title: Modeling the anesthetic effect of ropivacaine after a femoral nerve block in orthopedic patients: a population pharmacokinetic-pharmacodynamic analysis.
abstract: BACKGROUND
  Even though ropivacaine is frequently used during orthopedic surgery, the relationship between plasma concentrations and degree of sensory anesthesia after a peripheral nerve block is currently unknown. The aim of this study was to characterize this relation using population pharmacokinetic-pharmacodynamic modeling.
  
  
  METHODS
  Femoral nerve block was performed by the anterior approach using a single injection (20 ml) of 0.5% ropivacaine hydrochloride in 20 patients scheduled for total knee arthroplasty under spinal anesthesia. Sensory thresholds in response to a gradual increase in transcutaneous electrical stimulation (primary endpoints), loss and recovery of ice-cold sensation, as well as total ropivacaine plasma concentrations were determined up to 4 days after administration of the local anesthetic. Using NONMEM (ICON, USA), sensory block was modeled by assuming an equilibration delay (ke0) between amount in the depot and effect-site compartments.
  
  
  RESULTS
  Mean effect-site amount producing 90% of the maximum possible effect (AE90) was estimated as 20.2 mg. At 2 × AE90, the sigmoid Emax model predicted a mean onset time of 23.4 min and mean duration of 22.9 h. Interindividual variability (IIV) for AE50 was 49%. Typical ke0 half-life was 34.7 min (IIV = 52%) and steepness parameter 8.7 (IIV = 48%). None of the pharmacodynamic model parameters showed sex, age, or body weight dependency.
  
  
  CONCLUSIONS
  A population pharmacokinetic/pharmacodynamic model was developed that quantitatively describes the sensory component of a femoral nerve block in orthopedic patients. Further clinical studies will be needed to validate the clinical relevance of this finding.
authors: From the Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada (F.G., F.V.); Department of Anesthesiology, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada (P.D.); and Department of Surgery, Hopital Maisonneuve-Rosemont, Montreal, Quebec, Canada (M.F.).
authors: François
authors: F
authors: Gaudreault
authors: Pierre
authors: P
authors: Drolet
authors: Michel
authors: M
authors: Fallaha
authors: France
authors: F
authors: Varin
mesh_terms: D000368:Aged; D000465:Algorithms; D000577:Amides / Q000493:pharmacokinetics / Q000494:pharmacology; D000779:Anesthetics, Local / Q000493:pharmacokinetics / Q000494:pharmacology; D003080:Cold Temperature; D004558:Electric Stimulation; D023381:Endpoint Determination; D005260:Female; D005267:Femoral Nerve; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009407:Nerve Block / Q000379:methods*; D019637:Orthopedic Procedures / Q000009:adverse effects*; D009985:Orthopedics; D017288:Pain Threshold / Q000187:drug effects; D000077212:Ropivacaine; D012677:Sensation / Q000187:drug effects
chemical_list: D000577:Amides; D000779:Anesthetics, Local; D000077212:Ropivacaine