USU Anesthesiology Researcher Works to Develop Less Invasive Malignant Hyperthermia Screening Method

By Vivian Mason

Dr. Luke Michaelson, an assistant professor in the Department of Anesthesiology at the Uniformed Services University of the Health Sciences (USU), has always been curious about the variable presentation of some diseases. This interest was derived from his experience assessing and treating patients as a nurse in the emergency department.

“What motivated me to focus on the research process was finding answers to questions I had while treating patients,” he said.

Michaelson is currently involved in malignant hyperthermia research. His work focuses on not only performing the diagnostic test for the disorder -- the caffeine halothane contracture test (CHCT) -- but also finding a higher throughput functional assay and discovering a less invasive screening method to determine if someone is susceptible to malignant hyperthermia or not.  

Malignant hyperthermia is a rare, inherited disease of skeletal muscle that presents as a hypermetabolic response (e.g., rise in body temperature, severe muscle contractions, etc.) commonly triggered by halogenated anesthetic gases or succinylcholine, a muscle relaxant normally administered to help secure the airway during procedures. Cases of non-anesthetic-induced malignant hyperthermia have also been well documented, with data suggesting high ambient temperature and exercise being potential triggers of malignant hyperthermia symptoms.

The malignant hyperthermia hypermetabolic response begins when the malignant hyperthermia stressor 
initiates release of excess intracellular calcium within the muscles. These high calcium levels within the muscle cells increase metabolism and also cause the muscles to contract and stay contracted. This results in production of heat, acidosis (a buildup of acid in the bloodstream), and muscle cell breakdown. 

USU is one of only four facilities in the United States that tests for Malignant Hyperthermia (MH). (Photo by Kyle Skerbe)

The Malignant Hyperthermia Association of the United States estimates that 1 in every 100,000 adults undergoing surgery encounters this condition. If a person expresses the genetic mutations associated with malignant hyperthermia, then there is a higher chance that a malignant hyperthermia reaction will occur when exposed to the medication or environmental stressor. Individuals who are susceptible to malignant hyperthermia are classified as “MHS,” and those who are “non susceptible” to malignant hyperthermia are classified as “MHN.”

Given the seriousness of this condition, it’s important that healthcare providers be able to recognize malignant hyperthermia promptly and treat it effectively.

In most cases, no symptoms of the disorder exist until a person is exposed to a clinical or environmental stressor. Signs and symptoms often include a dangerously high body temperature, muscle rigidity, dark brown urine, elevated carbon dioxide levels, severe muscle spasms, a fast heart rate, rapid breathing, breakdown of muscle fibers, and climbing acid levels―symptoms associated with a greatly increased metabolism. 

There are two ways to test for malignant hyperthermia: molecular genetic testing and muscle biopsy/contracture testing.  

“The CHCT is the gold standard for testing individuals. In this test, patients undergo a muscle biopsy that obtains tissue from one of the quadriceps muscles, the vastus lateralis,” said Michaelson. The CHCT is conducted within five hours of harvesting the muscle sample. 

Treatment consists of prompt recognition of the condition, removal of the triggering agents, rapid administration of dantrolene (a muscle relaxant), ice packs to cool the body, and supportive care. During an actual episode, treatment can include wrapping the patient in a cooling blanket and using fans to help reduce the core body temperature, in addition to administering dantrolene. Malignant hyperthermia can cause cardiac arrest, blood clotting deficiencies, renal failure, and eventually death.

Even though individuals may be hereditarily predisposed to this condition, they often may not realize that they may be MHS. For example, if a person requires surgery, knowledge of the malignant hyperthermia status is quite important. If the malignant hyperthermia status is detected before an anesthetic trigger is administered, then other non-malignant hyperthermia triggering anesthetics can be used instead. If a family member has the condition, then the risk of having malignant hyperthermia is higher.  

Michaelson performs his research at USU’s Sheila M. Muldoon Malignant Hyperthermia Diagnostic Laboratory.  Interestingly, USU is only one of four national centers actively testing for malignant hyperthermia using the CHCT. The other three national facilities are located at the University of California–Davis, the University of Minnesota, and Wake Forest Baptist Medical Center. 

USU maintains a significant clinical position because it coordinates the CHCT for both civilian and military members. Civilians receive the muscle biopsy through a longstanding relationship with Children’s National Medical Center, but the CHCT is performed at USU. This center ensures that service members and their families get screened for malignant hyperthermia and that military personnel are prepared appropriately for their mission. 

However, one of the major problems with malignant hyperthermia is that even though a genetic screening method does exist, there are currently 48 known diagnostic mutations associated with the disorder. The USU lab can initially screen a person genetically, and if that person has a mutation, then it is known that he or she will be classified as MHS. If the genetic results do not provide a resulting diagnostic mutation, then the standard for screening remains the actual muscle biopsy and CHCT.

Graphic Credit: Assignmentpoint.com

“What I’m trying to develop is a method to essentially use B cells removed from a blood sample as a way to detect differences between MHS and MHN individuals. I’m attempting to use different fluorescent and oxygen consumption tools to detect metabolic changes that will allow me to discriminate between the two types of individuals,” he said. “It will not only be beneficial to the general population, but also to our military population. Having a higher throughput screening mechanism can only help the readiness of our military force. That’s what I’m trying to evaluate and really develop.”

Military members who may not realize they are MHS may trigger malignant hyperthermia symptoms if they are exposed to the appropriate clinical or environmental stressors, whether they’re in a combat theater or garrison. 

Generally, an individual gets screened only if there is a family malignant hyperthermia history or if the person has suspected muscle symptoms associated with malignant hyperthermia (i.e., excessive contractures, unexplained muscle weakness, myalgias, etc.). That’s why malignant hyperthermia is considered rare. It’s most likely underreported. 

“Right now, the prevalence for being susceptible to malignant hyperthermia is approximately 1 in 2,000. This estimate is extrapolated from documented cases, but most likely that value is underreporting the true prevalence,” Michaelson said.

Detection of early signs and symptoms, awareness of risk factors, prompt treatment/management, and patient education are essential keys to preventing malignant hyperthermia symptoms and saving lives.