Association between known or strongly suspected malignant hyperthermia susceptibility and postoperative outcomes: an observational population-based study

  • Philip M. JonesEmail author
  • Britney N. Allen
  • Richard A. Cherry
  • Luc Dubois
  • Kelly N. Vogt
  • Salimah Z. Shariff
  • Krista M. Bray Jenkyn
  • Sheila Riazi
  • Duminda N. Wijeysundera
Reports of Original Investigations



Whether current standards of care management for malignant hyperthermia (MH)-susceptible patients result in acceptable postoperative clinical outcomes at a population level is not known. Our objective was to determine if patients with susceptibility to MH experienced similar outcomes as patients without MH susceptibility after surgery under general anesthesia.


This was a retrospective, population-based cohort study from 1 April 2009 until 31 March 2016 in the Canadian province of Ontario. Participants were adults who underwent common in- or outpatient surgeries under general anesthesia. The exposure studied was either known or strongly suspected MH susceptibility as determined by usage of a specific physician billing code. The primary outcome was a composite of all-cause death, hospital readmission, or major postoperative complications, all within 30 postoperative days. Separate analyses were employed, based on whether a patient had in- or outpatient surgery. Inverse probability of exposure weighting based on the propensity score was used to estimate adjusted exposure effects.


The cohort included 957,876 patients (583,254 in- and 374,622 outpatients). There were 2,900 (0.3%) patients with a known or strong suspicion of MH susceptibility. For inpatients, the primary outcome occurred in 146,192 (25.1%) of the non-MH-susceptible group and in 337 (20.1%) of the MH-susceptible group (unadjusted risk difference [RD], −5.0%; 95% confidence interval [CI], −6.9 to −3.1%; P < 0.001). In outpatients, the primary outcome occurred in 9,146 (2.4%) of the non-MH-susceptible group and in 32 (2.6%) of the MH-susceptible group (RD, 0.2%; 95% CI, −0.7 to 1.1%; P = 0.72). After adjustment, MH susceptibility was not associated with the primary outcome in either the inpatients (adjusted risk difference [aRD], 1.2%; 95% CI, −1.3 to 3.6%; P = 0.35) or outpatients (aRD, −0.1%; 95% CI −1.0 to 0.9%; P = 0.90).


Among adults in Ontario who underwent common surgeries under general anesthesia from 2009 to 2016, known or strongly suspected MH was not associated with a higher risk of adverse postoperative outcomes. These findings support the current standard of care management for MH-susceptible patients.

Association entre une susceptibilité connue ou fortement suspectée à l’hyperthermie maligne et l’évolution postopératoire : une étude observationnelle de population



Nous ignorons si les normes actuelles de gestion des soins de patients susceptibles d’hyperthermie maligne (HM) aboutissent à des résultats cliniques postopératoires acceptables à l’échelle d’une population. Notre objectif a été de déterminer si des patients présentant une susceptibilité à l’HM présentaient une évolution comparable à celle des patients non connus susceptibles après chirurgie sous anesthésie générale.


Il s’agissait d’une étude de cohorte rétrospective, basée sur une population de la province canadienne de l’Ontario allant du 1er avril 2009 au 31 mars 2016. Les participants étaient des adultes, hospitalisés ou ambulatoires, ayant subi des interventions sous anesthésie générale. L’exposition étudiée était une susceptibilité à l’HM connue ou fortement suspectée, déterminée par l’utilisation d’un code de facturation spécifique des médecins. Le critère d’évaluation principal était un critère composite incluant les décès toutes causes confondues, les réadmissions hospitalières ou les complications postopératoires majeures qui étaient survenus dans un délai de 30 jours postopératoires. Des analyses séparées ont été utilisées, selon que les patients avaient été hospitalisés ou opérés en chirurgie d’un jour. La probabilité inverse de la pondération de l’exposition basée sur le score pour la propension a servi à estimer les effets ajustés de l’exposition.


La cohorte a inclus 957 876 patients (583 254 patients hospitalisés et 374 622 patients ambulatoires). Parmi eux, 2 900 patients (0,3 %) avaient une susceptibilité à l’HM connue ou fortement suspectée. Pour les patients hospitalisés, le critère d’évaluation principal est survenu chez 146 192 (25,1 %) des patients du groupe non susceptible d’HM et chez 337 (20,1 %) patients du groupe susceptible d’HM (différence de risques [DR] non ajustée : −5,0 %; intervalle de confiance [IC] à 95 % : −6,9 % à −3,1 %; P < 0,001). Pour les patients ambulatoires, le critère d’évaluation principal est survenu chez 9 146 (2,4 %) des patients du groupe non susceptible d’HM et chez 32 (2,6 %) patients du groupe susceptible d’HM (différence de risques [DR] non ajustée : 0,2 %; IC à 95 % : −0,7 % à 1,1 %; P = 0,72). Après ajustement, la susceptibilité à l’HM ne s’est pas avérée associée au critère d’évaluation principal dans le groupe de patients hospitalisés (différence de risques ajustée [DRa], 1,2 %; IC à 95 % : −1,3 % à 3,6 %; P = 0,35) ou dans le groupe de patients ambulatoires (DRa : −0,1 %; IC à 95 % : −1,0 % à 0,9 %; P = 0,90).


Parmi les adultes de la province de l’Ontario ayant subi des interventions chirurgicales usuelles sous anesthésie générale entre 2009 et 2016, l’HM connue ou fortement suspectée n’a pas été associée à un plus grand risque d’évolution postopératoire défavorable. Ces constatations sont en faveur du maintien des normes des soins actuels pour la gestion des patients susceptibles d’HM.



The data were analyzed by Britney Allen, MSc (Biostatistician at ICES Western), and Philip Jones, MD MSc, both of whom had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Duminda N. Wijeysundera is supported in part by a New Investigator Award from the Canadian Institutes of Health Research. DNW and SR are both supported in part by a Merit Award from the Department of Anesthesia at the University of Toronto.

Conflicts of interest

None of the authors have any conflicts of interest to declare.

Editorial responsibility

This submission was handled by Dr. Hilary P. Grocott, Editor-in-Chief, Canadian Journal of Anesthesia.

Author contributions

All authors contributed substantially to the study’s conception, design, interpretation of data, and drafting the article. Philip M. Jones, Britney N. Allen, Salimah Z. Shariff, Krista M. Bray Jenkyn, and Duminda N. Wijeysundera contributed substantially to data acquisition and analysis.


This study was supported by the Department of Anesthesia & Perioperative Medicine at the University of Western Ontario. This project was conducted at the Institute for Clinical Evaluative Sciences (ICES) Western Site. ICES is funded by annual grants from the Ontario Ministry of Health and Long-term Care (MOHLTC). Core funding for ICES Western is provided by the Academic Medical Organization of Southwestern Ontario (AMOSO), the Schulich School of Medicine and Dentistry (SSMD), The University of Western Ontario, and the Lawson Health Research Institute (LHRI). The opinions, results, and conclusions are those of the authors and are independent from the funding sources. No endorsement by ICES, AMOSO, SSMD, LHRI, or the MOHLTC is intended or should be inferred. Parts of this material are based on data and information compiled and provided by the Canadian Institute for Health Information (CIHI). The analyses, conclusions, opinions, and statements expressed in the material are those of the authors and not necessarily those of CIHI.

Role of the sponsors statement

Neither the ICES nor the Ontario MOHLTC had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Supplementary material

12630_2018_1250_MOESM1_ESM.pdf (918 kb)
Supplementary material 1 (PDF 917 kb)


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Copyright information

© Canadian Anesthesiologists' Society 2018

Authors and Affiliations

  • Philip M. Jones
    • 1
    • 2
    • 11
    Email author
  • Britney N. Allen
    • 3
  • Richard A. Cherry
    • 1
  • Luc Dubois
    • 4
  • Kelly N. Vogt
    • 2
    • 4
  • Salimah Z. Shariff
    • 3
    • 5
  • Krista M. Bray Jenkyn
    • 3
  • Sheila Riazi
    • 6
    • 7
  • Duminda N. Wijeysundera
    • 6
    • 7
    • 8
    • 9
    • 10
  1. 1.Department of Anesthesia & Perioperative MedicineUniversity of Western OntarioLondonCanada
  2. 2.Department of Epidemiology & BiostatisticsUniversity of Western OntarioLondonCanada
  3. 3.Institute for Clinical Evaluative Sciences, Western Site (ICES Western)LondonCanada
  4. 4.Department of SurgeryUniversity of Western OntarioLondonCanada
  5. 5.Arthur Labatt School of NursingUniversity of Western OntarioLondonCanada
  6. 6.Department of Anesthesia and Pain ManagementToronto General HospitalTorontoCanada
  7. 7.Department of AnesthesiaUniversity of TorontoTorontoCanada
  8. 8.Li Ka Shing Knowledge Institute of St. Michael’s HospitalTorontoCanada
  9. 9.Institute of Clinical Evaluative Sciences, Central Site (ICES Central)TorontoCanada
  10. 10.Institute of Health Policy Management and EvaluationUniversity of TorontoTorontoCanada
  11. 11.London Health Sciences CentreUniversity HospitalLondonCanada

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