1.What is “Malignant Hyperthermia”?
Malignant Hyperthermia (MH) is the only hereditary disease known to cause perioperative death by conventional anesthetic drugs. It is a subclinical myopathy in which a patient with no usual abnormalities develops tonic contractions of skeletal muscle after exposure to volatile inhaled anesthetics (e.g. halothane, enflurane, isoflurane, etc.) and depolarizing muscarinic agents (succinylcholine) during general anesthesia, generating a large amount of energy and leading to a continuous and rapid increase in body temperature, which is difficult to control by general clinical hypothermia measures in the absence of specific therapeutic drugs. Eventually, the patient may die.
2.What is the most common group?
Malignant hyperthermia is more common in congenital disorders such as idiopathic scoliosis, strabismus, ptosis, umbilical hernia, inguinal hernia, etc. It has also been reported sporadically in other surgical conditions;
According to foreign reports, the incidence rate is 1/50,000 in adults and 1/15,000 in pediatric patients; male incidence is more than female; mortality rate (5-10%).
According to domestic literature, there were 34 cases of malignant hyperthermia in China with mortality rate: 73.8%. It is higher than the mortality rate reported abroad.
3.Pathogenesis?
Malignant hyperthermia susceptible persons have defects in the development of skeletal muscle cell membrane structure, and under the action of inducing drugs (mainly volatile anesthetics and succinylcholine), the concentration of calcium ions in myocyte plasma increases rapidly, causing muscle contracture, a sharp increase in heat production and a rapid rise in body temperature. At the same time, a large amount of lactic acid and carbon dioxide are produced, and a series of changes such as acidosis, hypoxemia, hyperkalemia and cardiac arrhythmia occur, which can cause death in serious cases.
4.What are the typical clinical manifestations?
(1) Sudden onset of hypercapnia;
(2) Rapid increase in body temperature, up to 45℃～46℃;
(3) Skeletal muscle rigidity;
5.How to diagnose “malignant hyperthermia” clinically?
(1) According to the typical clinical manifestations
(2) Combine with relevant laboratory test results (mainly phosphocreatine kinase CK and myoglobin MYO)
(3) Exclude the following possible causes of hypermetabolic state: hyperthyroidism, pheochromocytoma, infection, blood transfusion reaction and certain non-specific triggering drug reactions such as neuroleptic syndrome.
Combining the above three aspects, the clinical diagnosis of “malignant hyperthermia” can be made. It is worth noting that the diagnosis of malignant hyperthermia also requires caffeine halothane isolated skeletal muscle contraction test.
6.How to confirm the diagnosis of “malignant hyperthermia”?
The caffeine halothane isolated skeletal muscle contraction test is currently the gold standard for screening and diagnosis of malignant hyperthermia. For patients with (or suspected of having) a family history of malignant hyperthermia, a muscle biopsy should be performed to clarify the diagnosis as much as possible through the caffeine fluorane contraction test, in order to guide the use of anesthetic medication and the formulation of anesthetic plans.
Subjects receiving the test include patients with high clinical suspicion of malignant hyperthermia, first-degree relatives of patients with malignant hyperthermia, and those with occlusal muscle spasm during anesthesia. The Department of Anesthesiology at Peking Union Medical College Hospital is now able to perform this test.
7.What is the significance of genetic testing for the disease?
Although malignant hyperthermia is a hereditary disease, the gene responsible for malignant hyperthermia is not completely clear. Therefore, a definitive diagnosis by genetic testing is not yet possible. However, patients with a confirmed diagnosis (by skeletal muscle contraction test) are genetically tested for gene mutations, and if the same gene mutation is found in their relatives, their relatives can be diagnosed as susceptible to malignant hyperthermia.
The Department of Anesthesiology of Peking Union Medical College Hospital has established the method of gene testing and successfully detected a gene mutation in a family line of malignant hyperthermia.
8.Is there any specific drug for treatment?
Dantrolene is a potent drug for malignant hyperthermia. The possible mechanism of treatment is to relax skeletal muscle by inhibiting the release of calcium ions in the sarcoplasmic reticulum, which acts at the level of skeletal muscle excitation-contraction coupling.
When treating with dantrolene, it should be administered intravenously as early as possible to avoid inadequate perfusion of skeletal muscle blood after circulatory collapse, resulting in the inability of dantrolene to reach the site of action and achieve full muscarinic effect. The drug has side effects such as weakness, nausea and thrombophlebitis, which is rare in China.
9.How to prevent the occurrence of malignant hyperthermia?
(1) Take a detailed medical history, paying special attention to personal and family history of muscular disease and post-anesthesia hyperthermia;
(2) For suspected patients, the diagnosis should be clarified by preoperative muscle biopsy for caffeine halothane contraction test as much as possible to guide the anesthetic medication;
(3) For suspected patients, drugs that induce malignant hyperthermia should be avoided (see Table 3);
(4) In addition to the routine monitoring of pulse, blood pressure, ECG, etc., end-expiratory CO2 and body temperature should be monitored during anesthesia surgery to closely observe changes in the patient’s condition.
10.How to resuscitate after malignant hyperthermia occurs?
(1) Once MH is considered, inhaled anesthetics should be terminated immediately and hyperventilation with high-flow oxygen should be performed to complete the procedure as soon as possible; meanwhile, seek help;
(2)Give intravenous dantrolene as soon as possible; (no drug)
(3) Immediately start cooling (including physical cooling, intravenous infusion of cold saline, intra-gastric ice saline lavage, extracorporeal circulation for cooling);
(4) Establish invasive arterial pressure and central venous pressure monitoring as soon as possible;
(5) Monitor arterial blood gas: correct acidosis and hyperkalemia;
(6) Treatment of cardiac arrhythmias;
(7) Infusion of fluids according to fluid balance, appropriate application of antihypertensive drugs, diuretics, etc., to stabilize hemodynamics and protect renal function;
(8) Application of adrenal corticosteroids;
(9) Post-surgery monitoring and treatment should be strengthened to ensure that the patient safely passes the perioperative period;
11.After successful resuscitation, what else do we need to do?
After the disease is stabilized, muscle specimens of the patient should be taken for skeletal muscle contraction test to clarify the diagnosis, and further genetic testing should be performed to screen susceptible persons for their family members. An appropriate anesthetic protocol can be developed for susceptible individuals to avoid the occurrence of malignant hyperthermia.
Malignant hyperthermia can recur again, and successful initial resuscitation does not mean final success. Intensive monitoring and treatment are needed to ensure that the patient safely passes through the perioperative period.