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

Volume 26 Number 4Fall 2008

The Communicator

JHP Pharmaceuticals, LLC (JHP)and SpePharm Holding, B.V. are thenew suppliers of Dantrium® to hos-pitals and surgery centers. JHPwill supply Dantrium® to the U.S.,Canada, Australia, New Zealand,Israel and Chile, while SpePharmHolding, B.V. will supply Europeand selected other countries.

JHP and SpePharm Holding, B.V. acquired market-ing rights from Procter & Gamble Pharmaceuticals, Inc.(P&GP) for Dantrium® (dantrolene sodium) capsules andDantrium® Intravenous (dantrolene sodium for injection)in August of this year.

In its intravenous form, Dantrium® is used to treatMH (a life-threatening reaction to certain gaseous anesthet-ics and succinylcholine) and in its oral form, the control ofclinical spasticity resulting from upper motor neurondisorders (e.g., spinal cord injury, stroke, cerebral palsy, ormultiple sclerosis).

Stuart Hinchen, President of JHP commented, “Weare delighted to acquire the rights to Dantrium®. Thisproduct will fit well into our current portfolio of marketedproducts which already includes exports to Canada andAustralia.”

Jean-Francois Labbe, Chief Executive Officer ofSpePharm, said, “We have been pleased to partner withJHP in this acquisition and secure Procter & Gamble’srights to Dantrium® in the rest of the world (excluding theJHP territories). In Europe, Dantrium® will receive sup-

Dantrium® Now Supplied By New Company

In This Issue:

ASA Abstract Preview 2

Recognition Reception 3

Past, Present & Future

of Dantrolene 5

Hotline Receives Over

3200 Calls In Past Year 7

Hotline Summary 8

MHAUS’ Facebook 10

Happenings 12

port from SpePharm’s growing hospital sales and market-ing infrastructure.”

To enable product availability during this transi-tion period, the current ordering process will continuethrough P&GP and the customer service number willremain unchanged (1-800-448-4878) for the next severalmonths. As well, you can order Dantrium® IV directlyfrom JHP by calling or faxing your order to 1-877-547-4547, or emailing customerservice@jhppharma.com.

JHP and SpePharm are in the process of contactingcustomers regarding the ordering process. No action isrequired by customers at this time.

Margaret Link, Marketing Specialist with P&GP,said, “Procter & Gamble has determined that Dantrium®

intravenous and capsules no longer fit its long-termstrategic goals. As a result, P&GP has decided to divestthe franchise and redirect resources toward other opportu-nities.”

She added, “Over the past 28 years, P&GP andMHAUS have developed a strong partnership in increasingeducation of malignant hyperthermia around the globe.P&GP hopes that JHP and SpePharm will also valueMHAUS and choose to support their non-for-profit educa-tional goals.”

P&GP made itslast contribution toMHAUS this spring.

“I had a positiveconversation with thepresident of JHP Phar-maceuticals,” said HenryRosenberg, MHAUSPresident. “The twoprincipals (StuartHinchen and PeterJenkins) are very

Continued on page 4

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

Fay KelloggFulfillment Administrator

Nicole VieraAdministrative Assistant

Michael WesolowskiPublic Relations/Project Coordinator

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

ASA Abstract PreviewOctober 18, 20082:00 PM - 4:00 PM, Room Hall E2-Area ITemperature Changes Are Not LateSigns of Malignant Hyperthermia: ANAMH Registry of MHAUS StudyMarilyn G. Larach, M.D., F.A.A.P., GregoryC. Allen, M.D., FRCPC, Barbara W.Brandom, M.D., Erik B. Lehman, M.S.Department of Anesthesiology, Penn StateCollege of Medicine, Hershey, PAGoals: Current ASA/CAS standards do notmandate temperature (T) monitoringduring general anesthetics1,2. The authorsknow of 5 MH deaths in young, healthypatients during general anesthetics with noor just liquid crystal (LCT) skin T moni-tors. In 1987, the North American MHRegistry was established to study malignanthyperthermia (MH) epidemiology toimprove diagnosis, treatment, and preven-tion. The AMRA (adverse metabolic and/ormusculoskeletal reaction to anesthesia)form gathers data from anesthesia provid-ers. We analyzed AMRA data to determinewhen T signs occurred and whether Tprobe type affected time to beginning MHtreatment.

October 18, 20082:00 PM - 4:00 PM, Room Hall E2-Area ISerious Complications Associated withMalignant Hyperthermia Events: ANAMH Registry of MHAUS StudyMarilyn G. Larach, M.D., F.A.A.P., GregoryC. Allen, M.D., F.R.C.P., Barbara W.Brandom, M.D., Gerald A. Gronert, M.D.,Erik B. Lehman, M.S. Department ofAnesthesiology, Penn State College ofMedicine, Hershey, PAGOALS: In 1987, The North AmericanMH Registry (NAMHR) was established tostudy malignant hyperthermia (MH)epidemiology to improve diagnosis,treatment and prevention. The AMRA(adverse metabolic and/or musculoskeletalreaction to anesthesia) form gathers datafrom anesthesia providers. We analyzedAMRA data to determine MH complicationrate for: consciousness level change/coma,disseminated intravascular coagulation,hepatic dysfunction, pulmonary edema,and renal dysfunction. We studied whetherpatient, adverse anesthetic, or MH treat-ment characteristics were associated withserious complications.

October 19, 20082:00 PM - 4:00 PM, Room Hall E2-Area IA Novel Ryanodine Receptor (RYR1)Variant in Two Children with FatalSpontaneous MH like EventsS. Muldoon, M.D., N. Sambuughin, Ph.D.,M. Bayarsaikhan, Ph.D., R. Dirksen, Ph.D.,S. Karan, M.D. Anesthesiology, USUHS,Bethesda, MdBackground: Mutations in the ryanodinereceptor type 1 gene (RYR1) cause malig-nant hyperthermia (MH) on exposure topotent volatile anesthetics. Sudden deathin people with RYR1 mutations occurswith exertion, high environmental tem-peratures and febrile illnesses. We presenttwo children who are unrelated but share aRYR1 variant; both died during a febrileillness without exposure to anesthesia.

October 20, 20089:00 AM - 11:00 AM, Room Hall E2-Area BA Novel Minimally-Invasive MalignantHyperthermia (MH) Diagnostic Test inSwineSaiid Bina, Ph.D., Rolf Bunger, M.D.,Ph.D., Richard C. Kipp, M.D., FernandoTovar, M.D., John Capacchoine, M.D.Anesthesiology, Uniformed ServicesUniversity of the Health Sciences,Bethesda, MD

October 19, 20082:00 PM - 4:00 PM, Room Hall E2-Area IThe Causative MH MutationThr2206Met (Ryr1) May Be Associatedwith a Mild MyopathyHenrik Rueffert, M.D., Ralf Schober, M.D.,Markus Wehner, M.D., Vera Ogunlade,M.D., Udo X. Kaisers, M.D. Dept. ofAnesthesiology and Intensive Care Medi-cine, University Hospital, Leipzig, Ger-many

October 19, 20082:00 PM - 4:00 PM, Room Hall E2-Area IThree Mutations in Ryanodine1 Gene inan MH FamilyYasuko Ichihara, M.D., Ph.D., HirosatoKikuchi, M.D., Ph.D., Keiko Mukaida,M.D., Ph.D., Ichizo Nishino, M.D., Ph.D.,Yayoi Narita, M.D., Ph.D. Anesthesiology,Tokyo-Rinkai Hospital, Edogawa-ku,Tokyo, Japan

Continued on page 3

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October 19, 20082:00 PM - 4:00 PM, Room Hall E2-Area IVolatile Anesthetics Induce DifferentContractures in Muscle Bundles ofMH Susceptible IndividualsThomas Metterlein, M.D., FrankSchuster, M.D., Helga Horbaschek,M.D., Martin Anetseder, M.D., NorbertRoewer, M.D. Department Anesthesiol-ogy, University Hospital Wuerzburg,Wuerzburg, Germany

October 20, 20089:00 AM - 11:00 AM, Room HallE2-Area EStatin-Induced Myotoxicity inMalignant Hyperthermia SusceptibleSwine MuscleJohn F. Capacchione, M.D., Saiid Bina,Ph.D., Dale F. Szpisjak, M.D., David A.Fish, M.D., Timothy Bruehwiler, B.S.Anesthesiology, Uniformed ServicesUniversity of the Health Sciences,Bethesda, Maryland

October 18, 20082:00 PM - 4:00 PM, Room HallE2-Area NPreparation of the Datex-OhmedaAestiva Anesthetic Machine forMalignant Hyperthermia CasesKelly S. Shinkaruk, M.D., Kevin Nolan,M.D., F.R.C.P.C., Marylou Crossan, B.S.Anesthesiology, University of Ottawa,Ottawa, ON, Canada

October 20, 20089:00 AM - 11:00 AM, Room HallE2-Area BA Novel Minimally-Invasive In VitroDiagnostic Test for MalignantHyperthermia in HumansSaiid Bina, Ph.D., John Capacchione,M.D., Giovana Tosato, M.D., RolfBunger, M.D., Ph.D., Sheila Muldoon,M.D. Anesthesiology, UniformedServices University of the HeathSciences, Bethesda, MD

October 19, 20082:00 PM - 4:00 PM, Room Hall E2-Area ISkeletal Uncoupling Protein 3Expression in MDMA ("Ecstasy")Induced Malignant Hyperthermia ofSwine

Christiane Hoetzel, M.D., Mark U.Gerbershagen, M.D., Ph.D., MBA,Sascha Burmester, M.D., Ute Schäfer,Ph.D., Frank Wappler, M.D., Ph.D.Department of Anesthesiology andIntensive Care Medicine, University ofWitten-Herdecke, Cologne, Germany

October 19, 20082:00 PM - 4:00 PM, Room Hall E2-Area IIs the Skeletal Uncoupling Protein 3Upregulated in Porcine MalignantHyperthermia?Mark U. Gerbershagen, M.D., Ph.D.,MBA, Christiane Hötzel, M.D., Jan K.Schütte, M.D., Ute Schäfer, Ph.D.,Frank Wappler, M.D., Ph.D.Departement of Anesthesiology andIntensive Care Medicine, University ofWitten/Herdecke, Cologne, Germany

October 19, 20082:00 PM - 4:00 PM, Room Hall E2-Area I

Impact of a Quality Procedure on theSurvival of Malignant HyperthermiaCasesRenee Krivosic-Horber, M.D., ThierryDepret, M.D., Bruno Marciniak, M.D.,Lia Mazzoli, M.D., Julia Salleron, Ph.D.Anesthesiology and Malignant Hyper-thermia, Hospital Jeanne de Flandre,Lille, France

October 19, 20082:00 PM - 4:00 PM, Room Hall E2-Area ISystemic Effects of MDMA ("Ec-stasy") in Malignant HyperthermiaSusceptible and Normal SwineJan Karl Schuette, M.D., Mark U.Gerbershagen, M.D., Ph.D., AlexanderStarosse, M.D., Sandra Becker, M.D.,Frank Wappler, M.D., Ph.D. Depart-ment of Anesthesiology and IntensiveCare Medicine, University of Witten-Herdecke, Cologne, Germany

You are cordially invited to attend the upcoming

MALIGNANT HYPERTHERMIAASSOCIATION OF THE UNITED STATES

Recognition Reception

In honor of the2008 Hotline Partnership Award

given to highlight the partnership betweena Hotline Consultant and a Medical Professional

contacting the MH Hotline for help

Daniel Massik – MHAUSAnesthesiology Residents Award

andMHAUS Media Award

6:00 - 8:00 p.m.Monday, October 20, 2008

Rosen Plaza HotelSalon 4 Room, 2nd Floor9700 International Drive

Orlando, FL

Continued from page 2

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interested in partnering withMHAUS.”

JHP, (www.jhppharma.com),headquartered in New Jersey, is aspecialty pharmaceutical companywhich manufactures and sells phar-maceutical products, primarilyaseptic injectable products into thehospital segment, and providescontract manufacturing of sterileproducts for innovator pharmaceuti-cal companies. JHP is a privatecompany wholly owned by JHPHoldings, LLC whose equity ownersare Morgan Stanley Principal Invest-ments, Peter Jenkins and StuartHinchen.

SpePharm Holding, B.V.(www.spepharm.com) is a Dutchcompany with its registered office inAmsterdam, and its European opera-tions based in Paris, France.SpePharm is an emerging pan-European specialty pharmaceuticalcompany focused on acquiring,registering and marketing high

medical value specialty medicinesessentially for the hospital market.Particular areas of therapeutic interestare oncology, critical and supportcare. SpePharm was founded inSeptember 2006 by Jean-FrancoisLabbe together with leading lifescience investment firms, TVMCapital and Signet Healthcare Partners(part of the Sanders Morris HarrisGroup). Jean-Francois Labbe is aformer top executive of HoechstMarion Roussel and Park Davis withover 30 years of experience in interna-tional pharmaceutical management.To date SpePharm has an establishedcommercial presence in the U.K.,Germany, Italy, Benelux and theNordic area where it currentlylaunches its first product, Loramyc,for the treatment of oropharyngealcandidiasis in immune-compromisedpatients.

A separate company, U.S.WorldMeds, based in Louisville, KYbegan marketing a generic form ofdantrolene last year.(www.usworldmeds.com)

Continued from front page

To enable product avail-ability during this tran-sition period, the cur-rent ordering processwill continue throughP&GP and the cus-tomer service numberwill remain unchanged(1-800-448-4878) forthe next severalmonths. As well, youcan order Dantrium® IVdirectly from JHP bycalling or faxing yourorder to1-877-547-4547,or emailingcustomerservice@jhppharma.com.

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by Henry Rosenberg, M.D.

As all of you know who arereading this, dantrolene sodium, is“the” drug to treat malignant hyper-thermia (MH). There are someimportant and interesting changesand insights developing with thisdrug that I would like to explore withyou.

First, a bit of history:dantrolene was developed by a smallcompany in Upstate NY, NorwichEaton Pharmaceuticals, not far fromour home office in Sherburne, NY, inthe early 1970s. A very brightscientist, Dr. Keith Ellis, found that amodification of a drug that NorwichEaton had developed for the treat-ment of urinary tract infections,Macrodantin, had rather peculiarproperties. When injected in animals,the animals appeared motionless,muscles flaccid, but still breathing.Curious about this, he did somestudies in the lab and found that thedrug reduced muscle tone, but didnot act on the nerves or the neuro-muscular junction.

Dr. Ellis had been followingthe developing malignant hyperther-mia story and noted that MH was adisorder involving increased muscletone and increased metabolismarising from the muscle. He wasanxious to test the drug in the MHsituation and was put in touch withDr. Gai Harrison in South Africa whowas investigating MH in susceptibleswine. He had tried numerouscompounds in the treatment of MH,with limited success. When hereceived the dantrolene compound,he was astonished to see that the drugrapidly and predictably reversed thesyndrome.

While I was attending the“Second International Workshop onMH” in Denver in 1975, the newswas announced about this wonderful

The Past, Present & Future of Dantrolene

Continued on page 6

compound. However, the drug wasnot yet in an intravenous form, so allsorts of homemade brews weredeveloped using the crusheddantrolene pills.

In about 1982 Procter andGamble Pharmaceuticals (P&GP)acquired Norwich Eaton and devel-oped the intravenous formulation weknow of today. However, the drughad to be approved by the FDA first.So, Mary Elizabeth Kolb was giventhat task. She arranged for the drugto be available to certain centers andwithin a few years about 30 cases ofMH or presumed MH were collected,scrutinized by a panel (I participated)and concluded that the drug wasindeed effective. The drug wasapproved in record time by the FDAin 1979.

It was one of the seminaladvances in the field of anesthesia.(Dantrolene in Human MalignantHyperthermia: A Multicenter Study.Anesthesiology. 56(4):254-262, April1982.)

Intravenous dantrolene is adifficult drug to get into solution.The compound comes as a freezedried powder to which sterile watermust be added. Furthermore, thedrug is packaged in 20mg vials only.For the average person, at least ninevials are needed to be reconstitutedand injected. P&GP and theiradvisors then felt that in order tomake sure an adequate amount of thedrug was available for treatment ofMH, 36 vials should be purchased,no less.

No one could deny thatwithout dantrolene the likelihood ofdying from MH was over 50%, butwith its use, less than 5%.

So, the company andMHAUS, which was created in 1981,began to urge that all hospitals,ambulatory centers, and officesurgery suites using the MH trigger

agents have a full supply of dantroleneavailable. There must be thousands ofpatients whose lives were saved bythis drug over the years.

This is how the situationstood until 2007 when a start upcompany, U.S. WorldMeds, LLC beganto market a generic version ofdantrolene. It was still the samecompound.

This past month P&GPannounced the sale of its product totwo companies, JHP Pharmaceuticalsand SpePharm. The former acquiredthe rights to North America, Australia,New Zealand, Israel and Chile, thelatter to Europe and certain othercountries. They will work with P&GPto insure that the product is availableduring the transition. Both companiesare committed to providing the drugand perhaps improving its formula-tion.

Still, there is yet anothercompany, Lyotropic Therapeutics,based in Virginia that has developed aconcentrated, soluble form ofdantrolene containing 50mg /ml of thedrug. This means no more reconstitu-tion and the entire dose can be storedin a syringe. The compound, calledRyanodex, has been used to treat andreverse MH crises in swine success-fully, but has yet to be approved bythe FDA or the European regulators.However, they are moving ahead withproduct testing. As far as I know ithas not been used in any humans todate.

Competition is always helpfulin improving products and loweringcosts. We now have multiple compa-nies distributing dantrolene andanother with a new formulation. Thiscan only be of benefit for those whodeal with MH.

Meanwhile, there are someother interesting developments

6Continued from page 5regarding the therapeutic value ofdantrolene. It has been known for awhile that in many cases dantrolene iseffective in reversing extreme tem-perature elevation from a variety ofcauses. For example, it has beenused successfully and sometimesdramatically in the treatment ofneuroleptic malignant syndrome andin the treatment of hyperthermia,acidosis and muscle breakdown fromdrugs of abuse such as MDMA(Ecstasy). An animal model ofMDMA toxicity has been developedby researchers Wappler and col-leagues from Cologne, Germany andthey have demonstrated thatRyanodex reverses the biochemicalchanges of MDMA toxicity.

Another peculiar and raresyndrome is extreme temperatureelevation and muscle breakdown innew onset diabetes in young people.A number of case reports has shownthat when this occurs, unlessdantrolene is given, fatality is likely.It is not known whether this syn-drome occurs in MH susceptiblesonly or in those who are not MHsusceptible.

What is the link betweenthese hyperthermic and hypermeta-bolic syndromes and dantrolene? Is ita non-specific effect on reducingmuscle tone which is capable ofgenerating heat or is it a specific effectof dantrolene’s action on the calciumchannel (the ryanodine receptor) towhich it binds as demonstrated byDr. Jerry Parness?

Although this is still specula-tive, the recent finding that theryanodine receptor is involved in thedevelopment of heat-induced MH inthe genetically engineered MHmouse, by Susan Hamilton’s group,may be informative. (RyR1 S-nitrosylation underlies environmentalheat stroke and sudden death inY522S RyR1 knockin mice. Cell.133(1):53-65, 2008) On exposure to

high environmental temperatureleading to high body temperature, avariety of reactive nitrogen com-pounds are produced that bind to theryanodine receptor. At least in themouse model, with the abnormalryanodine receptor, these compoundswill open the channel, therebyreleasing calcium into the cytoplasmwhich leads to all the changes foundin MH.

One possibility is that incertain hypermetabolic states, such asthose that develop in cocaine andEcstasy overdose, even with normalryanodine receptors, the reactiveintermediates may alter the ryanodinereceptor sufficiently to lead to thetypical changes of MH. The investi-gators, Feige, Wappler and colleaguesfrom Cologne, have shown thatMDMA toxicity in even non-MHswine will produce an MH-likepicture that is reversed by dantrolene.

One other intriguing hint onthis subject: from time to time theMH Hotline is called concerning ayoung patient who, after open heartsurgery, develops hyperthermia,acidosis and other signs of MH butwithout a family history of MH. Ifuntreated, the patient becomesprogressively unresponsive to pressordrugs, develops muscle breakdownand may die. There is one report onsuch cases published many years agoin the nowdefunct journal,The AmericanJournal ofAnesthesiology,by investigatorsfrom JohnsHopkins.Another sucharticle by thesame authors is“Creatine kinaseactivity andtemperature inchildren aftercardiac surgery.”

(Journal of Cardiothoracic Anesthesia.2(2):156-63, 1988.) There weresimilarities and differences to MH,but none of the patients were testedfor MH. Dantrolene reverses thissyndrome.

Because this problem is souncommon and there is no animalmodel, there is, to my knowledge, noongoing investigation of the phenom-enon.

Another untapped area is therole of dantrolene in heat stroke.Certainly, most heat stroke is notrelated to MH, but is environmentallyinduced, but there is definite evi-dence that some small number ofpatients who develop heat stroke areMH susceptible.

Unfortunately, this is anotherarea that is virtually devoid of con-trolled scientific studies, except in themilitary where the relationshipbetween heat, exercise, and musclebreakdown is under investigation inthe laboratory of Dr. Pat Deuster atthe Uniformed Services University ofthe Health Sciences.

With the advent of moleculargenetic testing and more widespreadawareness of MH and other drug-induced hyperthermic syndromes, weundoubtedly will learn more aboutdantrolene, its mode of action and itsutility in the treatment of disordersother than classic MH.

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MH Hotline Received Over 3200 Calls In Past YearThe MH Hotline continues to

be one of our strongest programs,receiving in the past year over 3200calls. Primary users of the MHHotline are anesthesiologists andother anesthesia care providerssearching for help in handlingcomplex issues involving patient care.Because some of the MH HotlineConsultants are well known byanesthesiologists, they may be calleddirectly by a doctor.

The percentage of accurateMH diagnosis by the caller continuesto increase.

“We feel the callers arebecoming more and more educatedthrough the educational materialsthat MHAUS provides, via TheCommunicator newsletter, website,exhibits, and panel discussions givenby the Hotline Consultants,” saysHotline Coordinator Gloria Artist.

MHAUS is always interestedin recruiting and training newHotline Consultants. Indeed, if youare a current consultant and knowsomeone who you think would be agreat addition to the team, contactMs. Artist at 607-674-7901 or emailgloria@mhaus.org.

“Once a consultant hasrecommended someone,” says Ms.Artist, “that person is contacted to gettheir curriculum vitae (CV) in orderto be considered as a possible MHHotline Consultant. The CV isreviewed by the Hotline QualityAssurance Committee, and a mentoris partnered with the new consult-ant.”

The mentor acts as an advisorthe first few times the new consultanttakes a call. The mentor reviews andsupplies feedback on the content ofthe reports the new consultantsubmits during a scheduled two-weekcoverage period. This feedback isimportant to the learning process andassures a high degree of quality in the

gathering of important data.Additionally, the new con-

sultant receives a copy of the HotlineConsultant Handbook, a sample copyof the AMRA form for the NorthAmerican MH Registry, copies ofvarious other procedural forms and acopy of the most recent QualityAssurance Review.

“We send them the quarterlyQuality Assurance Review withoutthe answers and have them review itwith their mentor to see how theywould respond in the same situa-tions,” says Ms. Artist. “This givesthem an idea of what kind of casesare coming through on the Hotlineand the correct way to handle them.”

While there is no official jobdescription, the Hotline Consultant isa highly trained medical specialistwho answers phone calls frommedical professionals when theyencounter MH, or suspected MH, in

the field. Volunteering on rotatingshifts, they help callers work throughtheir situations to help them diagnoseand treat MH symptoms.

They serve for many differentreasons. Some are drawn to helptheir colleagues, some see the Hotlineas a way to further serve and protectpatients, and some remember theirown first MH experience and want tobe that calm voice on the end of thephone for someone in need.

“What I like best about mywork with the Hotline is the chanceto speak with health care providersfrom around the country,” said Dr.Margaret Weglinski, a Hotline Con-sultant since 1997, in a recentinterview. “Whether it’s answering astraightforward question about MH ortrying to determine whether or not apatient is experiencing an MHepisode, I find it rewarding to (hope-fully) be of assistance.”

The Lila and Jerry Lewis Memorial FundThere are many special people who take the time each year to remember their loved ones in a way

that helps MHAUS. The people below have made gifts during FY 07-08 (Oct. 2007 - Sept. 2008) inmemory 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

PatronsBrad & Julie Shames

SponsorsArline A. HammerBarry & Beverly KurtzGloria LeonardLenny RobertsMark Zamel

DonorsLarry & Linda Blumenfeld

Allen JacobsSheldon & Doreen QueridoBill & Linda RouseLes & Diane SurfasErven & Beatrice Tallman

FriendsLois SoterGeorge & Miriam Trustman

HonorariaHonor of Marilyn Glassman by Lenord RobertsHonor of the Marriages ofJacey Glassman & Dan Hayes andGreg Glassman & Courtney Grenfell by Diane & Bob WintersHonor of the 60th Birthdays of JudyLevine & Steve Lewis by Marilyn Glassman

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MH Hotline Activity – August – December 2007 by James W.Chapin M.D.During the monthsof August throughDecember 2007,16 volunteerphysicians an-swered 86 calls tothe MH Hotline.Fifty-four involved

clinical situations where signs andsymptoms indicated the potential forthe occurrence of an MH event.Thirty-two calls involved onlyquestions about MH or follow upcalls about a previous MH event.Consultants working the Hotlineduring this period included Drs.Adragna, Allen, Gronert, Litman,Melton, Miller, Millman, Rosenbaum,Rosenberg, Shukry, Skoog, Tobin,Watson, Weglinski and Wong. Elevenof the calls were thought to beprobably or definitely MH by theconsultants. There were no deathsreported from this group. Nine callswere from a hospital setting. Twowere in outpatient surgery centers. Alleleven of the probable or definitecases received dantrolene and twelveof the non-MH or unlikely MH callsreceived dantrolene prior to theHotline call. Calls came from 32states, Guam Naval Hospital and theNaval Hospital in Okinawa, Japan.

Elevated CO2 is an early signof MH and the skeletal muscle is thesource of the CO2. An excess amountof calcium in the skeletal musclecauses increased metabolism produc-ing extraordinarily large amounts ofCO2 and respiratory acidosis. Inaddition to MH, elevated CO2 can becaused by under ventilation, anesthe-sia machine problems such as ex-hausted soda lyme (which removesCO2 from the gas circuit),laparoscopic surgical procedures(there were six reports during thisperiod) where CO2 is insufflated into

the patient’s abdomen to create spaceto do the surgical procedure. CO2 isabsorbed into the patient’s blood-stream. One report during this periodwas an elevated CO2 from a coronaryartery bypass procedure where theyused CO2 insufflation to harvest avein from the leg to use for a coro-nary graft.

Muscle rigidity is a sign ofMH reactions. Eleven patients in thisgroup displayed some rigidity. Sevenhad isolated jaw rigidity; four of theseven had profound jaw rigidity(called trismus) which is highlysuspicious for MH susceptibility.Some patients had body or limbrigidity. Some of the cases werecancelled if the rigidity occurredbefore the surgical incision. Otherscontinued with the operative proce-dure and switched to non-triggeringanesthetic technique. Most of thetrismus reports followed administra-tion of succinylcholine, used formuscle relaxation and trachealintubation. The consultants recom-mended having the patients with jawrigidity observed overnight andwatched for onset of MH. Then theyreferred them to an MH musclebiopsy testing center. Two of therigidity patients were thought to haveMH.

There were two calls regard-ing Neuroleptic Malignant Syndrome(NMS), a condition that mimics MH

but is a reaction to the antipsychoticmedications given to patients withschizophrenia. The antipsychoticmedications lower brain dopaminelevels and some patients develop MH–like symptoms. The antidote isBromocriptine, which increases thedopamine levels in the brain.Dantrolene can lower the temperatureand prevent complications from veryhigh fever. Both calls were referred toconsultants who are experts in NMS.

A call was received by aHotline consultant regarding a patientto be anesthetized later in the day.The patient had polymyositis and wason steroids. The anesthesiologist whocalled had read in Stoelting’s textbookthe recommendation of using a non-triggering technique. The caller askedif polymyositis was associated withMH. The MH Hotline consultant said“no.” In Stoelting’s book “Anesthesiaand Co-Existing Diseases,” SecondEdition, it says: “It has been recom-mended that drugs capable of trigger-ing MH be avoided in these patients(polymyositis) if the serum creatinekinase is increased.” He goes on tosay there could be an abnormalresponse to neuromuscular blockerswith enhanced weakness. (Reference:Brown S, Shupak R.C., Patel C:Neuromuscular blockade in a patientwith active dermatomyositis. Anes-thesiology 1992;77:1031-3).

Meet This Issue’s Hotline ConsultantJames W. Chapin M.D., is Professor ofAnesthesiology, University of NebraskaMedical Center, Omaha, Nebraska. He hasbeen on faculty for over 30 years. He hasbeen a Hotline Consultant over 20 years.UNMC was an MH muscle biopsy center formany years. He worked with Dr. DanWingard on MH research, and he is Directorof Liver Transplant Anesthesia and AnesthesiaResidency Program Coordinator.

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Some Helpful Malignant Hyperthermia TermsCreatine kinaseAn enzyme found in cells, especially musclecells. Normal levels are up to about 200 iu/L.In cases of muscle membrane breakdown, theenzyme leaks out of the cell. This may occurfrom any type of muscle trauma, includingmalignant hyperthermia. After surgery CKlevels may normally rise to 1,000 to 2,000 iu/L. When there is severe muscle damage thelevel may rise to 10,000 or more. At theselevels, the muscle pigment, myoglobin, can beexpected to be elevated in the blood as aresult of muscle damage. In other words,elevated CK is a marker for leakage ofmyoglobin from the cell. Elevated levels ofmyoglobin can lead to temporary or perma-nent kidney damage. After an episode of MHthe CK levels may be mildly or dramaticallyelevated depending in part on the promptnessof treatment. In general, peak levels of CKoccur about 24 hours after injury and may beelevated for days. Hence, in suspected cases ofMH it is important to determine CK levels. Incase of heart muscle damage, CK may beelevated, but this represents a slightly differentform of CK. CK from regular muscle is termedCK MM, from heart muscle, CK-MB.

General anestheticsCompounds that produce loss of conscious-ness, pain relief and amnesia. Generalanesthetics are either gaseous agents such ashalothane, sevoflurane, and desflurane (alltriggers of MH). Nitrous oxide is often used asan adjunct to these agents. It is not a completeanesthetic, and also not an MH trigger. Thereare a variety of agents that are given intrave-nously that also may produce anesthesia suchas the barbiturates (e.g. thiopental), propofol,and ketamine. None are MH triggers. Avariety of other agents are often used duringanesthesia such as the narcotics, benzodiaz-epines (e.g. Valium and Versed) whichproduce pain relief and sedation.

Local anestheticsThese compounds block transmission of nerveimpulses involved in pain sensation. These arethe “caine” drugs - novocaine, bupivicaine,lidocaine, mepivicaine. None trigger MH andare safe to use in the MH susceptibles. Thesedrugs are commonly used by dentists,anesthesiologists, pain physicians andsurgeons among others.

Molecular geneticsGenetics is the study of inheritance. Moleculargenetics is the study of how changes in DNAstructure, such as mutations, affect thefunction of the genes. Molecular, because the

study of DNA entails understanding ofmolecular or submicroscopic changes.

Muscle relaxantsThese are drugs that are more properly termedparalyzing agents. There are two classes ofmuscle relaxants, non-depolarizing anddepolarizing agents based on their mode ofaction. Typical non-depolarizing agents arevecuronium, pancuronium and rocuronium.None are triggers of MH. However, the onedepolarizing agent, succinylcholine is a potenttrigger of MH. These agents are administeredintravenously and are therefore given byanesthesiologists, emergency room physiciansand intensive care physicians.

RhabdomyolysisWhen muscle is damaged and cells aredisrupted, the intracellular constituents beginto leak into the blood stream. This includescreatine kinase, myoglobin and the electrolytepotassium. This is termed rhabdomyolysis.This breakdown may be manifested by musclepain and in extreme cases dark or cola coloredurine.

Tracheal intubation and mainstem intuba-tionIn order to control gas exchange duringanesthesia a plastic tube is often placed in thetrachea (windpipe). This is done usuallywhen the patient is first anesthetized. Oneend of the tube is connected to a ventilator orrespirator to control ventilation. Since thewindpipe bifurcates just below the neck line,if the tube is inserted too deeply, the end maygo into one of the branches of the trachea(usually the right side) and therefore only onelung will be ventilated. This may lead to adecrease in oxygen in the blood, and rarely anincrease in carbon dioxide as well.

LMA – laryngeal mask airwayThis device was introduced into practice onlya few years ago. The device is often usedwhen tracheal intubation is not needed, butcontrol of the airway is desirable. It is a tubethat is so constructed that it does not enter thetracheal but forms a seal around the entranceto the trachea (the glottis). Insertion of theLMA is not as traumatic as insertion of anendotracheal tube and does not require deeplevels of anesthesia or muscle paralysis.

Contracture testThis is the test that is used to determine apatientís susceptibility to MH. Muscle istaken from the thigh (about the size of afingernail) and cut into strips of about one

half inch long and mounted in a chamber andmade to contract by electrical stimulation.When the anesthetic halothane is introducedin the chamber the muscle not only contractsbut develops a contracture (a sustainedcontraction). This contracture is typical forMH susceptibles. The drug caffeine may alsolead to an abnormal contracture, as may avariety of other anesthetics. Although the testis highly accurate, the inconvenience of thebiopsy and the requirement for specialtechnical expertise limits its use.

Neuroleptic malignant syndrome (NMS)This is a constellation of signs and symptomsmarked by high fever, muscle breakdown,acidosis, muscle rigidity and other signssimilar to MH. However, the syndrome isinduced by drugs used in the treatment ofmajor psychiatric disorders. These drugsinclude thorazine, haloperidol (Haldol),olanzapine and other potent antipsychoticagents. The syndrome is not inherited anddoes not predispose to MH. That is, there isno greater frequency of MH in those experi-encing NMS or vice versa. Interestingly,dantrolene is effective in treating NMS. Thereis no diagnostic test specific for NMSsusceptibility.

Reversal agentsThere are several drugs that can antagonize or“reverse” the effects of other drugs. The drug,Narcan, or naloxone reversed the effect ofnarcotics (including the analgesia from theseagents). Some drugs, neostigmine andpyridostigmine and edrophonium, reverse theeffects of the non-depolarizing muscleparalyzing drugs.

Oxygen saturationThe main purpose of the blood is to carryOxygen to the various parts of the body alongwith nutrients and to remove carbon dioxideand other byproducts of metabolism. Theamount of Oxygen in a given quantity ofblood is not easy to measure, however thesaturation level of the hemoglobin in theblood that carries the Oxygen can easily bemeasured with an external probe attached to apulse oximeter. Normal Oxygen saturation isabove 98%. At levels below about 90%insufficient oxygen is delivered to the blood,which may lead to many problems.

Triggering agents for MHThese are drugs that will lead to the onset ofMH. These include all the potent gasanesthetics and succinylcholine.

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Social Networking 101: MHAUS On Facebookby Michael WesolowskiSocial network services focus onbuilding online communities ofpeople who share interests andactivities, or who are interested inexploring the interests and activitiesof others. Major networks such asFacebook, Myspace, Bebo, and Orkutare web-based and provide a varietyof ways for users to share e-mail,instant messages, video, and digitalimages. MHAUS & NMSIS arepresently represented on Facebook.This article addresses the basics ofFacebook.

Facebook is defined by itscreators as: ''a social utility thatconnects people with friends andothers who work, study and livearound them. People use Facebook tokeep up with friends, upload anunlimited number of photos, sharelinks and videos, and learn moreabout the people they meet.''

Though Facebook was onlylaunched in 2004 it has over 50million active members.

First StepThe first step in joining Facebook iscreating a profile. Don't worry, youcan control who is able to see eachindividual part of your profile; justclick on privacy located to the topright of any Facebook page. Click onedit settings for any sections youwant to modify. Go towww.facebook.com to get started.Finding Your Way AroundLayout of Facebook is uniformthroughout the site. The blue baracross the top of the page will alwaysbe there to take you to your ownprofile, and this is where your friendswill be taken if they click on yourname anywhere within the site.Your ProfileYour profile page is where you resideon Facebook. There is a mini-feedwhich is a summary of your recent

activity on Facebook and is updatedautomatically.FriendsFinding friends is the next step, typesomeone's name in the search box tothe top left. If they have a Facebookaccount then they should be in thelist of results. To find them in thefuture you can either type their namein the search box (links will pop upas you type) or click on the friends'link in the blue navigation bar.ApplicationsApplications are programs thatoperate on the Facebook Platform.You might have noticed a couple ofthe Facebook applications already:Photos and Groups. The photoapplication is an easy way to sharepictures with friends. Click on thelink and you will see some photosfrom your friends. You can then tagfriends in the photo; this is basicallyletting Facebook know who is in eachphoto so that the photo can be linkedto their profile pages. The groupapplication is fairly self-explanatory.You can browse groups which peoplehave created, join groups, or evencreate your own. To add applicationsclick the edit link next to applicationsin the left-hand navigation bar. This iswhere both MHAUS Cause andGroup pages can be found.

In addition, social networksare beginning to be adopted byindustry such as healthcare profes-sionals as a means to manage institu-tional knowledge, disseminate peer-to-peer knowledge and to highlightindividual physicians and institu-tions. The advantage of using adedicated medical social networkingsite is that all the members arescreened against the state licensingboard list of practitioners.

The role of social networks isespecially of interest to pharmaceuti-cal companies who spend approxi-

mately "32 percent of their marketingdollars" attempting to influence theopinion leaders of social networks.

A new trend is emerging withsocial networks created to help itsmembers with various physical andmental ailments. For people sufferingfrom life altering diseases,“PatientsLikeMe” offers its membersthe chance to connect with othersdealing with similar issues andresearch patient data related to theircondition. For alcoholics and addicts,“SoberCircle” gives people in recoverythe ability to communicate with oneanother and strengthen their recoverythrough the encouragement of otherswho can relate to their situation.“Daily Strength” is also a website thatoffers support groups for a wide arrayof topics and conditions, includingthe support topics offered by“PatientsLikeMe” and “SoberCircle.”

SuccessAll Social network services rely onpeople who share interests andactivities keeping their content fresh;so if you do join Facebook, make sureto interact often. One way to do thatis to stop by the MHAUS Cause Pageand write on the Wall. You’ll findpeople from all over the world there,and make sure to ask your friends tojoin, too. Happy Facebooking!

Do you have an MHsurvival story? Tell usabout it and include apicture. Visit the MHAUSwebsite at www.mhaus.organd click on “Faces ofMH” in the lower left ofthe patient or professionalsection, located just abovethe “Facebook” link.

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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. The program is arranged so it canalso be used as a self-study program toenhance individual knowledge of MHand the risks involved.

Cost is $165 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

NONPROFITUS POSTAGE PAID

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!

❑ NMSIS Announces PromisingNew Investigators Travel Schol-arship for 2008-2009The Neuroleptic Malignant Syn-drome Information Service

(NMSIS) is pleased to announcea competition to recognizepromising new investigatorsbased on a scholarly paperaddressing “New insights onpsychotropic drug safety andside effects.”

Consistent with itsmission to advance pharmaco-therapy and patient safety,NMSIS offers two travel scholar-ships to promote education andresearch by early career psychia-trists. Two prizes of $2000 and$1000 will be awarded towardtravel costs to attend the Ameri-can Psychiatric AssociationMeeting in San Francisco, CA, inMay 2009, where the scholar-ships will be presented.

Papers should addressspecific issues related to thescholarship theme and be nolonger than 15 double-spacedtyped pages in length. Literature

reviews, case reports, or originalstudies that are not in press orpublished are acceptable. Primaryauthor must be a student, residentor fellow. Papers will be judged onoriginally, scholarship, relevanceand methodology.

To participate, papers andcurriculum vitae of the primaryauthor must be submitted byFebruary 6, 2009 to Ms. DianneDaugherty, 11 East State,Sherburne, NY 13460, fax607-674-7910, or via email todianne@mhaus.org.

Winners will be announcedby March 6, 2009. Last year’swinners were, first place, Dr. TedSatterthwaite, who authored, “Riskof Extrapyramidal Symptoms withIntramuscular Antipsychotics: ASystematic Review,” and, secondplace, Dr. Alejandra Clark, whoauthored, “The Use of Antidepres-sants in Bipolar Illness.”