Aims To determine the effects of hepatic cirrhosis on the pharmacodynamics and pharmacokinetics of rocuronium bromide. Methods We studied 21 healthy patients and 17 patients with mild or moderate cirrhosis (Child-Pugh Class A and B). Patients were premedicated with diazepam orally; anaesthesia was induced with fentanyl and thiopentone, and maintained with isoflurane 0.6% (end-tidal) and nitrous oxide 66% in oxygen. The compound action potential of the adductor pollicis muscle in response to supramaximal stimulation of the ulnar nerve was recorded using the train-of-four (TOF) twitch technique. A bolus dose of rocuronium 0.6 mg kg −1 was then given. Venous blood samples were taken for up to 8 h, and plasma rocuronium concentrations determined by h.p. Keywords: hepatic cirrhosis, neuromuscular block, rocuronium (Child's class B), and eight healthy patients, Khalil and Introduction colleagues [6] found that the onset of neuromuscular block was slower in cirrhotic than in healthy patients (158 s vs Rocuronium bromide is an aminosteroid non-depolarizing neuromuscular blocking agent with a more rapid onset of 108 s), and that recovery of twitch height (T 1 5T 0 ) to 75% and 90% was prolonged. The plasma concentrations of action than other currently available non-depolarizing drugs, but a duration of action comparable with vecuronium [1].rocuronium were more variable in the cirrhotic patients, and pharmacokinetic analysis showed that the central volume The other aminosteroid non-depolarizing neuromuscular blocking drugs, pancuronium and vecuronium, have been of distribution and mean residence time were greater in the cirrhotic. Although the mean clearance was lower in the shown to have a prolonged effect and an increased elimination half-life in hepatic cirrhosis [2,3]. Rocuronium, cirrhotic group (2.41 vs 2.79 ml kg −1 min −1 ), this did not achieve statistical significance. More recently, Magorian and like vecuronium, is a monoquaternary cation and might be expected to undergo considerable biliary excretion [4], and colleagues studied a group of 10 patients with liver dysfunction of diverse aetiology and compared them with this has been directly suggested by work in the cat [5].There have been two previous studies of the pharmaco-10 healthy patients studied previously [7]. They found no difference in either time to onset of block or recovery of dynamics and pharmacokinetics of rocuronium in cirrhosis, with conflicting findings. In a study of 10 cirrhotic patients twitch height (T 1 5T 0 ) to 25% (clinical duration). They applied a population approach to pharmacokinetic analysis, and found an increase in initial volume of distribution (V 1 ), and also an increase in the peripheral compartments (V 2 and

SummaryWe have compared the pharmacokinetics of cisatracurium with atracurium when given by bolus dose followed by continuous infusion. Twenty healthy patients were anaesthetised with thiopentone, midazolam, fentanyl and 70% nitrous oxide in oxygen. Ten patients (Group C) were randomly allocated to receive cisatracurium 0.1 mg.kg ¹1 and 10 patients (Group A) were given atracurium 0.5 mg.kg ¹1. Neuromuscular block was monitored using a mechanomyograph. When the first twitch of the train-of-four had recovered to 5% of control, an infusion of cisatracurium 3 mg.kg ¹1 .min ¹1 was started in Group C and an infusion of atracurium 10 mg.kg ¹1.min ¹1 was started in Group A. The infusion rates were adjusted to maintain the first twitch of the train-offour at 5% of control. The times to 90% and maximum depression of the first twitch of the trainof-four were significantly longer after cisatracurium than atracurium (2.2 and 3.4 min compared with 1.3 and 1.8 min, respectively; p < 0.01 in each instance). No significant differences were found in recovery parameters between the two groups. Blood samples were taken at regular intervals following the bolus, during the infusion and for 8 h thereafter. The plasma samples were analysed using high-performance liquid chromatography for cisatracurium and atracurium (using a method which distinguishes between the three geometric isomer groups), laudanosine and monoquaternary alcohol. The results were analysed using the Non-linear Mixed Effects Model program. A two-compartment model was fitted to the data. The different isomer groups of atracurium have different pharmacokinetics, the trans-trans group having the highest clearance (1440 ml.min ¹1 ) and the cis-cis group the lowest (499 ml.min ¹1). The clearance of cisatracurium (425 ml.min ¹1 ) is less than that of cis-cis atracurium and its elimination half-life is longer (34.9 min and 21.9 min, respectively). The plasma concentration of laudanosine after cisatracurium was onefifth of that after atracurium. The neuromuscular blocking agent atracurium besylate consists of three groups of geometric isomers: three cis-cis, four cis-trans and three trans-trans [1]. The properties of each of the isomers have been studied to determine whether any possess fewer side-effects than the parent drug. One of the cis-cis isomers, cisatracurium (51W89: 1R-cis 1 0 R-cis atracurium) makes up 15% of atracurium

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