Malignant hyperthermia—the perioperative nurse's role

AORN Journal, Jan, 2006 by Ruth Hommertzheim, Elaine E. Steinke

Malignant hyperthermia (MH), also known as malignant hyperpyrexia, is a rare, genetic, autosomal-dominant, life-threatening disease. This hypermetabolic disorder of skeletal muscle, which is a true emergency in the OR, can result in death if left untreated. Malignant hyperthermia usually is triggered during or after administration of commonly used general anesthetics. This article examines the relationship of MH to the use of anesthetics in the perioperative arena.

EPIDEMIOLOGY OF MALIGNANT HYPERTHERMIA

In the 19th century, ether and chloroform were commonly used anesthetic agents. Monitoring of anesthetized patients was minimal, however, and usually included only placing a finger on the patient's pulse and observing respirations and skin color changes; body temperature rarely was measured. Death was not infrequent and often was unexplained. (1) By the beginning of the 20th century, medical literature included reports of fulminate fever and tachycardia during or immediately after anesthesia that often ended in death.

The first documented case of MH to be reported in modern literature was in the 1960s. (1) The case involved a 21-year-old trauma patient who had a strong family history of temperature-related complications of anesthesia. The patient experienced hypotension and tachycardia and became cyanotic and extremely hot after 10 minutes under general anesthesia. The anesthesia care provider immediately stopped the anesthesia, and team members packed the patient in ice. The patient recovered without sequelae.

Not all causes of MH involve anesthesia pharmacology. There have been reported cases of MH triggered by events such as

* certain myopathies (ie, Evans, KingDenborough);

* emotional stress;

* heatstroke;

* neuroleptic malignant syndrome;

* strenuous exercise exertion; and

* trauma. (2)

Mutations in different genes have been identified in families with susceptibility to MH, including genes encoding a voltage-dependent calcium channel (ie, Iq32), an L-type voltage-dependent calcium channel (ie, 7q21-q22), and a ryanodine receptor (ie, 19q13.1). (3)

Malignant hyperthermia occurs most commonly between the ages of two and 42 years. More than two-thirds of people who experience MH are men. (4) The incidence of MH is between one in 50,000 to one in 100,000 adults and one in 300,000 to one in 500,000 children. (5) First-degree relatives of someone who has had MH or been diagnosed as MH susceptible are much more susceptible to MH than the general population. Second-degree relatives are less susceptible than first-degree relatives but have a greater than normal risk compared to the general population. (5) In the past, mortality from MH was reported to be as high as 70%. (6) With awareness and rapid treatment, mortality is now less than 10%. (6) Mortality during MH is a result of

* acidosis,

* hyperkalemia,

* organ failure because of hyperthermia,

* disseminated intravascular coagulation, and

* renal failure because of myoglobinuria.

NORMAL MUSCLE PHYSIOLOGY

A normal muscle contraction starts with an action potential, which releases calcium from the sarcoplasmic reticulum (Figure 1). The calcium binds to troponin, producing adenosine triphosphate (ATP), which breaks down to adenosine diphosphate (ADP) plus phosphate (P) plus heat. This causes actin and myosin to contract (ie, a muscle contraction). Calcium pumps rapidly transfer calcium from the muscle back into the sarcoplasmic reticulum. Relaxation occurs when the concentration of calcium in the sarcoplasmic reticulum is less than the mechanical threshold.

[FIGURE 1 OMITTED]

PATHOPHYSIOLOGIC MECHANISMS OF MH

Malignant hyperthermia is a fulminating hypermetabolic state triggered by an abnormality of calcium release or reuptake by the sarcoplasmic reticulum with muscle contraction (Figure 2). Malignant hyperthermia occurs

   in genetically predisposed individuals
   when exposed to triggering agents. It is
   now known that the primary defect in
   MH resides in the skeletal muscle at the
   level of calcium transfer in the muscle
   cell. The resultant intracelhdar hypercalcemia
   leads to hypermetabolism,
   which in turn results in increased sympathetic
   activity, increased carbon
   dioxide production, increased oxygen
   consumption, and disruption of the cell
   membranes. Because of the inability of
   muscle tissue to return to a resting
   state in the susceptible patient, the primary
   signs of MH begin to appear. (6(p133))

[FIGURE 2 OMITTED]

According to one researcher, MH is initiated by two processes--an abnormality of a cell, making it predisposed to MH, and a triggering agent. (5) "The most common clinical presentation of MH is ... in response to certain anesthetic agents (ie, the triggering agents). The most notable of these agents are succinylcholine and halogenated volatile anesthetics." (5(p6))

One group of researchers studied the interaction of halothane and dantrolene with sarcoplasmic reticulum membranes from normal pigs and pigs with MH. (7) Dantrolene is a skeletal muscle relaxant that works by inhibiting the release of calcium from the sarcoplasmic reticulum during muscle contraction. The researchers found that dantrolene stabilized the organization of the membranes in a lamellar phase. The researchers concluded that MH syndrome is not directly related to the polar heads of phospholipids, and dantrolene nonspecifically counteracts the disturbing effect of halothane on the lipids. The modifications in the core of the bilayer already reported in MH sarcoplasmic reticulum membranes could explain the different behavior of the small vesicles obtained from MH sarcoplasmic reticulum membranes in the presence of halothane. (7)