THE CARDIOVASCULAR EFFECTS AND HISTAMINE-RELEASING PROPERTIES OF 51W89 IN PATIENTS RECEIVING NITROUS-OXIDE OPIOID BARBITURATE ANESTHESIA

Background: Atracurium consists of a mixture of ten stereoisomers. One of these isomers, 51W89, is a potent intermediate-acting nondepolarizing neuromuscular blocking agent. Its ED(95) is 0.05 mg . kg(-1) in patients receiving nitrous oxide/opioid anesthesia. In preclinical trials, 51W89 did not show evidence of histamine release in cats at doses up to 80 times the human ED(95). This study was undertaken to determine the cardiovascular effects and histamine-releasing properties of 51W89 in patients undergoing elective surgical procedures. Methods: Sixty patients, ASA physical status 1 or 2, anesthetized with nitrous oxide/fentanyl/thiopental were studied. Patients received either 2 times the ED(95) of atracurium or 51W89 or 4 or 8 times the ED(95) of 51W89 as a rapid intravenous bolus under stable anesthesia, before surgical stimulation. Blood pressure and heart rate were measured by oscillometry and the electrocardiogram in patients receiving 2 times the ED(95) of 51W89 or atracurium and by an intraarterial catheter and a tachograph triggered by the arterial pulse waveform in patients receiving 4 or 8 times the ED(95) of 51W89. Maximal blood pressure and heart rate changes during the 5 min after administration of the muscle relaxant were recorded. Venous blood samples were obtained before the administration of relaxant and at 2 and 5 min after the administration of relaxant for determination of plasma histamine concentrations by radioenzymatic assay. Results: Maximal blood pressure and heart rate changes in all groups of patients receiving 51W89 were small and similar to those observed in patients receiving 2 times the ED(95) of atracurium. The mean maximum percent changes (+/- SE) in heart rate and mean arterial pressure were -0.6 +/- 1.5 and 0.4 +/- 2.5, respectively, in the group receiving 2 times the ED(95) atracurium; -1.3 +/- 3.3 and 2.3 +/- 4.4, respectively, in the group receiving 2 times the ED(95) 51W89; -2.6 +/- 1.0 and 2.6 +/- 1.5, respectively, in the group receiving 4 times the ED(95) 51W89; and -2.4 +/- 1.5 and -1.0 +/- 1.3, respectively, in the group receiving 8 times the ED(95) 51W89. No patient developed a decrease in blood pressure greater than or equal to 20% or an increase in heart rate greater than or equal to 20% that was attributable to muscle relaxant administration. There was no dose-related change in plasma histamine concentration associated with the administration of 51W89. One patient in the study developed transient facial hushing after the administration of atracurium. Conclusions: 51W89 is a benzylisoquinolinium-type, nondepolarizing muscle relaxant that does not affect plasma histamine concentrations. No cutaneous hushing or clinically important cardiovascular effects were noted after rapid injection of doses up to and including 8 times its ED(95) (0.4 mg . kg(-1)) in healthy patients undergoing elective surgical procedures.