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      Preemptive versus postoperative lumiracoxib for analgesia in ambulatory arthroscopic knee surgery

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          We compared the efficacy and safety of preemptive vs postoperative dosing of lumiracoxib 400 mg in patients undergoing minor ambulatory arthroscopic knee surgery. Eligible patients were randomized to preemptive lumiracoxib, postoperative lumiracoxib, and placebo. The main efficacy parameter was pain intensity (PI) (0–100 mm visual analog scale) in the target knee upon movement, 2 hours after surgery. Other efficacy variables included PI in the target knee at rest and upon movement at 1, 3, 4, and 24 hours, time to first rescue medication intake. In the lumiracoxib preemptive and postoperative groups, the estimated treatment difference compared to placebo for primary endpoint was −4.0 (95% CI: −9, −1; p = 0.007) and −3.5 (95% CI: −8.5, 0; p = 0.052), respectively. There was no statistical significant difference between two active treatment groups ( p = 0.602). Both preemptive and postoperative lumiracoxib resulted in significantly lower PI scores at rest and after movement at all time-points and no statistically significant difference was observed between the active treatments. Time to rescue medication intake was comparable for both active treatments. The proportion of adverse events was similar among all groups. We conclude that the efficacy of lumiracoxib 400 mg is not affected by the timing of administration (preemptive or postoperative).

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          Most cited references 24

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          A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia.

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            Effects of perioperative administration of a selective cyclooxygenase 2 inhibitor on pain management and recovery of function after knee replacement: a randomized controlled trial.

            Controlling postoperative pain after knee replacement while reducing opioid-induced adverse effects and improving outcomes remains an important challenge. To assess the effect of combined preoperative and postoperative administration of a selective inhibitor of cyclooxygenase 2 on opioid consumption and outcomes after total knee arthroplasty (TKA). Randomized, placebo-controlled, double-blind trial conducted June 2001 through September 2002, enrolling 70 patients aged 40 to 77 years and undergoing TKA at a university hospital in the United States. Patients were randomly assigned to receive 50 mg of oral rofecoxib at 24 hours and at 1 to 2 hours before TKA, 50 mg daily for 5 days postoperatively, and 25 mg daily for another 8 days, or matching placebo at the same times. Postoperative outcomes including postsurgical analgesic consumption and pain scores achieved, nausea and vomiting, joint range of motion, sleep disturbance, patient satisfaction with analgesia, and hematologic and coagulation parameters. Total epidural analgesic consumption and in-hospital opioid consumption were less in the group receiving rofecoxib compared with the group receiving placebo (P .05 for both intraoperative and postoperative blood loss). Perioperative use of an inhibitor of cyclooxygenase 2 is an effective component of multimodal analgesia that reduces opioid consumption, pain, vomiting, and sleep disturbance, with improved knee range of motion after TKA.
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              Upregulation of prostaglandin E2 and interleukins in the central nervous system and peripheral tissue during and after surgery in humans.

              The central and peripheral inflammatory response to surgery may influence patient outcomes. This study examines the time course and clinical relevance of changes in prostaglandin E2 and cytokines in cerebrospinal fluid, local tissue (surgical site), and circulating blood during and after total hip replacement. Thirty osteoarthritis patients undergoing primary total hip arthroplasty with spinal anesthesia were randomly allocated to three groups (n = 10/group): placebo for 4 days before surgery and on the morning of surgery; placebo for 4 days before surgery and oral rofecoxib 50 mg on the morning of surgery; oral rofecoxib 50 mg for 4 days before surgery and the morning of surgery. Cerebrospinal fluid and plasma were collected before surgery and up to 30 h after incision for measurement of prostaglandin E2 and interleukins. When hip replacement was complete, a drain was placed in the hip wound and exudates were collected at 3 to 30 h after incision. Cerebrospinal fluid showed an initial increase in interleukin 6 and a later rise in prostaglandin E2 concentration after surgery; interleukin 1beta and tumor necrosis factor alpha were undetectable. Hip surgical site fluid evidenced an increase in prostaglandin E2, interleukin 6, interleukin 8, and interleukin 1beta; tumor necrosis factor alpha decreased at 24 and 30 h. Preoperative administration of the cyclooxygenase 2 inhibitor rofecoxib reduced cerebrospinal fluid and surgical site prostaglandin E2 and cerebrospinal fluid interleukin 6. Cerebrospinal fluid prostaglandin E2 was positively correlated with postoperative pain and cerebrospinal fluid interleukin 6 with sleep disturbance. Poorer functional recovery was positively correlated with increased surgical site prostaglandin E2. These results suggest that upregulation of prostaglandin E2 and interleukin 6 at central sites is an important component of surgery induced inflammatory response in patients and may influence clinical outcome.

                Author and article information

                J Pain Res
                Journal of Pain Research
                Journal of pain research
                Dove Medical Press
                1 November 2008
                : 1
                : 27-34
                [1 ] Orthopädische Klinik der Univ, Regensburg, Germany
                [2 ] DiaMed Centrum, Klinik Neuendettelsau, Neuendettelsau, Germany
                [3 ] Orthopädische Fachpraxisgemeinschaft, Jena Zwätzen, Deutschland, Germany
                [4 ] Novartis Pharma AG, Basel, Switzerland
                [5 ] Novartis Pharma GmbH, Nürnberg, Germany
                [6 ] Novartis Pharma AG, East Hanover, NJ, USA
                Author notes
                Correspondence: Gerhard Krammer, Novartis Pharma AG, Postfach, CH-4002 Basel, Switzerland, Tel +41 61 32 46119, Fax +41 61 3245628, Email gerhard.krammer@ 123456novartis.com
                © 2008 Grifka et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                Original Research


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