• Georgios Ekatodramis, Alain Borgeat, Gunilla Huledal, Lennart Jeppsson, Lars Westman, and Jan Sjövall.
• *Consultant, dagger Professor and Chief of Staff, Department of Anesthesiology, University Clinic of Zurich/Balgrist. double dagger AstraZeneca R&D, Södertälje, Sweden.
• Anesthesiology. 2003 Jan 1;98(1):143-50.

BackgroundIn this open, randomized study, the pharmacokinetics, clinical efficacy, and safety of a 48-h continuous interscalene infusion of 2 mg/ml ropivacaine for postoperative pain relief were investigated in patients undergoing open major shoulder surgery.MethodsAn initial interscalene block with 30 ml ropivacaine, 7.5 mg/ml (225 mg), was performed. After completion of interscalene block, all patients (n = 24) received general anesthesia, and 6 h after interscalene block, a 48-h continuous interscalene infusion of 12 or 18 mg/h using 2 mg/ml ropivacaine was started. Total and unbound plasma concentrations of ropivacaine and 2.6-pipecoloxylidide (PPX; a major active metabolite) were determined during and up to 6 h after the interscalene infusion. Postoperative pain at rest was assessed by a visual analog scale. Supplementary analgesics and adverse events were recorded.ResultsPlasma concentrations of total and unbound ropivacaine were proportional to the total dose. At the end of the interscalene infusion of 9 ml/h, the mean +/- SD plasma concentrations of total and unbound ropivacaine were 1.40 +/- 0.54 and 0.03 +/- 0.01 mg/l, respectively, and of total and unbound PPX were 0.70 +/- 0.38 and 0.30 +/- 0.20 mg/l, respectively. Plasma concentrations of unbound ropivacaine and unbound PPX, added together, remained well below threshold levels for systemic central nervous system toxicity. There were no significant differences between the groups for postoperative pain (median maximum of about 20 mm on the visual analog scale in both groups), analgesic consumption, or quality of pain relief assessed by the patient. No signs or symptoms of systemic local anesthetic toxicity were observed.ConclusionA 48-h continuous interscalene infusion of 6 or 9 ml/h ropivacaine, 2 mg/ml, started 6 h after an initial interscalene block of 30 ml ropivacaine, 7.5 mg/ml, provided satisfactory postoperative pain relief after major shoulder surgery and was well tolerated. Unbound plasma concentrations of ropivacaine and PPX remained well below threshold levels for systemic central nervous toxicity.

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