Introduction

This July marks the 60th anniversary of the publication of a Letter to the Editor describing the inherited condition, now known as Malignant Hyperthermia (MH), in a young man who developed metabolic derangements when exposed to halothane.¹ The worldwide scientific community has come a long way since then to characterize the condition. We now have a better understanding of the pathophysiology, presentation, and treatment of this potentially fatal condition. Although difficult to truly characterize, MH crisis prevalence is estimated to be 1 in 100,000 administered anesthetics,² which means, thankfully, most anesthesia professionals may only participate in a true MH crisis once in their career, if at all. This fact, coupled with the possible fatality of an MH crisis, makes the preparation to manage these rare events paramount for the safety and good outcome of those patients.

We focus on two essential steps in the preparation to manage an MH crisis: stocking a dedicated MH Cart to be used during an acute crisis, and developing an institutional multidisciplinary mock MH drill for anesthesia and operating room personnel. Lastly, we discuss the special considerations of MH preparedness for offsite and remote anesthetizing locations.

MH Cart

The Malignant Hyperthermia Association of the United States (MHAUS) recommends medications and supplies be readily available for use, within 10 minutes of recognizing an MH crisis.³ Since the likelihood of complications increases 1.6 times with every 30-minute delay in treatment with dantrolene,⁴ having a centrally located cart with the necessary medications and equipment expedites the initiation of treatment. When dantrolene administration was delayed beyond 50 minutes, complication rates increased to 100%.⁵

The organization of the MH cart should be divided into two main categories; (1) medications and (2) supplies necessary for an MH crisis. There are many commercially available MH carts offered for purchase. Regardless of the type of cart use, however, dantrolene is the crux of the treatment of MH and should be the easiest to access (preferably located in the top drawer). Currently two formulations of dantrolene exist. Dantrium®/Revonto® is the older formulation, which provides 20-mg dantrolene sodium in 60 mL following reconstitution in sterile water USP. The second formulation, Ryanodex®, is a new formulation that is an injectable suspension of dantrolene sodium providing 250 mg of dantrolene sodium in 5 mL following reconstitution with sterile water USP. Selection between the two formulations should dictate how many vials should be stocked. If Dantrium®/Revonto® is stocked, MHAUS recommends having 36 vials available in each institution. If Ryanodex® is stocked, MHAUS recommends having 3 vials available. Sterile water should be stocked alongside the dantrolene in the first drawer as it is necessary to reconstitute the powdered dantrolene. The amount stocked should reflect the formulation of dantrolene (larger volume is required for Dantrium®/Revonto® compared to Ryanodex®). If Dantrium®/Revonto® is the stocked formulation, we would recommend stocking thirty-six 100 ml vials of sterile water rather than one-liter bags of sterile water to prevent the inadvertent intravenous administration of a hypotonic solution. Three 10 ml vials of sterile water can be stocked if Ryanodex® is the stocked formulation. Although clinical effectiveness and dosing are similar between the two formulations, the lower storage space needed for Ryanodex®, the lower number of staff needed to mix it and the increased speed of mixing and administering the loading dose makes Ryanodex® more practical during a crisis, especially when number of staff available is limited.

Other medications stocked in the cart should be focused on the treatment of the sequalae of the hypermetabolic condition, such as severe acidemia, hyperkalemia, cardiac arrhythmias, and severe hyperthermia. Sodium bicarbonate (8.4% 50 ml vials x 4) should be stocked to aid in correction of severe acidemia. Calcium chloride 10% (10 ml vials x 2), Dextrose 50% (50 ml vials x 2), and regular insulin (100 unit/ml 1 vial) should be stocked for treatment of hyperkalemia. Lidocaine (100 mg/5 ml or 100 mg/10 mls x 3) or amiodarone (150 mg vial x 4) should be stocked according to ACLS/PALS guidelines for any cardiac derangements. Refrigerated one-liter saline bags are recommended for cooling (some commercially available MH carts have a small refrigerator for saline and insulin, but every institution can decide on this matter).

Supplies within the MH cart should be focused on the administration of MH medications, temperature management, patient monitoring, and laboratory testing. Central location of equipment can provide a quicker response and more coordinated care. Syringes (60 ml x 5) to dilute Dantrium®/Revonto® or (5 ml x 3) for Ryanodex® should be located close to dantrolene. Two pairs of activated charcoal filters (Vapor-Clean™, Dynasthetics, Salt Lake City, UT) should be included. These filters attach to the inspiratory and expiratory ports of the anesthesia machine to quickly reduce the concentration of gas (<5ppm). Two pairs are recommended as the filters may become saturated after one hour of use and a replacement could be needed. Other patient care equipment includes intravenous catheters of various sizes for intravenous and arterial access, and a large sterile drape that can be used to rapidly cover a surgical wound.

Temperature management of MH patients is very important as the risk of death increases with increasing temperature.⁴ Following discontinuation of the triggering agent, dantrolene administration is the most important pharmacologic temperature management strategy. Noninvasive treatments for hyperthermia include strategic ice packing, forced air cooling, circulating cool water blankets, cold intravenous fluids, and ice-water immersion.⁶ An ice bucket, large and small plastic bags for ice, and disposable cold packs can be placed next to the patient easily to help with cooling measures. A pressure bag should also be included for rapid administration of cold saline.

Monitoring equipment should focus on accurate and reliable measurements. For temperature monitoring, esophageal or other core (nasopharyngeal, tympanic, or rectal) temperature probes should be considered. Central and arterial lines should be considered for critically ill patients and transducer kits should be available. Foley catheters and a urometer are also important for monitoring urine output to insure adequate diuresis to prevent acute renal injury from myoglobinurea.

The last category of equipment is laboratory supplies. Frequent laboratory testing is performed in a MH crisis and the laboratory testing equipment should be readily available and labeled for use. Equipment for blood gas measurement capability such as heparinized blood gas syringes or syringes for point of care testing should be included. Blood specimen tubes for creatinine kinase, myoglobin, comprehensive metabolic panel (Na+, K+, Ca+, BUN, HCO,³ Mg+), lactate, complete blood count, and coagulation studies should be easily accessible. Lastly, a collection device for urine with testing supplies for myoglobin should be considered. Myoglobinuria can be quickly screened for by the presence of pigmenturia and blood on a urine dipstick, if available in your institution, and should be followed up with a formal urinalysis and quantitative urine myoglobin level.

Mock MH Drill

The utility of medical simulation is well demonstrated and its application to rare medical events can improve familiarity while providing hands-on experience.⁷ Each facility is different in their training options, but MHAUS recommends teams perform mock MH drills every year;⁸ we provide a few tips to maximize the team’s benefit from these valuable exercises.

Selection of a clinical scenario should be based on the applicability to the team and organization. It would not be worthwhile to use a scenario of an elderly patient if the team solely provides care for pediatrics, for example. The development of a scenario is best drawn from prior experiences inside the organization; otherwise, commercially available ones can be used. Besides the selection of the scenario, selecting a leader or facilitator is also a critical decision. Managing an MH crisis is a team sport and everyone needs to engage and participate. By selecting an anesthesia professional to lead these drills, participants’ buy-in improves since most health care providers look to anesthesia personnel for guidance during an MH crisis.

The training during a mock MH drill should focus on two main aspects: rapid recognition of MH signs and symptoms and the logistics of coordinating the clinical management team. Once the diagnosis is made, the leader should assign roles to participants based on skill levels. If personnel resources are limited, such as in a surgery center for example, staff may need to handle multiple roles. The danger of only assigning one role to a participant is that when an actual MH crisis occurs, that person may not be in the facility.

Once roles are clearly delineated, the drill should focus on the logistics of providing care in an MH crisis rather than physically treating the patient. For example, the insertion of lines and a Foley catheter should not be the focus. Rather, the focus should be on locating the MH cart, contents of the MH cart, who is reconstituting dantrolene, who is getting ice, who is calling the MH Hotline, etc. If available, the team should reconstitute an expired vial or two of dantrolene, especially if the institution uses the 20 mg/60 ml formulation, as this process is very laborious.

In a surgery center, the drill should include a post-stabilization transport plan. This is crucial to have in place before an actual MH episode occurs. Depending on how far the facility is, we recommend, whenever staffing allows, an anesthesia professional, from the transferring or receiving facility, accompany the patient to the receiving hospital to allow for the continued administration of dantrolene during transport and for a formalized face-to-face transfer of care with the receiving team.

As mentioned before, MHAUS recommends MH drills every year, but these authors perform it in their institution every 6 months to keep information relatively fresh with the staff. Another consideration is to rotate between scheduled and unscheduled drills. If the purpose of the drill is to assess readiness, there is no better way than an unexpected drill. This is obviously more time-consuming, but may be more effective.

Following any simulated drill, it is important to have a debriefing session. Debriefing allows team members to discuss what went well and what could be improved. Debriefing also acts as an opportunity to clarify any lingering question team members may have. It is also an opportune time to discuss the importance of contacting the North American MH Registry of MHAUS at 888-274-7899 for all confirmed or suspected MH cases to assist in completing an online form (AMRA) in order to capture valuable MH data. All debriefings should be done in a safe and nonjudgmental way. Lastly, it is important to develop a contingency plan. What if an MH crisis happens in the middle of the night? Who else can be deployed to assist? Will someone be called in? Those questions need to be discussed and ironed out before an actual crisis.

Offsite/Remote Preparedness

The growth of free-standing surgical facilities using only intravenous anesthesia techniques without inhalational agents has increased steadily. In an effort to contain cost, MHAUS was requested to reconsider the recommendations related to dantrolene stocking at centers that only have succinylcholine for emergency airway management. The request is related to the perceived infrequent use of succinylcholine, the low incidence of MH susceptibility in the general population, and the cost of stocking dantrolene.

As of today, MHAUS recommends facilities that stock and have the potential to administer any triggering agent, including succinylcholine without volatile agents, should have dantrolene immediately available in the event a patient in that facility develops MH.⁶ In contrast, the Society for Ambulatory Anesthesia (SAMBA) Position Statement on the Use of Succinylcholine for Emergency Airway Rescue permits class B facilities to stock succinylcholine for airway rescue without dantrolene in situations where no volatile agents are used.⁹ Larach et al. demonstrated succinylcholine administered in the absence of volatile agents, over a wide dose range to manage difficult ventilation, can trigger MH events that warrant dantrolene treatment.¹⁰ This report shifts the consideration of succinylcholine-induced MH from the realm of highly unlikely into the realm of similarly rare but devastating emergencies, such as cardiac arrest and anaphylaxis. With such events, successful management depends upon the presence of well-established protocols for early recognition and prompt treatment. Office-based anesthesia professionals also need to consider the relatively remote nature of the practice when establishing their malignant hyperthermia protocol. Dantrolene treatment delay increased complications every 10 minutes, reaching 100% with a 50-minute delay.⁹

As a patient safety organization, MHAUS contends the availability of dantrolene allows clinicians to administer succinylcholine for life-threatening airway emergency without delay due to fear of patients developing MH without the only known antidote immediately available.

Conclusion

Early recognition and treatment of MH is essential to improve survival rates. Stocking a dedicated MH cart, routinely performing simulated MH crisis drills, and having enough dantrolene stocked can save lives.

 

Dr. Hamlin is an assistant professor in the Department of Anesthesiology at the University of Nebraska and Children’s Hospital & Medical Center Omaha, NE.

Dr. Shukry is a professor & vice chairperson of Pediatric Anesthesiology in the Department of Anesthesiology at University of Nebraska and Children’s Hospital & Medical Center Omaha, NE.

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Drs. Hamlin and Shukry are volunteer Hotline Consultants for MHAUS

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