OBJECTIVE: The pharmacokinetics of ropivacaine 0.2% were evaluated during a 48-hour continuous extrapleural infusion with 2 different infusion rates in patients undergoing cardiovascular surgery. The hypotheses that no toxic plasma concentrations of ropivacaine would be reached and that proportionality exists among plasma concentrations and dosage used were tested. DESIGN: A prospective, randomized, nonblinded study. SETTING: The investigation was performed as a single-center study in the Division of Cardiovascular Anesthesia, University Hospital of Zurich, in Switzerland. PARTICIPANTS: Seventeen consenting adults scheduled for elective cardiovascular surgery, with or without extracorporeal bypass, via the lateral thoracotomy approach were enrolled. INTERVENTIONS: For postoperative pain relief, patients were randomly assigned to receive continuous extrapleural infusion of ropivacaine 0.2% at a rate of either 6 or 9 mL/h over 48 hours. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of ropivacaine reached toxic levels (>2.2 mg/L) in 25% of cases. No proportionality of plasma concentrations of ropivacaine existed when the 2 dosing regimens were compared. CONCLUSIONS: Plasma concentrations of ropivacaine, administered at the given dose and rates during continuous extrapleural infusion, are unpredictable and may reach toxic levels in patients undergoing major cardiothoracic surgery.