Peripheral mu opioid receptor antagonists for recovery of bowel function after radical cystectomy: a systematic review and meta-analysis

Background: Postoperative ileus (POI) is common after radical cystectomy (RC) and contributes to prolonged hospital stay, increased healthcare costs, and reduced patient quality of life. Peripheral μ-opioid receptor antagonists (PAMORAs), including alvimopan, naloxegol, and methylnaltrexone, have been investigated as strategies to reduce POI while preserving opioid-mediated analgesia. Previous systematic reviews have shown benefit of PAMORAs, particularly alvimopan, in abdominal procedures such as bowel resection and hysterectomy, but evidence specific to RC remains heterogeneous and limited. We aimed to evaluate whether incorporation of PAMORAs (alvimopan, naloxegol, or methylnaltrexone) into enhanced recovery pathways reduces postoperative ileus compared with enhanced recovery pathways alone in patients undergoing radical cystectomy.

Methods: A literature search of PubMed, MEDLINE, Embase, and CENTRAL was conducted to identify studies evaluating PAMORAs for prevention of POI following RC. Search terms included alvimopan, naloxegol, methylnaltrexone, and radical cystectomy. Eligible study designs included randomized controlled trials, non-randomized trials, and observational studies comparing PAMORAs with placebo or standard care. Two independent reviewers extracted data using Covidence software. Outcomes included time to gastrointestinal recovery, time to first flatus, time to first bowel movement, length of stay (LOS), POI incidence, adverse events (including cardiovascular events), and costs. Results were summarized in a Summary of Findings table.

Results: Across included studies, PAMORAs were associated with improved postoperative gastrointestinal recovery, although certainty of evidence varied. PAMORAs shortened time to first flatus by approximately one day (MD −0.97 days, 95% CI −1.07 to −0.87) across six observational studies with no detectable heterogeneity (I² = 0%), but certainty of evidence was very low due to non-randomized designs and risk of bias. Time to first bowel movement was reduced by approximately 1.3 days (MD −1.30 days, 95% CI −1.81 to −0.79) across nine studies, although substantial heterogeneity was observed (I² = 84%).

Conclusions: PAMORAs appear to improve postoperative gastrointestinal recovery following RC. However, overall certainty of evidence remains low due to reliance on non-randomized studies and heterogeneity. Alvimopan has the strongest supporting evidence, while data for naloxegol and methylnaltrexone remain limited.