Influence of age on flurbiprofen axetil requirements for preventing pain on injection of propofol in Japanese adult surgical patients: a prospective, randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study.
BACKGROUND
Pain on injection is a recognized adverse event (AE) of propofol administration for the induction of general anesthesia. Preceded by venous occlusion, flurbiprofen axetil, a prodrug of the NSAID flurbiprofen, has been associated with a reduction in pain induced by propofol injection. A review of the literature determined that no published data were available on the influence of age on the requirements for flurbiprofen axetil dose.


OBJECTIVE
This study was undertaken to examine the influence of age on flurbiprofen axetil requirements for the treatment of propofol-induced pain on injection in Japanese adult surgical patients.


METHODS
This prospective, randomized, double-blind, vehicle-controlled, parallel-group, dose-ranging study was conducted at the Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan. Young (age 20-40 years) and older (age 60-80 years) Japanese patients scheduled for various types of surgery (eg, cholecystectomy) were eligible. Patients were randomized to receive flurbiprofen axetil at 1 of 2 doses (25 or 50 mg, regardless of body weight) or inactive vehicle (saline), preceded by manual venous occlusion with a rubber tourniquet for 2 minutes and followed by the infusion of the first 25% of calculated propofol dose (0.5 mg/kg at room temperature, 23 degrees C) into the largest dorsal vein of the hand through a 20-G IV cannula (without local anesthesia), followed by the release of the occlusion and delivery of propofol 2 mg/kg. An investigator blinded to treatment questioned each patient about pain intensity during propofol injection which was assessed using a verbal rating scale: 0 = none; 1 = mild; 2 = moderate; and 3 = severe. The overall prevalence of pain was calculated in each group. AEs at the injection site (pain, edema, wheal, inflammation) were assessed by the study investigator for 24 hours after surgery using spontaneous reporting and patient interview.


RESULTS
A total of 150 patients, 75 young adults (38 men, 37 women; mean [SD] age, 31 [5] years; mean [SD] height, 163 [7] cm; mean [SD] body weight, 58 [9] kg) and 75 older adults (38 men, 37 women; mean [SD] age, 70 [6] years; mean [SD] height, 154 [8] cm; mean [SD] body weight, 53 [10] kg), were enrolled. Each treatment group comprised 25 patients. No differences in demographic characteristics were observed among the 3 study groups. In young patients, the overall prevalence of propofol-induced pain was significantly lower in patients who received flurbiprofen axetil 50 mg (12 [48%]) compared with that in patients who received flurbiprofen axetil 25 mg (20 [80%]) or vehicle (22 [88%]) (P < 0.05 and P < 0.01, respectively). The median pain intensity score was significantly lower in patients who received flurbiprofen axetil 50 mg (0) compared with that in patients who received flurbiprofen axetil 25 mg (1) or vehicle (2) (P < 0.05 and P < 0.01, respectively). In older patients, the overall prevalences of pain on propofol injection were 9 (36%) in the flurbiprofen axetil 50-mg group and 11 (44%) in the flurbiprofen axetil 25-mg group compared with 21 (84%) in the vehicle group (both, P < 0.01). The median pain score was significantly lower in patients who received flurbiprofen 50 mg (0) or 25 mg (0) than in those who received vehicle (1) (both, P < 0.01). All treatments were well tolerated.


CONCLUSIONS
In this small clinical trial in Japanese surgical patients undergoing general anesthesia, flurbiprofen axetil requirements for the reduction of pain during injection of propofol were found to be 50 mg in young adults (age 20-40 years) and 25 or 50 mg in older adults (age 60-80 years), regardless of weight, preceded by venous occlusion for 2 minutes.
Fujii
Yoshitaka
Y
First Department of Anesthesiology, Toho University School of Medicine, Tokyo, Japan. Electronic address: yfujii@med.toho-u.ac.jp.
Nakayama
Masahiro
M
Department of Anesthesiology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
D000328:Adult; D000367:Age Factors; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005480:Flurbiprofen / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007275:Injections, Intravenous / Q000009:adverse effects*; D008297:Male; D010146:Pain / Q000517:prevention & control*; D014677:Pharmaceutical Vehicles; D015742:Propofol / Q000008:administration & dosage* / Q000009:adverse effects; D011446:Prospective Studies; D013514:Surgical Procedures, Operative
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014677:Pharmaceutical Vehicles; D005480:Flurbiprofen; C504422:flurbiprofen axetil; D015742:Propofol