title: A Dose-Finding Study of Dexketoprofen in Patients Undergoing Laparoscopic Cholecystectomy: A Randomized Clinical Trial on Effects on the Analgesic Concentration of Oxycodone.
abstract: BACKGROUND
  Dexketoprofen has been shown to provide efficient analgesia and an opioid-sparing effect after orthopedic surgery. In this dose-finding study, we evaluated the analgesic efficacy and opioid-sparing effect of dexketoprofen administered intravenously (i.v.) after laparoscopic cholecystectomy (LCC).
  
  
  METHODS
  Twenty-four patients undergoing LCC were randomized to receive dexketoprofen 10 or 50 mg i.v. 15 min before the end of the surgery. Subjects were provided with 0.2 mg/kg of oxycodone at anesthesia induction. In the recovery room, pain was assessed with an 11-point numerical rating scale (NRS; score of 0 = no pain, score of 10 = most severe pain) every 10 min. When the NRS score was ≥3/10 at rest or ≥5/10 at wound compression, a plasma sample was taken for analysis of oxycodone [to determine the minimum effective concentration (MEC)], its metabolites, and dexketoprofen. After that, subjects were titrated with oxycodone 2 or 3 mg i.v. every 10 min until the NRS score was <3/10 at rest and <5/10 at wound compression. At this point, a second plasma sample was taken for analysis of oxycodone [minimum effective analgesic concentration (MEAC)], its metabolites, and dexketoprofen.
  
  
  RESULTS
  At the onset of pain, the plasma oxycodone concentrations (MEC) were similar in the two groups: median 60 ng/mL (range 37-73) in the 10 mg group and median 52 ng/mL (range 24-79) in the 50 mg group. At the time of pain relief, the MEACs were 98 ng/mL (range 59-150) in the 10 mg group and 80 ng/mL (range 45-128) in the 50 mg group. The total doses of oxycodone needed to achieve pain relief were similar: 0.11 mg/kg (range 0-0.33) in the 10 mg group and 0.08 mg/kg (range 0-0.24) in the 50 mg group. Eleven subjects developed mild desaturation or a decreased respiratory rate after oxycodone titration.
  
  
  CONCLUSIONS
  In the present double-blinded, randomized clinical trial, the need for a rescue opioid analgesic, oxycodone, was similar with the two dose levels of dexketoprofen-10 and 50 mg i.v.-after LCC.
authors.affiliation: Anaesthesiology and Intensive Care Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.|Department of Anesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, Finland.
authors.forename: Annika
authors.initials: A
authors.lastname: Piirainen
authors.affiliation: Anaesthesiology and Intensive Care Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland.|Department of Anesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kokki
authors.affiliation: Department of Anesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, Finland.|School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Satu
authors.initials: S
authors.lastname: Immonen
authors.affiliation: Department of Surgery, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Matti
authors.initials: M
authors.lastname: Eskelinen
authors.affiliation: School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
authors.forename: Merja R
authors.initials: MR
authors.lastname: Häkkinen
authors.affiliation: Admescope Ltd, Oulu, Finland.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hautajärvi
authors.affiliation: Anaesthesiology and Intensive Care Medicine, School of Medicine, University of Eastern Finland, Kuopio, Finland. merja.kokki@kuh.fi.|Department of Anesthesia and Operative Services, Kuopio University Hospital, PO Box 100, 70029, Kuopio, Finland. merja.kokki@kuh.fi.
authors.forename: Merja
authors.initials: M
authors.lastname: Kokki
mesh_terms: D000328:Adult; D000701:Analgesics, Opioid / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D017081:Cholecystectomy, Laparoscopic; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007660:Ketoprofen / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010098:Oxycodone / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D014325:Tromethamine / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D014325:Tromethamine; D007660:Ketoprofen; D010098:Oxycodone; C118296:dexketoprofen trometamol