Pharmacology - Complications Specific to Anesthetic Agents
Malignant Hyperthermia
Malignant hyperthermia (MH) is a hypermetabolic muscle disease that is usually triggered by exposure to volatile anaesthetic agents or succinylcholine. The disease is rare; however, it is potentially life-threatening if not recognized and treated appropriately.
Pathophysiology
MH is caused by abnormal release of calcium from the sarcoplasmic reticulum in skeletal myocytes. The large increase in intracellular calcium causes sustained muscle contraction. The resulting hypermetabolic state leads to acidosis and hyperthermia. If this state is prolonged, increasing hypoxia will lead to lysis of myocytes, releasing potassium, myoglobin and creatine kinase into the circulation. Complications include acute kidney injury and disseminated intravascular coagulation.
Inheritance
MH involves a complex inheritance pattern involving numerous genes. One gene that likely plays a large role is the gene for the ryanodine receptor, which encodes the ion channels responsible for calcium release from the sarcoplasmic reticulum. There is no screening test for MH; diagnosis through muscle biopsy is available at select centres but is not routinely performed.
Susceptibility
All patients should be assessed for previous personal or familial adverse reactions to anesthetics. However, MH does not occur after exposure to every triggering agent, and so an uneventful history does not rule out MH. Susceptibility to MH is also increased in some myopathies such as central core disease and King-Denborough syndrome. Muscular dystrophies (e.g. Duchenne muscular dystrophy, Becker muscular dystrophy) are possibly associated with MH, although the evidence is controversial.
Clinical Manifestations
It is important to promptly recognize the signs of MH, which include hypercarbia, tachycardia, hypertension, and muscle rigidity (often seen in the masseter muscle). Tachypnea can be appreciated if muscle relaxants are not used. Hypertension and later on hypotension may be present. Despite the name, hyperthermia can be delayed. Myoglobinuria from lysis of myocytes can cause dark-coloured urine and lead to kidney injury. Laboratory abnormalities include hypoxemia, acidosis, hyperkalemia, increased serum creatine kinase and elevated myoglobin.
Treatment
Treatment involves discontinuation of any triggering agents (volatile anaesthetic agents or succinylcholine), and hyperventilation with 100% oxygen. Dantrolene, a skeletal muscle relaxant, needs to be administered. If hyperthermia is present, the patient should be cooled with cold intravenous fluids, surface cooling, or iced saline lavage. Acid-base and electrolyte abnormalities should be monitored and corrected.
For patients with a previous history of MH or are at increased risk, non-triggering anesthetic agents should be used, and patients should be carefully monitored for signs of MH. Residual volatile anaesthetic agents should be flushed from the breathing circuit. Prophylactic dantrolene can also be considered.
Pseudocholinesterase Deficiency
Pseudocholinesterase deficiency (or “succinylcholine apnea”) is a condition which can lead to prolonged muscular paralysis following administration of succinylcholine. Pseudocholinesterase metabolizes the neuromuscular blocking agent succinylcholine. Some patients have a qualitative decrease in pseudocholinesterase; enzyme levels might be normal but enzyme activity is decreased. In these patients, following administration of succinylcholine, muscle paralysis is prolonged. These patients have abnormal genes for pseudocholinesterase. Depending on whether the patient is heterozygous or homozygous for these abnormal alleles, the block can be prolonged from 20-30 minutes up to 4-8 hours, respectively. The treatment is continuous mechanical ventilation and sedation until muscle paralysis self-revolves. Afterwards, these patients can receive genotyping to confirm the diagnosis.
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