title: [Systemic toxicity of local anesthetics. Pharmacokinetic and pharmacodynamic factors].
abstract: Local anaesthetics can have systemic adverse effects, mostly affecting the central nervous system and the heart. The physicochemical characteristics of the different local anaesthetics are recalled, for they determine the relationship between structure, activity and toxicity. The pharmacokinetic factors involved in the toxic effects of local anaesthetics, whether the drug is given in a single extravascular dose or, accidentally, within a blood vessel, are discussed. The toxic effects of repeated administrations of local anaesthetics depend on the metabolism of the drug as well as on pharmacokinetic factors. Possible maximal doses and drug interactions are also discussed. The mechanism of action of local anaesthetics, which block the sodium channel, explains their tissue toxicity and, more specifically, their central nervous and cardiovascular toxicities, which are more pronounced for the more potent local anaesthetic agents (bupivacaine, etidocaine). Systemic maternal effects and transplacental passage probably explain their foetal toxicity. Specific toxic effects are seen with some drugs, such as methaemoglobinaemia and allergic reactions (rarely for amide agents). Overall, local anaesthetic accidents are rare, but they must be prevented.
authors.affiliation: Département d'Anesthésie-Réanimation, Hôpital Général, Dijon.
authors.forename: M
authors.initials: M
authors.lastname: Freysz
authors.forename: J L
authors.initials: JL
authors.lastname: Béal
authors.forename: Q
authors.initials: Q
authors.lastname: Timour
authors.forename: L
authors.initials: L
authors.lastname: Bertrix
authors.forename: G
authors.initials: G
authors.lastname: Faucon
mesh_terms: D000771:Anesthesia, Intravenous / Q000009:adverse effects; D000779:Anesthetics, Local / Q000009:adverse effects* / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects; D004342:Drug Hypersensitivity / Q000209:etiology; D004347:Drug Interactions; D005333:Fetus / Q000187:drug effects; D006329:Heart Conduction System / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007269:Injections, Intra-Arterial / Q000009:adverse effects; D008708:Methemoglobinemia / Q000139:chemically induced; D011485:Protein Binding / Q000187:drug effects
chemical_list: D000779:Anesthetics, Local
vernacular_title: Toxicité systémique des anesthésiques locaux. Facteurs pharmacocinétiques et pharmacodynamiques.