Impact of higher enteral protein delivery on gastrointestinal dysfunction in critical illness: A systematic review and meta‐analysis

Background Protein delivery is currently of interest in critical illness. It is plausible that higher protein delivery, targeting international recommendations, may cause gastrointestinal (GI) dysfunction. We aimed to determine relationships between enteral protein delivery and GI dysfunction in critically ill adults. Methods A systematic review and meta‐analysis according to a predetermined protocol (PROSPERO CRD42022345591) encompassing MEDLINE, Embase, EMCARE, CENTRAL, and CINAHL databases (between January 1, 2000, and August 5, 2025) was conducted. Parallel‐group randomized trials using an enteral nutrition intervention reporting (1) statistically significant differences in protein delivered and (2) any GI dysfunction–related outcome were included. Data are presented as mean ± SD or risk ratio (RR) with 95% CI. Results From 15 studies (5277 patients), mean protein delivery was 1.05 ± 0.38 vs 0.47 ± 0.23 g/kg/day in higher‐ vs lower‐protein groups, respectively (nine studies), and 66.00 ± 23.83 vs 42.70 ± 12.99 g/day (six studies reporting protein delivery as grams per day). The higher‐protein group had an increased risk of vomiting (RR, 1.25; 95% CI, 1.11–1.42; P = 0.0004), with no evidence of heterogeneity ( I 2 = 0%; P = 0.58) and no influence on gastric residual volumes (GRVs) ≥300 ml (RR, 1.18; 95% CI, 0.69–2.00; P = 0.55), prokinetic administration (RR, 1.24; 95% CI, 0.98–1.56; P = 0.07), abdominal distension (RR, 0.67; 95% CI, 0.40–1.13; P = 0.14), diarrhea (RR, 0.99; 95% CI, 0.81–1.20; P = 0.90), or constipation (RR, 1.02; 95% CI, 0.92–1.13; P = 0.68). There was no evidence of publication bias. Conclusion Higher protein delivery is associated with increased rates of vomiting. Several important confounders (feed volume, concurrent energy delivery, supplemental parenteral nutrition) significantly influence this outcome.