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Plasma Ropivacaine Concentrations Following Local Infiltration Analgesia in Total Knee Arthroplasty: A Pharmacokinetic Study to Determine Safety Following Fixed-Dose Administration
  1. Reuben J. Miller, MBChB*,
  2. Andrew J. Cameron, MBChB, FANZCA*,
  3. Julian Dimech, PhD, MBChB, FANZCA*,
  4. Robert J. Orec, MBChB, FRACS and
  5. Nicholas J. Lightfoot, MBChB, FANZCA*
  1. *Department of Anaesthesia and Pain Medicine, Middlemore Hospital, Auckland, New Zealand
  2. Department of Orthopaedic Surgery, Middlemore Hospital, Auckland, New Zealand
  1. Address correspondence to: Reuben J. Miller, MBChB, Department of Anaesthesia and Pain Medicine, Middlemore Hospital, Private Bag 93311, Otahuhu, Auckland 1640, New Zealand (e-mail: reuben.j.miller{at}


Background and Objectives The primary aim of this study was to examine the pharmacokinetics of ropivacaine in patients undergoing elective total knee arthroplasty with local infiltration analgesia as the primary analgesic method. We also sought to determine the incidence of biochemical toxicity through measurement of plasma ropivacaine concentrations over the first 24 hours postoperatively.

Methods This was a prospective, observational study of 15 patients undergoing elective total knee arthroplasty. Local infiltration analgesia was administered by standard technique with 300 mg ropivacaine and epinephrine 5 μg/mL. Total ropivacaine concentrations were taken at specified time intervals in the 24 hours after tourniquet release and analyzed by liquid chromatography–mass spectrometry.

Results Fifteen patients were enrolled into the study. The median peak ropivacaine concentration was 0.57 μg/mL, with a range of 0.32 to 0.88 μg/mL, and occurred between 6 and 24 hours. Age (P = 0.04), weight (P = 0.04), creatinine (P = 0.02), and female sex (P = 0.03) were important predictors of peak concentration. Age (P = 0.02), female sex (P = 0.01), and baseline α1 acid glycoprotein concentrations (P = 0.03) were important predictors for the area under the curve from a ropivacaine concentration versus time plot.

Conclusions The peak total ropivacaine concentration was below quoted toxic concentrations (2.2 μg/mL) in all patients. This peak occurred later than has previously been described in those undergoing neuraxial or peripheral nerve block, occurring between 6 and 24 hours. The influence of age, weight, and renal function on systemic ropivacaine concentration should be considered when planning local infiltration analgesia. Female sex is a factor that has not previously been associated with peak ropivacaine concentrations.

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  • The authors declare no conflict of interest.

    This research was funded in part by the Counties Manukau Health TUPU fund and the South Auckland Anaesthetic Research Trust.