title: Pharmacokinetics of 450 mg ropivacaine with and without epinephrine for combined femoral and sciatic nerve block in lower extremity surgery. A pilot study.
abstract: OBJECTIVE
  No pharmacokinetic data exist on doses of ropivacaine larger than 300 mg for peripheral nerve block in man, although in clinical practice higher doses are frequently used. The purpose of the present study was to describe the pharmacokinetic profile in serum of 450 mg ropivacaine with and without epinephrine in patients undergoing anterior cruciate ligament reconstruction.
  
  
  METHODS
  Twelve patients were randomly allocated to receive a single shot combined sciatic/femoral nerve block with 60 ml of either ropivacaine 0.75% alone (group R, n = 6) or ropivacaine 0.75% plus epinephrine 5 μg ml(-1) (group RE, n = 6). Venous blood samples for total and free ropivacaine serum concentrations were obtained during 48 h following block placement. Pharmacokinetic parameters were calculated using a non-compartmental approach.
  
  
  RESULTS
  Results are given as mean (SD) for group R vs. group RE (95% CI of the difference). Total Cmax was 2.81 (0.94) μg ml(-1) vs. 2.16 (0.21) μg ml(-1) (95% CI -0.23, 1.53). tmax was 1.17 (0.30) h vs. 1.67 (0.94) h (95% CI -1.40, 0.40). The highest free ropivacaine concentration per patient was 0.16 (0.08) μg ml(-1) vs. 0.12 (0.04) μg ml(-1) (95% CI -0.04, 0.12). t(1/2) was 6.82 (2.26) h vs. 5.48 (1.69) h (95% CI -1.23, 3.91). AUC was 28.35 (5.92) μg ml(-1)  h vs. 29.12 (7.34) μg ml(-1)  h (95% CI -9.35, 7.81).
  
  
  CONCLUSIONS
  Free serum concentrations of ropivacaine with and without epinephrine remained well below the assumed threshold of 0.56 μg ml(-1) for systemic toxicity. Changes in pharmacokinetics with epinephrine co-administration did not reach statistical significance.
authors.affiliation: Department of Anesthesiology, Sint Maartenskliniek, Hengstdal 3, 6574 NA, Nijmegen, The Netherlands.
authors.forename: Karin P W
authors.initials: KP
authors.lastname: Schoenmakers
authors.forename: Tom B
authors.initials: TB
authors.lastname: Vree
authors.forename: Nigel T M
authors.initials: NT
authors.lastname: Jack
authors.forename: Bart
authors.initials: B
authors.lastname: van den Bemt
authors.forename: Jacques
authors.initials: J
authors.lastname: van Limbeek
authors.forename: Rudolf
authors.initials: R
authors.lastname: Stienstra
mesh_terms: D000293:Adolescent; D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000493:pharmacokinetics*; D059549:Anterior Cruciate Ligament Reconstruction; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D004837:Epinephrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D005267:Femoral Nerve / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009407:Nerve Block / Q000379:methods; D010865:Pilot Projects; D011897:Random Allocation; D000077212:Ropivacaine; D012584:Sciatic Nerve / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D014662:Vasoconstrictor Agents; D000077212:Ropivacaine; D004837:Epinephrine