title: Preoperative administration of etoricoxib in patients undergoing hip replacement causes inhibition of inflammatory mediators and pain relief.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Erlangen, Germany. renner@pharmakologie.uni-erlangen.de
authors.forename: B
authors.initials: B
authors.lastname: Renner
authors.forename: G
authors.initials: G
authors.lastname: Walter
authors.forename: J
authors.initials: J
authors.lastname: Strauss
authors.forename: M F
authors.initials: MF
authors.lastname: Fromm
authors.forename: J
authors.initials: J
authors.lastname: Zacher
authors.forename: K
authors.initials: K
authors.lastname: Brune
mesh_terms: D000368:Aged; D000700:Analgesics / Q000008:administration & dosage; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D015331:Cohort Studies; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D000077613:Etoricoxib; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy / Q000517:prevention & control*; D017060:Patient Satisfaction; D011300:Preoperative Care / Q000379:methods*; D011453:Prostaglandins / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013450:Sulfones / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D052246:Cyclooxygenase 2 Inhibitors; D018836:Inflammation Mediators; D011453:Prostaglandins; D011725:Pyridines; D013450:Sulfones; D000077613:Etoricoxib