Gastrointestinal dysfunction during enteral nutrition delivery in ICU patients: Risk factors, natural history and clinical implications. A post-hoc analysis of the TARGET trial

Abstract Background Slow gastric emptying occurs frequently during critical illness and is roughly quantified at bedside by large gastric residual volumes (GRVs). A previously published trial (The Augmented versus Routine approach to Giving Energy Trial; TARGET) reported larger GRVs with energy-dense (1.5kcal/ml) compared with standard (1.0kcal/ml) enteral nutrition (EN), warranting further exploration. Objective To assess the incidence, risk factors, duration and timing of large GRVs (≥250ml) and its relationship to clinical outcomes in mechanically ventilated adults. Design A post-hoc analysis of TARGET data in patients with at least one GRV recorded. Data are n (%) or median [IQR]. Results Of 3876 included patients, 1777 (46%) had at least one GRV≥250ml, which was more common in males (50 vs 39%; P < 0.001) and in patients receiving energy-dense compared with standard EN (52 vs 40%; RR=1.27 (95% CI: 1.19, 1.36); P < 0.001) in whom it also lasted longer (1 [0-2] vs 0 [0-1] days; P < 0.001), with no difference in time of onset after EN initiation (Day 1 [0-2] vs 1 [0-2]; P = 0.970). Patients with GRV≥250ml were more likely to have the following: vasopressor administration (88 vs 76%; RR=1.15 (1.12, 1.19); P < 0.001), positive blood cultures (16 vs 8%; RR=1.92 (1.60, 2.31); P < 0.001), intravenous antimicrobials (88 vs 81%; RR=1.09 (1.06, 1.12); P < 0.001), and prolonged ICU stay (ICU-free days to day 28; 12.9 [0.0-21.0] vs 20.0 [3.9-24.0]; P < 0.001), hospital stay (hospital-free days to day 28: 0.0 [0.0-12.0] vs 7.0 [0.0-17.6] days; P < 0.001), ventilatory support (ventilator-free days to day 28: 16.0 [0.0-23.0] vs 22.0 [8.0-25.0]; P < 0.001) and a higher 90-day mortality (29 vs 23%; adjusted: RR=1.17 (1.05, 1.30); P = 0.003). Conclusion Large GRVs were more common in males and those receiving energy-dense formulae, occurred early and were short-lived, and were associated with a number of negative clinical sequelae, including increased mortality, even when adjusted for illness severity. Clinical trial registration number: NCT02306746. URL: https://clinicaltrials.gov/ct2/show/NCT02306746.