Different definitions of feeding intolerance and their associations with outcomes of critically ill adults receiving enteral nutrition: a systematic review and meta-analysis

Abstract Background A unified clinical definition of feeding intolerance (FI) is urged for better management of enteral nutrition (EN) in critically ill patients. We summarized the comprehensive evidence for the associations of different FI definitions with patient-centered outcomes. Methods This systematic review and meta-analysis included searches of PubMed, Web of Science, the Cochrane Library, ClinicalTrials.gov, and several Chinese medical databases from inception to April 26, 2022, for clinical studies comparing FI with non-FI premised on a clear FI definition and patient-centered outcomes in critical illness adults receiving EN. We summarized the evidence by random-effect meta-analyses and rated the certainty of evidence by the Grading of Recommendations Assessment, Development, and Evaluation frameworks. Results 5525 records were identified by our search, of which 26 studies enrolled 25189 adult patients. Except for all-cause long-term mortality and mechanical ventilation days, all patient-centered outcomes were associated with FI. Moderate to low certainty evidence established FI defined as large gastric residual volume (GRV) combined with any other gastrointestinal symptoms (GISs) had a significant association with high mortalities in particular all-cause intensive care unit (ICU) mortality (odds ratio [OR] 2.29, 95% confidence interval [CI] 1.98 to 2.65) and prolonged length of ICU stay (mean difference 4.21, 95% CI 2.52 to 5.90), with a moderate ICU prevalence (40.36%, 95% CI 33.73–46.99%). GRV ≥ 500 ± 50 mL (24-hour cumulative) alone had a higher risk of all-cause ICU mortality (OR 2.58, 95% CI 2.08 to 3.19) but with a low ICU prevalence (11.25%, 95% CI -10.3–32.79%) while enteral feeding (EF) percentage < 80% had a higher ICU prevalence (50.29%, 95% CI 14.25 to 86.32) but a marginally significant association with all-cause ICU mortality (OR 1.87, 95% CI 1.08 to 3.24) as overlapping the prespecified upper limit value for the minimally important difference of 1.2 times the baseline risk. Conclusions In critically ill adult patients receiving EN, the large-GRV-centered GISs to define FI proved superior to EF-based or large GRV alone in terms of both close associations with all-cause ICU mortality and acceptable ICU prevalence. The study was registered with PROSPERO: CRD42022326273. Registered 10 May 2022.