title: Epidural Blockade Affects the Pharmacokinetics of Propofol in Surgical Patients.
abstract: BACKGROUND
  Neuraxial blockade reduces the dose requirements of sedative agents. It is unclear whether neuraxial blockade affects the pharmacokinetics and/or the pharmacodynamics of IV hypnotics. We therefore studied the influence of epidural blockade on the pharmacokinetics of propofol in patients scheduled for general surgery.
  
  
  METHODS
  Twenty-eight patients were randomly divided into 4 groups, in a double-blind manner, to receive 0, 50, 100, or 150 mg epidural ropivacaine. When the epidural blockade had stabilized, a target-controlled infusion of propofol was started at a target concentration of 1, 2.5, 4, and 6 µg/mL at 0, 6, 12, and 18 minutes, respectively. The infusion was terminated at 24 minutes. Arterial blood samples for blood propofol concentration determination were taken during and up to 150-minute postinfusion. The influence of epidural blockade on propofol pharmacokinetics was determined by mixed-effects modeling.
  
  
  RESULTS
  With a ropivacaine dose increasing from 0 to 150 mg, the number of blocked segments (median [range]) increased from 0 (0-3) to 16 (6-21). With increasing epidural dose, blood propofol concentration increasingly exceeded target concentration. An epidural blockade of 20 segments reduced propofol's elimination clearance from 2.64 ± 0.12 to 1.87 ± 0.08 L/min. Adjusting for weight and sex further improved the propofol pharmacokinetic model.
  
  
  CONCLUSIONS
  Epidural blockade affects the pharmacokinetics of propofol and the performance of a target-controlled infusion of propofol. At an epidural ropivacaine dose that blocks 20 segments, the propofol dosage or target concentration may be reduced by 30% compared with when no epidural blockade is present. An epidural-induced reduction in hepatic and/or renal blood flow may explain this pharmacokinetic interaction.
authors.affiliation: From the Department of Anesthesiology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Elske
authors.initials: E
authors.lastname: Sitsen
authors.forename: Erik
authors.initials: E
authors.lastname: Olofsen
authors.forename: Agnes
authors.initials: A
authors.lastname: Lesman
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.forename: Jaap
authors.initials: J
authors.lastname: Vuyk
mesh_terms: D000328:Adult; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects*; D015360:Analgesia, Epidural / Q000009:adverse effects*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D000779:Anesthetics, Local / Q000008:administration & dosage / Q000009:adverse effects*; D001835:Body Weight; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009043:Motor Activity / Q000187:drug effects; D009426:Netherlands; D015742:Propofol / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D012079:Renal Circulation / Q000187:drug effects; D000077212:Ropivacaine; D012737:Sex Factors; D013514:Surgical Procedures, Operative; D013697:Thermosensing / Q000187:drug effects
chemical_list: D000577:Amides; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D000077212:Ropivacaine; D015742:Propofol