The effect of acid-base balance on neostigmine antagonism of d-tubocurarine-induced neuromuscular blockade.
d-Tubocurarine (dTc) was infused intravenously into 35 cats anesthetized with chloralose and urethane at a constant continuous rate to produce and maintain 90 per cent depression of twitch height of the anterior tibial muscle following supramaximal stimulation of the peroneal nerve. The mean infusion rates that produced 90 per cent depression were not significantly altered by respiratory acid-base changes. Metabolic alkalosis decreased (32.5 per cent) and metabolic acidosis increased (27.7 per cent) the required infusion rate of dTc. When pH and Paco2 were maintained at 7.37 and 38 torr, respectively, the addition of a bolus of neostigmine, 10.5 mug/kg, intravenously, to the continuing infusion of dTc produced 50 per cent antagonism of the dTc-depressed twitch. Respiratory alkalosis and metabolic acidosis did not alter the dose of neostigmine needed to produce 50 per cent antagonism. However, during respiratory acidosis (pH 7.13, Paco2 66 torr) and metabolic alkalosis (pH 7.59, Paco2 36 torr) 20.0 and 18.0 mug/kg neostigmine, respectively, were needed to produce 50 per cent antagonism. Still larger doses of neostigmine (75 mug/kg) could not completely antagonize the block unless pH and Paco2 were returned to 7.30-7.50 and 35-45 torr, respectively. It is concluded that respiratory acidosis and metabolic alkalosis limit and oppose antagonism of dTc by neostigmine.
D000136:Acid-Base Equilibrium; D000138:Acidosis / Q000097:blood / Q000503:physiopathology; D000142:Acidosis, Respiratory / Q000097:blood / Q000503:physiopathology; D000471:Alkalosis / Q000097:blood / Q000503:physiopathology; D000472:Alkalosis, Respiratory / Q000097:blood / Q000503:physiopathology; D000771:Anesthesia, Intravenous; D000818:Animals; D001769:Blood; D002245:Carbon Dioxide / Q000097:blood; D002415:Cats; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D009119:Muscle Contraction / Q000187:drug effects; D009388:Neostigmine / Q000008:administration & dosage / Q000494:pharmacology*; D010313:Partial Pressure; D014403:Tubocurarine / Q000037:antagonists & inhibitors*
D002245:Carbon Dioxide; D009388:Neostigmine; D014403:Tubocurarine