Reversal of neuromuscular blockade: dose determination studies with atropine and glycopyrrolate given before or in a mixture with neostigmine.

Glycopyrrolate and atropine were studied in doses of 5, 10, or 15 microgram/kg and 10, 20, or 30 microgram/kg, respectively, given intravenously either before or in a mixture with neostigmine, 50 microgram/kg, at the time of reversal of neuromuscular block. When given first, both anticholinergic drugs produced a dose-related increase in heart rate; following the administration of neostigmine the heart rates decreased. When administered in a mixture with neostigmine, the 20- and 30-microgram/kg doses, but not the 10-microgram/kg dose of atropine were associated with an initial increase in heart rate. This was, however, absent with all the doses of glycopyrrolate. The 5-microgram/kg dose of glycopyrrolate and 10-microgram/kg dose of atropine given either before or in a mixture with neostigmine were associated with unacceptable decreases in heart rate and needed further anticholinergic drug administration. The 10-microgram/kg dose of glycopyrrolate, when administered in a mixture with neostigmine, was associated with the most stable heart rates. Increasing the dose to 15 microgram/kg was not associated with undue tachycardia and is not hazardous. Atropine, 20 microgram/kg, necessitated a further administration of atropine in nearly a third of patients in this group due to bradycardia (heart rate of 50 beats/min or less) and would be considered inadequate. Increasing the dose to 30 microgram/kg prevented bradycardia but was accompanied by significant initial tachycardia and a higher incidence of dysrhythmias when administered before neostigmine. The frequency of dysrhythmias was otherwise similar. It is recommended that anticholinergic drugs be administered in a mixture with neostigmine. Glycopyrrolate, administered in this way in a dose of 10 microgram/kg, is associated with stable heart rates.