title: Pretreatment with flurbiprofen axetil, flurbiprofen axetil preceded by venous occlusion, and a mixture of flurbiprofen axetil and propofol in reducing pain on injection of propofol in adult Japanese surgical patients: a prospective, randomized, double-blind, placebo-controlled study.
abstract: BACKGROUND
  Pain on injection of propofol is a common clinical problem. Flurbiprofen axetil, an injectable prodrug of flurbiprofen, with or without venous occlusion has been reported to reduce this pain. A search of the existing literature did not identify comparative studies of 3 different techniques, including pretreatment with flurbiprofen axetil, flurbiprofen axetil preceded by venous occlusion, and mixture of propofol and flurbiprofen axetil, for reducing pain on injection of propofol.
  
  
  OBJECTIVE
  The aim of this study was to compare the effectiveness of these 3 different techniques of flurbiprofen axetil administration in reducing pain on injection of propofol.
  
  
  METHODS
  This prospective, randomized, doubleblind, placebo-controlled study was conducted at the Department of Anesthesiology, Ushiku Aiwa General Hospital, Ibaraki, Japan. Japanese elective surgical patients, aged 20 to 65 years, were enrolled and were randomly divided into 6 groups: the control group received placebo (saline) before administration of IV propofol 0.5 mg/kg; the flurbiprofen group was pretreated with IV flurbiprofen axetil 50 mg before injection of propofol 0.5 mg/kg; the tourniquet control group received placebo (saline) with a tourniquet for 2 minutes followed by administering propofol 0.5 mg/kg; the tourniquet flurbiprofen group was pretreated with flurbiprofen axetil 50 mg with a tourniquet for 2 minutes followed by administering propofol 0.5 mg/kg; the mixed control group was induced with a mixture of placebo (saline) and propofol 0.5 mg/kg; and the mixed flurbiprofen group was induced with a mixture of flurbiprofen axetil 50 mg and propofol 0.5 mg/kg. Immediately after administering propofol into the largest vein of the hand through a 20-gauge intravenous cannula, an investigator blinded to group assignment asked the patient to assess pain intensity at the injection site using a 4-point verbal rating scale: 0 = none, 1 = mild, 2 = moderate, and 3 = severe. Adverse effects (AEs) at the injection site (pain, edema, wheal, or inflammation) were assessed by the investigator for 24 hours after surgery using spontaneous reporting and patient interview.
  
  
  RESULTS
  One hundred fifty-five patients were assessed for inclusion. A total of 150 patients (71 males, 79 females; mean [SD] age, 41 [10] years; mean [SD] height, 161 [9] cm; mean [SD] body weight, 58 [9] kg) were enrolled and completed the study. Each treatment group comprised 25 patients. No significant differences in the demographic characteristics were observed among the 6 groups. The overall incidence of pain on injection of propofol was 92% (23 of 25 patients) in the control group versus 60% (15/ 25) in the flurbiprofen group (P = 0.009); 84% (21/25) in the tourniquet control group versus 32% (8/25) in the tourniquet flurbiprofen group (P = 0.001); and 92% (23/25) in the mixed control group versus 80% (20/25) in the mixed flurbiprofen group (P = NS). The median pain score was significantly lower in the flurbiprofen group (1) compared with the control group (2) (P = 0.002); this score was significantly lower in the tourniquet flurbiprofen group (0) compared with the tourniquet control group (2) (P = 0.001); the score was comparable between the mixed control and mixed flurbiprofen groups (2 vs 2, respectively; P = NS). The incidence and severity of pain on injection of propofol were significantly less in the tourniquet flurbiprofen group compared with the flurbiprofen group (both, P < 0.05). No AEs at the injection site were observed or reported.
  
  
  CONCLUSIONS
  In this study of adult Japanese surgical patients, pretreatment with flurbiprofen axetil 50 mg preceded by venous occlusion was found to be more effective in reducing pain on injection of propofol than the other flurbiprofen axetil administration strategies tested.
authors.affiliation: First Department of Anesthesiology, Toho University School of Medicine, Ohta-ku, Tokyo, Japan. yfujii@med.toho-u.ac.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
authors.forename: Michiyo
authors.initials: M
authors.lastname: Itakura
mesh_terms: D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005542:Forearm / Q000098:blood supply; D006801:Humans; D007275:Injections, Intravenous; D007564:Japan; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010147:Pain Measurement; D011355:Prodrugs; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects*; D011446:Prospective Studies; D012720:Severity of Illness Index; D013514:Surgical Procedures, Operative / Q000379:methods; D014111:Tourniquets; D055815:Young Adult
chemical_list: D018686:Anesthetics, Intravenous; D016861:Cyclooxygenase Inhibitors; D011355:Prodrugs; D005480:Flurbiprofen; C504422:flurbiprofen axetil; D015742:Propofol