title: Is there any analgesic benefit from preoperative vs. postoperative administration of etoricoxib in total knee arthroplasty under spinal anaesthesia?: A randomised double-blind placebo-controlled trial.
abstract: Optimal postoperative analgesia is a challenge for the anaesthesiologist, with the ideal combination of methods, drugs, doses and timing of administration still the subject of research. The COX-2 inhibitors are a class of NSAIDs that may provide useful perioperative analgesia but the optimal timing of administration has not been elucidated.
  
  
  
  We hypothesised that etoricoxib given 1 h before total knee arthroplasty under spinal anaesthesia will decrease the cumulative dose of intravenous and subcutaneous morphine required to maintain pain intensity of 3 or less on a 10-point numerical rating scale (NRS) during the first postoperative 48 h compared with the same dose of etoricoxib given after surgery.
  
  
  
  Randomised, double-blind, placebo-controlled trial.
  
  
  
  University hospital, between January and September, 2014.
  
  
  
  Overall, 165 patients scheduled for total knee arthroplasty under spinal anaesthesia.
  
  
  
  The patients were randomised into one of three groups: the ETORICOX-PREOP group received etoricoxib 120 mg orally 1 h before surgery, one placebo pill at the end of surgery and a further 120 mg etoricoxib after 24 h; the ETORICOX-POSTOP group received one placebo pill 1 h before surgery and etoricoxib 120 mg at the end of surgery and after 24 h. The PLACEBO group received one placebo pill 1 h before surgery, one at end of surgery and a third after 24 h.
  
  
  
  The primary outcome measure was the cumulative dose of intravenous and subcutaneous morphine required during the first postoperative 48 h to maintain a 10-point numerical pain rating scale value of 3 or less. Secondary outcomes measures were duration of analgesia from initiation of spinal anaesthesia until the first analgesic requirement and the side-effects of the treatment.
  
  
  
  The quantity of morphine over the first postoperative 48 h required by the ETORICOX-PREOP group (44 ± 16 mg) and the ETORICOX-POSTOP group (52 ± 23 mg) were both significantly less than the PLACEBO group (71 ± 20 mg) (P = 0.001), demonstrating a morphine-sparing effect of etoricoxib of the order of 30%; the difference between the PRE vs. POST groups was statistically significant (P = 0.02), favouring a preemptive analgesic effect. Also, there was evidence of a longer time to first analgesia compared with PLACEBO in the PREOP group (P = 0.02) but no significant difference between PREOP and POSTOP groups (P = 0.30). There was no difference in side-effects among the three study groups and there were no serious adverse effects of etoricoxib.
  
  
  
  Preemptive administration of etoricoxib 120 mg orally in patients undergoing total knee arthroplasty under spinal anaesthesia is superior to postoperative administration of the same dose in terms of its morphine-sparing effect during the first postoperative 48 h, but not in prolonging the time to first analgesia, and is associated with a similar incidence of side-effects.
  
  
  
  Clinicaltrials.gov identifier: NCT 02534610.
authors.affiliation: From the Department of Anaesthesiology, Clinical Hospital of Orthopaedics Foisor (AMM, SCF, DMA), and Clinical Hospital of Orthopaedics Foisor, University of Medicine and Pharmacy 'Carol Davila', Bucharest, Romania CIS.
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Munteanu
authors.forename: Simona
authors.initials: S
authors.lastname: Cionac Florescu
authors.forename: Denisa Madalina
authors.initials: DM
authors.lastname: Anastase
authors.forename: Cristian Ioan
authors.initials: CI
authors.lastname: Stoica
mesh_terms: D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage; D000775:Anesthesia, Spinal / Q000379:methods*; D019645:Arthroplasty, Replacement, Knee / Q000009:adverse effects*; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage*; D004311:Double-Blind Method; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000008:administration & dosage; D010149:Postoperative Pain / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control; D011182:Postoperative Care / Q000379:methods*; D011300:Preoperative Care / Q000379:methods*; D011725:Pyridines / Q000008:administration & dosage*; D013450:Sulfones / Q000008:administration & dosage*
chemical_list: D000701:Analgesics, Opioid; D052246:Cyclooxygenase 2 Inhibitors; D011725:Pyridines; D013450:Sulfones; D009020:Morphine; D000077613:Etoricoxib