation of dantrolene, called Ryanodex (web site: www.ryanodex.com). The new preparation is a nanosuspension of dantrolene and the great advantage is that only a small volume of water is needed to reconstitute the drug to a final concentration of 50mg/ml. So, instead of the typical 10-12 vials of the previous formulation of dantrolene (available as either Dantrium® or Revonto®) mixed with 60 ml of sterile water in each vial to treat an average adult; only 4-5 ml of Ryanodex is needed. This greatly facilitates the preparation of dantrolene and allows more rapid injection of the drug during a crisis. The company that developed the new preparation is Eagle Pharmaceuticals. To date the drug is only available in the US. The cost of Ryanodex is more than the previous formulations of dantrolene, but the ease of use is greater.
During the same period of time, the Dantrium formulation was acquired from the previous manufacturer and distributor, JHP Pharmaceuticals, by Par Sterile Products, one of the largest generic drug manufacturers in the world. Representatives of MHAUS have worked with both companies to answer questions and provide advice on how best to educate those using dantrolene.
In September 2014, a meeting of hotline and selected professional advisory council members met in Chicago to review current statements related to MH and discuss others that will provide perspective and advice on some common questions MHAUS receives on a regular basis. For example, after the conference, changes were made in our educational material concerning the use of Ryanodex. In addition, enhanced advice concerning the use of activated charcoal filters (made by a company called Dynasthetics) during preparation of the anesthesia machine for a patient susceptible to MH and for management of an MH crisis was also updated.
At about the same time, a study performed by Drs. Marilyn Larach, Barbara Brandom, Greg Allen and others based on data in the North American MH Registry of MHAUS was published, demonstrating how monitoring “core” body temperature during anesthesia reduces death from MH. They showed that those patients who did not have their core temperature monitored during anesthesia were at 14 times increased risk of dying from MH during a crisis! An accompanying editorial in the journal Anesthesia and Analgesia underlined that all patients undergoing general anesthesia for more than a few minutes should have their body temperature monitored continuously. The MHAUS statement concerning temperature monitoring was placed on the MHAUS web site for comment and will be posted as a final recommendation very soon.
As usual, MHAUS exhibited at a variety of medical and nursing meetings. Exhibits at the American Association of Nurse Anesthetists, the Association of OR Nurses and the American Society of Anesthesiologists (ASA) allow us to disseminate the latest information and answer questions concerning MH for thousands of clinicians. Many of our experts give presentations at these meetings. For example, Dr. Ron Litman, Medical Director of the Hotline, gave a lecture at the ASA reviewing the essential elements of MH. During the ASA, I was surprised to learn that I will be awarded the Distinguished Service Award by the ASA at the Annual Meeting in October 2015. There were many who advocated for me to receive this award, without my knowledge, and I thank them and the ASA for the recognition.
In December, MHAUS exhibited at the New York Post Graduate Assembly, the second largest meeting of anesthesia clinicians in the US. We held a reception in conjunction with the meeting and had the opportunity to meet many anesthesiologists, nurse anesthetists, OR nurses and patients at that time. Dr. Charlie Watson, one of our most devoted hotline consultants and chair of the hotline quality improvement committee, was given an award for his dedicated service to the organization. Dr. Watson is the Chairman of Anesthesia at Bridgeport Hospital in Connecticut.
Another first for MHAUS was the support of the first MH symposium in India in collaboration with the Indian College of Anesthesiologists and the Department of Anesthesiology, University of Minnesota in November 2014 at Bengaluru, India. Special thanks go to Dr. Kumar Belani for helping to organize a very successful meeting. People in many parts of the world are hungry for information about MH. MHAUS is happy to fulfill that need and provide guidance in helping form local organizations for patients and clinicians. This has been one of my long term goals. Our restriction for more aggressively meeting this need is limited resources.
Another innovative program that began in 2014 is the MHAUS Partnership membership. This effort was suggested and advanced by Board Member, Bonnie Denholm. Now members of the Association of OR Nurses may obtain full membership in MHAUS at a greatly reduced rate. The American Association of Nurse Anesthetists (AANA) and the Society of Ambulatory Anesthesia (SAMBA) have also taken advantage of this opportunity. The concept has been and will be extended to other organizations as well. This is yet another way that we extend the reach of MHAUS.
Although great advances are being made concerning the role of molecular genetics in diagnosing disorders and guiding clinicians in the use of pharmaceuticals, progress in applying molecular genetic diagnostic techniques to MH is progressing at a rate that is slower than I would like. In a large part this is due to the low incidence of MH and the complexity of interpreting DNA changes in the very large gene responsible for most cases of MH; and because there are probably other genes or gene changes that lead to susceptibility to MH. The good news is that more specialties, particularly pediatric neurologists, have recognized the connection between the ryanodine receptor gene and a variety of muscle disorders. They, in turn, have begun to focus their laboratory studies on the RYR 1 gene and the relationship between MH and other disorders. A few centers, such at the one in Leeds, England, have begun to employ “next generation” sequencing techniques to the study of MH in the hope of identifying other genetic changes that predispose to the disorder.
The European MH group made up of clinicians and scientists interested in MH continues to refine the muscle biopsy contracture test and also to add to the list of DNA changes (mutations) that predispose an individual to the disorder. The hope is that a panel of genetic changes will be used to screen, or more easily confirm, susceptibility to MH than current tests, but it is unlikely to happen very soon.
Other exciting and potentially significant developments that are in process are:
Two new foundations related to muscle disorders associated with the ryanodine receptor were formed recently. Concerned that research into diagnosis and treatment of muscle disorders associated with the ryanodine receptor was not getting the attention it deserved, the Goldberg family of Baltimore and Pittsburgh established the RYR1 Foundation (www.ryr1.org). The newly formed foundation will enhance awareness of such muscle disorders as Central Core Disease, Multiminicore Disease, and Nemaline myopathy, which may be associated with muscle weakness and stimulate research into treatment of the disorders. Another foundation “Cure CMD” ( www.curecmd.org) was introduced a few years ago emphasizing the need for more research into congenital muscle disorders of all kinds. This group is facilitating connections between patients and researchers interested in such muscle disorders.
Finally, I must express gratitude to all those who support the mission of MHAUS. Special thanks go to Par Sterile Products, Eagle Pharmaceuticals, the Kaufman family, the Napolitano family and to all those who took me up on the end of the year President’s Challenge, as well as the many members and supporters of MHAUS, especially those who responded to our Year End Appeal. The work of MHAUS cannot go forward without the dedicated efforts of our hotline consultants, professional advisory council members, the Board of Directors and the dedicated staff of MHAUS: Dianne Daugherty, Gloria Artist, Fay Kovak, Michael Wesolowski, Elaina Morgan and Sara Prosser.
I would like to wish you a very Happy and Healthy New Year.
What follows is a selection of peer-reviewed publications on MH and related topics during 2014 (and a few from 2013): Underlined are members of the Professional Advisory Council and Hotline consultants.