Patients intoxicated with organophosphorous compounds may need general anaesthesia to enable
mechanical ventilation or for control of epileptiform
seizures. It is well known that
cholinergic overstimulation attenuates the efficacy of general anaesthetics to reduce spontaneous network activity in the cortex. However, it is not clear how
propofol, the most frequently used intravenous anaesthetic today, is affected. Here, we investigated the effects of
cholinergic overstimulation induced by
soman and
acetylcholine on the ability of
propofol to depress spontaneous action potential activity in organotypic cortical slices measured by extracellular voltage recordings.
Cholinergic overstimulation by co-application of
soman and
acetylcholine (10 μM each) did not reduce the relative inhibition of
propofol (1.0 μM; mean normalized action potential firing rate 0.49 ± 0.06 of control condition, p < 0.001, Wilcoxon signed rank test) but clearly reduced its efficacy. Co-application of
atropine (10 nM) did not improve the efficacy.
Propofol preserved its relative inhibitory potential but did not produce a degree of neuronal depression which can be expected to assure
hypnosis in humans. Since a combination with
atropine did not improve its efficacy, an increase in dosage will probably be necessary when
propofol is used in victims suffering from organophosphorous intoxication.