What Drugs Trigger Malignant Hyperthermia?

Malignant hyperthermia is a disorder which triggers high fever, an increased heartbeat, rigidity in muscles and disintegration of muscle fibers when individuals prone to it are exposed to certain drugs used in surgical procedures.

Malignant hyperthermia is a disorder inherited by individuals which when exposed to a skeletal muscle relaxant named succinylcholine used during intubation or surgery, and general anesthesia via inhalation experience a severe possibly fatal reaction leading to hypermetabolism. This is caused due to increased release of intracellular calcium due to an abnormality caused on account of mutations in mainly the ryanodine receptor type 1 (RYR1) and CACNA1S genes in skeletal muscle of the individuals which are susceptible to this disorder.

The ryanodine receptor in the skeletal muscle has control over the amount of intracellular calcium released while CACNA1S controls the transportation of calcium ions which in turn are responsible for a cell’s electrical signals. The condition can also be triggered a while after exposure to these anesthetic drugs and muscle relaxants and the symptoms may not be realized until hours later. In certain cases, the vital signs and other parameters are all fine except for extreme muscle pain and high fever.

Some other severe symptoms due to this hypermetabolism in malignant hyperthermia are tachycardia, respiratory and metabolic acidosis, and cardiac arrest, impairment of blood coagulation, kidney failure, other organ failures and very high levels of potassium (hyperkalemia) which is critical to the function of nerve cells.

What Drugs Trigger Malignant Hyperthermia?

According to the Malignant Hyperthermia Association of the United States (MHAUS) the following drugs except for inhalational general anesthetics and succinylcholine, the following drugs trigger malignant hyperthermia:

  • Halothane
  • Isoflurane
  • Desflurane
  • Enflurane
  • Ether
  • Methoxyflurane
  • Sevoflurane

These are either volatile anesthetic agents or depolarizing muscle relaxants. But there is no certainty of a trigger reaction. People who have malignant hyperthermia may not experience a reaction to these drugs on multiple occasions and might just be triggered in another instance. There have been incidents when reactions have been reported even with safe drugs being administered and you can never know for sure if a reaction could occur. According to MHAUS all local anesthetics are safe.

Safe Anestheic Agents For Malignant Hyperthermia

Barbiturates / intravenous anesthetics for malignant hyperthermia:

  • Hexobarbital
  • Diazepam
  • Etomidate (Amidate)
  • Methohexital (Brevital)
  • Midazolam
  • Ketamine (Ketalar)
  • Pentobarbital
  • Thiopental (Pentothal)
  • Propofol (Diprivan)

Inhaled non-volatile general anesthetics for malignant hyperthermia:

  • Methadone
  • Morphine
  • Naloxone
  • Oxycodone
  • Nitrous Oxide
  • Narcotics (Opioids)
  • Alfentanil (Alfenta)
  • Phenoperidine
  • Remifentanil
  • Sufentanil (Sufenta)
  • Anileridine
  • Codeine (Methyl Morphine)
  • Diamorphine
  • Fentanyl (Sublimaze)
  • Hydromorphone (Dilaudid)
  • Meperidine (Demerol)

Safe muscle relaxants for malignant hyperthermia:

  • Arduan (Pipecuronium)
  • Neuromax (Doxacurium)
  • Nimbex (Cisatracurium)
  • Norcuron (Vecuronium)
  • Pavulon (Pancuronium)
  • Curare (The active ingredient is Tubocurarine)
  • Gallamine
  • Methocarbamol (Robaxin, Robaxin-750, Carbacot, Skelex)
  • Metocurine
  • Mivacron (Mivacurium)
  • Tracrium (Atracurium)
  • Zemuron (Rocuronium)

Anxiety Relieving Medications

  • Ativan (Lorazepam)
  • Centrax
  • Midazolam (Versed)
  • Paxil (paroxetine)
  • Paxipam (Halazepam)
  • Restoril (Temazepam)
  • Serax (Oxazepam)
  • Dalmane (Flurazepam)
  • Halcion (Triazolam)
  • Klonopin
  • Librax
  • Librium (Chlordiazepoxide)
  • Tranxene (Clorazepate)
  • Valium (Diazepam)

The most widely used method to test for malignant hyperthermia is the caffeine halothane contracture test (CHCT). Genetic testing is also recommended if such a reaction is observed. On early detection, doctors usually give the patients varied doses of Dantrolene and use hyperventilation. Dantrolene is used as an antidote which takes care of muscle rigidity and restores normal metabolism by checking the abnormal calcium. But the individual may still suffer from muscle pain and high fever for prolonged periods of time.

The MHAUS has a hotline number for help for incidents taking place in the U.S as well as outside the country. Post the acute event doctors need to pay utmost attention to the patient and monitor various metrics like ECG, ETCO2, heart rate, breathing, urine samples, potassium levels and coagulation. The United States also has a registry for Malignant Hyperthermia susceptible patients in Neuroleptic Malignant Syndrome Information Service for reference in the future so that the patient does not have to go through another traumatic experience of the same kind.

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