title: Malignant hyperthermia deaths related to inadequate temperature monitoring, 2007-2012: a report from the North American malignant hyperthermia registry of the malignant hyperthermia association of the United States.
abstract: BACKGROUND
  AMRA (adverse metabolic or muscular reaction to anesthesia) reports submitted to The North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States from 1987 to 2006 revealed a 2.7% cardiac arrest and a 1.4% death rate for 291 malignant hyperthermia (MH) events. We analyzed 6 years of recent data to update MH cardiac arrest and death rates, summarized characteristics associated with cardiac arrest and death, and documented differences between early and recent cohorts of patients in the MH Registry. We also tested whether the available data supported the hypothesis that risk of dying from an episode of MH is increased in patients with inadequate temperature monitoring.
  
  
  METHODS
  We included U.S. or Canadian reports of adverse events after administration of at least 1 anesthetic drug, received between January 1, 2007, and December 31, 2012, with an MH clinical grading scale rank of "very likely MH" or "almost certain MH." We excluded reports that, after review, were judged to be due to pathologic conditions other than MH. We analyzed patient demographics, family and patient anesthetic history, anesthetic management including temperature monitoring, initial dantrolene dose, use of cardiopulmonary resuscitation, MH complications, survival, and reported molecular genetic DNA analysis of RYR1 and CACNA1S. A one-sided Cochran-Armitage test for proportions evaluated associations between mode of monitoring and mortality. We used Miettinen and Nurminen's method for assessing the relative risk of dying according to monitoring method. We used the P value of the slope to evaluate the relationship between duration of anesthetic exposure before dantrolene administration and peak temperature. We calculated the relative risk of death in this cohort compared with our previous cohort by using the Miettinen and Nurminen method adjusted for 4 comparisons.
  
  
  RESULTS
  Of 189 AMRA reports, 84 met our inclusion criteria. These included 7 (8.3%) cardiac arrests, no successful resuscitations, and 8 (9.5%) deaths. Of the 8 patients who died, 7 underwent elective surgeries considered low to intermediate risk. The average age of patients who died was 31.4 ± 16.9 years. Five were healthy preoperatively. Three of the 8 patients had unrevealed MH family history. Four of 8 anesthetics were performed in freestanding facilities. In those who died, 3 MH-causative RYR1 mutations and 3 RYR1 variants likely to have been pathogenic were found in the 6 patients in whom RYR1 was examined. Compared to core temperature monitoring, the relative risk of dying with no temperature monitoring was 13.8 (lower limit 2.1). Compared to core temperature monitoring, the relative risk of dying with skin temperature monitoring was 9.7 (1.5). Temperature monitoring mode best distinguished patients who lived from those who died. End-tidal CO2 was the worst physiologic measure to distinguish patients who lived from those who died. Longer anesthetic exposures before dantrolene were associated with higher peak temperatures (P = 0.00056). Compared with the early cohort, the recent cohort had a higher percentage of MH deaths (4/291 vs 8/84; relative risk = 6.9; 95% confidence interval, 1.7-28; P = 0.0043 after adjustment for 4 comparisons).
  
  
  CONCLUSIONS
  Despite a thorough understanding of the management of MH and the availability of a specific antidote, the risk of dying from an MH episode remains unacceptably high. To increase the chance of successful MH treatment, the American Society of Anesthesiologists and Malignant Hyperthermia Association of the U.S. monitoring standards should be altered to require core temperature monitoring for all general anesthetics lasting 30 minutes or longer.
authors.affiliation: From *The North American Malignant Hyperthermia Registry of the Malignant Hyperthermia Association of the United States, Pittsburgh, Pennsylvania; †Department of Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania; ‡Olympia Anesthesia Associates, Olympia, Washington; §Department of Anesthesiology and Pain Medicine, University of California at Davis, Davis, California; and ∥Department of Public Health Sciences, Penn State College of Medicine, Hershey, Pennsylvania.
authors.forename: Marilyn Green
authors.initials: MG
authors.lastname: Larach
authors.forename: Barbara W
authors.initials: BW
authors.lastname: Brandom
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Allen
authors.forename: Gerald A
authors.initials: GA
authors.lastname: Gronert
authors.forename: Erik B
authors.initials: EB
authors.lastname: Lehman
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000768:Anesthesia, General / Q000009:adverse effects / Q000401:mortality*; D001833:Body Temperature Regulation; D015220:Calcium Channels / Q000235:genetics; D020746:Calcium Channels, L-Type; D002170:Canada / Q000453:epidemiology; D002423:Cause of Death; D005260:Female; D020022:Genetic Predisposition to Disease; D006323:Heart Arrest / Q000401:mortality; D006801:Humans; D008297:Male; D008305:Malignant Hyperthermia / Q000175:diagnosis / Q000235:genetics / Q000401:mortality* / Q000503:physiopathology; D008875:Middle Aged; D016343:Monitoring, Intraoperative / Q000009:adverse effects / Q000401:mortality*; D009154:Mutation; D011237:Predictive Value of Tests; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D019837:Ryanodine Receptor Calcium Release Channel / Q000235:genetics; D062125:Thermometry / Q000009:adverse effects / Q000401:mortality*; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult
chemical_list: C412223:CACNA1S protein, human; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019837:Ryanodine Receptor Calcium Release Channel