TGI MH Friday, March 26, 2021

In today’s TGI MH Friday, we’ll try to unpack a thorny issue that lies at the intersection between politics, economics, and patient safety: Should a free-standing surgicenter that ONLY uses IV anesthesia be required to stock dantrolene? And if so, how much is enough? The logical extension of that question is: What is the risk of a patient developing acute MH from a dose of succinylcholine? And finally, what is the likelihood that a patient will be administered succinylcholine during an IV anesthetic? Before we try to answer these questions, some background…and a disclaimer:

Disclaimer: I am currently a member of the Malignant Hyperthermia Association of the U.S (MHAUS), and in the past I have held the positions of Medical Director of the MHAUS hotline, Vice-President for Scientific Affairs, and I have served on the Board of Directors. However, the views I write today are not in any way to be construed as official statements or positions of MHAUS or its officers or other members.

As a patient safety and advocacy organization, MHAUS recommends thatDantrolene must be available for all anesthetizing locations where MH trigger agents are used.” Triggering agents are commonly considered to be all inhalational anesthetics and succinylcholine. Furthermore, MHAUS recommends that centers stock a minimum of 36 20-mg vials of generic dantrolene (total dose 720-mg), or three 250-mg vials of Ryanodex (total dose 750-mg). These amounts of dantrolene were originally determined by the analysis of MH event data showing that some cases of acute MH required up to or more than 10-mg/kg body weight, and therefore, these total dose amounts would suffice for the majority of average-sized patients that develop MH.

Over the past several decades MHAUS received numerous requests from anesthesiologists at many surgi-centers, as well as from representatives of the Ambulatory Surgery Committee of the American Society of Anesthesiologists, and the Society of Ambulatory Anesthesia, to amend the recommendations for stocking dantrolene in these facilities. The requests were based on three arguments. The first is the assumption that since the incidence of MH susceptibility in the general population is low, and the need for succinylcholine to treat an airway emergency in these centers is unusual, then the likelihood of the above two events happening to the same patient is so low that it renders the cost of stocking dantrolene prohibitively high when compared to its potential usefulness. The second is that accrediting agencies such as The Joint Commission and others have traditionally relied on the expert opinion of patient safety organizations such as MHAUS to determine accreditation criteria. These accreditation organizations, in line with MHAUS recommendations, have taken the stance that surgical facilities must stock dantrolene if they also stock succinylcholine as a requirement to become accredited by the Center for Medicare and Medicaid Services (CMS). The third is that to acquire accreditation, some ambulatory surgery facilities that do not want to incur the cost of dantrolene may choose to not stock succinylcholine, thus putting their patients’ lives at risk in the event of a life-threatening airway obstruction (Joan Rivers?). Of course, this last point does not take into account the availability of sugammadex, which may facilitate the use of high-dose nondepolarizing muscle relaxants to treat life-threatening airway obstruction.

With that as background, let’s try to estimate the risk-benefit relationships for whether we should stock dantrolene when volatiles are not used. First, we need to know the prevalence of MH susceptibility in the general surgical population. This is hard to do because it varies by geographic variation, and we need to exclude those patients that already know about MH susceptibility in themselves or their families. The most conservative (ie, highest) estimate seems to be about 1 in 1,500 patients.

Second, what is the chance that one of your patients who is receiving TIVA will require succinylcholine for an airway emergency? This is impossible to know, as there are no published numbers, so we must rely on one’s notoriously unreliable memory for unpleasant complications. I’ll venture a guess, thinking about laryngospasm in babies for ear tubes and say 1 in 200. But I could be way off in either direction (obviously it’s less in my hands!).

Third, and most important, what is the chance that MH will occur from one dose of succinylcholine? It’s pretty rare, but it’s not zero. The vast majority of MH cases are triggered by a volatile anesthetic agent with or without succinylcholine, but in a small percentage of cases MH appears to be triggered by succinylcholine alone in the absence of a volatile agent. In a report from the University of Toronto MH testing center, 20 of 129 (15.5%) biopsy-proven MH events were triggered by succinylcholine alone. In Europe, 2 of 200 (1%) biopsy proven MH events were due to succinylcholine alone. These numbers are somewhat helpful, but their case control nature introduces plenty of bias as to the real incidence. Think of how many thousands of patients receive succinylcholine in emergency rooms or ambulances and don’t develop MH.

So, armed with those numbers, what is the chance that one of your TIVA patients is unknowingly MH susceptible, and then receives succinylcholine, and then develops MH? Let’s try the math:

1 in 1,500 x 200 x 100 = 1 in 30 million anesthetics! (If we use the conservative Toronto numbers it’s about 1 in 2 million, but these estimates are not based on any reliable data.) Given this rarity, who would buy and stock dantrolene, and re-order it every 3 years, knowing that it will never be used?

In 2016, MHAUS convened a consensus conference of hotline consultants, members of the board of directors, and professional advisory council to discuss the advantages and disadvantages of stocking dantrolene in these types of facilities and whether or not we should change the recommendations. Opinions varied widely and generally fell into one of two approaches. The majority of MH experts believed that as a patient advocacy organization that was originally chartered by MH susceptible patients and has MH susceptible families on the board of directors, the primary responsibility of MHAUS is to protect the health of patients, both known MH susceptibles, and those who will subsequently develop MH, but are as yet unaware of their MH susceptible status. Experts in this group felt that the cost of stocking dantrolene, even if never used, is a relatively small price to pay for the security and confidence of knowing that anesthesiologists can be free to stock and administer succinylcholine for life-threatening airway obstruction without fear of patients developing MH without the only known antidote immediately available. These experts held strong beliefs that one of the missions of MHAUS is to make an MH death a “never event”, and that having an adequate supply of dantrolene wherever triggering agents are administered is crucial to this mission, especially in light of data that demonstrates a convincing relationship between the length of time it takes to administer dantrolene and subsequent patient outcomes.

Other MHAUS experts, however, acknowledged the very low incidence of MH caused by succinylcholine alone and the cost to health expenditures on a more global basis if every surgical facility was required to continuously buy and stock a dantrolene supply that is never used. This group of experts also worried about the health consequences of anesthetized patients if these surgical facilities choose not to stock succinylcholine solely for the reason to avoid the obligation of purchasing dantrolene, and they strongly opposed a recommendation that was not evidence-based. Some experts in this latter group thought that another reasonable option would be to require less than a full recommended dose of dantrolene, reasoning that a “starter” dose would be useful prior to transferring the patient to a full-service medical center.

In the end, the consensus was that the incidence of MH induced by succinylcholine alone was not deemed rare enough to justify the absence of dantrolene wherever succinylcholine may potentially be administered. MHAUS continues to recommend that facilities that stock and have the potential to administer any triggering agent, including succinylcholine without volatile agents, should have a full dose (at least 10 mg/kg corresponding to the estimated size of their patients) of dantrolene immediately available (i.e., the ability to administer dantrolene within 10 minutes of the first sign of MH) in the event that a patient in that facility develops MH, and that organizations that inspect healthcare facilities on behalf of CMS, as well as individual state-based licensing agencies should be the purveyors of decisions that involve healthcare costs to society.

I hope everyone has a relaxing weekend, and for those working for the rest of us, will send out quiet on-call vibes from Philly.



Pediatric Anesthesia Article of the Day

Ron Litman, Pediatric anesthesiologist, Children’s Hospital of Philadelphia, Med Director, ISMP, Past Chair FDA AADPAC