Related articles: Malignant hyperthermia
Definition
Malignant hyperthermia is a drug-genetic syndrome characterized by an elevation of the life-threatening body temperature.
This pathological condition is generally secondary to a hypermetabolic response to the concomitant administration of a depolarizing muscle relaxant (such as succinylcholine) and a powerful inhaled anesthetic (halogenated gases, such as halothane, sevoflurane and desflurane). Rarely, in humans it occurs after secondary physical stresses to excessive exercise or to heat.
Malignant hyperthermia recognizes a genetic predisposition and is inherited as an autosomal dominant trait. In most cases, the cause of the disorder is a mutation involving the rianodine receptor (calcium channel protein of the sarcoplasmic reticulum of the musculoskeletal fiber), encoded in the q12-q13.2 region of chromosome 19. However, they are More than 22 different genetic alterations involved in the syndrome have been identified.
In predisposed patients, the mechanism underlying malignant hyperthermia can be related to an uncontrolled increase, induced by the anesthetic, of calcium leakage from the sarcoplasmic reticulum of the skeletal musculature.
As a result, the biochemical reactions triggered by calcium are accelerated, producing severe muscle contractions and increasing the metabolic rate.
Malignant hyperthermia is potentially lethal.
Most common symptoms and signs *
- Respiratory acidosis
- Arrhythmia
- Coma
- Hypercapnia
- hyperkalaemia
- Hypocalcemia
- Hypoxia
- Rhabdomyolysis
- Stiffness in the muscles of the back and neck
- Muscle spasms
- Tachycardia
- tachypnoea
- Dark urine
Further indications
In genetically predisposed individuals, malignant hyperthermia occurs, during anesthesia (from 10 minutes to a few hours after the concomitant administration of a volatile anesthetic gas and a depolarizing muscle relaxant) or in the post-operative period (immediately after the intervention).
The clinical picture is variable and depends on the drug combination and the patient's predisposition.
The manifestations include muscle stiffness (especially in the maxillary region), tachycardia, arrhythmias and tachypnea. Hyperthermia is marked: body temperature is usually above or equal to 40 ° C and sometimes can be extremely high (ie> 43 ° C).
Typical signs are also the increase in expired carbon dioxide (hypercapnia) and oxygen consumption (hypoxemia).
Urine may appear brown or frankly ematuric in the case of rhabdomyolysis (destruction of many muscle fibers).
The possible complications of malignant hyperthermia include respiratory and metabolic acidosis, hyperkalemia (increased potassium in the blood), hypocalcemia, myoglobinuria and coagulation abnormalities (in particular, disseminated intravascular coagulation).
The diagnosis is clinical and is based on the in vitro detection of muscle contraction on biopsies in response to halothane, caffeine and other substances.
Patients at risk, on the basis of a family history of the disorder or a previous adverse reaction to general anesthesia, can undergo a genetic test that evaluates the possible susceptibility to malignant hyperthermia.
In case of malignant hyperthermia, the high priority treatments consist in rapid cooling in order to avoid damage to the central nervous system and in support measures to correct the metabolic abnormalities present. In some patients, tracheal intubation and pharmacological coma are necessary in order to control symptoms and provide the necessary support for vital functions.
Malignant hyperthermia has a high mortality rate and may not respond to therapy, even if it is established early and aggressively.
