Org NC 45, pancuronium, metocurine and d-tubocurarine in dogs. Anttth. Analg., 59,26. Krieg, N., and Crul, J. F. (1980). Intradermal histamine releasing effect ...
Br. J. Anaesth. (1983), 55,125
CLINICAL COMPARISON OF ATRACURIUM AND VECURONIUM (ORG NC 45) E. N. ROBERTSON, L. H. D. J. BOOIJ, R. J. FRAGEN AND J. F. CRUL SUMMARY
The potency, histamine releasing ability, cardiovascular effects, and pharmacodynamics of vecuronium and atracurium were investigated in 64 healthy patients following administration i.v. Cumulative dose-response curves showed vecuronium to be 4.4 times as potent as atracurium. Using the calculated EQ90 of each drug (43 fig kg' 1 for vecuronium and 188 fig kg' 1 for atracurium), vecuronium had a significantly more rapid onset time and shorter duration of action than atracurium. When three times the ED90 doses were used (129jigkg" 1 for vecuronium and 564 fig kg"1 for atracurium), no statistically significant differences in the pharmacodynamics were seen between the two drugs, although vecuronium tended to be shorter-acting. There was no clinical evidence of histaminr release during the study. No clinically significant changes in arterial pressure or heart rate were seen after the injection of either drug, although vecuronium caused a statistically significant decrease in heart rate (—5%) at 5 arid 10 min after administration. Both drugs would appear to have certain advantages over existing non-depolarizing neuromuscular blocking drugs.
Two new, potent, short-acting, non-depolarizing neuromuscular blocking drugs have been introduced recently. Vecuronium, the monoquaternary homologue of pancuronium, has been shown to be free from cardiovascular side-effects (Booij et al., 1980; Krieg, Crul and Booij, 1980), and histamine releasing properties (Booij, Krieg and Crul, 1980). Atracurium, a bisquaternary tetrahydropapaverum derivative, has also been shown to be free from cardiovascular side-effects (Payne and Hughes, 1981) and to cause histaminff release only in doses 8-16 times the neuromuscular blocking dose (Hughes and Chappie, 1981). Vecuronium was found to be about five times more potent than atracurium and to result in comparable intubating conditions (Gramstad and Lilleaasen, 1982). In this study, the pharmacodynamics of these two drugs, their cardiovascular effects, and any evidence of histamine release were compared at various doses following i.v. administration. PATIENTS AND METHODS Studies were performed in 64 healthy (ASA I and II) patients aged between 18 and 65 yr. Informed consent to participate in the study was obtained at the time of the preoperative visit. The study was apE.N. ROBERTSON, F.F^JLC.S.JL.H. D. J.BOOIJ,M.D.,PH.D.; J. F. CRUL, M.D., PH.D., F.F.A.R.C.S.; Department of Anesthesiology, Catholic University, Nijmegen, The Netherlands. R. J. FRAGEN, M.D., Department of Anesthesiology, Northwestern University, Chicago, U.S.A. 0OO7-O912/83/020125-O5 $01.00
proved by the hospital Ethics committee. Each patient was premedicated with diazepam 10 mg by mouth 2 h before induction of anaesthesia, plus droperidol 2.5-5 mg with piritramide 7.5-15mg i.m., 30-60min before induction of anaesthesia. Anaesthesia was induced with fentanyl 4f\igkg~I and thiopentone 5mgkg~' i.v. Intubation of the trachea was achieved 3-5 min after spraying the pharynx, larynx and trachea with 4% lignocaine spray. Maintenance of anaesthesia was with 67% nitrous oxide in oxygen. Mechanical ventilation was instituted and FEco2 maintained between 4.5 and 5vol%. Incremental doses of fentanyl 0.05 mg, thiopentone 50 mg, or droperidol 2.5 mg were given as required. The ulnar nerve was stimulated through surface electrodes at the wrist. Supramaximal pulses were delivered using a nerve stimulator at a rate of 0.1 Hz with a duration of 0.2 ms. The isometric twitch tension produced by this stimulation, as quantified by a force displacement transducer, was continuously recorded on a polygraph. The electrocardiogram (ECG), finger plethysmogram and end-expiratory carbon dioxide concentration (FE'cCh) were measured continuously in each patient. Evidence of rmtaminp release, for example, urticaria, skin rash, bronchospasm (Bowman, 1982), was sought following each administration of either neuromuscular blocking drug. The study was divided into three main sections in © The Macmillan Press Ltd 1983
126
which atracurium and vecuronium were compared with each other. Patients were assigned randomly to either drug group. Preparations of drugs used were in the form supplied by the manufactures. Atracurium was kept at 4 °C until the time of administration.
BRITISH JOURNAL OF ANAESTHESIA was calculated as: diastolic pressure + (pulse pressure/3). Pharmacodynamic results were analysed statistically using Student's unpaired ttest and cardiovascular results using Student's paired rtest. P
