Changes in Effective and Lethal Doses of Intravenous Anesthetics and Lidocaine When Used in Combination in Mice

We studied the interactions between a local anesthetic agent, lidocaine, and two general anesthetic drugs, propofol and ketamine, in mice. We used two end points: hypnosis, reflected by loss of the righting reflex, and death. The ED50 for hypnosis and the LD50 were determined for each drug separately, and a dose-response curve was prepared for each drug, using combinations of propofol-lidocane and ketamine-lidocaine at three different dose ratios. Probit and isobolographic analyses revealed supra-additive (synergistic) interactions between lidocaine and each of the other anesthetic agents regarding both the effective dose and the lethal dose. No significant difference was found between propofol and ketamine regarding the supraadditive effect.