Early clinical signs, triggering agents, time to onset of reaction, mortality and methods of treatment were identified in 123 suspected malignant hyperthermia reactions. In vitro contracture test results were compared with clinical signs and the Malignant Hyperthermia Clinical Grading Scale. Increased end-tidal carbon dioxide is the earliest sign when not preceded by masseter spasm. Earlier diagnosis reduces the incidence of rigidity and severe metabolic acidosis. The combination of suxamethonium and a potent volatile anaesthetic agent triggers an earlier reaction compared with a volatile agent alone. There has been zero mortality since 1981, essentially due to a combination of advanced monitoring capability, increased anaesthetist awareness of malignant hyperthermia, and dantrolene availability.
DNA analysis has identified nine New Zealand families with ryanodine receptor gene mutations. A positive DNA test indicates malignant hyperthermia susceptibility with “causative” mutations but discordance requires that negative DNA tests are confirmed with in vitro contracture test. This test also demonstrated the shortcomings of the Malignant Hyperthermia Clinical Grading Scale.
SiggD.C., IaizzoP.A.Malignant hyperthermia phenotype. Hypotension induced by succinylcholine in susceptible swine.Anesthesiology2000; 92: 1777–1788.
15.
RosenbergH., FletcherJ.E.An update on the malignant hyper-thermia syndrome.Ann Acad of Med1994; 23: 84–97 (Suppl).
16.
MaeharaY., MukaidaK., KawamotoM., YugeO.Review of fatal malignant hyperthermia cases since 1990 in Japan.IXth International Workshop on Malignant Hyperthermia, Copenhagen 1999.
17.
GarridoS., FragaM., MartinM.J., BeldaJ.Malignant hyper-thermia during desflurane-succinylcholine anesthesia for orthopaedic surgery.Anesthesiology1999; 90: 1208–1209.
18.
HopkinsP.M.Malignant Hyperthermia: advances in clinical management and diagnosis.Br J Anaesth2000; 85: 118–128.
19.
WapplerF., FiegeM., SteinfathM.Evidence for susceptibility to malignant hyperthermia in patients with exercise-induced rhabdomyolysis.Anesthesiology2001; 94: 95–100.
20.
DavisM., JamesD., NorgateM.Malignant hyperthermia associated with exercise-induced rhabdomyolysis, congenital abnormalities and a novel RYR1 mutation in New Zealand and Australian pedigrees.Br J Anaesth (in press).
21.
GronertG.A., HildeJ.H.Variations in onset of porcine malignant hyperthermia.Anesth Analg1981; 60: 499–503.
22.
GronertG.A., HildeJ.H., TheyeR.A.Porcine malignant hyperthermia induced by halothane and succinylcholine.Anesthesiology1976; 44: 124–132.
23.
FroemmingG.R., OhlendieckK.The role of the ion-regulatory membrane proteins of excitation-contraction coupling and relaxation in inherited muscle diseases.Front Biosci2001; 6: 65–74.
BrownR.L., PollockA.N., CouchmanK.G.A novel receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree.Hum Mol Genet2000; 9: 1515–1524.
26.
KolbM.E., HorneM.L., MartzR.Dantrolene in human malignant hyperthermia.Anesthesiology1982; 56: 254–262.
27.
LarachM.G., SimonL.J., AllenG.C., The North American Malignant Hyperthermia Registry. Safety and efficacy of dantrolene sodium for the treatment of malignant hyper-thermia events.Anesthesiology1993; 79: A1079.
28.
FlewellenE.H., NelsonT.E., JonesW.P., ArensJ.F., WagnerD.L.Dantrolene dose response in awake man: Implications for management of malignant hyperthermia.Anesthesiology1983; 59: 275–280.
29.
Malignant Hyperthermia Association United States. Suggested therapy for malignant hyperthermia emergency2000. (poster).
30.
Procter and Gamble datasheet.Dantrium Intravenous (dantro-lene sodium for injection) 2001.
31.
BlankJ.W., BoggsS.D.Successful treatment of an episode of malignant hyperthermia using a large dose of dantrolene.J Clin Anesth1993; 5: 69–72.
32.
IsaacsH., BadenhorstM.False-negative results with muscle caffeine halothane contracture testing for malignant hyper-thermia.Anesthesiology1993; 79: 5–9.
33.
WedelD.J., NelsonT.E.Malignant hyperthermia—diagnostic dilemma: False-negative contracture responses with halothane and caffeine alone.Anesth Analg1994; 78: 787–792.
34.
OrdingH., BrancadoroV., CozzolinoS.In vitro contracture test for diagnosis of malignant hyperthermia following the protocol of the European MH Group: results of testing patients surviving fulminant MH and unrelated low-risk subjects. The European Malignant Hyperthermia Group.Acta Anaesthesiol Scand1997; 41: 955–966.
35.
ChristiaensF., GeptsE., D'HaeseJ., CamuF.Malignant hyper-thermia suggestive hypermetabolic syndrome at emergence from anesthesia.Acta Anaesthesiologica Belgica1995; 46: 93–97.
36.
AllenG.C., LarachM.G., KunselmanA.R., The North American Malignant Hyperthermia Registry. The sensitivity and specificity of the caffeine-halothane contracture test.Anes-thesiology1998; 88: 579–588.
37.
Von RichthofenV., WapplerF., FiegeM., ScholzJ., Schulte am EschJ.Can the clinical grading scale improve prediction of malignant hyperthermia susceptibly? XVIth Annual Meeting, European Malignant Hyperthermia Group, Nijmegen, Netherlands May 1997.
38.
IslanderG., BendixenD., Ranklev TwetmanE., OrdingH.Results of in vitro contracture testing of both parents of malignant hyperthermia susceptible probands.Acta Anaesthesiol Scand1996; 40: 579–584.
39.
IslanderG., Ranklev TwetmanE.Comparison between the European and North American protocols for diagnosis of malignant hyperthermia susceptibility in humans.Anesth Analg1999; 88: 1155–1160.
40.
McCarthyT.V., QuaneK.A., LynchP.J.Ryanodine receptor mutations in malignant hyperthermia and central core disease.Hum Mutat2000; 15: 410–417.
41.
RichterM., SchleithoffL., DeufelT., Lehmann-HornF., Herrmann-FrankA.Functional characterisation of a distinct ryanodine receptor mutation in human malignant hyper-thermia-susceptible muscle.J Biol Chem1997; 272: 5256–5260.
42.
TongJ., OyamadaH., DemaurexN., GrinsteinS., McCarthyT.V., MacLennanD.H.Caffeine and Halothane sensitivity of intra-cellular Ca2+ release is altered by 15 calcium release channel (ryanodine receptor) mutations associated with malignant hyperthermia and/or central core disease.J Biol Chem1997; 272: 26332–26339.
43.
ChamleyD., PollockN.A., StowellK.M., BrownR.L.Malignant hyperthermia in infancy and identification of novel RYR1 mutation.Br J Anaesth2000; 84: 500–504.
44.
LynchP.L., TongJ., LehaneM.A mutation in the transmembrane/luminal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease.Proc Natl Acad Sci USA1999; 96: 4164–4169.
45.
FardeauM., LunardiJ.An autosomal dominant congenital myopathy with cores and rods is associated with a neomutation in the RYR1 gene encoding the skeletal muscle ryanodine receptor (In Process Citation).Hum Mol Genet2000; 9: 2599–2608.
46.
ScacheriP.C., HoffmanE.P., FratkinJ.D.A novel ryanodine receptor gene mutation causing both cores and rods in congenital myopathy.Neurology2000; 55: 1689–1696.
