Lobmeyer, Erica; Gravenstein, Nikolaus; Smith, Cameron; Gunnett, Amy; Woods, Anna; McDougall, Heather
Introduction: Dantrolene is the primary injection treatment for malignant hyperthermia (MH). Dantrolene powder requires considerable effort to reconstitute because in its traditional formulations (dantrolene sodium for injection), it takes approximately 129 seconds to dissolve 20 mg in the required 60 mL of sterile water1. In 2015, a more concentrated and soluble dantrolene formulation (lyophilized dantrolene sodium injectable suspension) entered the market. This newer formulation takes approximately 10 seconds to dissolve 250 mg in 5 ml of sterile water but is more expensive and has a shorter shelf life according to package insert.
Methods: After IRB approval (IRB# 201901131), we gathered data from the North American Malignant Hyperthermia Registry on patients who received dantrolene as part of their treatment for MH from 2013 to the present. We assessed whether the traditional formulation (dantrolene sodium for injection) or the new formulation (lyophilized dantrolene sodium injectable suspension) was administered and also collected the MH Clinical Grading Scale scores2 of the cases in the registry where either formulation was used.
Results: The Clinical Grading Scores of 97 cases where dantrolene was administered ranged from 15 to 100, with a mean of 43.75 (Figure 1). There were three cases where dantrolene was administered but a Clinical Grading Scale score was not computed. The distribution of cases where old and new formulations were used is shown in Figure 2. Dantrolene sodium for injection is shown in blue, the lyophilized dantrolene sodium injectable solution in orange, and where the formulation was not specified in gray.
Conclusion: From the registry data, it appears that in the 5 years since the lyophilized dantrolene came on the market, the new formulation has exceeded 50% use in cases reported to the North American Malignant Hyperthermia Registry where dantrolene was administered. This new formulation, though much more concentrated, requires less time and volume of sterile water to dissolve lending itself to quicker administration. These data reflect a fairly quick but still incomplete adoption of the new formulation for the initial treatment of a presumed MH event. The Clinical Grading Scale scores in the registry reported cases where dantrolene was administered ranged from an MH likelihood score of “somewhat less than likely” through “almost certain,” with a mean likelihood of MH score of “very likely.”
- Anesth Analg 2019;129:e201–e202.
- Anesthesiology 1994;80:771–779.
- Presented to the International Anesthesia Research Society (IARS) 2020: Lobmeyer, Erica; Gravenstein, Nikolaus; Smith, Cameron; Gunnett, Amy; Woods, Anna; McDougall, Heather: A Retrospective Review of the Dantrolene Formulations Administered to Subjects Registered in NAMHR.
- Presented to the International Anesthesia Research Society (IARS) 2015: Werneid K, Riazi S, Brandom BW: Long-term sequelae in patients who experienced a malignant hyperthermia event.
- Presented to the American Society of Anesthesiologists (ASA) 2013: Larach MG, Brandom BW, Allen GC, Gronert GA: Failure to rescue from fulminant malignant hyperthermia: deaths and their genetic variants 2007-2012.
- Presented to the American Society of Anesthesiologists (ASA) 2011: Barbara W. Brandom, M.D., James Wilde, B.A., Michael C. Young, M.S.: Pain Reported by Malignant Hyperthermia Susceptible Subjects.
- Presented to the American Society of Anesthesiologists (ASA) 2011: Brandom BW, Wilde J, Young MC: Chronic pain symptoms in malignant hyperthermia.
- Presented to the European Malignant Hyperthermia Group 2010: Brandom BW, Muldoon, SM, Sambuughin N: More than Anesthetic Induced Malignant Hyperthermia (MH).
- Presented to the European Malignant Hyperthermia Group 2009: Brandom BW, Muldoon SM, Wong C, Rosenberg H, Tautz T, Sambuughin N: An Update on the Ryanodine Receptor Gene Variants found in the USA.
- Presented to the American Society of Anesthesiologists (ASA) 2008: Larach MG, Allen GC, Brandom BW, Gronert GA, Lehman EB: Temperature changes are not late signs of malignant hyperthermia: A NAMH Registry of MHAUS Study
- Presented to the American Society of Anesthesiologists (ASA) 2008: Scientific Papers, in review. Larach MG, Allen GC, Brandom BW, Gronert GA, Lehman EB: Serious complications associated with malignant hyperthermia events: A NAMH Registry of MHAUS Study.
- Presented to the American Society of Anesthesiologists (ASA) 2007: Sambuughin N, Brandom B, Capacchione J, Rosenberg H, Muldoon S: Toward updating the North American Malignant Hyperthermia Mutation Panel.
- Presented to the American Society of Anesthesiologists (ASA) 2006: Larach MG, Brandom BW, Allen GC, Gronert GA, Lehman EB: Deaths associated with malignant hyperthermia (1987-2006). A North American MH Registry of MHAUS Study.
- Presented to the American Society of Anesthesiologists (ASA) 2005: Torp KD, Brandom BW, Capacchione JF, Voelkel ML, Muldoon SM: Caffeine halothane contracture test and ryanodine receptor type 1 analysis in patients who experienced MH episodes.
- Presented to the American Society of Anesthesiologists (ASA) in 2005: Burkman JM, Posner KL, Domino KB: Analysis of the clinical variables associated with recrudescence after malignant hyperthermia reactions.
- Presented to the American Society of Anesthesiologists (ASA) in 2004: Sambuughin N, Holley H, Brandom B, Nelson T, Muldoon S: Comprehensive screening of the RYR1 gene for malignant hyperthermia susceptibility.
- Presented to the European Congress of Nursing in 2004, previously presented to the American Association of Nurse Anesthethists 2003: Ciceron MC, Lauriello R, McCarthy EJ, McDonough JP: Differences in clinical manifestations in malignant hyperthermia episodes with succinylcholine or volatile anesthetics.
- Presented to the Society for Pediatric Anesthesia 2003: Brandom BW, Larach MG, Gurgis F: Comparison of pediatric and adult patients with regard to the safety and efficacy of dantrolene.
- Presented to the American Society of Anesthesiologists 2002: Kozack JK: A survey of chronic muscle pain and other symptoms in malignant hyperthermia susceptible individuals.
- Presented to the American Society of Anesthesiologists 2002: Brandom BW, Larach MG: Reassessment of the safety and efficacy of dantrolene.
The following articles include data from or otherwise depend upon the North American MH registry.
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- Wu X, Brady JE, Rosenberg H, Li G. Emergency Department Visits for Heat Stroke in the United States, 2009 and 2010. Inj Epidemiol. 2014;1(1):8.
- Larach MG, Brandom BW, Allen GC, Gronert GA, Lehman EB. 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. Anesth Analg 2014; 119(6): 1359-1366
- Nelson P, Litman RS. Malignant hyperthermia in children: an analysis of the North American Malignant Hyperthermia Registry. Anesth Analg 2014; 118: 369-374
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- Brandom BW, Bina S, Wong CA, Wallace T, Visoiu M, Isackson PJ, Vladutiu GD, Sambuughin N, Muldoon SM. Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States. Anesth Analg 2013; 116:1078-86
- Lavezzi WA, Capacchione JF, Muldoon SM, Sambuughin N, Bina S, Steele D, Brandom BW. Death in the emergency department: an unrecognized awake malignant hyperthermia-like reaction in a six-year-old. Anesth Analg 2013; 116:420-3
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- Larach MG, Gronert GA, Allen GC, Brandom BW, Lehman EB. Clinical presentation, treatment, and complications of malignant hyperthermia in North America from 1987 to 2006. Anesth Analg 2010; 110:498-507
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- Fink EL, Brandom BW, Torp KD. Heat stroke in the super-sized athlete. Pediatric Emergency Care 2006; 22: 510-3
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- Barbara W. Brandom, M.D., Sheila M. Muldoon, M.D. Anesthesiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania. Estimation of the Incidence of Malignant Hyperthermia Using a Capture-Recapture Method in the USA. Anesthesiology 2004; 101:A1267
- Muldoon SM, Deuster P, Brandom BW, Bunger R: Is there a link between malignant hyperthermia and exertional heat illness. Exercise and Sport Sciences Reviews 2004; 32:174-179
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