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Preoperative administration of etoricoxib in patients undergoing hip replacement causes inhibition of inflammatory mediators and pain relief.

ABSTRACT: Administering cyclooxygenase-2 inhibitors preoperatively appears attractive since these drugs reduce post-operative pain, but do not increase the risk of post-operative bleeds, asthmatic attacks and stress-related gastrointestinal ulcers. In a former investigation, we could show that post-operative administration of etoricoxib reduces prostaglandin production in wound fluid, but the onset of action is variable due to delayed post-operative absorption.In this study, we investigated the preoperative administration of etoricoxib in patients undergoing hip replacement. They received 120 mg etoricoxib or placebo 2 h before surgery and 1 day after in a double-blinded, randomized, parallel group design.A total of 11 patients were randomized (placebo n = 5; verum n = 6). We found high and constant levels of the drug in blood, central nervous system and wound fluid already at the end of surgery (t(max) < 2 h). This was accompanied by inhibition of prostaglandin production in the wound tissue (treatment p < 0.05), suppression of interleukin 6 increase in plasma (treatment p < 0.01), and - despite existing standard pain relief procedures - higher satisfaction with analgesics (time vs. treatment p < 0.05) and less demand for opioids (treatment p < 0.01) and intrathecal bupivacaine (treatment p = 0.05) administration.Administration of etoricoxib 2 h before surgery allows for an effective drug concentration in critical tissues, a reduction of the production of pro-inflammatory mediators and for better pain relief.

SUBMITTER: Renner B

PROVIDER: S-EPMC3437501 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Preoperative administration of etoricoxib in patients undergoing hip replacement causes inhibition of inflammatory mediators and pain relief.

Renner B B Walter G G Strauss J J Fromm M F MF Zacher J J Brune K K

European journal of pain (London, England) 20111219 6

<h4>Objective</h4>Administering cyclooxygenase-2 inhibitors preoperatively appears attractive since these drugs reduce post-operative pain, but do not increase the risk of post-operative bleeds, asthmatic attacks and stress-related gastrointestinal ulcers. In a former investigation, we could show that post-operative administration of etoricoxib reduces prostaglandin production in wound fluid, but the onset of action is variable due to delayed post-operative absorption.<h4>Methods</h4>In this stu ...[more]

PMID: 22337568

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Project description:Optimal postoperative pain management is important to ensure patient comfort and early mobilization.In this double-blind, placebo- and active-controlled, randomized clinical trial, we evaluated postoperative pain following knee replacement in patients receiving placebo, etoricoxib (90 or 120 mg), or ibuprofen 1800 mg daily for 7 days. Patients ?18 years of age who had pain at rest ?5 (0-10 Numerical Rating Scale [NRS]) after unilateral total knee replacement were randomly assigned to placebo (N = 98), etoricoxib 90 mg (N = 224), etoricoxib 120 mg (N = 230), or ibuprofen 1800 mg (N = 224) postoperatively. Co-primary endpoints included Average Pain Intensity Difference at Rest over Days 1-3 (0- to 10-point NRS) and Average Total Daily Dose of Morphine over Days 1-3. Pain upon movement was evaluated using Average Pain Intensity Difference upon Knee Flexion (0- to 10-point NRS). The primary objective was to demonstrate analgesic superiority for the etoricoxib doses vs. placebo; the secondary objective was to demonstrate that the analgesic effect of the etoricoxib doses was non-inferior to ibuprofen. Adverse experiences (AEs) including opioid-related AEs were evaluated.The least squares (LS) mean (95% CI) differences from placebo for Pain Intensity Difference at Rest over Days 1-3 were -0.54 (-0.95, -0.14); -0.49 (-0.89, -0.08); and -0.45 (-0.85, -0.04) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.05 for etoricoxib vs. placebo). Differences in LS Geometric Mean Ratio morphine use over Days 1-3 from placebo were 0.66 (0.54, 0.82); 0.69 (0.56, 0.85); and 0.66 (0.53, 0.81) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively (p < 0.001 for etoricoxib vs. placebo). Differences in LS Mean Pain Intensity upon Knee Flexion were -0.37 (-0.85, 0.11); -0.46 (-0.94, 0.01); and -0.42 (-0.90, 0.06) for etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively. Opioid-related AEs occurred in 41.8%, 34.7%, 36.5%, and 36.3% of patients on placebo, etoricoxib 90 mg, etoricoxib 120 mg, and ibuprofen, respectively.Postoperative use of etoricoxib 90 and 120 mg in patients undergoing total knee replacement is both superior to placebo and non-inferior to ibuprofen in reducing pain at rest and also reduces opioid (morphine) consumption.NCT00820027.

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Preoperative administration of etoricoxib in patients undergoing hip replacement causes inhibition of inflammatory mediators and pain relief.

Publications

Preoperative administration of etoricoxib in patients undergoing hip replacement causes inhibition of inflammatory mediators and pain relief.

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