Malignant hyperthermia is a condition characterized by acute hypermetabolism of skeletal muscles. Occurs under the influence of drugs for inhalation anesthesia, caffeine, succinylcholine, stressful situations. It manifests itself in the form of metabolic, cardiovascular, and muscular disorders. Later, DIC syndrome develops, multiple organ failure. The diagnosis is made on the basis of the clinical picture, the results of the analysis for ABB and the data obtained during the caffeine-halothane test. Treatment involves the elimination of all possible triggers, the introduction of a solution of sodium bicarbonate, dantrolene. Physical methods are used to reduce body temperature.
T88.3 Malignant hyperthermia caused by anesthesia
Malignant hyperthermia (MH) is an acute pathological condition characterized by a significant increase in metabolic processes occurring in striated skeletal muscles. It has a pharmacogenetic origin. The frequency of occurrence, according to various sources, varies within 1 case per 3-15 thousand general anesthesia. In adult patients, this indicator is 1 case per 50-100 thousand anesthesia. In reality, there are more cases, but it is not possible to track all abortive forms. In addition, practitioners do not always provide information about such complications. In men, pathology occurs 4 times more often than in women.
The main reason for the development of MH is the effect of drugs and products with a trigger effect. The drugs that can provoke an attack include all inhalation anesthetics, curare-like muscle relaxants, and caffeine. There are fragmentary data on the development of pathology in people who have been subjected to severe mental shock or physical exertion. It is believed that in this case, the production of sympathoadrenal substances (adrenaline, norepinephrine) occurs, which lead to the development of a crisis in people predisposed to this.
People with a dominant mutation of the ryanodine receptor gene of chromosome 19 are considered to be more prone to the occurrence of MH. However, there are cases when, in the presence of obvious prerequisites for the occurrence of hypermetabolic muscle reactions, the gene responsible for the defective receptor was absent in the patient. Predisposition to the disease is usually traced in all blood relatives.
The pathogenesis is based on an increase in the duration of the opening of muscle calcium channels. This leads to an excessive accumulation of calcium ions in the sarcoplasm. The processes of polarization and depolarization are disrupted, which causes generalized muscle contracture (rigidity). ATP reserves are depleted, the splitting of which leads to increased oxygen consumption by cells and the release of thermal energy. Tissue hypoxia develops, lactate accumulates in the muscles, the phenomena of rhabdomyolysis occur. The concentration of potassium, calcium, magnesium, myoglobin and creatine phosphokinase ions in the blood plasma increases.
The primary lesion affects only skeletal muscles. However, the accumulation of toxic products of destruction of muscle tissue within an hour leads to the formation of multiple organ failure, violation of hemodynamics, critical shifts in acid-base balance. Edema of the lungs and brain may develop. A cascade of inflammatory reactions of the oxidative type is triggered. There is an DIC syndrome, which leads to the development of hidden internal and external bleeding.
Malignant hyperthermia can occur in several clinical variants, which differ in the rate of development of pathological processes and the time elapsed from the onset of the trigger to the manifestation of the crisis. In addition, there are differences in the severity and set of symptoms, the severity of the course. There are the following types of pathology:
- Classic. It occurs in 20% of cases. It differs in a detailed clinical picture, occurs immediately after the administration of a drug with trigger activity. Pathology usually develops on the operating table in front of an anesthesiologist who has everything necessary to stop a hyperthermic reaction. The mortality rate is relatively low, the mortality rate does not exceed 5%.
- Abortive. It accounts for about 75% of all cases. It is characterized by a relatively mild course, an incomplete set of clinical symptoms. In many cases, there is no significant increase in body temperature. The most mild variants of the course sometimes go unnoticed or mistakenly refer to other pathological conditions. The mortality rate is 2-4%.
- Deferred. It occurs in 5% of cases, develops a day or more after contact with the provoking factor. It flows relatively easily. The danger for the patient is that 24 hours after the operation, the control of doctors over him weakens. Malignant hyperthermia at the initial stage of development often goes unnoticed or is misdiagnosed.
Symptoms of malignant hyperthermia
Signs of MH are divided into early and late. The early ones occur directly during the development of the crisis, the later ones – after 20 minutes or more. The first symptom is a spasm of the masticatory muscles, followed by generalized muscle contracture. Respiratory acidosis develops, CO2 at the end of exhalation is more than 55 mm Hg. Sweating increases, the skin becomes marbled. Oxygen consumption increases. As metabolic disorders worsen, changes occur in the work of the cardiovascular system: fluctuations in blood pressure, tachyarrhythmia.
The processes of myolysis and cleavage of ATP, developing in spasmodic muscles, lead to a sharp increase in body temperature. Usually this indicator does not exceed 40 °C. There are cases of fever reaching 43-45 ° C, which caused the death of the patient. Due to excessive accumulation of potassium, cardiac arrhythmias increase. Urine becomes dark in color, concentrated, anuria may be noted. The condition is reversible if the treatment measures were started on time. Otherwise, the patient develops complications.
Malignant hyperthermia can cause myocardial infarction, multiple organ failure, disseminated intravascular coagulation. A heart attack develops as a consequence of electrolyte disturbances and generalized muscle spasm. Volumetric areas of myocardial necrosis lead to cardiogenic shock and asystole. Multiple organ failure is characterized by a violation of the function of vital structures, which in 80% of cases leads to the death of the patient. With DIC syndrome, microthrombs form in the vascular bed, which contribute to the strengthening of multiple organ failure. In the future, the resource of the coagulation system is depleted, severe bleeding occurs.
Diagnosis of already developed MH is carried out on the basis of existing symptoms, as well as laboratory examination data. The predisposition to the occurrence of a crisis is determined by the results of specific testing methods. The patient examination algorithm includes:
- Collecting anamnesis. It is possible to determine the presence of a predisposition to the disease in preparation for surgery. To do this, a thorough interview of the patient and his relatives is carried out. A high risk is indicated if among the blood relatives of the patient there are people who have previously suffered a hyperthermic crisis, sudden death during anesthesia, having episodes of unexplained seizures in the anamnesis.
- Laboratory diagnostics. With MH, signs of metabolic acidosis are detected in the blood (pH less than 7.25, base deficiency more than 8 mmol / l), an increase in the concentration of CK to 20 thousand. Units / l and more, concentrations of potassium ions more than 6 mmol / l. Pathological changes in the plasma increase as the process develops. Normalization of indicators occurs within a day from the moment of relief of the crisis.
- Caffeine is a halothane test. It is a specific analysis that reveals a tendency to the occurrence of muscle contracture. During the test, a muscle biopsy is placed in a container filled with trigger solutions. If there is a predisposition to MH, muscle tissue contracts, contracture occurs. The test is carried out only for patients who are at risk, since the procedure for taking biomaterial is traumatic.
- Genetic examination. Patients with a burdened medical history are shown a genetic study. It is aimed at identifying the gene responsible for the predisposition to the development of generalized muscle contractures. A positive study is considered, during which mutations of the RYR1 and CACNA1S genes are detected. Genetic analysis is not used as a general screening method due to the high cost and technical complexity of the work.
Genetically determined attacks of skeletal muscle rigidity should be differentiated with anaphylactic reactions, signs of insufficient analgesia, cerebral ischemia, thyroid crisis, malignant neuroleptic syndrome, insufficient ventilation. An undoubted sign of MH is a decrease in the severity of symptoms shortly after the introduction of dantrolene.
Treatment of malignant hyperthermia
The effectiveness of treatment directly depends on the time that has elapsed since the onset of the attack before the start of resuscitation. In the operating room, the patient is assisted on the spot, interrupting the operation. Treatment consists in the use of non-specialized and etiotropic pharmacological methods, hardware aids, the use of physical methods of hypothermia. The main activities include:
- Termination of contact with the trigger. The supply of inhalation anesthesia is stopped, the contours of the anesthesia-breathing device are purged with a clean breathing mixture. Replacement of the device, contour, intubation tube is not performed. The method of hyperventilation with 100% oxygen is used. The minute volume of breathing in this case is 2-3 times higher than the norm. The duration of the procedure is 10-15 minutes.
- Etiotropic therapy. Patients diagnosed with malignant hyperthermia are shown the introduction of dantrolene, a relaxant with the ability to block ryanodine receptors. The drug reduces the intracellular concentration of Ca, inhibits the transmission of neuromuscular impulse, leads to the rapid elimination of the symptoms of the crisis. The drug is administered dosed, until the patient’s condition normalizes.
- Symptomatic therapy. Depends on the available clinical picture. To maintain hemodynamics, a titrated supply of dopamine through an injectomat can be used. The decrease in body temperature is carried out by applying ice bubbles to the projection area of large vessels, the introduction of cold infusion solutions. A 4% solution of sodium bicarbonate is injected to correct the ABB. Elimination of excess electrolytes, toxins and maintenance of kidney function requires the introduction of loop diuretics.
Prognosis and prevention
The prognosis is favorable if malignant hyperthermia was noticed and stopped in a timely manner. With a prolonged stay of the patient in a state of metabolic acidosis and hypoxia, ischemic damage to the central and peripheral nervous system, disturbances in the work of the cardiovascular apparatus up to atrioventricular blockade, myocardial infarction, fibrillation is possible. In the abortive form, the chances of a successful outcome are much higher than in the classical form.
Specific prevention consists in a thorough preoperative examination aimed at establishing the fact of the patient’s predisposition to muscle contractures. People with a confirmed genetic mutation are recommended to give up coffee and caffeinated beverages, minimize psychological stress in everyday life.