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      Parecoxib relieves pain and has an opioid-sparing effect following major gastrointestinal surgery

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          Abstract

          Purpose

          Parecoxib provides analgesia following a variety of surgeries, including minor gastrointestinal procedures. To our knowledge, there is no data on parecoxib following major gastrointestinal surgery. This study assessed the efficacy and opioid-sparing effects of parecoxib following major gastrointestinal surgeries.

          Patients and methods

          Patients in this analysis were a subset from a large, randomized, double-blind, placebo-controlled trial of parecoxib following noncardiac surgeries and consisted of those undergoing a variety of major gastrointestinal surgeries via laparotomy. Pain, pain interference with function, supplemental opioid utilization, opioid-related symptoms, and Patient/Physician Global Evaluation of Study Medication were compared between placebo and parecoxib groups in the 2−3 days following surgery.

          Results

          Significantly ( p<0.001) lower pain scores were observed in the parecoxib group (n=111), relative to placebo (n=126), on Day 2 (−33%) and Day 3 (−35%). Pain interference with function scores was also significantly ( p<0.001) lower among patients receiving parecoxib compared with placebo on Day 2 (−29%) and Day 3 (−36%). At 24, 48, and 72 hours, the cumulative amount of supplemental morphine consumed was 45%, 41%, and 40% less in patients receiving parecoxib compared with placebo (all p<0.001). The risk of experiencing ≥1 opioid-related symptoms was also significantly lower with parecoxib than with placebo on Day 2 (relative risk=0.75; p<0.001). Specifically, the risks of fatigue and drowsiness were significantly (both p<0.05) lower in patients receiving parecoxib compared to those receiving placebo. Patient and Physician Global Evaluation of Study Medication scores were significantly better in the parecoxib group than in the placebo group ( p<0.001).

          Conclusion

          This study is the first to demonstrate that multiple-dose parecoxib, initiated upon recovery from anesthesia, provides analgesia and opioid-sparing effects following a variety of major gastrointestinal surgeries employing laparotomy.

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          Most cited references24

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          Enhanced Recovery After Surgery (ERAS) for gastrointestinal surgery, part 2: consensus statement for anaesthesia practice

          Background The present interdisciplinary consensus review proposes clinical considerations and recommendations for anaesthetic practice in patients undergoing gastrointestinal surgery with an Enhanced Recovery after Surgery (ERAS) programme. Methods Studies were selected with particular attention being paid to meta‐analyses, randomized controlled trials and large prospective cohort studies. For each item of the perioperative treatment pathway, available English‐language literature was examined and reviewed. The group reached a consensus recommendation after critical appraisal of the literature. Results This consensus statement demonstrates that anaesthesiologists control several preoperative, intraoperative and postoperative ERAS elements. Further research is needed to verify the strength of these recommendations. Conclusions Based on the evidence available for each element of perioperative care pathways, the Enhanced Recovery After Surgery (ERAS ®) Society presents a comprehensive consensus review, clinical considerations and recommendations for anaesthesia care in patients undergoing gastrointestinal surgery within an ERAS programme. This unified protocol facilitates involvement of anaesthesiologists in the implementation of the ERAS programmes and allows for comparison between centres and it eventually might facilitate the design of multi‐institutional prospective and adequately powered randomized trials.
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            Adverse events associated with postoperative opioid analgesia: a systematic review.

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              COX-1 and COX-2 inhibitors.

              By inhibiting prostaglandin synthesis, non-steroidal anti-inflammatory drugs (NSAIDs) cause mucosal damage, ulceration and ulcer complication throughout the gastrointestinal tract. The recognition that there are two cyclo-oxygenase enzymes, one predominating at sites of inflammation (COX-2) and one constitutively expressed in the gastrointestinal tract (COX-1), has led to the important therapeutic development of COX-2 inhibitors. COX-2 is phylogenetically more primitive that COX-1 and, while very similar, has critical differences, particularly the existence of a small pocket half way down the active enzyme site. A number of drugs achieve selectivity by binding to this pocket, including presumptively rofecoxib and celecoxib. Others, such as meloxicam, may inhibit COX-2 by different mechanisms. Truly selective COX-2 inhibitors have been shown to have no effect on gastric mucosal prostaglandin synthesis, to cause no acute injury, and no chronic ulceration compared to placebo. Rofecoxib has, in a prospective systematic evaluation involving 8076 patients, been shown to reduce clinically significant ulcers, ulcer complications and gastrointestinal bleeding significantly compared to naproxen. Outcomes data for celecoxib have also been published although differences from the combined comparator agents (diclofenac and ibuprofen) did not reach statistical significance. Use of aspirin in the class study has shown that the benefits of COX-2 inhibitors may be reduced by aspirin use. The VIGOR study has raised the possibility that some NSAIDs, particularly naproxen, may protect against vascular disease compared to COX-2 inhibitors (or placebo). Copyright 2001 Harcourt Publishers Ltd.
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                Author and article information

                Journal
                Int J Gen Med
                Int J Gen Med
                International Journal of General Medicine
                International Journal of General Medicine
                Dove Medical Press
                1178-7074
                2017
                28 September 2017
                : 10
                : 319-327
                Affiliations
                [1 ]Global Medical Affairs, Pfizer, New York, NY, USA
                [2 ]Department of General Surgery, Jiangsu Province Hospital, Nanjing, China
                [3 ]Medical Affairs, Pfizer Investment Co. Ltd., Beijing, China
                [4 ]Statistics, Pfizer, Madison, NJ, USA
                Author notes
                Correspondence: Margaret Noyes Essex, Global Medical Affairs, Pfizer, 235 East 42nd Street, New York, NY, 10017, USA, Tel +1 212 733 8018, Email Margaret.essex@ 123456pfizer.com
                Article
                ijgm-10-319
                10.2147/IJGM.S143837
                5627739
                29026330
                a7cca66e-e151-4b98-9445-618fd136aafa
                © 2017 Essex et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                History
                Categories
                Original Research

                Medicine
                parecoxib,gastrointestinal,laparotomy,postoperative pain,opioid sparing
                Medicine
                parecoxib, gastrointestinal, laparotomy, postoperative pain, opioid sparing

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