Succinylcholine Use and Dantrolene Availability: Reply

We thank Drs. Joshi, Desai, Valedon, and Gayer for their interest in our database analyses and systematic literature review of succinylcholine use and dantrolene availability for malignant hyperthermia treatment.¹  Joshi et al. state that our analyses do not include data from Class B ambulatory care facilities. The American Association for Accreditation of Ambulatory Surgery Facilities (Gurnee, Illinois) defines Class B facilities as those that allow minimally or moderately invasive surgical, endoscopic and/or pain management procedures under moderate sedation with intravenous sedation, and/or parenteral sedation, and/or field and peripheral nerve blocks, and/or dissociative drugs excluding propofol.²  Because the Multicenter Perioperative Outcomes Group (Ann Arbor, Michigan) uses different classifications for its participating institutions, we do not know how many of the 24 freestanding ambulatory surgery centers captured in our study also might have been Class B facilities.

Joshi et al. may have missed our systematic literature review of succinylcholine use for treatment of laryngospasm (appendix 2, query 5 and key words with combinations, supplemental digital content 3).¹  Unfortunately, we found no published studies containing data on succinylcholine administration rate in ambulatory surgery centers for airway rescue.

Joshi et al. are correct as regards our Multicenter Perioperative Outcomes Group investigation. We could not do a retrospective analysis of laryngospasm in the Multicenter Perioperative Outcomes Group database because laryngospasm is not reported in a consistent, discrete fashion across the millions of cases included in our study. We chose grades III/IV mask ventilation as a surrogate for airway rescue to facilitate examination of 6,938,341 anesthetic cases. Succinylcholine was administered in freestanding ambulatory surgery centers in 1,388 cases of documented grade III/IV airway (table 2). For all anesthetizing locations, the succinylcholine dose for the 560 grade IV (impossible to ventilate) mask ventilation cases with a recorded succinylcholine amount and weight was 1.2 mg/kg (first quartile, 0.97; third quartile, 1.44; range, 0.12 to 3.02 mg/kg).¹ 

Malignant hyperthermia cases triggered by low-dose succinylcholine without volatile anesthetic administration have been reported by Riazi. Two adult patients developed “almost certain” malignant hyperthermia after receiving 0.5 mg/kg and 0.8 mg/kg of succinylcholine to facilitate electroconvulsive therapy. Both of these patients had positive malignant hyperthermia diagnostic biopsies; one had a malignant hyperthermia causative mutation (supplemental digital content 6, reference 27 [table 3]).¹ 

Although Joshi et al. quote part of Dr. Hopkins’ statement, the remainder of his observations were omitted. We cite the entire paragraph with the omitted portions italicized. “Although the evidence presented in this article is insufficient to convince me that succinylcholine in the absence of volatile anesthetics can trigger a life-threatening progressive hypermetabolic response in MH-susceptible patients, the evidence is similarly insufficient to rule out that this is the case. My view, therefore, is that equipoise is retained on this issue, and while it remains, patient safety is served by mandating that dantrolene be stocked where succinylcholine is available.”³ 

Although Joshi et al. state that there is a high likelihood of overdiagnosis of malignant hyperthermia, we cannot find evidence to support this comment. Also, we could not find data to support the statement that “offering the alternative to stocking succinylcholine without dantrolene is prudent from patient safety and cost-effective perspectives.”

What will be included in a malignant hyperthermia drill for Class B facilities that have no dantrolene to administer? We reiterate that time to dantrolene administration affects the likelihood of complications including coagulation, heart, lung, liver, kidney, and brain dysfunction (reference 9 [table 6]). Malignant hyperthermia complications increase substantially with every 10-min delay in initiating dantrolene treatment. If clinicians wait more than 50 min, complications increase to 100% (reference 27 [fig. 1].¹ 

Drs. Joshi, Desai, Valedon, and Gayer emphasize the need for transfer arrangements at Class B Ambulatory Facilities. We agree that transfer arrangements are essential for all freestanding facilities so that appropriate care for unanticipated medical, anesthetic, and/or surgical issues may be obtained. In 2012, four physicians representing the Society for Ambulatory Anesthesia (Drs. Belani, Metz, Piccone, and Valedon) helped to create a guide for the transfer of care of the malignant hyperthermia patient from ambulatory surgery centers to receiving hospital facilities. These physicians agreed that IV dantrolene therapy should be initiated before patient transfer.⁴  Why is this guide no longer relevant to the care of ambulatory surgery center patients?

We stand by our conclusion that our data support stocking dantrolene wherever succinylcholine or volatile anesthetics may be used, even when succinylcholine is used solely for airway rescue.

Many of the authors are unpaid volunteers for the nonprofit Malignant Hyperthermia Association of the United States (MHAUS; Sherburne, New York). They have served variously as directors of The North American Malignant Hyperthermia Registry of MHAUS and members of the board of MHAUS, the Professional Advisory Council of MHAUS, and/or the Malignant Hyperthermia Hotline of MHAUS. All of these positions are voluntary and unpaid. Many participated in the drafting of the current MHAUS recommendation for dantrolene availability in anesthetizing locations. Many of the authors have traveled to malignant hyperthermia conferences in the United States or Canada with MHAUS financial support. MHAUS receives funding support from MHAUS members, customers, medical associations and societies, foundations, and various corporations, including Eagle Pharmaceuticals (Woodcliff Lake, New Jersey), PAR Pharmaceuticals (Chestnut Ridge, New York), and U.S. WorldMeds, LLC (Louisville, Kentucky). Dr. Belani received several vials of Ryanodex from Eagle Pharmaceuticals, Inc., for use in a research study. Dr. Mashman has received a grant from Eagle Pharmaceuticals, Inc., for three vials of Ryanodex to bring on a medical mission trip. Dr. Riazi has received a consulting fee from Norgine Pharmaceuticals (Amsterdam, The Netherlands) and is also a member of the scientific advisory board of the RYR1 Foundation (Pittsburgh, Pennsylvania). Dr. Sivak has been a principal investigator for a Merck (Kenilworth, New Jersey) sponsored study of sugammadex (November 7, 2017 through August 3, 2018).