Episode #234 Malignant Hyperthermia Preparedness: Insights and Updates

Hello and welcome back to the Anesthesia Patient Safety Podcast. My name is Alli Bechtel, and I am your host. Thank you for joining us for another show. We are back for an all-new show to cover one of the October 2024 APSF Newsletter articles. We are talking about the serious anesthesia complication of malignant hyperthermia and the 4C’s of MH Management. This is a high yield topic for all anesthesia professionals so stay tuned.

Before we dive into the episode today, we’d like to recognize Preferred Physicians Medical Risk Retention Group, a major corporate supporter of APSF. Preferred Physicians Medical Risk Retention Group has generously provided unrestricted support to further our vision that “no one shall be harmed by anesthesia care”. Thank you, Preferred Physicians Medical Risk Retention Group – we wouldn’t be able to do all that we do without you!”

Our featured article today is, “Malignant Hyperthermia Moves Out of the OR: The Role of the Anesthesia Professional” by Henry Rosenberg and colleagues. To follow along with us, head over to APSF.org and click on the Newsletter heading. The first one down is the current issue. From here, scroll down until you get to our featured article today. I will include a link in the show notes as well.

To help kick off the show today, we have one of the authors. I will let him introduce himself now and give us a little background information.

[CLIP 4] “Hello, this is Dr. Henry Rosenberg  In 1981, I was one of the founders of the Malignant Hypothermia Association of the United States. I have been a practicing anesthesiologist for many years since I first started my training in the early 1970s.  I was fortunate enough to attend the first international workshop on malignant hypothermia in Toronto, Canada in 1981 where the first detailed descriptions of the syndrome and its implications were described.”

[Bechtel] I asked Rosenberg why he wrote this article. Let’s take a listen to what he had to say.

[CLIP 5] “I wrote the current article in the APSF newsletter bulletin because there are significant changes that are taking place in the diagnosis of malignant hypothermia evolving from the muscle biopsy contracture test to a DNA diagnostic test with high accuracy.

[CLIP 6 or 7] “The diagnostic test is important for all physicians and certainly all anesthesia personnel to be well aware of since the confirmation of the diagnosis is essential in order to prevent the syndrome from occurring in the patient in the future or in family members.”

[CLIP 2 again] “Although the DNA diagnostic test is not 100 percent accurate, it is at least 80 percent sensitive and specific and avoids the trauma of the muscle biopsy contracture test.”

[CLIP 8] “Other principles of management of malignant hypothermia have also been enhanced, namely, after a patient develops the syndrome, he or she should be evaluated by genetics department, as well as neurology department to offer continued  guidance for the patient and his or her family, and to detect underlying myopathies which may have precipitated the syndrome.”

[Bechtel] Thank you so much to Rosenberg for writing this article and highlighting this important threat to anesthesia patient safety. Don’t worry this show will not just be about how malignant hyperthermia or MH can develop suddenly leading to muscle rigidity, hyperthermia, elevated end tidal CO2, respiratory and metabolic acidosis, and even death if not recognized and treated without delay. We are going even further than just highlighting that MH is inherited in an autosomal dominant manner with a higher incidence in males than females and at a higher rate in children than adults. Remember, we are bringing you the latest in perioperative anesthesia patient safety which today means the latest on malignant hyperthermia.

The authors start with the case of an otherwise healthy 11-year-old girl who presented to the operating room for laparoscopic removal of an ovarian teratoma. She had never had surgery before or received an anaesthetic. Induction included administration of sevoflurane with rocuronium for paralysis followed by intubation. Shortly after intubation, she developed the following:

• Tachycardia to heart rate of 120 from her baseline in the 80s
• Temperature increased to 39.4 degrees Celsius.
• End-tidal CO2 rising to 110mmHg.
• Arm muscle rigidity despite receiving a non-depolarizing neuromuscular blocking agent.

The anesthesia professional called for help and treatment for malignant hyperthermia commenced. The sevoflurane was discontinued and Ryanodex was administered.

Within minutes, the patient’s condition improved. Additional supportive measures included starting total intravenous anesthesic or TIVA, obtaining additional IV access and an arterial line, active cooling with administration of cold IV fluids, and aggressive hydration. After the patient was stable, the surgery was able to be completed quickly, and the patient was transported to the ICU where she continued to receive Dantrolene. The creatine kinase was found to be high at 34,000 IU. She was extubated on postoperative day #1 and continued to improve with resolution of her rhabdomyolysis.

Following the event, additional information about the patient’s personal and family history were discovered. The patient suffered from episodes of heat intolerance and the patient’s grandmother had a chronic elevation in her CK levels but had never undergone genetic testing. A geneticist and neurologist were consulted. Genetic testing revealed an alteration in the ryanodine receptor confirming the diagnosis of MH and consistent with the RYR1 variant which is  a variant of unknown significant by the National Human Genome Institute and the American College of Medical Genetics, but it is labelled as a pathogenic variant by the European MH group and has been associated with elevated CK levels, rhabdomyolysis, and weakness. The patient was discharged home after 5 days and closely followed by medical genetics, neurology, and neuromuscular clinics.

Have you ever been involved in a case of MH followed by successful treatment and management? It has taken many years and scientific breakthroughs to get from the first description of MH in Melbourne, Australia in 1960 by Denborough and Lovell to where we are now with an effective treatment and increased knowledge about MH around the world. The mortality rate has decreased from 70% to about 10% in countries with access to Dantrolene and other supportive measures, a coordinated approach to diagnosis and management in the ICU, and post-episode coordination with family members of the MH patient.

Check out Table 1 in the article for a list of supplies that should be included in your emergency MH cart. First up, here are the medications and recommendations.

• Dantrolene with the ability to administer the full dose (up to 10mg/kg) within 10 minutes. This may include 36 vials of Dantrium/Revonto or 3 vials of Ryanodex.
• Sterile Water with 100mL vials, not bags to avoid accidental administration of large volumes of hypotonic solution.
• Refrigerated saline with 3L minimum.
• Sodium bicarbonate with 4 50mL vials
• 50% Dextrose including 2 50mL vials.
• Regular insulin 100U/mL 1 vial
• Calcium chloride 10% 2 10mL vials
• And 2% Lidocaine including 3 100mg vials.

Next up, here are the supplies that you should be included in your MH cart:

• 2 pairs of charcoal filters
• 4 packs of disposable cold packs
• Foley catheter in various sizes
• Small and large clear plastic bags for ice
• IV, arterial line, and central line supplies in various sizes
• Oesophageal temperature probe or other core temperature monitor.

After you finish listening to this episode, we hope that you will go find the MH cart in your areas of anesthesia practice and check out the contents. You can print off table 1 from the article and make sure that the medications and equipment match up so that you will be prepared to treat a patient with MH.

Now, let’s talk about what’s new when it comes to Malignant Hyperthermia. This requires a shift in the way we think about MH from an episodic, idiosyncratic disorder to a pharmacogenetic disorder and inherited myopathy with effects that may be seen outside of the operating room and anesthetic exposure.

We still have important questions when it comes to furthering our understanding of the RYR1 variant. Is there a relationship between statin-induced myopathy, exertional rhabdomyolysis, heat stroke, and chronically elevated CK syndromes and MH susceptibility? Plus, can we use dantrolene to help treat these other conditions?

Historically, it was the muscle biopsy caffeine halothane contracture test that served as the gold standard for MH diagnostic testing. Now, genetic testing has taken a front row seat. Did you know that the European MH Society formally changed their recommendation to use genetic testing as the first line for MH Susceptibility diagnosis in 2015? Most MH experts around the world agree with this recommendation. In the United States, there are only two centers that perform the muscle biopsy test, and the testing can cost up to $20,000 USD which is usually not paid by insurance companies. Genetic testing is becoming more cost effective and may be reimbursed by insurance companies. The authors provide the example of a panel test for the three genes associated with MH susceptibility which include RYR1, CACNA1s, and STAC3 which costs less than $500 USD compared to the comprehensive metabolic and myopathy panel which costs about $1,500USD.

Another important consideration is the role of the anesthesia professional after an MH episode and the patient is transferred out of the operating room. Is this an area where anesthesia professionals should be called upon to consult with geneticists and neurologists and advise the patient and family members about the genetic testing results? That may be quite difficult depending on the type of practice and understanding of the genetic testing. This is quite new after all. Anesthesia professionals should be able to discuss the MH episode, treatment received, and prognosis and expected recovery after an event. Patients may have questions about muscle weakness or predisposition to rhabdomyolysis and the time frame. Does your institution have a way to flag or highlight a diagnosis of MH susceptibility including the specific gene variant in the patient’s chart or electronic medical record. This can go a long way to helping to keep patients with MH susceptibility safe during anesthesia care. Artificial intelligence or third-party services may be used to process data across genetic testing platforms and help improve communication of this critical diagnosis to clinicians.

Remember, all MH susceptible patients should be treated with a clean non-triggering anesthetic technique that includes the following:

• Avoidance of succinylcholine and volatile anesthetics
• Preparation of the anesthesia machine by flushing the circuit and ventilator with high flows over the manufacturer recommended amount of time or insertion of activated charcoal filters in the breathing circuit
• Use of fresh CO2 absorbent
• Taping off vaporizers or removing them from the room to prevent accidental use.
• Use of routine monitors for EKG, pulse oximetry, blood pressure, core body temperature, and capnography

We zoom out to look at the global impact of MH, we can see that there is no known ethnic propensity to MH susceptibility. The authors ask the question, “How do resource-limited countries balance the cost of a life-saving drug dantrolene for an infrequent disorder, versus the need for expenditures on more frequently occurring disorders? A recent study from China reported the mortality rate from MH in areas without Dantrolene to be over 50%. Many anesthesia professionals working at ambulatory facilities in the US have found themselves in discussions about the need to stock Dantrolene if volatile agents are not routinely used, and succinylcholine is only used for emergency airway management. However, there is evidence that keeping Dantrolene on hand is cost effective and optimal for safe patient care wherever triggering agents can be administered to patients.

And now it’s time to introduce the four 4 C’s of MH Management. This represents an enhanced role for anesthesia professionals to be perioperative physicians who provide the highest level of safe anesthesia care in the operating room and even after the patient leaves the operating room. After the acute management of MH, a multidisciplinary team is necessary to complete the diagnosis, treatment, genetic testing, and genetic counseling for patients and their families. Here are the 4 C’s.

1. Controlthe acute syndrome.
2. Consult genetic and neurologic colleagues.
3. Confirm with genetic testing.
4. Communicate the results and plans for care with the patient, family, and other health care providers.

Check out the infographic in the article with the 4 C’s for a visual reminder of this MH management strategy. Going forward, the authors leave us with several important action items.

• The revision of the MH susceptibility diagnostic testing recommendations by the Malignant Hyperthermia Association of the United States to include genetic testing after all suspected MH cases
• The creation of a system to connect anesthesia professionals who manage MH to clinical geneticists, genetic testing platforms, and neurologists familiar with MH.
• Assurance of communication of an MHS diagnosis in electronic medical records
• Dissemination of MH education globally, including advocating for stocking dantrolene in all centres where triggering agents may be used.

This is an area where anesthesia professionals can continue to have a big impact in improving anesthesia patient safety for patients with MH susceptibility.

Before we wrap up for today, we are going to hear from Rosenberg again. I also asked him what he envisions for the future when it comes to Malignant Hyperthermia. This is what he had to say.

[CLIP 8 again] “In the future, it will be possible to detect malignant hypothermia susceptibility by genetic testing such as whole exome genetic sequencing.  Whenever there is a question of malignant hypothermia susceptibility, it will be possible to determine the risk of the syndrome. Furthermore, rapidly developing is  newborn genetic sequencing for all newborns, much the same way as it has been done for determination of 30 to 35 inborn errors of metabolism.”

[CLIP 9 again] “Anesthesia providers need to be aware of and be able to interpret genetic results and how to apply them to patients and their families.  I envision a time when the syndrome of malignant hypothermia will occur  ever more infrequently than at the present time, thanks to DNA testing. Furthermore, the application of genetic testing for malignant hypothermia susceptibility has been advocated and employed by members of the European Malignant Hypothermia Group for several years already.”

[Bechtel] Thank you so much to Rosenberg for contributing to the show today. Many anesthesia professionals will never see a case of malignant hyperthermia, but we must be prepared to treat it, and we need to be prepared to provide safe anesthesia care for patients who are susceptible to MH.

If you have any questions or comments from today’s show, please email us at [email protected]. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today.

And that’s a wrap on our shows for 2024, but don’t worry we will be back next week, which is next year with another show. We are looking forward to bringing you another great year of anesthesia patient safety podcast episodes in 2025. Thanks for listening and sharing this podcast. Please continue to do so…and rate us and leave us a 5-star review if you get a chance…so that we can continue our mission.

Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

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