Perioperative Interventions for Prevention of Prolonged Postoperative Ileus and Gastrointestinal Recovery After Colorectal Surgery: A Systematic Review of Randomized Controlled Trials

Background: Prolonged postoperative ileus (PPOI) remains a common complication after colorectal surgery, leading to delayed gastrointestinal recovery, prolonged hospitalization, and increased healthcare costs. Despite minimally invasive surgery and enhanced recovery protocols, postoperative gastrointestinal dysfunction remains frequent. Interpretation of current evidence is limited by substantial heterogeneity in PPOI definitions and outcome reporting. Methods: This systematic review was conducted according to PRISMA 2020 and Cochrane Handbook recommendations, following a protocol prospectively registered for PROSPERO (CRD420261307668). PubMed/MEDLINE, Embase, and CENTRAL were searched for randomized controlled trials published since January 2000 involving adult colorectal surgery patients. Studies evaluating all perioperative factors associated with PPOI were included. Screening, data extraction, and risk-of-bias assessment were independently performed by multiple reviewers. Findings were synthesized narratively according to perioperative phase and intervention type. Results: Of the 36 included RCTs, 7 (19.4%) reported an operational definition of POI/PPOI, of which 5 (13.9% of all included trials) applied a predefined time-based definition corresponding specifically to PPOI. The remaining studies reported POI/PPOI without sufficiently detailed diagnostic criteria or primarily assessed surrogate measures of gastrointestinal recovery. Across the included trials, effects on postoperative gastrointestinal recovery were heterogeneous, although selected analgesia strategies, early oral feeding, gum chewing, and selected pharmacological interventions showed potentially favorable effects on gastrointestinal recovery outcomes. Non-opioid and multimodal analgesic strategies were associated with earlier bowel recovery, with time to first flatus within 1.5–2 days and first bowel movement within 2–3 days. Although leukocyte count and CRP remained elevated postoperatively in the limited number of trials reporting these markers, no significant between-group differences were observed; therefore, these data do not establish an independent association between postoperative inflammation and PPOI. Conclusions: Because clinically defined PPOI was assessed in only a small proportion of included trials, the available evidence relates predominantly to postoperative gastrointestinal recovery rather than to prevention of clinically defined PPOI. PPOI remains a multifactorial complication arising within the complex interplay of surgical, pharmacological, inflammatory, and perioperative factors; however, the independent effects of opioid exposure, postoperative inflammation, and background recovery protocols cannot be established from the included trials unless these factors are directly randomized. Potential signals of benefit were observed with selected analgesic strategies, early feeding, gum chewing, and some pharmacological interventions; however, heterogeneity in PPOI definitions, interventions, and outcome reporting precludes definitive conclusions regarding their efficacy for PPOI prevention. Persistent heterogeneity in PPOI definitions limits direct comparison between studies. The randomized intervention–control comparisons identified potential signals of benefit for selected strategies, although their efficacy for preventing clinically defined PPOI remains uncertain.