Background and objective: Similar doses of ketamine are employed in regional and general anaesthesia. In contrast to commonly used local anaesthetic agents, accidental systemic application of local anaesthetic doses of ketamine will not result in seizure, dysrhythmia or cardiovascular depression. However, there is some doubt about the quality of regional analgesia induced by ketamine. As human sodium channels constitute an important molecular target of local anaesthetics, the study was designed to establish concentration-dependent effects of ketamine on conductance, steady-state activation and steady-state inactivation of human neuronal sodium channels. This information — that has, so far, not been published — will help to characterize further local anaesthetic properties of ketamine.

Methods: Whole-cell patch-clamp recordings were made of sodium channels natively expressed in human neuroblastoma SH-SY5Y cells.

Results: The sodium channels activated at a threshold of −60 mV and exhibited a maximal peak current at −10 mV. The voltage of half-maximal activation was −20 mV. The Na+ currents depended on the prepulse potential. The voltage of half-maximal inactivation was —80 mV. Ketamine inhibited the sodium conductance in a concentration-dependent manner (IC50 = 1140 µmol). A concentration-dependent hyperpolarizing shift of both steady-state activation and steady-state inactivation accounted for at most 5 mV.

Conclusions: The effects of ketamine on these human ion channels occur at clinical concentrations. They are consistent with the local anaesthetic action of ketamine. Whether ketamine helps to decrease the incidence of severe side-effects during regional anaesthesia needs to be addressed in further clinical studies.

We investigated the effect of a small dose of midazolam, ketamine, droperidol or lidocaine on the propofol dose required for hypnosis during induction of general anaesthesia. These drugs were randomly administered to 100 patients about to undergo scheduled surgery. Propofol was then infused at a rate of 250 μg kg−1 min−1 and the hypnotic dose to produce hypnosis was evaluated. Midazolam (20 μg kg−1) and droperidol (20 μg kg−1) significantly reduced the mean hypnotic dose of propofol (mean) S.D.) compared with the placebo (43.7 ± 17.8 mg, 61.9 ± 10.6 mg and 72.5 ± 27.7 mg after pretreatment with midazolam, droperidol and placebo, respectively), whereas ketamine (0.1 mg kg−1) and lidocaine (1 mg kg−1) did not significantly affect the hypnotic dose of propofol (63.1 ± 25.6 mg and 65.1 ± 24.8 mg, respectively). Only midazolam when compared with saline administration, (176 ± 66s and 298 ± 126s, respectively), shortened the time to achieve hypnosis. The changes in blood pressure (non-invasive) and heart rate were not significantly different in all groups during the induction of anaesthesia and oro-tracheal intubation. These results raise the possibility that new combinations of central nervous system drugs, such as droperidol and propofol, have a potential to reduce the dose of intravenous anaesthetics, including propofol, that produce hypnosis without significant adverse effects.