Department of Anesthesiology

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Pharmacokinetics of cisatracurium in patients receiving nitrous oxide/opioid/barbiturate anesthesia.

TitlePharmacokinetics of cisatracurium in patients receiving nitrous oxide/opioid/barbiturate anesthesia.
Publication TypeJournal Article
Year of Publication1996
AuthorsLien CA, Schmith VD, Belmont MR, Abalos A, Kisor DF, Savarese JJ
JournalAnesthesiology
Volume84
Issue2
Pagination300-8
Date Published1996 Feb
ISSN0003-3022
KeywordsAdult, Aged, Anesthetics, Inhalation, Anesthetics, Intravenous, Atracurium, Female, Fentanyl, Humans, Isoquinolines, Male, Midazolam, Middle Aged, Neuromuscular Nondepolarizing Agents, Nitrous Oxide, Opium, Stereoisomerism, Thiopental
Abstract

BACKGROUND: Cisatracurium, one of the ten isomers in atracurium, is a nondepolarizing muscle relaxant with an intermediate duration of action. It is more potent and less likely to release histamine than atracurium. As one of the isomers composing atracurium, it presumably undergoes Hofmann elimination. This study was conducted to describe the pharmacokinetics of cisatracurium and its metabolites and to determine the dose proportionality of cisatracurium after administration of 2 or 4 times the ED(95).

METHODS: Twenty ASA physical status 1 or 2 patients undergoing elective surgery under nitrous oxide/opioid/barbiturate anesthesia were studied. Patients received a single rapid intravenous bolus does of 0.1 or 0.2 mg x kg-1 (2 or 4 times the ED(95), respectively) cisatracurium. All patients were allowed to recover spontaneously to a train-of-four ratio > or = 0.70 after cisatracurium-induced neuromuscular block. Plasma was extracted, acidified, and stored frozen before analysis for cisatracurium, laudanosine, the monoquaternary acid, and the monoquaternary alcohol metabolite.

RESULTS: The clearances (5.28 +/- 1.23 vs. 4.66 +/- 0.67 ml x min(-1) x kg(-1) and terminal elimination half-lives (22.4 +/- 2.7 vs. 25.5 +/- 4.1 min) were not statistically different between patients receiving 0.1 mg x kg(-1) and 0.2 mg x kg(-1), respectively. Maximum concentration values for laudanosine averaged 38 +/- 21 and 103 +/- 34 ng x ml(-1) for patients receiving the 0.1 and 0.2 mg x kg(-1) doses, respectively. Maximum concentration values for monoquaternary alcohol averaged 101 +/- 27 and 253 +/- 51 ng x ml(-1), respectively. Monoquaternary acid was not quantified in any plasma sample.

CONCLUSIONS: Cisatracurium undergoes Hofmann elimination to form laudanosine. The pharmacokinetics of cisatracurium are independent of dose after single intravenous doses of 0.1 and 0.2 mg x kg(-1).

Alternate JournalAnesthesiology
PubMed ID8602660