APSF Newsletter: Online-Only

MH Survival without Dantrolene

August 25, 2020

Wayne Simmons, DO; Dandan Feng, MD; Zhengliang Ma, MD; Xiaoping Gu, MD; Jeffrey Huang, MD

IV Hookup

Disclaimer: Viewers of this material should review the information contained within it with appropriate medical and legal counsel and make their own determinations as to relevance to their particular practice setting and compliance with state and federal laws and regulations. The APSF has used its best efforts to provide accurate information. However, this material is provided only for informational purposes and does not constitute medical or legal advice. This response also should not be construed as representing APSF endorsement or policy (unless otherwise stated), making clinical recommendations, or substituting for the judgment of a physician and consultation with independent legal counsel.

Treatment of intraoperative malignant hyperthermia (MH) usually involves administration of IV dantrolene, which reduces the mortality from over 80% if untreated to less than 10%.1 When dantrolene is simply not available, physical and metabolic treatments must be employed. Patient survival is possible, as illustrated in three cases from one hospital in China.

Current Recommended Therapy

Malignant Hyperthermia (MH) is a rare but life-threatening pharmacogenetic disorder seen in approximately 1:100,000 adults and in 1:30,000 children.2 The most important immediate treatment of acute intraoperative MH is discontinuing MH triggering agents, hyperventilation, and administration of dantrolene. Initial dosing of dantrolene is 2.5mg/kg IV. After the acute MH crisis, maintenance dantrolene should be continued 1 mg/kg every 4-6 hours while monitoring for signs of recrudescence.3 Following successful treatment of acute MH, the Malignant Hyperthermia Association of the United States (MHAUS) has a follow-up protocol to follow until all signs have abated.3

Treatment of hypercarbia and acidosis is critical, but prolonged hyperthermia worsens patients’ outcomes and should also be treated. Noninvasive treatments of hyperthermia include skin cooling, strategic ice packing, forced air cooling, circulating cool water blankets, cold intravenous fluids, and ice-water immersion. Invasive treatments can involve instillation of iced saline into the bladder and peritoneal cavity, or even in the most extreme circumstance, cardio-pulmonary bypass or extracorporeal membrane oxygenation. When dantrolene is not available, metabolic and physical treatments are necessary.

Case Reports from an orthopedic hospital in China

Three cases have been reported involving MH during scoliosis surgery in otherwise healthy teenaged pediatric patients where dantrolene was unavailable and was not administered. All 3 patients survived with supportive treatment only. All patients received midazolam, propofol, fentanyl, vecuronium, and remifentanil. During maintenance, 2 received isoflurane and 1 sevoflurane. An increased CO2 and tachycardia were the first signs that began at about 1 hour post induction with isoflurane and 3 hours with sevoflurane. Ventilation changes were made to counteract hypercarbia. Temperature elevation was a later sign in all 3 cases, which prompted discontinuation of presumed causative inhalation agents, and then active cooling measures, including external cooling in various forms (ice packs/cooling blankets/alcohol sponge bath) and to multiple body locations (head, axillae, groin), as well as chilled saline IV boluses. Acid/base imbalances were treated with sodium bicarbonate, and electrolyte maintenance was given. Volume resuscitation and vasopressors were required for hemodynamic stability. One patient required CPR, but ultimately return of spontaneous circulation was achieved. All 3 patients were mechanically ventilated in the ICU. Two patients received diuretics to help remove tubular myoglobin5 One patient required continuous renal replacement therapy. All 3 patients ultimately survived without major morbidity resulting from the episode of MH. No dantrolene was ever administered.

Discussion

In suspected MH, triggering agents should be discontinued immediately and providers should call for help. The patients should be hyperventilated with 100% oxygen at maximum fresh gas flow, increasing minute ventilation 2-3-fold, aiming for a normal PETCO2. Hyperthermia is treated as indicated in these cases until the body temperature reaches 38.5°C.4 Reliable core temperature measurement was found to be important. If the Internet is available during an acute event, the MHAUS recommended diagnostic and treatment protocols can be accessed for reference in real time.

Case review concluded that the inhalational agents were the most likely MH triggers. While the gold standard of DNA analysis was not available to definitively confirm MH susceptibility in these 3 patient; the widely accepted Clinical Grading Scale for MH showed 2 patients were category 6 (“almost certain”) and the 3rd was a 5 (“very likely”)6. In all three cases, keys to treatment were active cooling, volume status, plus acid-base and electrolyte balance.

This hospital had 3 cases in 7000 scoliosis surgeries over an 11-year span, indicating the low incidence of MH. However, valuable protocols were established as a result of these cases in which the patients ultimately survived without significant morbidity for future similar circumstances in which dantrolene is not available.

 

HCA Disclaimer

“This article was supported (in whole or part) by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this presentation represent those of the author and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.”

 

Wayne Simmons is a CA2 Anesthesiology resident of the HCA Healthcare / USF Morsani College of Medicine GME/Oak Hill Hospital Anesthesiology Residency Program in Brooksville, FL.

Dandan Feng is a staff Anesthesiologist of the Department of Anesthesiology, Drum Tower Hospital of Medical School of Nanjiang University in Nanjiang, China

Zhengliang Ma is Professor and Chair of the Department of Anesthesiology, Drum Tower Hospital of Medical School of Nanjiang University in Nanjiang, China

Xiaoping Gu is Professor and Vice-Chair of the Department of Anesthesiology, Drum Tower Hospital of Medical School of Nanjiang University in Nanjiang, China

Jeffrey Huang is program director of the HCA Healthcare/USF Morsani College of Medicine GME Anesthesiology Residency/Transitional Year Residency at Oak Hill Hospital in Brooksville, FL, Professor at the USF Morsani College of Medicine and Professor at the University of Central Florida College of Medicine. He serves on the APSF Committee on Education and Training.


The authors have no conflicts of interest.


References

  1. Krause T, Gerbershagen MU, Fiege M, et al. Dantrolene – A review of its pharmacology, therapeutic use and new developments. Anaesthesia, 2004;59:364–373.
  2. MHAUS.org https://www.mhaus.org/mhau001/assets/File/Recommendations%20with%20Table%20of%20Contents(1).pdf, accessed August 10, 2020.
  3. Burkman JM, Posner KL, Domino KB. Analysis of the clinical variables associated with recrudescence after malignant hyperthermia reactions. Anesthesiology. 2007;106:901-906.
  4. Glahn KP, Ellis FR, Halsall PJ, et al. Recognizing and managing a malignant hyperthermia crisis: guidelines from the European Malignant Hyperthermia Group. Br J Anaesth. 2010;105:417–420.
  5. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361:62–72.
  6. Larach MG, Localio AR, Allen GC, et al. A clinical grading scale to predict malignant hyperthermia susceptibility. Anesthesiology. 1994, 80:771-779.