• Mark Borthwick, Anders Granholm, Søren Marker, Mette Krag, Theis Lange, Matt P Wise, Stepani Bendel, Frederik Keus, Anne Berit Guttormsen, Joerg C Schefold, Jørn Wetterslev, Anders Perner, and MøllerMorten HylanderMH0000-0002-6378-9673Department of Intensive Care, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.Collaboration for Research in Intensive Care (CRIC), Copenhagen, Denmark..
• Departments of Pharmacy and Critical Care, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
• Acta Anaesthesiol Scand. 2024 Oct 1; 68 (9): 124412531244-1253.

BackgroundEnteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole.MethodsExtended Cox models with time-varying co-variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed.ResultsEnteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause-specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19-0.44, p < .001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14-1.82, p = .003), and lower risk of all-cause mortality (HR: 0.22, 95% CI: 0.18-0.27, p < .001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21-0.35, p < .001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13-0.23, p < .001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63-1.09, p = .179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all-cause mortality (HR: 1.27, 95% CI: 0.99-1.64, p = .061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all-cause mortality was statistically significant (p = .024).ConclusionsEnteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study.© 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

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