title: Comparison of lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patients: a prospective, randomized, double-blind, parallel-group, placebo-controlled study.
abstract: BACKGROUND
  Pain on injection is a recognized adverse event (AE) of propofol administration for the induction of general anesthesia. Pretreatment with lidocaine, metoclopramide, or flurbiprofen axetil has been reported to be effective in reducing propofol-induced pain. However, no studies comparing the efficacy of these 3 drugs for preventing pain on injection of propofol have been identified.
  
  
  OBJECTIVE
  The aim of this study was to compare the efficacy of lidocaine, metoclopramide, and flurbiprofen axetil for reducing pain on injection of propofol in Japanese adult surgical patients.
  
  
  METHODS
  This prospective, randomized, double-blind, parallel-group, placebo-controlled study was conducted at the Department of Anesthesiology, Ushiku Aiwa General Hospital, Ibaraki, Japan. Japanese patients scheduled to undergo elective surgery were eligible for inclusion in the study. Patients were randomized into 4 groups to receive IV lidocaine 40 mg, metoclopramide 10 mg, flurbiprofen axetil 50 mg, or placebo (saline), preceded by venous occlusion with a rubber tourniquet for 2 minutes, and followed by the administration of propofol 0.5 mg/kg into the largest vein of the hand through a 20-gauge IV cannula. Immediately after the administration of propofol, an investigator blinded to treatment interviewed each patient on injection-site pain. Responses were scored on a 4-point verbal rating scale (0 = none, 1 = mild pain, 2 = moderate pain, and 3 = severe pain). Incidence and intensity of pain (as assessed by mean pain scores) were determined in each of the 4 study groups. AEs at the injection site (eg, pain, edema, wheal, inflammation), extrapyramidal disturbance, and symptoms or signs associated with gastrointestinal (GI) ulceration were assessed by the study investigator for 24 hours following surgery using spontaneous reporting and patient interview.
  
  
  RESULTS
  A total of 100 patients (54 women, 46 men) aged 22 to 65 years were enrolled in the study. The patients' mean (SD) age was 42 (12) years. Their mean (SD) height was 161 (8) cm and their mean (SD) weight was 59 (9) kg. Each treatment group comprised 25 patients. There were no significant differences in demographic characteristics between treatment groups. The overall incidence of propofol-induced pain was 24% (6/25 patients) with lidocaine (P = 0.001), 28% (7/25 patients) with metoclopramide (P = 0.001), and 36% (9/25 patients) with flurbiprofen axetil (P = 0.001), compared with placebo (92%, [23/25 patients]). The median pain score was less in patients who had received lidocaine (0), metoclopramide (0), or flurbiprofen axetil (0) than in those who received placebo (2) (all, P = 0.001). The incidence and severity of such pain were not significantly different between the lidocaine-, metoclopramide-, and flurbiprofen axetil-treated groups. There were no reported injection-site AEs, extrapyramidal disturbance, or symptoms or signs associated with GI ulceration observed.
  
  
  CONCLUSIONS
  In this study of Japanese adult surgical patients, lidocaine 40 mg, metoclopramide 10 mg, and flurbiprofen axetil 50 mg, preceded by venous occlusion for 2 minutes, were effective in reducing pain during the injection of propofol. The analgesic efficacy of these 3 drugs was comparable for minimizing such pain.
authors.affiliation: First Department of Anesthesiology, Toho University School of Medicine, 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; D000700:Analgesics / Q000008:administration & dosage*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000779:Anesthetics, Local / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D005480:Flurbiprofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D007275:Injections, Intravenous / Q000009:adverse effects; D007564:Japan; D008012:Lidocaine / Q000008:administration & dosage*; D008297:Male; D008787:Metoclopramide / Q000008:administration & dosage*; D008875:Middle Aged; D010146:Pain / Q000209:etiology / Q000517:prevention & control*; D010147:Pain Measurement; D015742:Propofol / Q000008:administration & dosage*; D011446:Prospective Studies; D013514:Surgical Procedures, Operative; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000700:Analgesics; D018686:Anesthetics, Intravenous; D000779:Anesthetics, Local; D005480:Flurbiprofen; D008012:Lidocaine; C504422:flurbiprofen axetil; D008787:Metoclopramide; D015742:Propofol