Efficacy and safety of erythromycin and metoclopramide, alone or in combination, for successful feeding in critically Ill patients: a systematic review and network meta-analysis

Abstract

Background The comparative effectiveness and safety of erythromycin, metoclopramide, and their combination for enteral nutrition in critically ill patients remain uncertain. This network meta-analysis (NMA) synthesized available evidence. Methods A systematic search of seven electronic databases (Embase, PubMed, Web of Science, Cochrane Library, CNKI, Wanfang, VIP) from inception to February 6, 2026, was conducted with no language restrictions. Standard Cochrane methods were used for study selection, data extraction, and risk of bias assessment. A frequentist NMA was performed using STATA 18.0 with the mvmeta package. Effect estimates were calculated as odds ratios (OR) for binary outcomes and mean differences (MD) for gastric residual volume (GRV), each with 95% confidence intervals (CI). Random-effects models were used throughout. The surface under the cumulative ranking curve (SUCRA) was used to rank interventions. Sensitivity analyses excluded two pediatric studies. Certainty of evidence was assessed using the CINeMA framework (GRADE for NMA). Results Seventeen studies (2,654 patients) were included. For feeding success (5 trials), combination therapy was most effective [SUCRA 100.0%; OR vs. erythromycin 3.03 (1.90–4.83); vs. metoclopramide 4.89 (3.01–7.93)]. For postpyloric intubation success (10 trials), no significant pairwise differences were found; combination therapy ranked highest (SUCRA 76.4%) but with very wide confidence intervals. GRV change (3 trials) showed no significant differences. For any reported AEs (12 trials), placebo (SUCRA 80.0%) and metoclopramide (65.6%) had the most favorable safety profiles, while combination therapy ranked worst (7.5%). The certainty of evidence was moderate for feeding success, low to moderate for AEs, and very low for postpyloric intubation success and GRV. Conclusion Combination therapy may be the most effective for feeding success, though based on small trials. Metoclopramide had a better safety profile. No significant differences were observed for postpyloric intubation success or GRV. These preliminary findings require confirmation in larger, well-designed trials. Systematic review registration https://www.crd.york.ac.uk/prospero/, identifier CRD420251247900.