Pharmacokinetics and Pharmacodynamics of Vecuronium (ORG NC 45) in Patients with Cirrhosis

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Abstract
To evaluate the effect of liver cirrhosis on the pharmacokinetics and the pharmacodynamics of vecuronium, 12 patients with cirrhosis, aged (mean .+-. SD) 52 .+-. 12 yr, and 14 control patients, 42 .+-. 15 yr, undergoing elective surgery under general anesthesia were studied. The simultaneous time courses of the plasma concentration of vecuronium and of the neuromuscular blockade were studied after the administration of a bolus dose of 0.2 mg .cntdot. kg-1. Vecuronium plasma concentration declined biexponentially in both groups. Vecuronium plasma clearance was reduced significantly (P < 0.01) from 4.26 .+-. 1.38 ml .cntdot. min-1 .cntdot. kg-1 in the controls to 2.73 .+-. 1.19 ml .cntdot. min-1 .cntdot. kg-1 in the patients with cirrhosis. The elimination half-life was 58 .+-. 19 min in the controls and was prolonged significantly to 84 .+-. 23 min (P < 0.01) in the patients with cirrhosis. The total apparent volume of distribution was unchanged in patients with cirrhosis (0.253 .+-. 0.086 1 .cntdot. kg-1 vs. 0.246 .+-. 0.092 1 .cntdot. kg-1 in the controls). Cirrhosis caused a prolongation of the neuromuscular blockade induced by vecuronium: the duration of effect from injection to 50% recovery of the twitch height was prolonged by 100% (P < 0.01) from 62 .+-. 16 min in the controls to 130 .+-. 52 min in patients with cirrhosis. The recovery rate (TH 25-75) also was prolonged (P < 0.05) from 21 .+-. 7 min in the controls to 44 .+-. 18 min in patients with cirrhosis. Vecuronium plasma concentration measured during recovery from paralysis indicates that cirrhosis did not alter the sensitivity to the relaxant, the plasma concentration corresponding to 50% of recovery (Cp 50) being unchanged between the 2 groups: 247 .+-. 60 ng .cntdot. ml-1 in the controls vs. 281 .+-. 129 ng .cntdot. ml-1 in the cirrhotic patients. Thus, vecuronium seems to exert a prolonged neuromuscular blockade in patients with cirrhosis, and this change is mediated through its delayed elimination.