Antagonism of d-tubocurarine-induced neuromuscular blockade with a mixture of 4-aminopyridine and neostigmine in man

Abstract

The antagonistic properties of a mixture of 4-aminopyridine (4-AP) 3 mg.ml-1 and neostigmine 0.2 mg.ml-1 (in three patient groups) administered at 90 per cent d-tubocurarine block were compared with those of plain neostigmine (in three patient groups) in thirty-six patients during thiopentone-fentanyl-nilrous oxide-oxygen anaesthesia. The recovery variables included thumb Twitch height, thenar e.m.g. peak-to-peak amplitude, and train-of-four ratio in response to supramaximal ulnar nerve stimulation. In addition, mean arterial pressure, heart rate, apnoea time and time to responsiveness to verbal command after nitrous oxide was turned off at 20 minutes of recovery were examined as circulatory and central nervous system responses to antagonism. The addition of 4-AP 30 mg to neostigmine 2 mg enhanced the recovery of train-of-four ratio from 54.2 ± 5.2 toS0.2 ± 5.2 percent at 20 mins of antagonism (mean ± SEM;p < 0.01) white adding 4-AP 45 mg to neostigmine 3 mg increased the lrain-of-four ratio from 67.7 ± 2.3 to 92.3 ± 2.4 percent (p < 0.01) when compared with plain neostigmine. No statistically significant difference could be found between the groups in the recovery of twitch height or e.m.g. amplitude. The antagonism of d-tubocurarine block with 4-AP 30 mg plus neostigmine 2 mg was at least as effective as with neostigmine 3-4 mg. Mean arterial pressure increased in the group receiving 45 mg 4-AP plus 3 mg neostigmine. Apnoea time and responsiveness to verbal command after discontinuation of controlled ventilation and nitrous oxide, respectively, were shortest in groups that received 30-45 mg 4-AP. The major adverse effect observed was temporary postoperative confusion in three of six patients who received 45 mg 4-AP. It is suggested that the use of 4-AP in combination with neostigmine should be restricted to cases where antagonism is not adequate with neostigmine and that the dose should not exceed 30 mg. © 1984 Canadian Anesthesiologists.