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Author Copeland, Susan E. ♦ Ladd, Leigh A. ♦ Gu, Xiao-Qing ♦ Mather, Laurence E.
Source World Health Organization (WHO)-Global Index Medicus
Content type Text
Publisher Lippincott Williams & Wilkins
File Format HTM / HTML
Language English
Difficulty Level Medium
Subject Domain (in DDC) Natural sciences & mathematics ♦ Chemistry & allied sciences ♦ Life sciences; biology ♦ Physiology & related subjects ♦ Biochemistry ♦ Natural history of organisms ♦ Technology ♦ Medicine & health ♦ Human anatomy, cytology, histology ♦ Human physiology ♦ Pharmacology and therapeutics ♦ Diseases ♦ Manufacture for specific uses ♦ Precision instruments & other devices
Subject Domain (in MeSH) Cardiovascular System ♦ Nervous System ♦ Anatomy ♦ Eukaryota ♦ Organisms ♦ Organic Chemicals ♦ Heterocyclic Compounds ♦ Chemical Actions and Uses ♦ Chemicals and Drugs ♦ Diagnosis ♦ Therapeutics ♦ Investigative Techniques ♦ Analytical, Diagnostic and Therapeutic Techniques and Equipment ♦ Chemical Phenomena ♦ Metabolism ♦ Physiological Phenomena ♦ Biological Sciences
Subject Keyword Discipline Anesthesiology ♦ Anesthetics, Inhalation ♦ Pharmacology ♦ Anesthetics, Local ♦ Pharmacokinetics ♦ Halothane ♦ Amides ♦ Administration & Dosage ♦ Blood ♦ Toxicity ♦ Animals ♦ Bupivacaine ♦ Analogs & Derivatives ♦ Cardiovascular System ♦ Drug Effects ♦ Metabolism ♦ Central Nervous System ♦ Drug Interactions ♦ Female ♦ Infusions, Intravenous ♦ Lidocaine ♦ Mepivacaine ♦ Metabolic Clearance Rate ♦ Models, Biological ♦ Prilocaine ♦ Protein Binding ♦ Sheep ♦ Tissue Distribution ♦ Comparative Study ♦ Journal Article ♦ Research Support, Non-u.s. Gov't
Abstract BACKGROUND: Local anesthetic toxicity is often studied experimentally in anesthetized subjects, but clinical toxicity usually occurs in conscious patients. In this study, we determined the influence of general anesthesia on the pharmacokinetics of six local anesthetics administered i.v. at approximately the highest recommended doses. METHODS: Chronically instrumented ewes (approximately 45-50 kg, n = 18) were infused over 3 min with (base doses as HCl salts) bupivacaine (100 mg), levobupivacaine (125 mg), ropivacaine (150 mg), lidocaine (350 mg), mepivacaine (350 mg), or prilocaine (350 mg), on separate occasions when conscious and halothane anesthetized. Serial arterial, heart, and brain venous blood drug concentrations were measured by achiral/chiral high-performance liquid chromatography, as relevant. Whole body pharmacokinetics were assessed by noncompartmental analysis; heart and brain pharmacokinetics were assessed by mass balance. Drug blood binding, in the absence and presence of halothane, was assessed by equilibrium dialysis in vitro. RESULTS: Blood local anesthetic concentrations were doubled with anesthesia because of decreased whole body distribution and clearance (respectively, to 33% and 52% of values when conscious). Heart and brain net drug uptake were greater under anesthesia, reflecting slower efflux from both regions. Clearances of R-bupivacaine > S-bupivacaine and R-prilocaine > S-prilocaine, but, mepivacaine clearance was not enantioselective. Halothane did not influence blood binding of the local anesthetics. CONCLUSIONS: General anesthesia significantly changed whole body and regional pharmacokinetics of each local anesthetic as well as the systemic effects. General anesthesia is thus an important but frequently overlooked factor in studies of local anesthetic toxicity.
Description Country affiliation: Australia
Author Affiliation: Copeland SE ( Department of Anaesthesia and Pain Management, University of Sydney at Royal North Shore Hospital, Sydney NSW 2065, Australia.)
ISSN 00032999
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Reading ♦ Research ♦ Self Learning
Interactivity Type Expositive
Education Level UG and PG
Learning Resource Type Article
Publisher Date 2008-05-01
Publisher Place United States
e-ISSN 15267598
Journal Anesthesia & Analgesia
Volume Number 106
Issue Number 5


Source: WHO-Global Index Medicus