D Malignant hyperthermia
Definition and incidence
Malignant hyperthermia is an uncommon, life-threatening hypermetabolic disorder of skeletal muscle triggered in susceptible individuals by potent inhalation agents, including sevoflurane, desflurane, isoflurane, and halothane and the depolarizing muscle relaxant succinylcholine. About 52% of cases occur in patients younger than age 15 years, with a mean age of 18.3 years. The exact incidence of MH is unknown, but the rate of occurrence has been estimated to be one in 50,000 in adults and one in 15,000 in children.
Pathophysiology
Although the cause of MH is not yet known with certainty, it is generally agreed that MH is an inherited disorder of skeletal muscle in which a defect in calcium regulation is expressed by exposure to triggering anesthetic agents; intracellular hypercalcemia results. The ryanodine receptor is the major calcium release channel of the sarcoplasmic reticulum, and much attention has been focused on this receptor as the site of the MH defect. The defect involves skeletal muscle, and there is no evidence for a primary defect in cardiac or smooth muscle cells.
Malignant hyperthermia is initiated when specific triggering agents induce increased concentrations of calcium in the muscle cells of MH-susceptible (MHS) patients. Actomyosin cross-bridging, sustained muscle contraction, and rigidity result. Energy-dependent reuptake mechanisms attempt to remove excess calcium from the myoplasm, increasing muscle metabolism two- to threefold. The accelerated cellular processes increase oxygen consumption, augment carbon dioxide and heat production, deplete adenosine triphosphate (ATP) stores, and generate lactic acid. Acidosis, hyperthermia, and ATP depletion cause sarcolemma destruction, producing a marked regress of potassium, myoglobin, and creatine kinase (CK) to the extracellular fluid. Skeletal muscle constitutes 40% to 50% of our body mass, so relatively small changes in muscle metabolism may produce the dramatic systemic biochemical changes observed with MH.
Clinical manifestations
Not all cases of MH are fulminant, but rather there is a spectrum or continuum of severity, ranging from an insidious onset with mild complications to an explosive response with pronounced rigidity, temperature rise, arrhythmias, and death. Although MH may present in several ways, a typical MH episode begins while the patient is under general anesthesia with a volatile anesthetic. Use of succinylcholine may or may not precede the MH episode. The onset of MH symptoms may occur immediately after induction of anesthesia or several hours into the surgery. Desflurane is a weaker MH trigger and has been associated with delayed onset of MH, as long as 6 hours after induction of anesthesia. Succinylcholine appears to accelerate the onset and increase the severity of the MH episode. The presentation of MH may follow a dose-dependent response, with lower concentrations of volatile anesthetics resulting in a more protracted onset of hypermetabolic symptoms. Rarely, MH occurs in the recovery room, usually within 1 hour after general anesthesia.
The clinical features of MH reflect increased intracellular muscle Ca2+ concentration and greatly increased body metabolism and are listed in the following section. Common signs of MH include tachycardia, tachypnea, skin mottling, cyanosis, and total body or jaw muscle rigidity. Muscle rigidity is clinically apparent in 75% of cases. The most sensitive indicator of MH is an unanticipated increase in end-tidal carbon dioxide (ETCO2) levels out of proportion to minute ventilation. The increased ETCO2 may be abrupt, or it may rise gradually over the course of the anesthetic. Hyperthermia, which may climb at a rate of 1° to 2° C every 5 minutes and exceed 43.3° C (110° F), is often a late but confirming sign of MH.
Laboratory results
The combination of acidosis, hyperkalemia, and hyperthermia leads to cardiac irritability, a labile blood pressure, and arrhythmias that can rapidly progress to cardiac arrest. Laboratory findings mirror the muscle breakdown and include myoglobinuria and increased serum potassium and CK. Serum CK levels peak 12 to 24 hours after the onset of MH. Myoglobin appears in the plasma within minutes of the hypermetabolic muscle response. Arterial and venous blood gas analysis reveals decreased oxygen tension and mixed metabolic and respiratory acidosis. Late complications may include cerebral edema, myoglobinuric renal failure, disseminated intravascular coagulopathy, hepatic dysfunction, and pulmonary edema.
The variable time course and the nonspecific clinical features and laboratory findings can make the diagnosis of MH difficult. Insufficient anesthetic depth, hypoxia, neuroleptic malignant syndrome, propofol infusion syndrome, thyrotoxicosis, pheochromocytoma, and sepsis can share several characteristics with MH, making the clinical picture ambiguous and the differential diagnosis challenging to even the most experienced practitioner. Surgical procedures performed of necessity in a darkened operating room can further compromise the practitioner’s diagnostic acumen.
In addition to being a trigger of MH, succinylcholine may also induce hyperkalemic-mediated cardiac arrest in children with occult myopathies. Because of this concern, most anesthetists use nondepolarizing muscle relaxants for elective intubation in children and reserve the use of succinylcholine for treatment of laryngospasm or emergency airway management.
Preoperative assessment and prevention
Malignant hyperthermia–susceptible patients may be otherwise healthy and completely unaware of their risk until exposed to a triggering anesthetic. Furthermore, not everyone who has the MH gene develops an MH episode upon each exposure to triggering anesthetics. It is estimated that about 21% of MHS patients have at least one uneventful anesthetic before having an MH episode. Although MH susceptibility cannot be ruled out by history alone, every surgical patient should be questioned about the following information:
