What causes malignant hyperthermia?

Answer 1

WHAT IS MH?

The sudden unexpected death of a healthy individual undergoing minor surgery is a tragedy almost beyond comprehension in this day of modern medical miracles. Yet this still happens to patients susceptible to malignant hyperthermia (MH). Even when treated properly, the syndrome known as the MH crisis can cause death. In rare cases, survivors might be left with brain damage, failed kidneys, muscle damage or impaired function of other major organs.

Another cause of unexpected death during or shortly after anesthesia is a sudden cardiac arrest in a young male patient with muscular dystrophy. In some cases the patient may not be old enough to show the characteristic signs of muscle weakness. The anesthesia care team may therefore not realize that the patient may develop a marked increase in potassium in the blood sufficient to stop the heart when anesthetized. This phenomenon occurs with the use of drugs that "trigger MH," but the syndrome is distinct and different from MH. Another sign of this reaction is severe muscle breakdown manifested by brown urine and kidney failure. (See below: Are There Links Between MH and Other Diseases?)

WHAT IS MALIGNANT HYPERTHERMIA?

The MH crisis is a biochemical chain reaction response "triggered" by commonly used general anesthetics and the paralyzing agent succinylcholine within the skeletal muscles of susceptible individuals. The general signs of the MH crisis include tachycardia (a rise in heart rate), a greatly increased body metabolism, muscle rigidity and/or fever that may exceed 110 degrees F. Severe complications include: cardiac arrest, brain damage, internal bleeding or failure of other body systems. Thus, death, primarily due to a secondary cardiovascular collapse, can result.

WHO IS SUSCEPTIBLE TO MH?

There has been dramatic improvement in our understanding of what causes MH and who is at risk. Over 80 genetic defects have been associated with MH. MH susceptibility is inherited with an autosomal dominant inheritance pattern. This means that children and siblings of a patient with MH susceptibility usually have a 50% chance of inheriting a gene defect for MH and hence would also be MH susceptible. They, therefore, may develop an MH reaction upon exposure to triggers.

Nevertheless, those who are carriers for susceptibility may be completely unaware of this risk unless they or a family member developed a life-threatening crisis during anesthesia. It is important to know that not everyone who has a gene defect linked to MH develops the MH crisis upon each exposure to the triggering anesthetics. (See the section below on Testing for MH susceptibility.)

WHAT DRUGS TRIGGER MH?

The volatile gaseous inhalation anesthetics are MH triggers:

sevoflurane

desflurane

isoflurane

halothane

enflurane

methoxyflurane

Also, succinylcholine (Anectine), the depolarizing muscle relaxant

ARE OTHER ANESTHETICS SAFE?

Yes, all other anesthetic drugs are safe. Some examples of safe anesthetics are:

local anesthetics

nitrous oxide

barbiturates

narcotics

propofol

benzodiazepines

ketamine

etomidate

The non-depolarizing muscle relaxants (used to temporarily produce muscle paralysis) are also safe:

pancuronium

cisatracurium

atracurium

mivacurium

vecuronium

rocuronium

WHAT IS THE INCIDENCE OF MH?

The exact incidence of MH is unknown. The rate of occurrence has been estimated to be as frequent as one in 5,000 or as rare as one in 65,000 administrations of general anesthesia with triggering agents. The incidence varies depending on the concentration of MH families in a given geographic area. High incidence areas in the United States include Wisconsin, Nebraska, West Virginia and Michigan.

Answer 2

Malignant hyperthermia is caused by mutations in the gene for a membrane protein inside the muscle cell, called the ryanodine receptor, which controls calcium ion movement within the muscle.