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Chapter: Clinical Anesthesiology: Clinical Pharmacology: Neuromuscular Blocking Agents

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Nondepolarizing Muscle Relaxants: Vecuronium

Vecuronium is pancuronium minus a quaternary methyl group (a monoquaternary relaxant). This minor structural change beneficially alters side effects without affecting potency.

VECURONIUM

Physical Structure

Vecuronium is pancuronium minus a quaternary methyl group (a monoquaternary relaxant). This minor structural change beneficially alters side effects without affecting potency.

Metabolism & Excretion

Vecuronium is metabolized to a small extent by the liver. It depends primarily on biliary excretion and secondarily (25%) on renal excretion. Although it is a satisfactory drug for patients with renal failure, its duration of action is somewhat prolonged. Vecuroni-um’s brief duration of action is explained by its shorter elimination half-life and more rapid clearance compared with pancuronium. Long-term administration of vecuronium to patients inintensive care units has resulted in prolonged neuro-muscular blockade (up to several days), possibly from accumulation of its active 3-hydroxy metabo-lite, changing drug clearance, and in some patients, leading to the development of a polyneuropathy. Risk factors seem to include female gender, renal failure, long-term or high-dose corticosteroid ther-apy, and sepsis. Thus, these patients must be closely monitored, and the dose of vecuronium carefully titrated. Long-term relaxant administration and the subsequent prolonged lack of ACh binding at the postsynaptic nicotinic ACh receptors may mimic a chronic denervation state and cause lasting receptor dysfunction and paralysis. Tolerance to nondepolar-izing muscle relaxants can also develop after long-term use. Fortunately, the use of unnecessary paralysis has greatly declined in critical care units.

Dosage

Vecuronium is equipotent with pancuronium, and the intubating dose is 0.08–0.12 mg/kg. A dose of 0.04 mg/kg initially followed by increments of 0.01 mg/kg every 15–20 min provides intraop-erative relaxation. Alternatively, an infusion of 1–2 mcg/kg/min produces good maintenance of relaxation.

Age does not affect initial dose requirements, although subsequent doses are required less fre-quently in neonates and infants. Women seem to be approximately 30% more sensitive than men to vecuronium, as evidenced by a greater degree of blockade and longer duration of action (this has also been seen with pancuronium and rocuronium). The cause for this sensitivity may be related to gender-related differences in fat and muscle mass, protein binding, volume of distribu-tion, or metabolic activity. The duration of action of vecuronium may be further prolonged in post-partum patients due to alterations in hepatic blood flow or liver uptake.

Side Eects & Clinical Considerations

A. Cardiovascular

Even at doses of 0.28 mg/kg, vecuronium is devoid of significant cardiovascular effects. Potentiation of opioid-induced bradycardia may be observed in some patients.

B. Liver Failure

Although it is dependent on biliary excretion, the duration of action of vecuronium is usually not significantly prolonged in patients with cirrho-sis unless doses greater than 0.15 mg/kg are given. Vecuronium requirements are reduced during the anhepatic phase of liver transplantation.

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