Atracurium, vecuronium and pancuronium in end-stage renal failure. Dose-response properties and interactions with azathioprine.
Dose-response relations for atracurium, vecuronium and pancuronium were determined in patients in end-stage renal failure for the initial neuromuscular blockade (using three cumulative doses) and for the maintenance of stable 90% response (during continuous infusion). All measurements were during renal transplant surgery, and the interaction of azathioprine on neuromuscular blockade was estimated. Mean ED95 doses were (microgram kg-1): atracurium 375.6, vecuronium 67.2, pancuronium 86.6; the initial blockade required significantly larger doses than in normal patients (37%, 20% and 45%, respectively, using ED50 values). Mean infusion rates for 90% sustained blockade in renal failure were (microgram kg-1 h-1): atracurium 409.4, vecuronium 78.3, pancuronium 14.2. The atracurium dose was not influenced by renal function, whereas vecuronium and pancuronium requirements were significantly reduced by 23.2% and 61.5%, respectively, compared with normal patients (previous study). Azathioprine was injected at the rate of 1 mg kg-1 min-1 for 3 min at stable 90% neuromuscular blockade with constant-rate infusion of the neuromuscular blocking drug. This produced a relatively small and transient antagonism of blockade--probably of negligible clinical significance.
D000293:Adolescent; D000328:Adult; D001279:Atracurium / Q000494:pharmacology*; D001379:Azathioprine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009469:Neuromuscular Junction / Q000187:drug effects*; D010197:Pancuronium / Q000494:pharmacology*; D014673:Vecuronium Bromide / Q000494:pharmacology*
D001279:Atracurium; D014673:Vecuronium Bromide; D010197:Pancuronium; D001379:Azathioprine