title: Presurgical intravenous parecoxib sodium and follow-up oral valdecoxib for pain management after laparoscopic cholecystectomy surgery reduces opioid requirements and opioid-related adverse effects.
abstract: BACKGROUND
  Opioids are associated with numerous adverse effects. It is unclear if reduced postoperative opioid consumption lowers the incidence and severity of opioid-related adverse effects. This analysis -- from a multicenter, randomized, double-blind trial -- tested if the reduction of opioid consumption among patients who received intravenous preoperative parecoxib 40 mg, followed by oral valdecoxib 40 mg qd postoperatively, in Days 1-4 after outpatient laparoscopic cholecystectomy surgery, reduced opioid-related symptoms.
  
  
  METHODS
  Patients received intravenous fentanyl for pain before discharge, and oral acetaminophen 500 mg hydrocodone 5 mg q 4-6 h prn postdischarge for up to 7 days postsurgery. Patients also received intravenous parecoxib 40 mg administered 30-45 min preoperatively, and valdecoxib 40 mg qd up to Day 4 and prn Days 5-7 postsurgery, or placebo. Patients completed an opioid-related Symptoms Distress Scale (SDS) questionnaire every 24 h for 7 days. Opioid use was converted to morphine-equivalent doses (MEDs). Clinically meaningful events (CMEs) for 12 opioid-related symptoms were assessed by three ordinal measures: frequency, severity, and bothersomeness. Reduction of CMEs on Day 1 and number of patient-days with CMEs on Days 1-4 were examined.
  
  
  RESULTS
  Cumulative MEDs on Day 0, Day 1, and Days 1-4 were significantly lower in the parecoxib/valdecoxib group compared with the placebo group (P < 0.001). At the end of Day 1, parecoxib/valdecoxib-treated patients had significantly lower SDS scores (P < 0.02), a significantly reduced incidence of CMEs (P < 0.05), and significantly fewer patient-days with CMEs in Days 1-4 than placebo patients (P < 0.05). Patients in the parecoxib/valdecoxib group were less likely to have CMEs for multiple symptoms than those in the placebo group (P < 0.001).
  
  
  CONCLUSIONS
  Treatment with parecoxib and valdecoxib significantly reduced the cumulative MED requirements, the incidence of opioid-related adverse effects, and patient-days with CMEs.
authors.affiliation: Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA. gan00001@mcduke.edu
authors.forename: T J
authors.initials: TJ
authors.lastname: Gan
authors.forename: G P
authors.initials: GP
authors.lastname: Joshi
authors.forename: S Z
authors.initials: SZ
authors.lastname: Zhao
authors.forename: D B
authors.initials: DB
authors.lastname: Hanna
authors.forename: R Y
authors.initials: RY
authors.lastname: Cheung
authors.forename: C
authors.initials: C
authors.lastname: Chen
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D017081:Cholecystectomy, Laparoscopic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006853:Hydrocodone / Q000008:administration & dosage / Q000627:therapeutic use; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000187:drug effects; D007555:Isoxazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D010147:Pain Measurement / Q000187:drug effects; D010149:Postoperative Pain / Q000188:drug therapy / Q000517:prevention & control*; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D000096926:Benzenesulfonamides
chemical_list: D000701:Analgesics, Opioid; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D006853:Hydrocodone; D007527:Isoenzymes; D007555:Isoxazoles; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases; D013449:Sulfonamides; C406224:valdecoxib; D000096926:Benzenesulfonamides; C409945:parecoxib; C496540:PTGS2 protein, human