In a randomized study, we evaluated lag time (time from the end of injection of muscle relaxant until the first depression of the train-of-four response [TOF]), onset time (time from the end of injection of muscle relaxant until the maximum depression of the first twitch of the TOF [T1]), neuromuscular block, and endotracheal intubating conditions at 1 min after 1 mg/kg succinylcholine (n = 15) and 1.5 mg/kg Org 9487 (n = 30). Two minutes after administration of Org 9487, 15 of the 30 patients received neostigmine for reversal. Recovery of neuromuscular block after succinylcholine, Org 9487 without and Org 9487 with neostigmine were compared using the time until T1 was 90% for the succinylcholine group, and the time until TOF was 70% for the Org 9487 groups. Neuromuscular transmission was monitored mechanomyographically. Onset time was similar (67 [20] and 83 [38] s for succinylcholine and Org 9487, respectively) and endotracheal intubating conditions were also similar after both muscle relaxants. Times until clinically sufficient recovery of neuromuscular block induced by succinylcholine (time until T1 = 90%: 10.6 [3.3] min) and Org 9487 with neostigmine (time until TOF = 70%: 11.6 [1.4] min) were not different. In contrast, in the Org 9487 without neostigmine group, more time was required until complete recovery (24.1 [6.2] min) (P < 0.05). In conclusion, ORg 9487 is a muscle relaxant suitable for endotracheal intubation and short-lasting interventions.

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.

We have studied dose requirements, recovery times and pharmacokinetics of rocuronium in 32 intensive care patients. After an initial dose of 50 mg, rocuronium was administered as maintenance doses of 25 mg whenever two responses to train-of-four (TOF) stimulation reappeared (bolus group; n = 27) or by continuous infusion to maintain one response in the TOF (infusion group; n = 5). Median requirements for rocuronium were 27.4 (range 14.5-68.3) mg h-1 and 43.7 (30.9-50.3) mg h-1 in patients in the bolus and infusion groups, respectively. Median total duration of rocuronium administration was 29.0 (12.4-95.5) h and 63.4 (24.0-140.3) h, respectively. Median time from administration of the last bolus dose and end of infusion to recovery of the fourth twitch in the TOF was 100 (45-300) min and 60 (15-155) min, respectively. Arterial blood samples were obtained for up to 10 h after cessation of rocuronium administration, and concentrations of the parent compound and its putative metabolites were measured using high pressure liquid chromatography (HPLC). The plasma concentration profile (n = 12) was described adequately by a two-compartment model. Mean plasma clearance (Cl), steady-state distribution volume (Vss), mean residence time (MRT) and elimination half-life (T1/2 beta) were 3.16 (SD 1.15) ml kg-1 min-1, 769 (334) ml kg-1, 262 (120) min and 337 (163) min, respectively. Recovery times, Vss, MRT, and T1/2 beta differed from previously published data obtained after rocuronium infusion of moderate duration in surgical patients.

We have evaluated in 10 anaesthetized patients the time course of action, infusion requirements, reversibility and pharmacokinetics of Org 9487. Org 9487 was administered as a bolus dose of 1.5 mg kg-1, followed by an infusion to maintain a block of 75-85% for 60 min. After recovery from the bolus dose, a mean dose of Org 9487 3.4 (SD 1.0) mg kg-1 h-1 was administered to maintain a mean neuromuscular block of 83 (3)%. During the final 15 min of infusion, the infusion requirements were 2.5 (1.1) mg kg-1 h-1. In the five patients who were allowed to recover spontaneously, a TOF ratio of 0.7 was reached 37.9 (12.4) min after stopping the infusion of Org 9487. In the five patients who received neostigmine, a TOF ratio of 0.7 was reached after 14.5 (6.1) min. Plasma clearance was 8.5 (30%) ml kg-1 min-1. Volume of distribution at steady state was 293 (55%) ml kg-1. Terminal half-life and mean residence time were 71.7 (34%) and 33.4 (31%) min, respectively. The concentration of the 3-OH metabolite remained relatively low. Urinary excretion of Org 9487 and its metabolites was 22% in 24 h. In conclusion, a 1-h infusion of the short-acting drug Org 9487 changed its time course characteristics gradually from that of a short-acting neuromuscular blocking agent to that of a neuromuscular blocker with an intermediate duration of action.

This is a report of a very rare complication of lingual and hypoglossal nerve damage in an acromegalic patient. This incident suggests forceful laryngoscopy, hyperextension of the head and the throat pack (tightly packed in the oropharynx) can result in injury of the lingual and the hypoglossal nerves.

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Inhibition of the enzymic degradation of suxamethonium and mivacurium increases the onset time of submaximal neuromuscular block. Therefore, pharmacokinetics influence the onset time of submaximal neuromuscular block. These results imply that to obtain an ultrashort onset time, muscle relaxants should be developed that not only have a low affinity for the receptor but also rapidly disappear from plasma.

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