We have studied the onset and duration of action and pharmacokinetics of rocuronium bromide (Org 9426) during anaesthesia with nitrous oxide, fentanyl and isoflurane after a single bolus dose of rocuronium 0.6 mg kg'' in nine patients with chronic renal failure requiring regular haemodialysis, and in nine healthy control patients. Blood samples were collected over 390 min and concentrations of rocuronium and its putative metabolites measured using HPLC. Onset time for maximum block, duration of clinical relaxation (T1 2 s) and recovery index, were 61 (SD 25.0) s and 65 (16.4) s, 55 (26.9) min and 42 (9.3) min and 28 (12.3) min and 19 (8.8) min, respectively, for patients with and without renal failure. The time for TOF ratio to return spontaneously to 0.7 was 99 (41.1) min and 73 (24.2) min, respectively, in the two groups. None of these differences was significant. The pharmacokinetic data were best described by a three-exponential equation. There were significant differences between patients with and without renal failure in the rates of clearance (2.5 (1.1) ml kgr 1 min~' and3.7 (1.4) ml kg-' min-', respectively) and the mean residence times (97.1 (48.7) min and 58.3 (9.6) min) (P < 0.05). The differences in other kinetic parameters were not significant. We conclude that the effects of rocuronium may be prolonged in patients with renal disease, because of a decreased clearance of the drug. (Br. J. Anaesth.

Haemodynamic variables were measured following administration of rocuronium 0.6 mg.kg-1 or vecuronium 0.08 mg.kg-1 (approximately equivalent to 2 x ED95 doses) in patients anaesthetized with fentanyl 50 micrograms.kg-1 and scheduled to undergo elective coronary artery bypass grafting. There were increases in stroke volume index (+15%) and cardiac index (+11%), and a decrease in pulmonary capillary wedge pressure (-25%) following administration of rocuronium (P < 0.05). The changes in heart rate (+7%), mean arterial pressure (-5%), systemic vascular resistance (-12%) and other measured or derived indices were insignificant. In comparison the administration of vecuronium was associated with decreases in heart rate (-7%), mean pulmonary artery pressure (-17%), central venous pressure (-15%) and the rate-pressure product (-9%) (P < 0.05). The changes in mean arterial pressure (-7%), cardiac index (-6%) and systemic vascular resistance (-8%) following vecuronium were insignificant. There were no differences in any of the variables between rocuronium and vecuronium. The absolute values of all variables were, however, within acceptable clinical limits. There was no evidence of histamine release in any patient. The present study shows that rocuronium 0.6 mg.kg-1 is associated with changes of only small magnitude in haemodynamic variables.

We have studied the pharmacokinetics of a single bolus of rocuronium (Org 9426), followed by an infusion, in eight patients during anaesthesia with halothane and nitrous oxide in oxygen. Neuromuscular block was monitored using train-of-four (TOF) stimulation and recording the force of contraction of the adductor pollicis muscle. Rocuronium was administered as an initial bolus dose of 0.45 mg kg-1 followed by an infusion adjusted manually to maintain T1 (first response in the TOF) at 10% of control. Mean onset time and time to recovery of T1 to 10% were 72 (SD 19.6) s and 27 (9.6) min, respectively. The infusion rates were stable in 19.8 (6.5) min. The mean requirement for rocuronium for steady state 90% block of T1 was 528 (163.3) micrograms kg-1 h-1. After cessation of surgery the infusion was stopped and patients were allowed to recover spontaneously. The times to attain a T1 of 90% and a TOF ratio of 0.7 were 31 (11.7) min and 36 (7.3) min, respectively. Blood samples were collected for 390 min after cessation of infusion and concentrations of rocuronium and its putative metabolites measured using HPLC. A two-exponential equation was used to describe the pharmacokinetic data. The rate of clearance, mean residence time and volume of distribution at steady state were 3.3 (0.77) ml kg-1 min-1, 67.2 (18.8) min and 212.5 (40.1) ml kg-1, respectively. The distribution (T1/2 alpha) and elimination (T1/2 beta) half-lives were 7.5 (3.33) min and 85.6 (18.4) min, respectively. These values were not significantly different from previously published data for a single bolus dose of rocuronium.

SummaryThe use of rocuronium (Org 9426) as a single bolus followed by an infusion was assessed in 50 patients under anaesthesia with nitrous oxide-oxygen and halothane. Neuromuscular block was monitored using train-ofif our stimulation and recording the force of contraction of the adductor pollicis muscle. Rocuronium was administered in an initial bolus dose of 0.45 mg.kg-'followed by an infusion adjusted manual1.v to maintain the T I , the.first response in the train-of-four, at 10% of control. Following cessation of rocuronium itfusion the patients were either allowed to recover spontaneously I n = 10) or were given neostigmine 50 pg.kg-' or edrophonium I mg.kg-' at 10 or 25% recover), of the T I (n = IOJor each group). Adequate antagonism was dejned as attaining u sustained train-of-four ratio of 0.7. Rocuronium requirements showed marked variation among individual patients but were relatively constant in individual patients. The mean (SD) time to attain stable infusion rates was 17.4 (10.9) min. The mean ( S D ) requirement of rocuronium for steady state 90% block of T, was 572 (190) pg.kg-'.h-' (range 242-1104 pg.kg-'.h-'). The tnean ( S D ) time to attain a train-offour ratio of 0.7 in the group allowed to recover spontaneously was 36. I (7.3) min. Thisinterval was 7.5 (1.9), 9.3 (7.0), 4.6 (1.9) and 1.9 (0.9) min respectively in the groups receiving neostigmine at Ti of 10%.

SummaryThe neuromuscular effects of intravenous rocuronium bromide, 0.6 mg.kg-' or 0.9 mg.kg-', were studied in jour groups of I0 patients during anaesthesia with or without halothane (0.54