NMB and hyperparathyroidism

Hyperparathyroidism (HPT) is a common cause of hypercalcemia and the effects of calcium at the neuromuscular junction may cause pre-existing muscle weakness. However, this response is unpredictable and though it might seem that the pre-existing muscle weakness associated with HPT would reduce neuromuscular blocker requirements, it has been suggested that “hypercalcemia associated with primary HPTis associated with decreased sensitivity toneuromuscular blockers and thus a shortened time course of neuromuscular blockade.”

Nevertheless, it is advised that neuromuscular blockade be carefully titrated to effect.

Updated definition 2020:

The parathyroid gland, parathyroid hormone, and hyperparathyroidism:

Humans possess four small endocrine parathyroid glands located behind the lateral lobes of the thyroid gland. The parathyroid glands contain chief cells, which produce and secrete parathyroid hormone (PTH), a key regulator of serum and bone calcium, vitamin D, and phosphorus. Parathyroid gland chief cells secrete PTH in response to low serum calcium concentrations.

PTH regulates serum calcium concentration at multiple locations. In the bone, PTH indirectly stimulates osteoclast-mediated calcium resorption. In the kidney, PTH increases the reabsorption of calcium in the distal tubules and the renal collecting ducts. It also inhibits phosphate reabsorption from the tubular fluid, thereby decreasing plasma phosphate concentration and subsequently increasing ionized calcium concentrations. Also in the kidneys, PTH stimulates the conversion of 25-hydroxyvitamin D to its active form, calcitriol, which increases calcium uptake in the small intestine. Taken together, PTH increases serum calcitriol, decreases serum phosphate, and increases serum calcium concentrations.

Hyperparathyroidism (HPT) is the presence of excessive parathyroid hormone. It can be divided into three types: primary, secondary, and tertiary. Primary HPT occurs as a result of pathologies intrinsic to the parathyroid gland, such as PTH-secreting adenomas or multiple endocrine neoplasia syndromes. Secondary HPT includes appropriate parathyroid gland compensation in the face of extraglandular pathologies, e.g. calcium malabsorption, vitamin D deficiency, and chronic kidney failure unto hyperphosphatemia and hypocalcemia. Tertiary HPT results from autonomous parathyroid function following persistent parathyroid stimulation. Though mostly asymptomatic, patients with HPT of any variety exhibit the quartet of “stones, bones, groans, and psychiatric overtones” as a result of the HPT-mediated hypercalcemia.

Anesthetic Implications of Hyperparathyroidism:

Patients with HPT, especially longstanding and/or untreated HPT, must have their airway carefully evaluated. Special attention should be focused on their neck (presence of goiter unto potential mass effect) and any relevant imaging of the atlanto-axial joint (given the potential for osteopenic bone unto pathologic fractures). Patients usually have underlying causes of HPT that should be considered prior to anesthetizing (chronic renal failure, or less commonly MEN 1 or MEN2A syndromes). Efforts should be made to correct any hypercalcemia, either with adequate fluid hydration and/or calcium-wasting diuretics, such as loop diuretics.

Most of the anesthetic implications of HPT pertain to the physiologic changes associated with hypercalcemia. Severe hypercalcemia can result in an array of neurological dysfunction, including psychosis and coma. Cardiovascular implications include hypertension, hypovolemia, and conduction blockade (manifesting as decreased QTc, J waves, and in severe cases, ventricular irritability unto VF arrest). Respiratory muscle weakness, poor clearance, and laryngospasm must be evaluated both prior to and following airway instrumentation. These patients are also high risk for aspiration, anemia, and pathologic fractures, especially the mandible.

Hypercalcemia, independent of HPT, usually causes muscular weakness as free intracellular calcium blocks sodium channels, inhibiting nerve and muscle fiber depolarization. Profound muscle weakness, especially in proximal muscle groups may be seen. Pre-existing muscular weakness is usually associated with reduced neuromuscular blocker requirements. Hypercalcemia classically causes prolonged neuromuscular blockade and makes reversal of neuromuscular blockade unpredictable. Train-of-four ratio is especially important in determining adequate reversal of neuromuscular blockade in these patients as well as in titrating the doses of muscle relaxants during the intraoperative period.

In HPT, however, the resulting hypercalcemia is associated with resistance to neuromuscular blockade, manifesting as decreased sensitivity to neuromuscular blockers and decreased duration of action. Case reports of normocalcemic patients with HPT indicate patients with HPT have increased resistance to competitive blockade by rocuronium; the authors suggested that primary HPT may upregulate acetylcholine receptors, resulting in hyposensitivity to non-depolarizing muscle relaxants and an increased sensitivity to depolarizing muscle relaxants, such as succinylcholine.

In general, patients with HPT undergoing a general anesthetic should have their calcium checked and controlled prior to surgery (hydration, diuresis). Treatment of hypercalcemia should be continued perioperatively. Anesthesiologists should carefully monitor the depth of neuromuscular blockade with train-of-four stimulation and train-of-four ratio throughout induction of anesthesia, during maintenance of anesthesia, and prior to extubation. Neuromuscular blockers have an unpredictable effect in this patient population, and titrating neuromuscular blockers as well as reversal agents should be guided by train-of-four monitoring.