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

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: Randomised, double-blind, placebo-controlled trial. SETTING: University hospital, between January and September, 2014. PATIENTS: Overall, 165 patients scheduled for total knee arthroplasty under spinal anaesthesia. INTERVENTIONS: 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. MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: 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. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT 02534610.

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