Early Versus Delayed Enteral Nutrition in Mechanically Ventilated Patients with Circulatory Shock: A Prospective Multicenter, Multi-National Cohort Study

Abstract Introduction: Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in Intensive Care Unit (ICU) patients with circulatory shock are limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. Methods: We analyzed a dataset from an international, multicenter randomized clinical trial (RCT) evaluating protein dose in ICU patients. EEN was defined as initiating <48 hours from ICU admission and DEN >48 hours. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. Results: We included 626 patients. Median age was 60 years [18-93], 55% had septic shock, 99% received norepinephrine alone and 91% received EN alone. Forty-two percent of EEN patients had persistent organ dysfunction syndrome-plus death at day 28, compared to 53% in the DEN group (p=0.04) (adjusted OR 0.60, 95% confidence intervals, 0.38-0.93, p=0.02). EEN was associated with more ICU-free days (9.3±9.2 vs. 5.7±7.9, p=0.0002), more days alive and free of vasopressors (7.1±3.1 vs. 6.3±3.2, p=0.007), and shorter duration of MV among survivors (9.8±10.9 vs. 13.8±14.5, p=0.0002). There were no differences in ICU/60-day mortality or feeding intolerance rates between groups.Conclusion: In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.