Association between vasopressor dose and feeding intolerance in critically ill patients receiving enteral nutrition:...

Enteral nutrition (EN) is the preferred nutritional support for critically ill patients, but its implementation during vasopressor therapy remains controversial. The association between vasopressor dose and feeding intolerance (FI) has not been well characterized. This study aimed to investigate the association between norepinephrine equivalent (NEQ) dose and feeding intolerance in ICU patients receiving enteral nutrition.

This retrospective cohort study analyzed 8055 critically ill patients from the MIMIC-IV database (2008-2019) who received both vasopressor therapy and enteral nutrition. The primary dose-response analysis modeled NEQ as a continuous variable using restricted cubic splines; patients were additionally stratified into five descriptive groups based on maximum NEQ dose in the 24 h before EN initiation (<0.1, 0.1-0.2, 0.2-0.3, 0.3-0.5, and ≥0.5 μg/kg/min) for baseline characterization. The primary outcome was overt EN intolerance, defined as clinically documented vomiting during EN. Lactate elevation (peak lactate >2 mmol/L within 24 h after EN initiation) was examined as a secondary exploratory safety signal reflecting potential splanchnic hypoperfusion. Multiple analytical approaches including multivariable logistic regression, subgroup analysis, and sensitivity analysis were employed.

The overall overt EN intolerance rate (clinically documented vomiting) was 6.1% (492/8055); when lactate elevation was included as an additional exploratory signal, the composite rate was 9.7% (782/8055). Among vomiting-based analysis, overt intolerance rates showed a progressive trend across NEQ groups (P for trend <0.001). In fully adjusted models, NEQ ≥0.5 μg/kg/min was associated with significantly higher overt intolerance odds (OR 1.64, 95% CI: 1.05-2.45, p = 0.022), while the NEQ 0.3-0.5 group showed a non-significant trend (OR 1.31, 95% CI: 0.90-1.86, p = 0.138). Exposure window sensitivity analyses demonstrated consistent associations across 6 h (OR 1.91, 95% CI: 1.25-2.82), 12 h (OR 1.68, 95% CI: 1.17-2.35), and 24 h (OR 1.45, 95% CI: 1.07-1.94) pre-EN windows.

Using clinically documented vomiting as the primary outcome, a dose-dependent association between vasopressor dose and overt EN intolerance was observed, reaching statistical significance at NEQ ≥0.5 μg/kg/min. The association was stronger when using temporally proximate exposure windows (OR 1.91 for 6 h pre-EN), suggesting that temporally proximate hemodynamic context may be relevant when evaluating EN tolerance. The attenuation versus prior composite estimates suggests that lactate-based FI definitions may inflate apparent vasopressor-associated risk. These findings are hypothesis-generating and require prospective validation using standardized, gastrointestinal-specific FI definitions with comprehensive adjustment for potential confounders.