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      Effect of neuromuscular reversal with neostigmine/glycopyrrolate versus sugammadex on postoperative ileus following colorectal surgery

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          Abstract

          Background

          Postoperative ileus (POI) is a common complication following colorectal surgery and is mediated in part by the cholinergic anti-inflammatory pathway (CAIP). Neostigmine (acetylcholinesterase inhibitor), co-administered with glycopyrrolate, is frequently given for neuromuscular reversal before tracheal extubation and modulates the CAIP. An alternative reversal agent, sugammadex (selective rocuronium or vecuronium binder), acts independently from the CAIP. The aim of our study was to assess the impact of neuromuscular reversal agents used during anaesthesia on gastrointestinal recovery.

          Methods

          Three hundred thirty-five patients undergoing elective colorectal surgery at the Royal Adelaide Hospital between January 2019 and December 2021 were retrospectively included. The primary outcome was GI-2, a validated composite measure of time to diet tolerance and passage of stool. Demographics, 30-day complications and length of stay were collected. Univariate and multivariate analyses were performed.

          Results

          Two hundred twenty-four (66.9%) patients (129 [57.6%] males and 95 [42.4%] females, median age 64 [19–90] years) received neostigmine/glycopyrrolate and 111 (33.1%) received sugammadex (62 [55.9%] males and 49 [44.1%] females, median age 67 [18–94] years). Sugammadex patients achieved GI-2 sooner after surgery (median 3 (0–10) vs. 3 (0–12) days, p = 0.036), and reduced time to first stool (median 2 (0–10) vs. 3 (0–12) days, p = 0.035). Rates of POI, complications and length of stay were similar. On univariate analysis, POI was associated with smoking history, previous abdominal surgery, colostomy formation, increased opioid use and postoperative hypokalaemia ( p < 0.05). POI was associated with increased complications, including anastomotic leak and prolonged hospital stay ( p < 0.001). On multivariate analysis, neostigmine, bowel anastomoses and increased postoperative opioid use ( p < 0.05) remained predictive of time to GI-2.

          Conclusions

          Patients who received sugammadex had a reduced time to achieving first stool and GI-2. Neostigmine use, bowel anastomoses and postoperative opioid use were associated with delayed time to achieving GI-2.

          Supplementary Information

          The online version contains supplementary material available at 10.1007/s10151-022-02695-w.

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          Most cited references31

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          The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

          Erik von Elm, Douglas G. Altman, Matthias Egger … (2008)
          Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalisability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover three main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September, 2004, with methodologists, researchers, and journal editors to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles.18 items are common to all three study designs and four are specific for cohort, case-control, or cross-sectional studies.A detailed explanation and elaboration document is published separately and is freely available on the websites of PLoS Medicine, Annals of Internal Medicine, and Epidemiology. We hope that the STROBE statement will contribute to improving the quality of reporting of observational studies
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            The Clavien-Dindo classification of surgical complications: five-year experience.

            Pierre A. Clavien, Jeffrey Barkun, Michelle L. de Oliveira … (2009)
            The lack of consensus on how to define and grade adverse postoperative events has greatly hampered the evaluation of surgical procedures. A new classification of complications, initiated in 1992, was updated 5 years ago. It is based on the type of therapy needed to correct the complication. The principle of the classification was to be simple, reproducible, flexible, and applicable irrespective of the cultural background. The aim of the current study was to critically evaluate this classification from the perspective of its use in the literature, by assessing interobserver variability in grading complex complication scenarios and to correlate the classification grades with patients', nurses', and doctors' perception. Reports from the literature using the classification system were systematically analyzed. Next, 11 scenarios illustrating difficult cases were prepared to develop a consensus on how to rank the various complications. Third, 7 centers from different continents, having routinely used the classification, independently assessed the 11 scenarios. An agreement analysis was performed to test the accuracy and reliability of the classification. Finally, the perception of the severity was tested in patients, nurses, and physicians by presenting 30 scenarios, each illustrating a specific grade of complication. We noted a dramatic increase in the use of the classification in many fields of surgery. About half of the studies used the contracted form, whereas the rest used the full range of grading. Two-thirds of the publications avoided subjective terms such as minor or major complications. The study of 11 difficult cases among various centers revealed a high degree of agreement in identifying and ranking complications (89% agreement), and enabled a better definition of unclear situations. Each grade of complications significantly correlated with the perception by patients, nurses, and physicians (P < 0.05, Kruskal-Wallis test). This 5-year evaluation provides strong evidence that the classification is valid and applicable worldwide in many fields of surgery. No modification in the general principle of classification is warranted in view of the use in ongoing publications and trials. Subjective, inaccurate, or confusing terms such as "minor or major" should be removed from the surgical literature.
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              Neuroimmune mechanisms in postoperative ileus.

              Paul de Jonge, G Boeckxstaens (2009)
              Postoperative ileus (POI) is a common clinical condition arising after almost every abdominal surgical procedure, leading to increased patient morbidity and prolonged hospitalisation. Recent advances in insight into the underlying pathophysiology have identified intestinal inflammation triggered by handling of the intestine as the main mechanism. Not only does the local inflammatory process compromise the contractile activity of the handled intestine, but it also activates inhibitory neural pathways and possibly triggers inflammation at distant untouched areas, leading to a generalised impairment of gastrointestinal motility. Macrophages residing in the muscularis externa and mast cells are the key players in this inflammatory cascade. Pharmacological interventions preventing the activation of these immune cells reduce the influx of leucocytes into the intestine, an effect associated with a reduction of the duration of POI. New potential therapeutic strategies to shorten POI based on these new insights will undoubtedly enter the clinical arena soon.
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                Author and article information

                Contributors
                L. Traeger:
                ORCID: http://orcid.org/0000-0002-0327-7334
                luke.traeger@sa.gov.au
                Journal
                Journal ID (nlm-ta): Tech Coloproctol
                Journal ID (iso-abbrev): Tech Coloproctol
                Title: Techniques in Coloproctology
                Publisher: Springer International Publishing (Cham )
                ISSN (Print): 1123-6337
                ISSN (Electronic): 1128-045X
                Publication date (Electronic): 5 September 2022
                Publication date PMC-release: 5 September 2022
                Publication date (Print): 2023
                Volume: 27
                Issue: 3
                Pages: 217-226
                Affiliations
                [1 ]GRID grid.416075.1, ISNI 0000 0004 0367 1221, Colorectal Unit, Department of Surgery, , Royal Adelaide Hospital, ; Port Road, Adelaide, SA 5000 Australia
                [2 ]GRID grid.1010.0, ISNI 0000 0004 1936 7304, Adelaide Medical School, Faculty of Health and Medical Sciences, , University of Adelaide, ; Adelaide, SA Australia
                [3 ]GRID grid.414925.f, ISNI 0000 0000 9685 0624, Department of Anaesthesia, , Flinders Medical Centre, ; Bedford Park, SA Australia
                Author information
                http://orcid.org/0000-0002-0327-7334
                http://orcid.org/0000-0001-9330-625X
                http://orcid.org/0000-0002-8923-7527
                http://orcid.org/0000-0002-9775-3599
                http://orcid.org/0000-0002-4918-8871
                Article
                Publisher ID: 2695
                DOI: 10.1007/s10151-022-02695-w
                PMC ID: 9898426
                PubMed ID: 36064986
                SO-VID: 14cea536-011b-4e1e-83e6-01e14dc893ea
                Copyright © © The Author(s) 2022
                License:

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                Date received : 17 July 2022
                Date accepted : 24 August 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004267, Royal Adelaide Hospital;
                Award ID: Dawes Scholarship
                Award ID: Colorectal Research Group
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100001786, University of Adelaide;
                Award ID: a1175080
                Award Recipient :
                Funded by: The University of Adelaide
                Open Access :

                Open Access funding enabled and organized by CAUL and its Member Institutions

                Categories
                Subject: Original Article
                Custom metadata
                issue-copyright-statement © Springer Nature Switzerland AG 2023

                ScienceOpen disciplines: Gastroenterology & Hepatology
                Keywords: neostigmine,glycopyrrolate,sugammadex,gi-2,ileus,colorectal surgery,acetylcholinesterase inhibitor
                Data availability:
                ScienceOpen disciplines: Gastroenterology & Hepatology
                Keywords: neostigmine, glycopyrrolate, sugammadex, gi-2, ileus, colorectal surgery, acetylcholinesterase inhibitor

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