AMBULATORY ANESTHESIA SOCIETY FOR AMBULATORY ANESTHESIA SECTION EDITOR PAUL F. WHITE Effective Treatment of Laparoscopic Cholecystectomy Pain with Intravenous Followed by Oral COX-2 Specific Inhibitor Girish P. Joshi, MBBS, MD, Eugene R. Viscusi, MD, Tong J. Gan, MD, Harold Minkowitz, MD, Mark Cippolle, MD, PhD, Rienhard Schuller, MSc, Raymond Y. Cheung, BPharm, PhD, and John G. Fort, MD From the Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, Dallas, Texas In this multicenter, double-blinded, randomized, placebo-controlled study we evaluated the analgesic and opioid-sparing efficacy of a preoperative dose of IV parecoxib followed by oral valdecoxib in treating pain associated with elective laparoscopic cholecystectomy. Patients were randomized to receive a single IV dose of parecoxib 40 mg (n = 134) or placebo (n = 129) 30 – 45 min before induction of anesthesia. Six to 12 h after the IV dose, the parecoxib group received a single oral dose of valdecoxib 40 mg, followed by valdecoxib 40 mg qd on postoperative days 1– 4, then 40 mg qd prn days 5–7. The placebo IV group received oral placebo on an identical schedule. All patients were allowed sup- plemental IV fentanyl as needed during the first 4 h postoperatively (T0 –240 min) followed by hydroc- odone 5 mg/acetaminophen 500 mg (Vicodin ® ; 1–2 tab- lets orally every 4 – 6 h as needed). Patients taking pare- coxib used 21% less fentanyl than those receiving placebo (P = 0.011). The mean area under the curve of pain intensity (PI) scores over time from T0 –240 min was 55.2 for parecoxib and 61.2 for placebo (P = 0.083). At T180 and T240 min, mean PI score was 7.0 and 7.6 points lower in the parecoxib group, respectively (P  0.02). Fewer patients on valdecoxib required supple- mental analgesics (P  0.05) after discharge. At T240 min and at day 7, Patient’s and Physician’s/ Nurse’s Global Evaluations were significantly better in the parecoxib/valdecoxib group (P  0.05). Incidences of adverse events, adverse events causing withdrawal, and serious adverse events were less for parecoxib/ valdecoxib than for placebo. The authors conclude that preoperative parecoxib is a valuable opioid-sparing ad- junct to the standard of care for treating pain after lapa- roscopic cholecystectomy, and subsequent treatment with oral valdecoxib extends this clinical benefit. (Anesth Analg 2004;98:336 –42) F or laparoscopic cholecystectomy (LC), pain is both the most frequent complaint and the most common cause of delayed discharge after the procedure (1,2). Pain associated with outpatient LC is usually managed with opioid analgesics, often in con- junction with acetaminophen and/or nonsteroidal an- tiinflammatory drugs (NSAIDs). Opioids are effective analgesics, but their usefulness is limited by side ef- fects, such as somnolence, nausea and vomiting, con- stipation, and respiratory depression (3). Nonopioids (e.g., acetaminophen, NSAIDs, and local anesthetics) have opioid-sparing effects (4 – 6). Valdecoxib is a highly specific inhibitor of the cyclooxygenase-2 (COX-2) enzyme, recently approved in the United States for the treatment of arthritis and dysmenorrhea, that is being investigated for use in postsurgical pain (7). Parecoxib is a parenterally ad- ministered inactive prodrug that undergoes rapid amide hydrolysis in vivo to the pharmacologically ac- tive COX-2 inhibitor, valdecoxib (8). This study was performed to evaluate the analgesic efficacy of a pre- operative dose of IV parecoxib, followed by oral valdecoxib, for treating postoperative pain in patients undergoing elective LC. The principal hypothesis was that patients receiving these analgesics would experi- ence less pain and require less supplemental opioid analgesia than patients receiving placebo. Methods This multicenter, double-blinded, randomized, placebo-controlled study was conducted in accor- dance with good clinical practice and the Declaration of Helsinki. An IRB at each of the 24 study sites Supported, in part, by Pharmacia Corporation and Pfizer Inc. Accepted for publication August 14, 2003. Address correspondence to Girish P. Joshi, MBBS, MD, FFARCSI, Professor of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390-9068. Address email to girish.joshi@utsouthwestern.edu. DOI: 10.1213/01.ANE.0000093390.94921.4A ©2004 by the International Anesthesia Research Society 336 Anesth Analg 2004;98:336–42 0003-2999/04