What Drugs Can Trigger Malignant Hyperthermia?

Patient Presentation
A 4-year-old male was transferred to a regional children’s hospital for continued treatment of malignant hyperthermia.
He had a tonsillectomy the previous day and he tolerated the procedure well.
In the recovery room his heart rate was slightly elevated but he was discharged home.
Over the evening he developed a low grade fever and began to complain of pain in his extremities.
In the morning, the patient had muscular rigidity where his feet were dorsiflexed and relaxed.
His parents took him to see his regular physician who went with him to the emergency room of the local hospital.
His temperature was now elevated to 39 degrees Celsius.
In the emergency room, the patient was given intravenous fluids and dantrolene.
His mother reports that the muscular rigidity was lessened after the dantrolene was given but the muscle pain continued.
Laboratories in the emergency room showed normal electrolytes but a creatinine phosphokinase of 7684 U/L.
The past medical history showed that he had a previous pressure equalizing tube placement but he was not intubated for that surgery.
He also had multiple episodes of otitis medias in the past and significant snoring. He had 3 episodes of strep throat during the previous winter.
The family history revealed his parents had also had surgeries but did not know if they had been intubated. No other family members had problems with anesthesia.
The review of systems was otherwise normal.
The pertinent physical exam showed an anxious male with normal vital signs except for a temperature of 38 degrees Celsius. He could speak clearly, had no masseter muscle rigidity or trismus.
His cranial nerves were intact. Deep tendon reflexes were present without clonus. He had difficulty raising his arms or legs against gravity but could with some effort. He had to be carried.
He had tender muscles to palpation but no bone or joint pain. He did have back pain with flexion of legs to chest. He had full range of motion in all joints.
The diagnosis of malignant hyperthermia was again confirmed.
The laboratory evaluation was repeated as several hours had gone by since the last testing.
The electrolytes, urinalysis, coagulation profile and electrocardiogram were all normal.
The creatine phosphokinase was now 3408 U/L.
He received another dose of dantrolene. Laboratories were repeated every 6 hours.
The Malignant Hyperthermia Association of the United States (MHAUS) protocol was accessed by Internet before the patient arrived.
The MHAUS hotline was contacted and there also was verbal consultation with local anesthesia consultants after the patient was evaluated.
They both agreed with the treating team’s management plan.
The MHAUS also said that they would assist the family with obtaining a medical alert bracelet for the child and with genetic testing of the family.
The patient’s clinical course over the next 2 days found him gradually regaining his strength.
At discharge he had no pain and his neurological examination was normal. His CPK was 172 U/L.
He was to see his primary care physician the next day and genetic testing and counseling would be done at the children’s hospital within the next month.

Malignant hyperthermia is a medical emergency. It is caused by an abnormality where the metabolism of intracellular calcium is altered causing a hypermetabolic state.
It is triggered by various drugs used for anesthesia. It may occur during anesthesia and in the post-anesthesia period. Symptoms may not be recognized though until hours later.
Signs and symptoms of malignant hyperthermia include:

  • Tachycardia/tachypnea
  • Increasing temperature (may be a late sign)
  • Body rigidity including trunk or total body
  • Masseter muscle rigidity or trismus
  • Myoglobinuria
  • Increasing end tidal CO2
  • Mixed respiratory and metabolic acidosis

Malignant hyperthermia can cause extreme fever, rhabdomyolysis, coagulopathy and even cardiac arrest.
It should be considered with these signs and symptoms and treatment instituted promptly.
Treatment includes halting the procedure if possible, discontinuing volatile anesthetic agents and succinylcholine and/or changing to non-triggering anesthetic agents,
hyperventilating the patient with 100% oxygen, treating with dantrolene sodium, cooling the patient with ice and/or lavage of body cavities, giving intravenous fluids with bicarbonate and monitoring and treating electrolyte abnormalities particularly hyperkalemia.
Intensive care management and monitoring may be necessary in the acute phase.

Dantrolene sodium is given for acute crisis at a dose of 2.5 mg/kg intravenously. It is also available in oral form.
Intravenous treatment may be repeated as often as necessary until the hypermetabolic state is normalized and all symptoms have disappeared
Usually this is 1-4 doses. Other diagnoses should be considered if more than 20 mg/kg is used without benefit.

The MHAUS has a 24 hour hotline available for consultation in the United States and Canada at 800-644-9737,
and internationally at

Laboratory tests to order/monitor include (often done every 6 hours until normalized):

  • Electrolytes – particularly for hyperkalemia
  • Creatinine phosphokinase
  • Myoglobin
  • Arterial blood gas – particularly for acidosis
  • Coagulation profile
  • Electrocardiogram
  • Urine including for myoglobin
  • End tidal CO2

Some patients with malignant hyperthermia have identifiable genetic markers.
These markers may make it possible to identify at risk family members and therefore potentially they can be screened for mutations.
Some patients and family members need to have a muscle biopsy and contracture testing to evaluate malignant hyperthermia susceptibility.

Learning Point

According to the MHAUS, anesthetic agents that are unsafe for patients with malignant hyperthermia are listed below.
“All other anesthetic agents outside of these two categories of Volatile anesthetic agents and depolarizing muscle relaxants are considered safe.”

  • Depolarizing muscle relaxants
    • Succinylcholine (Suxamethonium)
  • Inhaled General Anesthetics
    • Chloroform (Trichloromethane, Methyltrichloride)
    • Desflurane
    • Enflurane
    • Halothane
    • Isoflurane
    • Methoxyflurane
    • Sevoflurane
    • Trichloroethylene
    • Xenon

Questions for Further Discussion
1. What consultants are available locally to manage suspected malignant hyperthermia?
2. How does dantrolene work?
3. Are patients with malignant hyperthermia more susceptible to heat illnesses?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Information prescriptions for patients can be found at MedlinePlus for these topics: Anesthesia and Muscle Disorders.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

Brandom BW.
The genetics of malignant hyperthermia.
Anesthesiol Clin North America. 2005;23(4):615-9, viii.

Dantrolene: Pediatric Drug Information. UpToDate.
Available from the Internet at http://www.uptodateol.com/online/content/topic.do?topicKey=ped_drug/52419&selectedTitle=23~46&source=search_result (rev. 2008, cited 7/20/08).

Malignant Hyperthermia Association of the United States. Medical Professionals
Available from the Internet at http://medical.mhaus.org/ (rev. 2008, cited 7/20/08).

Malignant Hyperthermia Association of the United States. Anesthetic Agent Choice for the MH-Susceptible Patient.
Available from the Internet at http://medical.mhaus.org/index.cfm/fuseaction/Content.Display/PagePK/AnestheticList.cfm (cited 7/20/08).

ACGME Competencies Highlighted by Case

  • Patient Care
    1. When interacting with patients and their families, the health care professional communicates effectively and demonstrates caring and respectful behaviors.
    2. Essential and accurate information about the patients’ is gathered.
    3. Informed decisions about diagnostic and therapeutic interventions based on patient information and preferences, up-to-date scientific evidence, and clinical judgment is made.
    4. Patient management plans are developed and carried out.
    5. Patients and their families are counseled and educated.
    6. Information technology to support patient care decisions and patient education is used.
    7. All medical and invasive procedures considered essential for the area of practice are competently performed.
    8. Health care services aimed at preventing health problems or maintaining health are provided.
    9. Patient-focused care is provided by working with health care professionals, including those from other disciplines.

  • Medical Knowledge
    10. An investigatory and analytic thinking approach to the clinical situation is demonstrated.
    11. Basic and clinically supportive sciences appropriate to their discipline are known and applied.

  • Practice Based Learning and Improvement
    12. Evidence from scientific studies related to the patients’ health problems is located, appraised and assimilated.
    13. Information about other populations of patients, especially the larger population from which this patient is drawn, is obtained and used.
    15. Information technology to manage information, access on-line medical information and support the healthcare professional’s own education is used.
    16. Learning of students and other health care professionals is facilitated.

  • Interpersonal and Communication Skills

    19. The health professional works effectively with others as a member or leader of a health care team or other professional group.

  • Systems Based Practice
    23. Differing types of medical practice and delivery systems including methods of controlling health care costs and allocating resources are known.
    24. Cost-effective health care and resource allocation that does not compromise quality of care is practiced.
    25. Quality patient care and assisting patients in dealing with system complexities is advocated.
    26. Partnering with health care managers and health care providers to assess, coordinate, and improve health care and how these activities can affect system performance are known.

    Donna M. D’Alessandro, MD
    Professor of Pediatrics, University of Iowa Children’s Hospital

    August 11, 2008