Malignant Hyperthermia: Causes, Symptoms & Treatment

Malignant hyperthermia is a rare but life-threatening complication of anesthesia. It is triggered by various trigger substances, including some anesthetic agents, when a genetic predisposition is present.

What is malignant hyperthermia?

The cause of malignant hyperthermia is a genetic alteration of receptors in skeletal muscle. Normally, skeletal muscle contracts by releasing calcium ions from the sarcoplasmic reticulum, a calcium store in skeletal muscle cells. When a muscle contraction is to be triggered, an electrical signal is transmitted to the muscle cell via the motor end plate. This leads to the activation of a voltage-dependent ion channel in the T-tubules, i.e. in special cell membrane protrusions. This ion channel lies adjacent to a calcium channel of the sarcoplasmic reticulum. This in turn is called the ryanodine receptor. It is subsequently opened. Calcium now flows into the cytosol, allowing contraction of the myosin and actin filaments of the muscle. This results in contraction of the entire muscle. If malignant hyperthermia is present, the aforementioned receptors are altered due to a genetic predisposition in such a way that calcium release occurs in the muscle even when certain trigger substances are administered, including narcotics. However, this is much stronger than in normal cases. Therefore, muscle fibers become overly activated.

Causes

This excessive activation is very critical because the effused calcium must subsequently be transported back into the sarcoplasmic reticulum. In addition, the contractile elements actin and myosin have to detach from each other again. For these two regenerative processes, the body requires ATP as an energy supplier. Due to the disproportion, an energy deficiency quickly occurs in the muscle cells. The free calcium ions greatly increase cell metabolism, which in turn causes increased oxygen turnover and increased carbon dioxide and heat production. Initially, the above-mentioned processes take place exclusively in the skeletal muscles, but as time goes on, necrosis and muscle breakdown occur due to the continuously deteriorating regenerative capacity. Furthermore, harmful carbon dioxide and lactate accumulate, which cause hyperacidity of the body. In connection with this, the body temperature increases, which in turn damages other organs. The heart muscles are not primarily affected by the pathological changes in malignant hyperthermia, but in the course of the above-mentioned processes, the heart is also damaged, so that death can occur due to circulatory failure.

Symptoms, complaints, and signs

The clinical picture of malignant hyperthermia is characterized by a severe metabolic derailment, particularly in the skeletal muscles. Further symptomatology varies widely. Depending on the time, the clinical picture presents itself differently and not all signs always appear. Early signs of malignant hyperthermia are an increased carbon dioxide concentration in the exhaled air and an increase in heart rate. In addition, there may be muscle rigidity, a spasm of the masseter muscle, a general lack of oxygen, and hyperacidity of the body. Only at a later stage does the eponymous significant increase in body temperature set in. Finally, cardiac arrhythmias, a drop in blood pressure, muscle breakdown and an increased release of potassium can also occur. Already the early signs must be paid attention to absolutely, because malignant hyperthermia leads to death if no countermeasures are taken.

Diagnosis and course of the disease

Because the development of malignant hyperthermia is acutely life-threatening, the diagnosis must be made as early as possible and then effective therapy initiated without delay. In all cases, priority is given to stopping the intake of triggering substances. Inhalational anesthetics are discontinued and anesthesia is continued with intravenous drugs. These do not normally exhibit malignant hyperthermia-triggering effects.

Complications

Usually, this condition leads to a life-threatening situation that must be treated immediately by a physician. Since this complaint usually occurs directly during anesthesia, it can also be diagnosed and eventually treated immediately by a physician.Patients suffer from an increased heart rate and also from an increased concentration of carbon dioxide in the air they breathe. Furthermore, muscle rigidity also occurs and the patients suffer from a lack of oxygen. The undersupply of oxygen to the organs can lead to severe damage to the internal organs, which is usually irreversible and can no longer be treated. In the worst case, the patient will die if the complaint is not treated immediately. There is discomfort to the heart and eventually cardiac death. The treatment of this complaint is done with the help of medication. This relieves the discomfort and stabilizes the circulation. In most cases, complications only occur if treatment is not initiated early. If treatment is successful, there is no reduction in life expectancy.

When should you see a doctor?

Malignant hyperthermia is a complication of anesthesia. Therefore, it is not a disease whose symptoms occur in everyday life and thus indicate a need for treatment. Since the patient is already under medical supervision during anesthesia, there is no need for action on the part of the patient. In addition, the patient has been placed in a state of unconsciousness during this phase. It is therefore not possible for him to indicate any existing complaints or irregularities of the autonomic nervous system. The occurring changes within the organism are noticed by the hospital staff present and immediately forwarded to the attending physician. Consultation with a physician is necessary as soon as a diagnosis of malignant hyperthermia has been made in a blood relative within the family. Special examinations and tests should be performed on the offspring to determine whether the disease has been inherited. Consultation with the treating physician is necessary before surgical intervention in those affected with an existing genetic disposition. He or she should be informed in detail about the incidents within the family, and existing test results should be provided.

Treatment and therapy

Specific drug therapy is possible with the active substance dantrolene. This is a substance administered intravenously that inhibits calcium release from the sarcoplasmic reticulum. In this way, malignant hyperthermia is treated causally. In parallel, however, symptomatic therapy also takes place. This includes circulatory stabilization, compensation for hyperacidity of the body, a supply of electrolytes and, if present, the treatment of cardiac arrhythmias. Hyperthermia, i.e. the increase in body temperature, is a late symptom. For this reason, active cooling of the body is not necessary until further progress. At all times, circulatory monitoring should be performed by invasive blood pressure registration via an arterial catheter. Once the patient is stabilized, it is imperative that he or she continue to be monitored in the intensive care unit for some time.

Outlook and prognosis

If left untreated, malignant hyperthermia leads to premature demise of the affected individual. Various symptoms occur simultaneously, so that acute oxygen deficiency is to be expected in addition to severe disturbances of organic activity. For this reason, the affected person must receive medical care as early as possible. If there are delays or no intensive medical care, the chances of survival are extremely low. The prognosis improves if circulatory stabilization is initiated immediately. Blood pressure must be monitored and the affected person requires a supply of electrolytes. If other diseases of the cardiac rhythm system are present, the prognosis worsens. The diseases can lead to significant complications and also cause the patient’s death. If the life-threatening condition can be averted, the affected person must continue to receive inpatient care for some time. His or her health must be monitored daily for several weeks so that any irregularities or changes can be documented. In some cases, follow-up treatments are necessary to ensure that the organism is adequately supplied. Nevertheless, patients who have survived this health emergency can usually be discharged from treatment after a few months, free of symptoms. This is especially true if no other diseases are present.Otherwise, the prognosis worsens the patient needs long-term medical monitoring by a physician.

Prevention

Various measures are taken today to prevent the development of malignant hyperthermia. Whenever anesthesia is planned, a possible occurrence of malignant hyperthermia in the patient’s family is inquired about in a preliminary interview. If there is a suspicion of a corresponding predisposition, further tests are carried out at least before planned interventions. Two important test procedures are in the foreground: the in vitro contracture test and molecular genetic diagnostics. In the in vitro contracture test, a muscle biopsy is taken, which is then exposed to the trigger substances caffeine and halothane. If patients show a corresponding predisposition, the sample taken contracts as a result. This test represents the gold standard in the diagnosis of malignant hyperthermia. In molecular genetic diagnostics, a blood sample is taken from the patient and examined for characteristic genetic changes. This method is less complex than the in vitro contracture test. However, it is also not as accurate. In summary, then, vigilance on the part of the treating personnel, as well as prior testing if predisposed, are the best ways to prevent malignant hyperthermia.

Follow-up

In malignant hyperthermia, affected individuals experience a life-threatening situation that must be treated immediately by a physician. The undersupply of oxygen can lead to severe damage to the internal organs. The damage is usually irreversible. If the complication is not treated immediately, the affected person usually dies quickly from the consequences. Aftercare focuses on gently reintroducing the patient to his or her usual life. In addition to medical check-ups, which should be performed regularly, it is sometimes helpful to have uplifting conversations with loved ones in the immediate vicinity. In this way, the mental strain can be lessened a little and a self-confident way of dealing with the experience can be promoted. Provided that the attending physician gives the ok, the patient can go through everyday life again independently.

Here’s what you can do yourself

In the event of an acute onset of malignant hyperthermia (MH) as a result of anesthesia, the patient must receive intensive care to prevent a lethal outcome. In this condition, there is no opportunity for self-medication or self-help. However, the patient has the opportunity to play a preventive role in preventing an acute crisis. Since this is a genetic predisposition, the patient is obligated to inform the anesthesiologist in advance of surgery if there is a history of MH in the family. The physician should also be aware of any muscle disorders. For example, MH may occur in the setting of various myopathies such as central core myopathy, multiminicore myopathy, periodic hypokalemic paralysis, or other muscle diseases, among others. The patient should also report any unusual symptoms, such as muscle paralysis, muscle weakness, or frequent muscle stiffness, to the physician in a medical history discussion before anesthesia is needed. This also includes any heat strokes suffered during sporting activities. It is also advisable for people who have already been tested to present test results from an MH laboratory and, if possible, an MH identification card. The safest examination method is the in vitro contracture test (IVKT). Prior to testing, it is imperative for the patient to contact the testing center in writing or by telephone to clarify which documents and examination results must be submitted. Since the muscle sample can only be examined in a live and fresh state, the patient must also make an appointment on site after submitting all the necessary documents.