Malignant Hyperthermia Association of the United States and theNorth American Malignant Hyperthermia Registry of MHAUS

Volume 26 Number 2Spring 2008

The Communicator

Fear and uncertainty can go hand-in-hand. This isespecially true when it comes to confronting hereditarymedical conditions such as heart disease or cancer ormalignant hyperthermia (MH). But if you remove uncer-tainty from the equation, fear can be managed, or evenovercome.

You’re not alone in confronting your fears when itcomes to a genetic test for MH. There are qualified andexperienced genetic counselors available to help you cometo terms with genetic testing, both before and after theresults.

“The most common fears and concerns thatpatients have are whether their children are at risk for MH.They also want to know if they need to take precautionswith surgery,” says Deanna Steele, a genetic counselor withMagee’s Center for Medical Genetics at the University ofPittsburgh Medical Center.

“I try to advise the patient that results may help toanswer their questions about their risk for MH. Based onthe results, we can help them to take proper precautions,and that in educated hands, an MH-susceptible patient canhave successful surgery.”

Ms. Steele has been a genetic counselor for 22years and has counseled quite a few patients that areinterested in MH testing. She’s had a number of face-to-face meetings with patients, but most occur over thephone.

“Patients are calling from all over the U.S.A. fortesting and counseling,” she says.

Jenny Geurts has been a genetic counselor for 15years and currently counsels patients at St. Luke’s MedicalCenter in Milwaukee, Wisconsin. She generally meetswith patients for one to two sessions, with the first sessiontaking place prior to the test and the second following thetest results.

MH Genetic Counselors Help PatientsOvercome Fear and Uncertainty of Testing

In This Issue:

MH Still a Concern in

Developing Countries 2

Planning for the

Unexpected MH Crisis 4

Dr. Gordon’s Relunctant

Career Choice 6

Meet Nicole Viera 7

Hotline Summary 8-10continued on page 3

“Some may choose not to have the test after thefirst session,” she says.

Ms. Geurts emphasizes that molecular genetictesting for MH susceptibility does not replace the musclebiopsy test, which is still the “gold-standard” for diagnosisof MH. A genetic test for MH is not especially sensitive,meaning approximately only 30% of those that are MH-susceptible will yield a positive test result.

However, although a genetic test for MH is notvery sensitive, it is very specific, meaning a positive reportlisting a documented causative RYR1 mutation virtuallyconfirms the patient of being at risk for MH. As well, if amutation is found in a family member, the other familymembers with that same mutation are considered MH-susceptible.

For some patients, painful emotions can resurfacewhen considering a genetic test for MH.

“Maybe they lost a relative years ago,” says Ms.Geurts, “and they wonder, ‘Could this happen to me?’”

Ms. Geurts canrelate to this concern.Her uncle suffered anMH episode. Fortu-nately, he survived.

“I explain thatevery family has some-thing, whether it’scancer, heart disease orMH. I try to stressprevention, because wedon’t want historyrepeating itself. I alsotalk about the ‘silver

The Communicator is published four timeseach year by the Malignant HyperthermiaAssociation of the United States (MHAUS)and is made possible by a generous grantfrom Procter & Gamble Pharmaceuticals,manufacturers of Dantrium®. TheCommunicator is intended to serve theinformation needs of MH-susceptiblefamilies, health care professionals, andothers with an interest in MH.

EDITORBrian Kamsoke

Editorial Advisory PanelScott Schulman, M.D.Henry Rosenberg, M.D., CPEBarbara Brandom, M.D.Cynthia Wong, M.D.Lena Sun, M.D.Ronald J. Ziegler

FOR MHAUSHenry Rosenberg, M.D., CPEPresident

Ronald J. ZieglerVice President

Sheila Muldoon, M.D.Vice President, Scientific Development(MHAUS/NMSIS/Registry)

Stanley Caroff, M.D.Vice President – Director of NMSIS

Steven V. Napolitano, Esq.Secretary

Joseph R. Tobin, M.D.Treasurer

Dianne DaughertyExecutive Director

Gloria ArtistHotline Coordinator

Diane Van SlykeNMSIS Development Coordinator

Fay KelloggFulfillment Administrator

Nicole VieraAdministrative Assistant

Malignant Hyperthermia (MH) is aninherited muscle disorder which, whentriggered by potent inhalation anestheticsand succinylcholine, may cause a life-threatening crisis. The incidence of MH islow, but, if untreated, the mortality rate ishigh. Since the advent of the antidote drug,dantrolene sodium, and with greaterawareness of the syndrome, the mortalityrate has decreased. Great advances in ourunderstanding of MH have been made sinceit was first recognized in the early 1960s,but the nature of the fundamental defect(s)is still unknown. MHAUS advocates that all surgicalpatients undergoing general anesthesiashould receive continuous temperaturemonitoring, that adequate supplies ofdantrolene be stocked near the OR and thatthorough family histories be obtained.

Copyright 2008 by MHAUS

Lack of MH Preparedness (andDantrolene) a Concern inDeveloping Countries

The North American MalignantHyperthermia Registry (NAMHR)recently received a case from the MiddleEast that highlights the lack of MHpreparedness in the developing world.

An adult female was undergoingplastic surgery on her nose when shedeveloped sinus tachycardia and exces-sive bleeding, with muscular rigidity,masseter spasm, heart rhythm distur-bance, elevated temperature and cardiacarrest, known signs of MH. The medicaldoctor terminated the procedure, butdantrolene was not immediately avail-able. It was necessary to obtaindantrolene from a nearby hospital, butthat source only provided three vials.Fortunately, the patient survived.

“That MD deserves a lot ofcredit. First, for rescuing the patient inthese adverse circumstances and sec-ondly for reporting the case to the MHRegistry,” said Dr. Barbara Brandom.

Dr. Henry Rosenberg, MHAUSPresident, feels MHAUS should be moreactive in providing education andinformation about MH to other coun-tries. But he recognizes the fundingconstraints, as well as the fact thatMHAUS is a United States-based associa-tion, whose first objective is promotingMH awareness and preparedness in thiscountry.

“I realize that Europe, Canada,Australia, New Zealand and perhapsJapan are pretty up-to-date concerningMH, but obviously many other countriesare not,” he said. “Some countries do nothave dantrolene at all, others only inlimited supply.”

MHAUS has translated some ofits educational material into Spanish andprovided this information to organiza-tions like “Operation Smile,” a non-profitorganization that provides free recon-

structive surgery in developing countriesfor children with facial deformities suchas cleft lips, cleft palates, burns andtumors. For its part, P&G Pharmaceuti-cals, which first introduced dantroleneinto the market 28 years ago, hasdonated Dantrium® IV to OperationSmile so that doctors venturing intothese countries are prepared should anMH crisis arise.

“Last year, P&G donated close to5,000 bottles of Dantrium® IV to ourorganization,” said Dena Liston, man-ager, Development and Gifts-in-Kind.“They have supported Operation Smilewith in-kind donations since 1993.”

Operation Smile(www.operationsmile.org) was foundedby Dr. William P. Magee, a plasticsurgeon, and his wife, Kathleen, a nurseand clinical social worker. In 1982, theMagees traveled to the Philippines with agroup of medical volunteers to repairchildren’s cleft lips and cleft palates.

Today, Operation Smile coordi-nates more than 30 medical mission sitesin 26 countries annually. Last year,medical volunteers provided free surger-ies for 9,221 children.

Operation Smile also provides aframework for its partner countries tocome together to share knowledge,technology and skills through the use ofprograms customized to each country’sspecific medical infrastructure. Theannual Operation Smile Physicians’Training Program (PTP) brings surgeonsfrom around the world to the UnitedStates for training in specialized surgicalskills.

Through organizations such asthis, MHAUS and P&G Pharmaceuticalsare working to promote MH awarenessand preparedness. But there’s still a longway to go.

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Genetic CounselingContinued from front page

lining’ and that is, if the test comesback negative, at least we know now.”

With the uncertainty re-moved, fear is gone.

All patients who have had apositive muscle contracture testshould consider the molecular genetictest. This is because a large fractionof such patients will return positivetest results and, once a causativemutation is found within a family,then propagation of this findingthroughout the family can beachieved for only a fraction of thecost of the muscle contracture test.

As well, all families with aclear history of MH should considerthe molecular genetic test. This isregardless of whether some membersof the family have already receivedthe muscle contracture test. It is veryimportant, however, that a memberwithin these families who either hashad a clear MH event or has had apositive contracture test result shouldbe the first one tested. Testingmembers of these families first, whodo not exhibit any evidence of MHsusceptibility, does not appear to beproductive.

The genetic test for MH issimple and relatively inexpensive.Patients have blood drawn in theirlocal doctor’s office and then shippedto a testing lab. Presently, there aretwo genetic testing sites for MH:PreventionGenetics, LLC, (715) 387-0484, www.preventiongenetics.com,and the University of PittsburghMedical Center, (412) 648-8519,http://path.upmc.edu/divisions/mdx/diagnostics.html

Paying for genetic and/ormuscle biopsy tests is often a prob-lem. Some health insurance planswill readily cover testing while otherswill not. MHAUS offers limitedfinancial support to assist those whoare advised to undergo genetic testingbut do not have the financial re-sources. Contact MHAUS at (607)674-7901 to learn more about thisprogram.

A gentic test can provide theprotection of knowing whether you’reMH-susceptible, and genetic testingalso helps the medical communitybetter understand MH so that diagno-sis and prevention can be improved.

A perfect example is therecent case report published in theAugust 2007 issue of “Anesthesiol-ogy” of a 73-year-old man whoexperienced a delayed MH episodefollowing laparoscopic and openresection of a rectal tumor, colostomy,and lysis of adhesions. This patient,his wife, and their daughter chose todonate blood for examination of theRYR1 gene.

This is the first report of anindividual with a compound het-erozygous RYR1 mutation in NorthAmerica. His wife had no variationswithin the portions of her RYR1 gene

examined. All of their offspring mustbe considered MH susceptiblebecause it is likely that each has oneof their compound heterozygotefather’s RYR1 variants.

MHAUS urges anyone testedto have their results recorded in theNorth American MH Registry(NAMHR). MHAUS supports theNAMHR, which contains clinicalinformation on more than 2,000individual cases of MH or suspectedMH together with muscle biopsycontracture test results.

MHAUS is working diligentlyto promote the development ofgenetic testing for MH and hassponsored several meetings of scien-tists interested in the genetic diagno-sis of MH. In 2006, MHAUS autho-rized a grant to Dr. Sheila Muldoon,Khishge Sambuughin and BarbaraBrandom for the in-depth study ofDNA changes in 100 MH-susceptiblepatients. As well, MHAUS hasprovided seed money to the clinicallaboratories to begin testing patientsfor known genetic changes related toMH.

MHAUS anticipates rapidadvances in the genetic diagnosis ofMH in the next few years.

Jenny Geurts, MS, CGC, CertifiedGenetic Counselor, Cancer Services,St. Luke’s Medical Center

Deanna Steele, Genetic Counselor,Magee’s Center for Medical Genetics,Magee Womens Hospital

A genetic test can provide theprotection of knowingwhether you’re MH-suscep-tible ... and helps the medicalcommunity better understandmalignant hyperthermia.

4

Planning for the Unexpected MH Crisis: SpecialConcerns for the Ambulatory Surgery Center

continued on page 5

Editor’s note: A probable MH death fourmonths ago of a patient with six previousuneventful anesthetics, and the death ofa 21-year-old woman during electiveplastic surgery at an ambulatory centerone year ago, show that MH remains avery real threat. MHAUS continues tostress vigilance and preparedness,whether in a hospital, ambulatorysurgery center (ASC), or transporting apatient. The following article firstappeared in “Outpatient SurgeryMagazine” in May 2007 and bearsreprinting in these pages as a heed toconstant vigilance.

by Henry Rosenberg, MDWhen you think of testing for malig-nant hyperthermia (MH), you prob-ably think of the pre-operativeinterview. It's standard to ask thepatient about her history with anes-thesia, follow with some questionsabout the family's experiences withanesthesia and determine whetherthere is a family history of unusualmuscle disorders or malignanthyperthermia syndrome. This maycatch the most obvious red flags, butfor practical purposes, it's really notthat effective for predicting a patient'srisk for developing MH. Even patientswho have low risk factors may laterpresent with an MH episode.

Regardless of whether you'reworking in a hospital or a freestand-ing facility, if you're administeringanesthesia you need a plan to recog-nize and treat this potentially fatalsyndrome as quickly as possible.Here's what you and your staff shouldknow about dealing with MH. Theinformation provided has beendeveloped over many years by thoseassociated with the Malignant Hyper-thermia Association of the UnitedStates (MHAUS), a not-for-profitpatient advocacy group led by

laypeople, physicians and scientistswith an interest in MH and alliedsyndromes.

MHAUS's advice: Be preparedEvery minute counts during an MHepisode as you and your team work toprevent a bad outcome, so the morepreparation you've done in advance,the better. Training for MH is animportant component. Everyoneshould be familiar with MH syndromeand the need for rapid and definitiveaction once it's diagnosed. Some ofthe tasks you need to delegate in-clude:❑ obtaining and mixing dantrolene;❑ getting ice, hypothermia blankets and other devices to cool the patient;❑ drawing blood samples for arterial blood gas;❑ running electrolyte and coagulation tests; and❑ alerting the nearest hospital to expect a patient who is experienc- ing an MH episode.

MHAUS' professional advi-sory council has recommended thatevery facility using general anesthesiawith potent volatile agents shouldhave a full supply of dantroleneimmediately available stored withsterile water for injection USP withouta bacteriostatic agent to reconstitutethe dantrolene and a plan to handlethe crisis.

To make sure everybodyknows what to do, I suggest having apractice drill once a year. It's also wiseto put the treatment plan in writingand post it near the ORs in case of anactual event. This will give everyone aquick reminder of what they have todo. You can include the MHAUSHotline number, (800) MH-HYPER(644-9737) if there is a suspicion that

the patient may be experiencing anMH episode.

If you administer gas anes-thetics such as sevoflurane orisoflurane or the muscle relaxantsuccinylcholine, be sure to keep a fullsupply of dantrolene immediatelyavailable stored with sterile water forinjection USP without a bacteriostaticagent to reconstitute the dantrolene.Having everything ready to mix letsyour staff treat a patient with MHpromptly, a valuable advantage,because every minute counts duringan MH crisis.

Most offices and ASCs don'thave the equipment to analyze arterialblood gases or electrolytes on-site; ifthat's the case in your facility, makesure you have arranged to rapidlytransport specimens to an approvedlaboratory that reports resultspromptly.

It's also especially importantfor freestanding ASCs to have transferpolicies and procedures to followonce a patient's condition is stabi-lized. In this context, stabilizingmeans administering enoughdantrolene so that the patient isn'ttachycardic, the end tidal carbondioxide levels are declining to lessthan 50 mmHg or less, there is norigidity and the core temperature ison the way down.

I also think that extradantrolene (about 1 mg/kg), mixedand ready to use during the move,should be prepared. The receivinghospital should have dantroleneimmediately available for administra-tion upon the patient's arrival.

Intraop temperatureExcept for very brief cases, youshould monitor temperature during

5

Continued from page 4

all general anesthetics. In many cases,temperature elevation is the confir-matory sign of MH, but it's usually alate symptom and, frighteningly, itdoesn't present in all cases.

The rate of a temperature'srise often indicates the syndrome'sseverity. During an MH crisis, aperson's body temperature can rise adegree every three to five minutes, soin a brief period of time, a patient cango from normothermia to 106°F.When temperature exceeds about106°F, coagulation abnormalitiesoften occur. If a patient develops suchhyperthermically-inducedcoagulopathy, the likelihood ofmortality is high. On the other hand,overly aggressive cooling may lead tomarked hypothermia, which can alsohave adverse consequences.

The anesthesia providershould have and be familiar with theequipment to measure and monitorbody temperature continuouslyduring anesthesia. Esophageal,

nasopharyngeal or oral temperaturemonitoring is the ideal way tomonitor temperature, but this isn'talways possible. It's acceptable tomeasure rectal, bladder or axillarytemperature. However, rememberthat axillary temperature is often oneto two degrees less than core tem-perature. A patient's forehead skintemperature bears a very roughcorrelation to the core temperature,and it has the virtue of being non-invasive. If there is a significantchange in skin temperature, a moreaccurate temperature monitor, suchas esophageal, should be used.

Temperature monitoring,personnel training and preparednessmay seem like a lot of work for what'sessentially a rather rare event. It'svery likely that the MH plan youmake for your facility is rehearsedmore often than it's actually used.However, over the course of ananesthesia provider's career he islikely to either detect an MH episode,assist in management of a case or dealwith a patient with a family history of

MH. Therefore, all anesthesia provid-ers should be aware of the syndromeand its symptoms, treatment andmanagement. Without such prepara-tion and training, an otherwisehealthy patient may suffer needlessmorbidity or mortality. In otherwords, this knowledge may save apatient's life.

Did you forgetsomething?If you’re moving, or planning tomove, don’t forget us! Pleaseremember to contact MHAUS toprovide us with your newaddress. Call (607) 674-7901 orsend your address change to:MHAUS, P.O. Box 1069,Sherburne, NY 13460-1069.

6

A Relunctant Career Choice Marked by Profound DedicationEditor’s Note: This is the second ina series of biographies related tothose who played an important rolein our understanding MH.

RoderickAngus Gordonhas beendescribed as a“RenaissanceMan” for hisvaried contri-butions andorganizationalskills that

furthered the study of anesthesia inCanada.

Born in 1911 in Watrous,Saskatchewan, Canada, he startedviolin lessons at age six, playing inlocal concerts throughout his earlyschool years. At age 16 he wasawarded a scholarship to the TorontoConservatory of Music, subsequentlyjoining the faculty, teaching violinand playing in string quartets.

Gordon’s dream of continuingas a concert violinist was shattered bythe Depression, and he enteredmedicine purely for financial reasons.He returned to Saskatchewan,graduating from the local universityin 1934 and continuing at the Univer-sity of Toronto (UT), where hereceived his MD degree in 1937.There were no openings in surgery,his choice of study, but an appoint-ment in anesthesiology was available:a reluctant start to a career marked byhis profound dedication to thespecialty.

Following a three-yearinternship at Toronto General, Dr.Gordon was commissioned in theRoyal Canadian Army Medical Corpsin 1939. Sent to London, he fur-thered his learning by observingBritish anesthetists in a variety ofmedical centers. Then as casualties ofthe war mounted, Gordon, by then aMajor, served as anesthetist to a team

doing plastic reconstructive surgery,especially on injuries of the face. Healso attended to civilians and wasparticularly interested in helpingchildren with cleft palates.

Gordon served six years inEngland and, returning to Toronto,continued in the Reserve Forces,becoming Consultant in Anesthesia tothe Canadian Armed Forces MedicalCouncil, with the rank of Colonel.

While at UT, Dr. Gordon wasdevoted to influencing others tostudy anesthesiology. He developed aformal training for residents requiringa year of study and research in theDepartment of Pharmacology. Re-cruiting staff members and increasingthe department’s funding were alsopriorities.

Dr. Gordon became inter-ested in the attempts of Drs. Britt andKalow of UT to examine the medicalhistories of malignant hyperthermia(MH) susceptible families, to deter-mine the anesthetic agents that triggerMH crises in these families and todevelop biopsy screening tests. Hejoined the researchers in a sympo-sium in which he presented thehistory of MH. While there were fewstudies of the syndrome prior to1966, he stated that hyperthermia asa reaction to anesthesia was firstreported in 1937 by Dr. ArthurGuedel who had encountered sixcases in a twenty-year period butnever reported whether the patientswere related. (Guedel, AE: InhalationAnesthesia. New York, Macmillin,1937).

The Canadian AnesthesiaSociety had been founded in 1921,and Dr. Gordon served as its Secre-tary-Treasurer from 1946 until 1961.His interests lay in the promotion ofeducation, the quality and theeconomics of practice, including afee-for-service arrangement. TheCanadian Anesthesia Society laterestablished the RA Gordon Clinical

Research Award in honor of his givinga strong voice to the specialty in themedical community.

In 1954 Dr. Gordon foundedthe Canadian Anesthetists SocietyJournal (now the Canadian Journal ofAnesthesia) in which he served aseditor until 1982 and as editoremeritus until his death in 1998.

Dr. Gordon’s teaching com-mitments extended far beyondCanada. He established the CanadianAnesthetists Society’s Training andRelief Fund (now the InternationalEducation Fund) in 1964 whichsupports anesthesia education indeveloping countries. Especiallyinterested in Nigeria, he helpeddevelop the Department of Anesthesiaat the University of Lagos.

He was Chairman of theOrganizing Committee of the SecondWorld Congress of Anesthesiologistsin Toronto in 1960 and Vice Presidentof the World Federation of Societiesof Anesthesiologists from 1968 to1972.

He was certified by theAmerican Board of Anesthesiology.Fellowships included the RoyalCollege of Physicians of Canada,Royal College of Surgeons in Englandand the American College of Anesthe-siologists. Honorary membershipswere also conferred by the Society ofAnesthetists in Great Britain andIreland and the Association of Sur-geons of West Africa.

In 1939 Dr. Gordon marrieda nurse from Toronto General, MissRuth Breithaupt. In later years, theyand their children and grandchildrenvacationed in a self-built home on anisland in Georgian Bay, where heinstilled a love of music in his familyand undertook a never-ending list ofcarpentry projects. At his death in1998, Dr. Gordon was still counselingfledgling anesthetists and participat-ing in his many endeavors related tohis specialty.

7

The Lila and Jerry Lewis Memorial FundThere are many special people who take the time each year to remember their loved ones in a waythat helps MHAUS. The people below have made gifts during FY 06-07 (Oct. 2006 - Feb. 2007) in

memory of Lila and Jerry Lewis. We are most grateful for their support and special tribute gifts.

Life BenefactorsDorothy GlassmanGregory Lewis GlassmanJacey Lila GlassmanMarilyn Lewis GlassmanSteve & Mickey LewisDr. Joseph SugermanBob & Dianne Winters

PatronsHillard FahnBrad & Julie Shames

SponsorsTerry & Cheryl DawesArline A. HammerBarry & Beverly Kurtz

Gloria LeonardGreg & Laura PerloffLenny RobertsJudy SwartzMark Zamel

DonorsLarry & Linda BlumenfeldSy & Estelle OpperAllen JacobsSheldon & Doreen QueridoBill & Linda Rouse

FriendsSam BirnbaumDoug BraunRob Gloria

Jon MatthewsJohn & Kerrie SadlerLois SoterGeorge & Miriam TrustmanMarilyn Tucker

HonorariaMarriage of Jacey Glassman & DanHayes and Greg Glassman &Courtney Grenfell by Marilyn Lewis GlassmanMemory of Renee Johnson’s UncleMelvin Rollin by Marilyn Lewis GlassmanMemory of Florence & DavidGoodman by Dorothy Glassman

MHAUS WelcomesNicole Viera

MHAUS is pleased toannounce the hiring of NicoleViera as Administrative Assistantat our Sherburne, NY office.Nicole is responsible for databasemaintenance/quality control,organization of discussion groupsynopses, coordination of meetingarrangements and exhibit boothsetup, as well as other generaloffice duties.

Nicole studied Securityand Law Enforcement and thenjoined the Norwich, NY FireDepartment after high school,where she took firefighting andEMT courses and was certified inSelf-Contained Breathing Appara-tus (SCBA). She had made 1stLieutenant before leaving the firedepartment and was recognizedwith a “Life Saving” pin forinvolvement in saving a person’slife. For the last eight years,Nicole has worked as a SpecialEducation Teacher’s Aide, whereshe worked closely with childrenwith a variety of disabilities:Traumatic Brain Injury (TBI),Cerebral Palsy, Mentally Retarded(MR), Autism, Spinal Bifida, andAsperser’s Syndrome.

“I started at MHAUS lastAugust, and it took about a monthor two to settle in,” she says. “Ienjoy what I do here, and I amcontinuing to learn about MH.”

By Diane Van SlykeNMSIS proposes toassemble a panel ofworldwide experts toreach a consensus ondiagnostic criteriaand recommend

treatment for NMS based on the bestavailable empirical evidence.

Reliable guidelines are criticalin raising awareness of NMS to assistpractitioners in identifying symptomsquickly, thus reducing morbidity andmortality from NMS and othersimilar-presenting disorders.

NMSIS Strives for Developmentof Diagnostic and TreatmentGuidelines for NMS

This project to achieveconsensus among a panel of expertsto standardize diagnostic criteria andrecommend treatment offers anopportunity to enhance the safety ofpatients exposed to these widely usedagents and to reduce morbidity andmortality from NMS.

Drs. Stanley N. Caroff,Ronald J. Gurrera and Paul E. Keck,Jr. co-chair this project, with Drs.Sharon Hirshey Dirksen, Jeffrey R.Strawn and Abigail Cohen as consult-ants and participants.

Third Annual MH Mini-ConferenceScheduled for September 27-28

Start making your plans nowfor the 3rd Annual MH Mini-Confer-ence in Phoenix, Arizona, on Septem-ber 27-28, 2008. The conferencebrings together medical professionalsand MH-susceptible families in anopen forum discussion of current MHresearch and testing, which includes

molecular genetic testing.The registration fee is yet

determined, but it is expected to beminimal. Last year’s registration feewas $25.00. Visit the MHAUSwebsite at www.mhaus.org for thelatest updates and announcement ofscheduled speakers.

8

MH Hotline Activity – January to April 2007by Henry Rosenberg,MD, President MHAUS

During the threemonth period ofJanuary to April 2007,15 Hotline consult-ants were called tohandle 65 cases andaddress 17 inquiriesrelated to MH. Theconsultants were Drs.

Brandom, Chapin, Belani, Kaplan, Melton,Wedel, Rosenbaum, Miller, Weglinski,Skoog, Theroux, Tobin, Wong, Millman,and myself.

Calls derived from communityhospitals, university hospitals, emergencyrooms, surgery centers (5). The calls wereplaced by anesthesiologists, nurse anesthe-tists, internists, pediatricians, emergencymedicine physicians and surgeons. Theyderived from all around the U.S.

There was one death clearlyrelated to MH that began during a surgicalprocedure in a surgery outpatient center.The patient died in the hospital followingtransfer from complications secondary tohigh fever. This case has been reportedpreviously in The Communicator (Vol 23,No. 3, Summer 2007).

In 16 cases, the consultantsthought the problem was clearly MH orlikely MH. In six cases the calls were relatedto increased muscle tone and rigidity, notrelated to MH. Thirty calls were related toincreases in body temperature, but theconsultants did not believe that MH was thecause. Seven calls were due to increasedcarbon dioxide excretion duringlaparoscopic surgery (see below) and fourcalls were related to increased carbondioxide levels not related to MH. The rest ofthe calls related to a wide variety of clinicalsituations.

Cases related to increase in bodytemperatureThere were 30 calls related to patients whodeveloped a high body temperature whichthe consultants thought were eitherdefinitely not or unlikely to be related toMH. One half of the calls concernedpatients less than four years of age.

In these cases the consultants relyheavily on the results of the determinationof the acid content and carbon dioxidetension in the arterial blood (i.e. arterialblood gases), the presence or absence ofrigidity or other circumstances that makethe diagnosis of MH unlikely. For example,if the patient has experienced an uneventful continued on page 9

anesthetic and several hours later developsa high fever (three cases) this is not MH, asMH episodes occur either during thesurgical period or within approximately onehour following the end of anesthesia.

In a few cases the cause of thefever was related to a preexisting infection,be it respiratory, ear or other evidence ofinfection. There were two cases of highfever after appendectomy. In one case thefever occurred well after the surgery and inthe other case, the patient had an elevatedbody temperature prior to surgery.

Other sources of infection thatcontributed to post operative fever includedental or oral surgery (the mouth is a“dirty” area and when instrumentedbacteria may enter the blood stream andcause fever) and the urinary tract. Feverafter drainage of infected ears occurredmost commonly in young children.

In some cases the temperatureelevation was very striking (over 108degrees) and dantrolene treatment, alongwith other forms of treatment of elevatedbody temperature, were employed.

In some cases the cause of thehyperthermia is related to aggressive patientwarming. This occurs because there isconcern that when a patient, particularly achild, becomes cold during surgery he/shemay develop a variety of complicationssuch as prolonged emergence fromanesthesia and increased risk of infection.Hence, heating blanket devices are used tokeep a patient warm. Careful attention isnecessary, however, so that the patient isnot warmed excessively. This was the casein at least one patient.

Here is an example of one relatedto body temperature elevation. An 18-month-old male had surgery for a repair ofa urethral deformity. In the recovery area hewas noted to have a temperature of 103degrees. He was breathing rapidly. Theblood gas test recommended by theconsultant did not indicate changes of MH.The patient was treated with Tylenol, fluidand conservative measures and thetemperature returned to normal. Inaddition, it was revealed that the child hadan upper respiratory tract infection oneweek previously. The patient recoveredcompletely. Rarely is the reason for theelevated temperature a faulty thermometerdevice, although that is also theoreticallypossible.

Elevated level of carbon dioxide excre-tion (end tidal C02)One of the earliest signs of MH is anunusually high level of carbon dioxide in

the exhaled gases which are routinelymeasured during anesthesia. However,there are several other reasons for increasedexcretion of C02.

Here is the primary one. One ofthe most significant advances in surgery hasbeen the introduction of minimally invasivetechniques to avoid large incision andsubsequent pain and prolonged hospitalstay as well as a variety of other complica-tions. The technique which is most oftenused during surgery in the abdomeninvolves expanding the abdomen byinsufflating carbon dioxide gas. This createsa space in the belly for the surgeon tointroduce thin instruments through tinyskin incisions (often through the umbilicusor belly button). With these probes thesurgeon can cut, suture, and removediseased tissues. The technique is calledlaparoscopy and is used extensivelythroughout the U.S. and Europe for suchprocedures as gall bladder removal andgynecologic surgery. In some situations thecarbon dioxide gas seeps out of theabdomen and spreads under the skin and/or is absorbed into the blood stream. Whenthat occurs, the gas is exhaled and theanesthesia provider notices an increase inend tidal carbon dioxide. It then raises thesuspicion that this might be an early sign ofMH. Often it is obvious that the elevation isrelated to the carbon dioxide absorption,but not always. About 10% of all Hotlinecase calls are related to increased end tidalcarbon dioxide during laparoscopy, oftenaccompanied by another sign of MH,increased heart rate. The Hotline consultantmust therefore carefully question thecircumstances, the type of anesthesia beingused, the presence of elevated temperature,or muscle rigidity to determine that thechange is or is not related to MH. If theelevated C02 is reduced by stopping thesurgery and removing the gas in theabdomen the diagnosis is clear (i.e., notMH). However, in some cases, because theC02 has infiltrated under the skin, it servesas a reservoir for excretion of C02 and theexhaled C02 levels remain elevatedsuggesting an MH episode. In two of the sixcalls for this problem, dantrolene was given,while in four others it was not. All thepatients did well. None had post operativesigns that they had experienced an MHevent.

The anesthesia and surgerymedical literature has not addressed thisissue in a quantitative manner and there are

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few guidelines to determine with accuracywhether the patient is experiencing MH orjust rapid absorption of carbon dioxide.Our MH Hotline consultants bring theirexperience and knowledge to analyzingsuch cases and helping out the patient.

Why is C02 used to inflate theabdomen? Because it is not flammable,inexpensive, is rapidly absorbed with fewphysiologic negative effects, and allows thesurgeon a clear view of the abdominalcontents.Patients who experienced isolatedmuscle rigidityMuscle rigidity on induction or duringanesthesia is very unusual and is one of theimportant signs indicating possible MH.Six calls related to muscle rigidity withoutother signs of MH. The causes were:insufficient depth of anesthesia when theanesthesiologist attempted to open themouth, a history of temporomandibular(TMJ) disease limiting mouth opening,increased muscle tone upon induction withthe anesthetic gas sevoflurane. Increasedmuscle tone upon induction or awakeningfrom sevoflurane anesthesia is an uncom-mon complication of the drug. Increasedjaw muscle tone upon induction with theparalyzing agent succinylcholine is often asign of MH, but only when there is greatrigidity of the jaw limiting or preventingmouth opening. However, the anesthesiaprovider must consider this jaw rigidity as asign of MH or impending MH until provenotherwise. Another cause of increasedmuscle tone is shivering or just increasedmuscle tone following anesthesia becausethe patient’s body temperature has fallenduring anesthesia or the patient is experi-encing the early onset of an infection.

In one case of prolonged jawrigidity after surgery in a six-year-old child,it was finally determined that the childrefused to open his mouth because of thepresence of a breathing tube in his nose andthe tape inhibited mouth opening.

Not included in these calls is theoccasional patient with a muscle disordersuch as myotonia who develops rigiditywith succinylcholine or on emergence from

anesthesia. In these cases the Hotlineconsultant prevented needless labeling ofthe patient as MH susceptible.

Miscellaneous conditionsAnesthesia providers often call the Hotlineconcerning patients with rather unusualproblems. There were 10 such calls. In onecase a 29-year-old patient developedmuscle contractures (rigidity) due tohyperventilation syndrome secondary toanxiety.

A 46-year-old patient who wasanesthetized for a kidney transplantdeveloped a cardiac arrest shortly afterinduction of anesthesia. No signs of MHwere present. A variety of other possibilitieswere discussed, but the common causeswere quickly eliminated. On autopsy thepatient was found to have significantinflammation of the heart muscle, acondition called myocarditis that is oftendifficult to diagnose with routine tests.

A most unusual case involved a46-year-old, 260 pound body builder whois very muscular and admitted to taking avariety of performance enhancing medica-tions along with a drug used to lowercholesterol (fenofibrate). The anesthesiolo-gist used succinylcholine and propofol forinduction and, although there was mildelevation of carbon dioxide, the bodytemperature was normal. Following thesurgery for a tumor of the thyroid gland,the patient awoke complaining of shoulderpain and armweakness. Theanesthesiologistwas concernedand had someblood tests done.The patientdevelopedevidence ofsignificant musclebreakdown(elevated creatinekinase, myoglobinin the urine) andevidence of kidneydysfunction. Heeventuallyrecovered. Theanesthesiologist

was seeking guidance as to whether thisrepresented MH susceptibility. Very difficultto state, since the lipid lowering drugs areoften associated with muscle breakdownand there is a possibility that the greatlyenhanced muscle strength might also havepredisposed the patient to muscle break-down from succinylcholine.

A 31-year-old man had emergencysurgery for a femur fracture with MHtrigger agents. After the surgery it waslearned that the patient had a family historyof MH! He had evidence of significantmuscle breakdown, but no other signs ofMH. He was lucky!

Questions, Questions, QuestionsMany questions requiring the expertise ofthe Hotline consultants were logged – thirtyto be exact. These ranged from questions asto the likelihood of MH in a patient withmyotonia (not likely) and a variety of othermuscle disorders, dantrolene prophylaxis inan MH patient (not needed), precautionsfor a baby when the father is a known MH-susceptible, but the mother is not (noknown problems during the delivery havebeen reported) , proper anesthesia care for awoman with a history of MH during labor,advice on testing for MH-susceptibility,death of a patient in an emergency depart-ment without having had anesthesia (not

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In the U.S. and Canada, the MH Hotline is1-800-MH-HYPER (1-800-644-9737)

Outside the U.S., call 1-315-464-7079

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Meet This Issue’sHotline ConsultantDr. Henry Rosenberg is Director of the Depart-ment of Medical Education and ClinicalResearch at Saint Barnabas Medical Center inLivingston, New Jersey, Professor of Anesthesi-ology and the current President of MHAUS.He has been a Hotline Consultant since thebeginning of the Hotline in 1982.

MH). A nurse called from a center thatspecialized in spine and joint surgeryrequesting information as to what labora-tory testing should be available on site, justin case of MH. They do have the capabilityof basic laboratory testing and this was feltto be adequate. This is just a sample of thetype of questions that we receive!

Cases where the consultant thought thatMH was certain or likelySixteen calls were in this category. The onedeath almost certainly related to MH tookplace in an office surgery suite. The patientwas having plastic surgery done usingisoflurane. At the end of the case theforehead skin temperature was 104 degreesF., and the oral temperature 107, withincreased end tidal carbon dioxide. Thepatient was treated with some amount ofdantrolene and sent to the local emergencyroom where she received more dantrolene.Unfortunately though, the damage wasdone (most likely the very elevated bodytemperature) and the patient expired within10 days. The tragedy is compounded sincethe patient was only 21-years-old andotherwise healthy.

MHAUS is extremely concernedabout the level of preparedness for treatingMH in ambulatory centers and in emer-gency rooms where patients who developMH are transferred. We will be developingguidelines for such management over thenext several months.

Three of the other patients whodeveloped MH were females. The youngestpatient was 13, the oldest 57 years of age.

In one situation the anesthesiolo-gist was treating a 31-year-old man whowas undergoing ankle surgery whodeveloped unexplained elevation of endtidal carbon dioxide and elevated potassiumlevel along with acidosis requiring aggres-sive treatment.

Although some colleagues werenot convinced that this represented MH,nevertheless dantrolene treatment was

begun and the treatment guided by one ofthe Hotline consultants. His creatine kinase(indicative of muscle damage) was quiteelevated. Eventually he was tested for MH-susceptibility and found to be positive. Idon’t know why some people are skepticalthat MH is occurring when just about allthe signs point to MH and the treatmentwith dantrolene has few side effects.

A very similar case occurredinvolving a 13-year-old patient undergoingorthopedic surgery but his temperaturewent up to about 101 degrees F. as well.Dantrolene was effective in treating thepatient. His post operative creatine kinasewas elevated. Testing for susceptibility wasnot carried out though.

It is of interest that in most of theother cases the signs of MH occurred afterseveral hours of anesthesia. In these cases,the onset of the syndrome was marked byincreased exhaled carbon dioxide that wasnot controlled by increased minuteventilation. Perhaps the reason for delayedonset is that one of the trigger agents(succinylcholine) was not used and perhapsthe concentration of the anesthetic gaseswas reduced because of the concomitantuse of intravenous narcotics that are nottriggers of MH

A second MH episode occurred inan ambulatory surgery center involving a23-year-old undergoing elective plasticsurgery. He was treated with dantrolene andthe elevated end expired carbon dioxidelevels that had been noted, declined. Hewas transported to the nearest hospital afterbeing treated with the recommended doseof dantrolene and survived.

A 23-year-old man who wasundergoing spine surgery with desflurane (agas anesthetic and MH trigger) andsufentanil (a short-acting narcotic) anesthe-sia developed rapid increase in expiredcarbon dioxide, increased heart rate, and arise in body temperature to 104 degrees. Hewas also somewhat stiff. He was treatedwith dantrolene acutely and after theepisode, guided by the Hotline consultant,and did well. His creatine kinase indicated

marked muscle breakdown since the valuewas 15,000 units (normal is about 250).

Other MH cases:A 57-year-old woman anesthe-

tized with sevoflurane developed increasedcarbon dioxide and increased temperatureafter three hours of anesthesia. She receiveddantrolene and did well. It was revealedafterwards that there is a family history ofMH-susceptibility. She should have had anMH ID tag!

A 32-year-old woman to undergoa C-section developed jaw muscle rigiditywith succinylcholine followed by increasedheart rate and increased carbon dioxide,increased potassium and acidosis, but norigidity. She was treated with dantroleneand she and the baby recovered well.

A 30-year-old man developedincreased carbon dioxide levels on emer-gence from anesthesia with sevoflurane. Hewas treated with dantrolene and vital signsreturned to normal

A 37-year-old man undergoingknee surgery developed increased carbondioxide levels and increased heart rate andtemperature elevation to 101.2 degrees F.after about six hours of anesthesia, alongwith elevated potassium. Fortunately, thisoccurred at the end of surgery. Nodantrolene was given and he recovered. Hewas lucky. The consultant advised that thepatient be tested for MH-susceptibility andbe considered as MH-susceptible eventhough he did not progress into full blownMH.

A 57-year-old man undergoingneck surgery developed hypertension,increased heart rate and elevated carbondioxide several hours after induction ofanesthesia. His temperature was going up aswell. He was treated with dantrolene withreversal of the signs. He was advised toobtain an MH ID bracelet and be tested forMH-susceptibility.

As you can see, although we arehappy to provide experts to help in themanagement of MH and situations thatseem to be MH, it is not always possible toconfirm the diagnosis as the event ishappening. Because the muscle biopsycontracture test is not available at manyplaces and genetic testing is poorlyunderstood by most practitioners, patientsare often left in the dark as to theirdiagnosis. I hope these cases demonstratethe vital role that MHAUS plays in assistingclinicians in the care of patients who areexperiencing potentially life threateningconditions. Although most cases turn outwell, even one death is too many.

Your support of MHAUS and itsprograms is vital in continuing our mission.Note: You can view a glossary of MH-related terms on the

MHAUS website at www.mhaus.org

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Yes! I want to support MHAUS in its campaign to prevent MH tragediesthrough better understanding, information and awareness.

A contribution of: ❑ $35 ❑ $50 ❑ $100 ❑ $250 ❑ $500 ❑ $1000 (President’s Ambassador) or ❑ (other amount) $ ___________, will help MHAUS serve the entire MH community.

Please print clearly:Name: ______________________________________________________________________________Address: ____________________________________________________________________________

City: ____________________ State: _____________ Zip: _________________Phone: __________________________ E-mail: _________________________

❑ I am MH-Susceptible ❑ I am a Medical Professional

Please charge my ❑ Visa ❑ Mastercard ❑ Discover ❑ American ExpressName on card: ____________________________________________________Credit Card Number: _______________________________________________Expiration: ___________________________

Please clip out thishandy coupon, or feelfree to photocopy ifyou prefer to keepyour issue intact, thenmail to: MHAUS, POBox 1069, Sherburne,NY 13460-1069

Slide ShowPresentation For

MH Risk AvailableMHAUS offers a slide show kit

(CD-ROM and slide format) withlecture notes on “Managing MalignantHyperthermia Risk in Today’s SurgicalEnvironment.” This presentationreviews the risk of MH and assessescurrent trends in the management ofMH in the inpatient and outpatientsettings. Two CME credits areavailable.

This is a valuable tool to assistin developing standard of care practiceguidelines and algorithms to ensurepatients at risk will have access toappropriate interventions for treatingMH. This program is arranged so it canalso be used as a self-study program toenhance individual knowledge of MHand the risks involved.

Cost is $135 plus shipping andhandling for the slides and CD. Call607-674-7901 or visit www.mhaus.orgto order.

Every MH-Susceptible Should Wear AMedical ID Tag

MHAUS has help available for the MH-susceptibles whohave no insurance or cannot afford to purchase a medicalID tag.

The Sandi Ida Glickstein Fund was established for thepurpose of providing free ID tags for MH-susceptible patientswho qualify.

To take advantage of this program, please send us a letterindicating why you would like MHAUS to provide you with acomplimentary ID tag.

The goal of the free ID tag program is to ensure thesafety of MH-susceptibles during an emergency situation and toprevent a tragic outcome from MH.

For further information, please contact MHAUS atP.O. Box 1069, Sherburne, N.Y. 13460-1069; call 607-674-7901, or visit www.mhaus.org.

Have you visited us lately? Log on to www.mhaus.orgto get the latest information on MH, order materials,

post a message to the bulletin board orlearn about the “Hotline Case of the Month.”

MHAUSP.O. Box 1069Sherburne, NY 13460-1069www.mhaus.org

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PERMIT #10SHERBURNE, NY 13460

MHAUS Happenings, Events and Notices❑ THANKS! MHAUS is gratefulfor the financial support of thefollowing State Societies of Anes-thesiology: California, Connecti-cut, Florida, Illinois, Maine,Maryland, Michigan, Nevada,Ohio and Pennsylvania. Ourappreciation also goes to thefollowing state components of theAmerican Society ofPeriAnesthesia Nurses: Arkansas,Colorado, Delaware, DC, Illi-nois, Kansas, Maryland, Mis-souri, Nebraska, New Hamp-shire, New Mexico, NorthCarolina, Pennsylvania, Texas,Vermont and Wyoming. Call theMHAUS office to ask how yourgroup can join their ranks!

❑ Upcoming MHAUS MeetingDates and LocationsAPA, Washington, DC, NMSMeeting, May 3-8; AACN-NTI,

Chicago, IL, May 5-8; ASPAN,Grapevine, TX, May 5-7; ASCAssociation, San Antonio, TX,May 14-17; AANA, Minneapolis,MN, August 9-13; MH Mini-Conference, Phoenix, AZ, Sep-tember 27-28; ASHRM, Boston,MA, October 2-5; APNA, Minne-apolis, MN, October 15-18; ASA,Orlando, FL, October 18-22.

❑ 27th Annual European MHGroup MeetingThe 27th Annual Meeting of theEuropean MH Group (EMHG) isset for May 28-30 in Lund,Sweden. For general informa-tion about the annual meeting,program information, abstractinformation, registration, Lundvenues, and how to there, visitwww.emhg.org and click on“meeting” on the left side of thepage. See you there.

❑ Speakers Bureau Brings MHExperts to Your FacilityMH experts can come to yourfacility or meeting and speak toyour staff about malignant hyper-thermia. MH experts are ready tooffer insight and suggestions on thetreatment regimen for MH shouldyou find yourself facing a possibleMH event. MHAUS offers thisservice as an important tool to helpyou keep your patients safe andwell. Contact Diane at (607) 674-7901 or email diane@mhaus.org.

❑ MHAUS Annual Report Avail-able OnlineDid you know you can downloadthe MHAUS Annual Report online?You can. Simply visitwww.mhaus.org and search for“annual report.” You’ll be able todownload a PDF of the 2006-07Annual Report.