title: Pharmacokinetics of 400 mg ropivacaine after periarticular local infiltration analgesia for total knee arthroplasty.
abstract: BACKGROUND
  Although considered safe, no pharmacokinetic data of high dose, high volume local infiltration analgesia (LIA) with ropivacaine without the use of a surgical drain or intra-articular catheter have been described. The purpose of this study is to describe the maximum total and unbound ropivacaine concentrations (Cmax, Cu max) and corresponding maximum times (Tmax, Tu max) of a single-shot ropivacaine (200 ml 0.2%) and 0.75 mg epinephrine (1000 μg/ml) when used for LIA in patients for total knee arthroplasty.
  
  
  METHODS
  In this prospective cohort study, 20 patients were treated with LIA of the knee for primary total knee arthroplasty. Plasma samples were taken at 20, 40, 60, 90, 120, 240, 360 min and at 24 h after tourniquet release, in which total and unbound ropivacaine concentrations were determined.
  
  
  RESULTS
  Results are given as median [IQR]. Highest ropivacaine concentration (Cmax) was 1.06 μg/ml [0.34]; highest unbound ropivacaine concentration (Cu max) was 0.09 μg/ml [0.05]. The corresponding time to reach the maximum concentration for total ropivacaine was 312 min [120] after tourniquet release, and for the unbound fraction 265 [110] min after tourniquet release.
  
  
  CONCLUSIONS
  Although great inter-individual variability was found between the maximum ropivacaine concentrations, both maximum total and unbound serum concentrations of ropivacaine remained well below the assumed systemic toxic thresholds of 4.3 and 0.56 μg/ml.
authors.affiliation: Department of Anesthesiology, Sint Maartenskliniek, Nijmegen, The Netherlands.|Department of Anesthesiology, Pain and Palliative Care, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: M G E
authors.initials: MG
authors.lastname: Fenten
authors.affiliation: Department of Anesthesiology, Sint Maartenskliniek, Nijmegen, The Netherlands.
authors.forename: S M K
authors.initials: SM
authors.lastname: Bakker
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: D J
authors.initials: DJ
authors.lastname: Touw
authors.affiliation: Department of Pharmacy, Sint Maartenskliniek, Nijmegen, The Netherlands.|Department of Clinical Pharmacy, Radboud University Medical Center, Nijmegen, The Netherlands.|Department of Clinical Pharmacy and Toxicology, Maastricht University Medical Center+, Maastricht, The Netherlands.
authors.forename: B J F
authors.initials: BJ
authors.lastname: van den Bemt
authors.affiliation: Department of Anesthesiology, Pain and Palliative Care, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: G J
authors.initials: GJ
authors.lastname: Scheffer
authors.affiliation: Research Department, Sint Maartenskliniek, Nijmegen, The Netherlands.
authors.forename: P J C
authors.initials: PJ
authors.lastname: Heesterbeek
authors.affiliation: Department of Anesthesiology, Sint Maartenskliniek, Nijmegen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Stienstra
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000577:Amides / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000698:Analgesia / Q000379:methods*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000493:pharmacokinetics*; D019645:Arthroplasty, Replacement, Knee / Q000379:methods*; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D000077212:Ropivacaine
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine