Malignant Hyperthermia
Myron Yaster MD, Henry Rosenberg MD, and Teeda Pinyavat, MD
Today’s PAAD, the Story behind the MH hotline,1 comes at a perfect time. Afterall, it’s summertime, with new residents, fellows, student CRNAs and AAs, who are just at the start of their life’s professional journey. And one of the first things they need to learn is that volatile vapor anesthetics and succinylcholine, the quintessential ingredients of a general anesthetic can, in certain individuals and families, actually trigger a potentially lethal disease, Malignant Hyperthermia (MH).
MH has a special meaning to the PAAD community. Throughout his professional career, Ron Litman who started the PAAD and in whose memory we continue it, was actively involved with the Malignant Hyperthermia Association of the United States (MHAUS). I know whenever I read an MH paper, it goes to the top of the list of articles I want to review to further honor Ron’s memory. And before you proceed to read this PAAD, I have 2 requests: I would urge all of you who are working with new trainees to share today’s PAAD, discuss MH, its triggers, causes, and treatment, and encourage those with an interest in pediatric anesthesia to join our PAAD community. Secondly, I would urge all of you and your students to download the free Society for Pediatric Anesthesia’s PediCrisis app V2, which is available in both the Apple and Android stores right now. You’ll need to look at the MH tab in the event list of the app to fully follow today’s PAAD.
Finally, although Ron was a true expert in the management of MH, I most certainly am not. Indeed, I used to joke that more anesthesia faculty studied, published, and got promoted for their clinical and basic science research and expertise on MH than patients who actually had or experienced the disease! To make up for my limitations, I’ve asked one of the world’s real experts on MH and my former teacher, Dr. Henry Rosenberg, to assist. Myron Yaster MD
Original article
Teeda Pinyavat, Henry Rosenberg, Cynthia A. Wong, Kumar G. Belani; The Story Behind the MH Hotline. ASA Monitor 2024; 88:1–8 doi: https://doi.org/10.1097/01.ASM.0001025836.53424.fe
MH is an inherited, autosomal, pharmacogenetic myopathy with multiple manifestations of which MH is the most dramatic example. The genetic site of the majority of mutations that have been found causative in MH are found in the gene for the skeletal muscle ryanodine receptor (RyR1), the primary Ca2+ release channel in sarcoplasmic reticulum (SR) responsible for Excitation-Contraction Coupling Indeed, the presumed pathophysiological trigger is the associated and wildly unregulated release of SR Ca2+ which dantrolene suppresses and even reverses.
MH usually strikes out of the blue and can rapidly lead to muscle rigidity, hyperthermia, elevated end tidal CO2, respiratory and metabolic acidosis, and if not treated promptly and specifically, it can result in death. What do you do when you suspect that your patient is in the midst of an MH crisis? Well, one thing you should definitely NOT do is rely on your memory for either the diagnosis (and differential diagnosis), the treatment algorithm, or dantrolene drug dosing. Since 1982, one of the first things to do has been to call the toll-free MH hotline, which is staffed 24/7 by vetted consultant volunteers….OK, but what’s the number? Good luck trying to figure that out during the first moments of a crisis! “When life-threatening, critical events occur in the operating room, the fast-paced, high-distraction atmosphere often leaves little time to or deliberate about management options. Success depends on applying a team approach to quickly implement well-rehearsed, systematic, evidence-based assessment and treatment protocols. The Society for Pediatric Anesthesia’s Pedi Crisis 2.0 application was developed as a resource to support clinician response decisions to pediatric perioperative life-threatening critical events. Human factors expertise and principles were applied to maximize usability, such as by clustering information into themes that clinicians utilize when accessing cognitive aids during critical events. The electronic environment allowed us to feature optional diagnostic support, optimized navigation, weight-based dosing, critical institution-specific phone numbers pertinent to emergency response, and accessibility for those who want larger font sizes. The design and functionality of the application were optimized for clinician use in real time during actual critical events,”2
Thus, after declaring an emergency and calling for help, the first thing to do is to OPEN the APP! OK. Let’s do that now, so if you haven’t done it yet download the app right now. Go to the Events List which is alphabetical and find Malignant Hyperthermia. The first tab is Verify the diagnosis (DX). The key features of hypermetabolism are listed BUT the order in the app is INCORRECT. Interestingly, the first thing to go awry is not temperature as listed in the tab, rather, it’s an increase in CO2 and a decrease in pH. Indeed, a rise in temperature may be the last thing to rise or may be so subtle you may miss it.
Next, let’s go to the Treatment (Tx) tab. Ahh, at the top of page is the MH hotline number 1-800-644-9737 (1-800-MH_HYPER). But you don’t have to dial. Because the app is built into your cell phone, simply touch the hyperlink and the phone will dial for you!
Follow the app’s algorithm:
Get the MH cart, dantrolene, and if you haven’t already done it, call for help (again if you’ve pre=populated the app’s phone number list, you won’t have to remember what the Board runner, overhead anesthesia assist call number, PICU, and other essential numbers are…they are already there and a simple tap away!
Turn off the volatile agents, put charcoal filters on both limbs of the anesthetic circuit, hyperventilate with 10 L/min O2 which will clear the anesthetic circuit of triggering agents and prevent rebreathing of the vapors. Switch to TIVA.
Next treat with Dantrolene. Undrape the patient if possible (will help with cooling) and have one of your helpers place a large bore IV (or 2!), draw basic labs including an arterial of venous blood gas and electrolytes, particularly potassium. Have your assistants place a Foley bladder catheter. Next, have your assistants turn up the IVs, and give a cold fluid bolus rapidly. Then give dantrolene 2.5 mg/kg rapidly, every 5 minutes until symptoms resolve. You may need to give 10 mg/kg. If no response, consider going to the Differential Diagnosis tab…your diagnosis may be wrong! In our experience the most common differential diagnosis when MH is suspected are sepsis, neuroleptic malignant syndrome or overzealous heating.
There are 2 types of dantrolene. Both are listed in the app with instructions on how to mix and prepare (again this is a job for your helpers!). If in the chaos you can’t think straight, the phone’s calculator can help you. Not stated in the app (and we think, this is something we need to add in the app’s next version) “Make sure the I.V. runs well and that the blood pressure cuff does not go up while the medication is going through. Because it is very alkaline, dantrolene can cause tissue necrosis if extravasated and thrombosis if given too slowly.”1
The app then gives instructions in how to cool the patient and to stop cooling efforts when the patient’s temperature is < 38 degrees C. If the patient is hyperkalemic treat with calcium, sodium bicarbonate, and potentially insulin and dextrose. The drug doses are in the Tx tab and in the DRUGS tab. If you need more help with hyperkalemia, you can also find its treatment on its own event list in the app.
Not stated in today’s article but is in the app, is the treatment for Vtach or atrial fibrillation. The key is to NOT use calcium channel blockers but to treat with amiodarone 5 mg/kg.
Finally, if the patient goes into a cardiac arrest, the app will help once again. Go to the cardiac arrest event tab and contact both the PICU and ECMO team (if available) using the phone numbers in your prepopulated phone call list.
Once stable, if you haven’t done it already call the MH hot line. They will give you instructions for the patient’s disposition, how to watch for recrudescence, how to continue dantrolene after the initial event, etc. The hotline will also give instructions for genetic testing for the patient and family, genetic and neurology follow up and testing, and entry into the registry. It is beyond the scope of the PAAD to go into the follow up in detail, however, in our (HR, TP) opinion it is time to broaden our perspective on the MH syndrome to regard the problem as not unique to anesthesiology and surgery. We need to expand patient care goals beyond the confines of managing the acute MH episode, to include appropriate follow up and assessment of other potentially associated skeletal muscle related conditions. A multidisciplinary approach to the diagnosis, treatment, and genetic counseling for patients and families is of utmost importance. Therefore, we propose the 4 C’s of MH Management:
1. Control the 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.
Send your thoughts and comments to Myron who will post in a Friday reader response.
PS: The MH hotline is sponsored and run by MHAUS(mhaus.org). This is an independent patient advocacy organization formed in 1981 and is funded mainly through donations and advertising. Please consider donating to keep it going.
References
1. Pinyavat T, Rosenberg H, Wong CA, Belani KG. The Story Behind the MH Hotline. ASA Monitor 2024;88(7):1-8. DOI: 10.1097/01.ASM.0001025836.53424.fe.
2. Clebone A, Strupp KM, Whitney G, et al. Development and Usability Testing of the Society for Pediatric Anesthesia Pedi Crisis Mobile Application. Anesthesia and analgesia 2019;129(6):1635-1644. (In eng). DOI: 10.1213/ane.0000000000003935.