Epidural infusion of ropivacaine for postoperative analgesia after major orthopedic surgery

Background: Changing plasma protein concentrations may affect the protein b inding and pharmacokinetics of drugs in the postoperative phase. Therefore, the authors evaluated the pharmacokinetics of ropivacaine, administered by 72-h epidural infusion to provide postoperative analgesia. Methods: Twenty-eight patients, scheduled for major orthopedic surgery duri ng combined epidural and general anesthesia received a bolus dose of ropiva caine (50 or 75 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 pl asma concentrations of ropivacaine and pipecoloxylidide and plasma concentr ations of alpha(1)-acid glycoprotein were determined. In addition, the urin ary excretion of ropivacaine and major metabolites was measured. Results: Total plasma concentrations of ropivacaine increased steadily duri ng the infusion, reaching 2.7 +/- 0.7 and 2.9 +/- 0.5 mg/l in groups 1 and 2 after 72 h constant-rate infusion. Unbound ropivacaine concentrations rea ched average steady state levels of approximately 0.06 and 0.07 mg/l. Total and unbound concentrations of pipecoloxylidide increased to 1.0 +/- 0.4 an d 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. alpha(1)-Acid glycoprotein concentrations initially d ecreased, but thereafter increased steadily to approximately twice the base line values. Conclusions: Postoperative increases in plasma alpha(1)-acid glycoprotein c oncentrations enhance the protein binding of ropivacaine and pipecoloxylidi de, causing divergence of total and unbound plasma concentrations.