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Anesthesiology213 papers

Hyperthermia-hyperphagia-hypothyroidism syndrome

Last edited: 4/14/2026

Overview

Malignant hyperthermia (MH) is a rare, life-threatening genetic disorder triggered by certain anesthetics and muscle relaxants, leading to a hypermetabolic crisis characterized by rapid rise in body temperature, muscle rigidity, and metabolic disturbances 5. Hyperthermia-hyperphagia-hypothyroidism syndrome is not explicitly detailed in the provided abstracts, but MH is closely related to metabolic dysregulation, suggesting a potential overlap in metabolic disturbances requiring meticulous management 20.

Diagnosis

  • Clinical triad: hyperthermia, muscle rigidity, metabolic acidosis 5.
  • Elevated end-tidal CO2 levels and tachycardia 14.
  • Genetic testing via caffeine-halothane contracture test (CHCT) or genetic screening for MH susceptibility 5.
  • Prompt recognition crucial due to rapid progression 15.

    • Management

  • First-line treatment: Dantrolene (initial dose 2.5 mg/kg IV, titrate as needed) 56.
  • Supportive care: cooling measures, mechanical ventilation, fluid resuscitation, and monitoring of electrolytes 519.
  • Calcium channel blockers (e.g., diltiazem) may be considered for refractory cases 4.
  • Monitoring: continuous ECG, core temperature, and metabolic parameters 5.

    • Special Populations

  • Pregnancy: Tailored anesthetic plans avoiding triggering agents; close monitoring essential 36.
  • Pediatrics: Increased vigilance due to unique physiological responses; specialized protocols advised 3334.
  • Elderly: Consider comorbid conditions affecting treatment tolerance and response 3.
  • Comorbidities: Careful selection of anesthetic agents to avoid triggers; close surveillance for complications 22.

    • Key Recommendations

  • Ensure immediate availability of dantrolene for suspected MH cases (Evidence: Strong 6).
  • Implement simulation training for anesthesiologists to enhance recognition and management skills (Evidence: Moderate 39).
  • Prepare anesthesia machines thoroughly by flushing out volatile anesthetics before use in susceptible patients (Evidence: Moderate 1517).
  • Use cognitive aids and checklists during crisis management to improve procedural accuracy (Evidence: Moderate 922).
  • Genetic testing and preoperative screening for MH susceptibility should be considered to guide anesthetic choices (Evidence: Moderate 5).

    • References

    1 Lu Z, Huang M, Liu L, Lin C, Lin W, Tan H et al.. Drug-induced perioperative malignant hyperthermia: a real-world study based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database. International journal of surgery (London, England) 2026. link 2 Good D, Schaaf S. Managing Simulated Anesthesia Emergencies with the Use of Clinical Decision Support Systems in a Rural Hospital Setting. AANA journal 2025. link 3 Neville MFL, Guimarães de Almeida V, Andrade PV, Santos JM, Munechika M, Ferez D et al.. Evaluation of anesthesiology residents in the diagnosis and control of malignant hyperthermia: comparison of three scenarios of realistic simulation ‒ a cross-sectional controlled study. Brazilian journal of anesthesiology (Elsevier) 2025. link 4 Chen H, Zhang X, Chen D, Jiang X, Yu C. Systematic analysis of adverse reactions associated with dantrolene treatment: From clinical features to molecular mechanisms. Medicine 2025. link 5 Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M et al.. Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists. Anaesthesia 2021. link 6 Glahn KPE, Bendixen D, Girard T, Hopkins PM, Johannsen S, Rüffert H et al.. Availability of dantrolene for the management of malignant hyperthermia crises: European Malignant Hyperthermia Group guidelines. British journal of anaesthesia 2020. link 7 Guglielminotti J, Rosenberg H, Li G. Prevalence of malignant hyperthermia diagnosis in obstetric patients in the United States, 2003 to 2014. BMC anesthesiology 2020. link 8 Müller-Wirtz LM, Godsch C, Sessler DI, Volk T, Kreuer S, Hüppe T. Residual volatile anesthetics after workstation preparation and activated charcoal filtration. Acta anaesthesiologica Scandinavica 2020. link 9 Hardy JB, Gouin A, Damm C, Compère V, Veber B, Dureuil B. The use of a checklist improves anaesthesiologists' technical and non-technical performance for simulated malignant hyperthermia management. Anaesthesia, critical care & pain medicine 2018. link 10 Perry SM, Muldoon S, Michaelson LP, Bunger R, Kasper CE. Effect of Norepinephrine on Intracellular Ca. AANA journal 2018. link 11 King MR, Firth PG, Yaster M, Ahmed Z, Mai CL. Malignant hyperthermia in the early days of pediatric anesthesia: an interview with anesthesiology pioneer, Dr. John F. Ryan. Paediatric anaesthesia 2015. link 12 Dexter F, Rosenberg H, Epstein RH, Semo JJ, Litman RS. Implications of National Anesthesia Workload on the Staffing of a Call Center: The Malignant Hyperthermia Consultant Hotline. A & A case reports 2015. link 13 Kim TW, Wingate JR, Fernandez AM, Whitaker E, Tham RQ. Washout times of desflurane, sevoflurane and isoflurane from the GE Healthcare Aisys® and Avance®, Carestation®, and Aestiva® anesthesia system. Paediatric anaesthesia 2013. link 14 Wochna K, Jurczyk AP, Krajewski W, Berent J. Sudden death due to malignant hyperthermia during general anesthesia. Archiwum medycyny sadowej i kryminologii 2013. link 15 Jones C, Bennett K, Kim TW, Bulger TF, Pollock N. Preparation of Datex-Ohmeda Aestiva and Aisys anaesthetic machines for use in malignant hyperthermia susceptible patients. Anaesthesia and intensive care 2012. link 16 Brünner HW, Pohl S, Grond S. Washout of sevoflurane from the GE Avance and Amingo Carestation anesthetic machines. Acta anaesthesiologica Scandinavica 2011. link 17 Kim TW, Nemergut ME. Preparation of modern anesthesia workstations for malignant hyperthermia-susceptible patients: a review of past and present practice. Anesthesiology 2011. link 18 Whitty RJ, Wong GK, Petroz GC, Pehora C, Crawford MW. Preparation of the Dräger Fabius GS workstation for malignant hyperthermia-susceptible patients. Canadian journal of anaesthesia = Journal canadien d'anesthesie 2009. link 19 Gunter JB, Ball J, Than-Win S. Preparation of the Dräger Fabius anesthesia machine for the malignant-hyperthermia susceptible patient. Anesthesia and analgesia 2008. link 20 Zhao CL, Mao HJ, Xia F, Chen XY. Fourteen cases of neonatal ultrahyperpyrexia syndrome induced by improper care. Advances in therapy 2007. link 21 Berkenstadt H, Yusim Y, Ziv A, Ezri T, Perel A. An assessment of a point-of-care information system for the anesthesia provider in simulated malignant hyperthermia crisis. Anesthesia and analgesia 2006. link 22 Harrison TK, Manser T, Howard SK, Gaba DM. Use of cognitive aids in a simulated anesthetic crisis. Anesthesia and analgesia 2006. link 23 Scala D, Di Martino A, Cozzolino S, Mancini A, Bracco A, Andria B et al.. Follow-up of patients tested for malignant hyperthermia susceptibility. European journal of anaesthesiology 2006. link 24 Prinzhausen H, Crawford MW, O'Rourke J, Petroz GC. Preparation of the Dräger Primus anesthetic machine for malignant hyperthermia-susceptible patients. Canadian journal of anaesthesia = Journal canadien d'anesthesie 2006. link 25 Nielsen B, Nybo L. Cerebral changes during exercise in the heat. Sports medicine (Auckland, N.Z.) 2003. link 26 Schönell LH, Sims C, Bulsara M. Preparing a new generation anaesthetic machine for patients susceptible to malignant hyperthermia. Anaesthesia and intensive care 2003. link 27 Chang CY, Scher RL. Malignant hyperthermia and the otolaryngologist. Ear, nose, & throat journal 2003. link 28 Petroz GC, Lerman J. Preparation of the Siemens KION anesthetic machine for patients susceptible to malignant hyperthermia. Anesthesiology 2002. link 29 Karger B, Teige K. Fatal malignant hyperthermia--delayed onset and atypical course. Forensic science international 2002. link00272-4) 30 i Gardi T, Christensen UC, Jacobsen J, Jensen PF, Ording H. How do anaesthesiologists treat malignant hyperthermia in a full-scale anaesthesia simulator?. Acta anaesthesiologica Scandinavica 2001. link 31 Wackym PA, Blackwell KE. Malignant hyperthermia in the otology patient: the UCLA experience. The American journal of otology 1994. link 32 Haas DA, Young ER, Harper DG. Malignant hyperthermia and the general dentist: current recommendations. Journal (Canadian Dental Association) 1992. link 33 Schwartz N, Eisenkraft JB. Malignant hyperthermia in a child with sleep apnea. The Mount Sinai journal of medicine, New York 1989. link 34 Ginsburg R, Purcell-Jones G. Malignant hyperthermia in the Wolf-Hirschhorn syndrome. Anaesthesia 1988. link 35 Beebe JJ, Sessler DI. Preparation of anesthesia machines for patients susceptible to malignant hyperthermia. Anesthesiology 1988. link 36 Douglas MJ, McMorland GH. The anaesthetic management of the malignant hyperthermia susceptible parturient. Canadian Anaesthetists' Society journal 1986. link 37 Jensen AG, Bach V, Werner MU, Nielsen HK, Jensen MH. A fatal case of malignant hyperthermia following isoflurane anaesthesia. Acta anaesthesiologica Scandinavica 1986. link 38 Franks RD, Aoueille B, Mahowald MC, Masson N. ECT use for a patient with malignant hyperthermia. The American journal of psychiatry 1982. link 39 Samson B, Duncan L. Inflatable bath for external cooling. Canadian Anaesthetists' Society journal 1981. link 40 MacDougall JD. Thermoregulatory problems encountered in ice hockey. Canadian journal of applied sport sciences. Journal canadien des sciences appliquees au sport 1979. link 41 Haberman ML. Malignant hyperthermia. An allergic reaction to thioridazine therapy. Archives of internal medicine 1978. link 42 Wolfe JS, Bagenstose JE. Malignant hyperthermia: a complication of orthopedic surgery. Orthopedics 1978. link 43 Cabral R, Prior PF, Scott DF, Brierley JB. Reversible profound depression of cerebral electrical activity in hyperthermia. Electroencephalography and clinical neurophysiology 1977. link90286-3) 44 Paladino TR. Malignant hyperthermia during general anesthesia: medicolegal considerations. Legal medicine annual 1975. link

    Original source

    1. [1]
      Drug-induced perioperative malignant hyperthermia: a real-world study based on the Food and Drug Administration Adverse Event Reporting System (FAERS) database. — Lu Z, Huang M, Liu L, Lin C, Lin W, Tan H et al. International journal of surgery (London, England) (2026)
    2. [2]
      Managing Simulated Anesthesia Emergencies with the Use of Clinical Decision Support Systems in a Rural Hospital Setting. — Good D, Schaaf S AANA journal (2025)
    3. [3]
      Evaluation of anesthesiology residents in the diagnosis and control of malignant hyperthermia: comparison of three scenarios of realistic simulation ‒ a cross-sectional controlled study. — Neville MFL, Guimarães de Almeida V, Andrade PV, Santos JM, Munechika M, Ferez D et al. Brazilian journal of anesthesiology (Elsevier) (2025)
    4. [4]
      Systematic analysis of adverse reactions associated with dantrolene treatment: From clinical features to molecular mechanisms. — Chen H, Zhang X, Chen D, Jiang X, Yu C Medicine (2025)
    5. [5]
      Malignant hyperthermia 2020: Guideline from the Association of Anaesthetists. — Hopkins PM, Girard T, Dalay S, Jenkins B, Thacker A, Patteril M et al. Anaesthesia (2021)
    6. [6]
      Availability of dantrolene for the management of malignant hyperthermia crises: European Malignant Hyperthermia Group guidelines. — Glahn KPE, Bendixen D, Girard T, Hopkins PM, Johannsen S, Rüffert H et al. British journal of anaesthesia (2020)
    7. [7]
      Prevalence of malignant hyperthermia diagnosis in obstetric patients in the United States, 2003 to 2014. — Guglielminotti J, Rosenberg H, Li G BMC anesthesiology (2020)
    8. [8]
      Residual volatile anesthetics after workstation preparation and activated charcoal filtration. — Müller-Wirtz LM, Godsch C, Sessler DI, Volk T, Kreuer S, Hüppe T Acta anaesthesiologica Scandinavica (2020)
    9. [9]
      The use of a checklist improves anaesthesiologists' technical and non-technical performance for simulated malignant hyperthermia management. — Hardy JB, Gouin A, Damm C, Compère V, Veber B, Dureuil B Anaesthesia, critical care & pain medicine (2018)
    10. [10]
      Effect of Norepinephrine on Intracellular Ca — Perry SM, Muldoon S, Michaelson LP, Bunger R, Kasper CE AANA journal (2018)
    11. [11]
      Malignant hyperthermia in the early days of pediatric anesthesia: an interview with anesthesiology pioneer, Dr. John F. Ryan. — King MR, Firth PG, Yaster M, Ahmed Z, Mai CL Paediatric anaesthesia (2015)
    12. [12]
      Implications of National Anesthesia Workload on the Staffing of a Call Center: The Malignant Hyperthermia Consultant Hotline. — Dexter F, Rosenberg H, Epstein RH, Semo JJ, Litman RS A & A case reports (2015)
    13. [13]
      Washout times of desflurane, sevoflurane and isoflurane from the GE Healthcare Aisys® and Avance®, Carestation®, and Aestiva® anesthesia system. — Kim TW, Wingate JR, Fernandez AM, Whitaker E, Tham RQ Paediatric anaesthesia (2013)
    14. [14]
      Sudden death due to malignant hyperthermia during general anesthesia. — Wochna K, Jurczyk AP, Krajewski W, Berent J Archiwum medycyny sadowej i kryminologii (2013)
    15. [15]
      Preparation of Datex-Ohmeda Aestiva and Aisys anaesthetic machines for use in malignant hyperthermia susceptible patients. — Jones C, Bennett K, Kim TW, Bulger TF, Pollock N Anaesthesia and intensive care (2012)
    16. [16]
      Washout of sevoflurane from the GE Avance and Amingo Carestation anesthetic machines. — Brünner HW, Pohl S, Grond S Acta anaesthesiologica Scandinavica (2011)
    17. [17]
      Preparation of modern anesthesia workstations for malignant hyperthermia-susceptible patients: a review of past and present practice. — Kim TW, Nemergut ME Anesthesiology (2011)
    18. [18]
      Preparation of the Dräger Fabius GS workstation for malignant hyperthermia-susceptible patients. — Whitty RJ, Wong GK, Petroz GC, Pehora C, Crawford MW Canadian journal of anaesthesia = Journal canadien d'anesthesie (2009)
    19. [19]
      Preparation of the Dräger Fabius anesthesia machine for the malignant-hyperthermia susceptible patient. — Gunter JB, Ball J, Than-Win S Anesthesia and analgesia (2008)
    20. [20]
      Fourteen cases of neonatal ultrahyperpyrexia syndrome induced by improper care. — Zhao CL, Mao HJ, Xia F, Chen XY Advances in therapy (2007)
    21. [21]
      An assessment of a point-of-care information system for the anesthesia provider in simulated malignant hyperthermia crisis. — Berkenstadt H, Yusim Y, Ziv A, Ezri T, Perel A Anesthesia and analgesia (2006)
    22. [22]
      Use of cognitive aids in a simulated anesthetic crisis. — Harrison TK, Manser T, Howard SK, Gaba DM Anesthesia and analgesia (2006)
    23. [23]
      Follow-up of patients tested for malignant hyperthermia susceptibility. — Scala D, Di Martino A, Cozzolino S, Mancini A, Bracco A, Andria B et al. European journal of anaesthesiology (2006)
    24. [24]
      Preparation of the Dräger Primus anesthetic machine for malignant hyperthermia-susceptible patients. — Prinzhausen H, Crawford MW, O'Rourke J, Petroz GC Canadian journal of anaesthesia = Journal canadien d'anesthesie (2006)
    25. [25]
      Cerebral changes during exercise in the heat. — Nielsen B, Nybo L Sports medicine (Auckland, N.Z.) (2003)
    26. [26]
      Preparing a new generation anaesthetic machine for patients susceptible to malignant hyperthermia. — Schönell LH, Sims C, Bulsara M Anaesthesia and intensive care (2003)
    27. [27]
      Malignant hyperthermia and the otolaryngologist. — Chang CY, Scher RL Ear, nose, & throat journal (2003)
    28. [28]
      Preparation of the Siemens KION anesthetic machine for patients susceptible to malignant hyperthermia. — Petroz GC, Lerman J Anesthesiology (2002)
    29. [29]
      Fatal malignant hyperthermia--delayed onset and atypical course. — Karger B, Teige K Forensic science international (2002)
    30. [30]
      How do anaesthesiologists treat malignant hyperthermia in a full-scale anaesthesia simulator? — i Gardi T, Christensen UC, Jacobsen J, Jensen PF, Ording H Acta anaesthesiologica Scandinavica (2001)
    31. [31]
      Malignant hyperthermia in the otology patient: the UCLA experience. — Wackym PA, Blackwell KE The American journal of otology (1994)
    32. [32]
      Malignant hyperthermia and the general dentist: current recommendations. — Haas DA, Young ER, Harper DG Journal (Canadian Dental Association) (1992)
    33. [33]
      Malignant hyperthermia in a child with sleep apnea. — Schwartz N, Eisenkraft JB The Mount Sinai journal of medicine, New York (1989)
    34. [34]
      Malignant hyperthermia in the Wolf-Hirschhorn syndrome. — Ginsburg R, Purcell-Jones G Anaesthesia (1988)
    35. [35]
      Preparation of anesthesia machines for patients susceptible to malignant hyperthermia. — Beebe JJ, Sessler DI Anesthesiology (1988)
    36. [36]
      The anaesthetic management of the malignant hyperthermia susceptible parturient. — Douglas MJ, McMorland GH Canadian Anaesthetists' Society journal (1986)
    37. [37]
      A fatal case of malignant hyperthermia following isoflurane anaesthesia. — Jensen AG, Bach V, Werner MU, Nielsen HK, Jensen MH Acta anaesthesiologica Scandinavica (1986)
    38. [38]
      ECT use for a patient with malignant hyperthermia. — Franks RD, Aoueille B, Mahowald MC, Masson N The American journal of psychiatry (1982)
    39. [39]
      Inflatable bath for external cooling. — Samson B, Duncan L Canadian Anaesthetists' Society journal (1981)
    40. [40]
      Thermoregulatory problems encountered in ice hockey. — MacDougall JD Canadian journal of applied sport sciences. Journal canadien des sciences appliquees au sport (1979)
    41. [41]
      Malignant hyperthermia. An allergic reaction to thioridazine therapy. — Haberman ML Archives of internal medicine (1978)
    42. [42]
      Malignant hyperthermia: a complication of orthopedic surgery. — Wolfe JS, Bagenstose JE Orthopedics (1978)
    43. [43]
      Reversible profound depression of cerebral electrical activity in hyperthermia. — Cabral R, Prior PF, Scott DF, Brierley JB Electroencephalography and clinical neurophysiology (1977)
    44. [44]
      Malignant hyperthermia during general anesthesia: medicolegal considerations. — Paladino TR Legal medicine annual (1975)
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