title: Interactions between atropine and etomidate in cortical and spinal networks during cholinergic crisis.
abstract: General anaesthesia is an important measure in the treatment of patients suffering from organophosphorus intoxication. The intravenous anaesthetic etomidate seems to be well suited for this purpose because of its stable haemodynamics. Here we raise the question whether the anaesthetic properties of etomidate are altered by cholinergic overstimulation and by the cholinergic antagonist atropine. As the neocortex and spinal cord mediate unconsciousness and immobility, organotypic cultures from these regions were used for pharmacological in vitro studies. The effects of etomidate on spontaneous action potential activity were assessed by extracellular action potential recordings under basal cholinergic tone, in the presence of acetylcholine, and in the additional presence of atropine. Etomidate (1μM) depressed neuronal activity in cortical slices by 47.5±6.9%, but only by 24.9±16.7% in the presence of acetylcholine. If atropine (10nM) was given in addition, the depression by etomidate was restored (53.4±4.2%). Similar results were obtained using cultured slices from the spinal cord. In summary, cholinergic overstimulation decreased the ability of etomidate to depress neuronal activity in neocortex and spinal cord. Atropine reversed this decrease. Hence, etomidate is potentially applicable for induction of anaesthesia in patients suffering from severe cholinergic crisis, preconditioned that atropine is co-applied.
authors.affiliation: Department of Anaesthesiology, Experimental Anaesthesiology Section, Eberhard-Karls-University, Schaffhausenstrasse 113, 72072 Tuebingen, Germany.
authors.forename: Berthold
authors.initials: B
authors.lastname: Drexler
authors.forename: Bernd
authors.initials: B
authors.lastname: Antkowiak
authors.forename: Horst
authors.initials: H
authors.lastname: Thiermann
authors.forename: Thomas
authors.initials: T
authors.lastname: Seeger
authors.forename: Christian
authors.initials: C
authors.lastname: Grasshoff
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000200:Action Potentials; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D004347:Drug Interactions; D005045:Etomidate / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D019579:Neocortex / Q000187:drug effects* / Q000378:metabolism; D009415:Nerve Net / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D011247:Pregnancy; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D018727:Muscarinic Antagonists; D001285:Atropine; D000109:Acetylcholine; D005045:Etomidate