Neuromuscular drug interactions of clinical importance

The addition of marginally effective concentrations of d-tubocurarine (d-Tc), neomycin, or polymyxin B to the organ bath of rat phrenic nerve-hemidiaphragm preparations significantly (p < 0.05 to 0.001) increased the neuromuscular (NM) blocking effect of lidocaine. When both d-Tc and neomycin or polymyxin B were added the increase of the NM effect of lidocaine was even greater (p < 0.001). Washout re-established NM transmission. The NM block produced by combinations of d-Tc, neomycin, or polymyxin and lidocaine could be reversed partially by Ca2+ or neostigmine, and completely by 4-aminopyridine. The block caused by d-Tc and lidocaine was partially antagonized by neostigmine or 4-aminopyridine., The neomycin-lidocaine or the polymyxin B-lidocaine block, however, was not antagonized by thse compounds. The concentrations of d-Tc, antibiotics, and lidocaine that caused significant block in this in vitro preparation may be present at the NM junction of patients, who in the perioperative period had received combinations of therapeutic doses of d-Tc, neomycin, other aminoglycosides, or polymyxin B and lidocaine. This may cause impairment of spontaneous respiration requiring assisted ventilation.