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REGIONAL ANESTHESIA

Pharmacokinetics of Ropivacaine in Uremic and Nonuremic Patients After Axillary Brachial Plexus Block

Pertti Pere, MD, PhD^*, Merja Salonen, MD^*, Mika Jokinen, MD^*, Per H. Rosenberg, MD, PhD^*, Pertti J. Neuvonen, MD, PhD, and Juhani Haasio, MD, PhD^*

*Department of Anesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Helsinki, Finland; and Department of Clinical Pharmacology, University of Helsinki, Helsinki, Finland

Address correspondence and reprint requests to Pertti Pere, MD, PhD, Department of Anesthesia and Intensive Care Medicine, Helsinki University Central Hospital, PO Box 580, 00029 HUS, Finland. Address e-mail to pertti.pere{at}hus.fi

Reports on the efficacy and pharmacokinetics of local anesthetics in uremic patients have been controversial. Our study involved 29 uremic and 28 nonuremic patients. We performed axillary block with ropivacaine 300 mg (50 mL). Venous blood samples were drawn for 24 h for assay of total and unbound plasma ropivacaine, 3-hydroxyropivacaine, pipecoloxylidide (PPX), and serum ₁-acid glycoprotein (AAG). Block quality was similar in both groups. No toxicity occurred. Plasma clearance of ropivacaine was smaller and the area under the concentration-time curve of ropivacaine, 3-hydroxyropivacaine, and PPX larger in the uremic patients. The plasma concentration of PPX increased until 24 h in uremic patients whose AAG concentrations were also larger throughout the study. The free fraction of ropivacaine in plasma was smaller in the uremic group when measured 60 min and 12 h after the block, but the unbound concentration of ropivacaine was larger in the uremic group at 12 h. Enhanced absorption of ropivacaine into circulation, increased binding to AAG, and probably reduced urinary excretion of the metabolites lead to larger total plasma concentrations of ropivacaine and its main metabolites in uremic patients.

IMPLICATIONS: In uremic patients, enhanced absorption and reduced clearance of ropivacaine and reduced urinary excretion of the ropivacaine metabolites could lead to toxicity. Increased plasma protein binding of ropivacaine in uremic patients reduces elimination of the local anesthetic but may protect against acute toxicity despite large total plasma concentrations of ropivacaine.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999