Anesthesia (3)

Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery. (Leiden University Medical Center, Leiden, The Netherlands) Anesthesiology 2000;93:395–403. This study evaluated the pharmacokinetics of ropivacaine administered by 72‐h epidural infusion to provide postoperative analgesia. Twenty‐eight patients scheduled for major orthopedic surgery during combined epidural and general anesthesia received a bolus dose of ropivacaine (50 or 70 mg), followed by constant‐rate (10 mL/h) epidural infusion of ropivacaine 2 mg/mL (Group 1) or 3 mg/mL (Group 2). Total and unbound plasma concentrations of ropivacaine and pipecoloxylidide and plasma concentrations of α 1 ‐acid glycoprotein were determined. The urinary excretion of ropivacaine and major metabolites was measured. Results showed that total plasma concentrations of ropivacaine increased steadily during infusion and unbound ropivacaine concentrations reached average steady levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 ± 0.4 and 0.4 ± 0.2 mg/l (Group 1) and 1.2 ± 0.4 and 0.5 ± 0.1 mg/l (Group 2) after 72 h infusion. α 1 ‐Acid glycoprotein concentrations initially decreased, but thereafter increased steadily to approximately twice the baseline values. Conclude postoperative increases in plasma α 1 ‐acid glycoprotein concentrations enhance the protein binding of ropivacaine and pipecoloxylidide, which causes divergence of total and unbound plasma concentrations.