Associations between enteral nutrition and outcomes in the SUP-ICU trial: Results of exploratory post hoc analyses

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; Morten Hylander Møller

doi:10.1111/aas.14471

Associations between enteral nutrition and outcomes in the SUP-ICU trial: Results of exploratory post hoc analyses

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, Morten Hylander Møller

^*Corresponding author for this work

Department of Intensive Care

4 Citations (Scopus)

Abstract

BACKGROUND: Enteral 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.

METHODS: Extended 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.

RESULTS: Enteral 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).

CONCLUSIONS: Enteral 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.

Original language	English
Journal	Acta Anaesthesiologica Scandinavica
Volume	68
Issue number	9
Pages (from-to)	1244-1253
Number of pages	10
ISSN	0001-5172
DOIs	https://doi.org/10.1111/aas.14471
Publication status	Published - Oct 2024

Keywords

2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use
Aged
Critical Illness
Enteral Nutrition/methods
Female
Gastrointestinal Hemorrhage
Humans
Intensive Care Units
Male
Middle Aged
Pantoprazole/therapeutic use
Pneumonia/epidemiology
Proportional Hazards Models
Proton Pump Inhibitors/therapeutic use
Treatment Outcome

Access to Document

10.1111/aas.14471Licence: CC BY

Cite this

Borthwick, M., Granholm, A., Marker, S., Krag, M., Lange, T., Wise, M. P., Bendel, S., Keus, F., Guttormsen, A. B., Schefold, J. C., Wetterslev, J., Perner, A., & Møller, M. H. (2024). Associations between enteral nutrition and outcomes in the SUP-ICU trial: Results of exploratory post hoc analyses. Acta Anaesthesiologica Scandinavica, 68(9), 1244-1253. https://doi.org/10.1111/aas.14471

Borthwick, M, Granholm, A, Marker, S, Krag, M, Lange, T, Wise, MP, Bendel, S, Keus, F, Guttormsen, AB, Schefold, JC, Wetterslev, J, Perner, A & Møller, MH 2024, 'Associations between enteral nutrition and outcomes in the SUP-ICU trial: Results of exploratory post hoc analyses', Acta Anaesthesiologica Scandinavica, vol. 68, no. 9, pp. 1244-1253. https://doi.org/10.1111/aas.14471

@article{0b8108fe232b49f595e96f3ff41c9558,

title = "Associations between enteral nutrition and outcomes in the SUP-ICU trial: Results of exploratory post hoc analyses",

abstract = "BACKGROUND: Enteral 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.METHODS: Extended 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.RESULTS: Enteral 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).CONCLUSIONS: Enteral 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.",

keywords = "2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use, Aged, Critical Illness, Enteral Nutrition/methods, Female, Gastrointestinal Hemorrhage, Humans, Intensive Care Units, Male, Middle Aged, Pantoprazole/therapeutic use, Pneumonia/epidemiology, Proportional Hazards Models, Proton Pump Inhibitors/therapeutic use, Treatment Outcome",

author = "Mark Borthwick and Anders Granholm and S{\o}ren Marker and Mette Krag and Theis Lange and Wise, \{Matt P\} and Stepani Bendel and Frederik Keus and Guttormsen, \{Anne Berit\} and Schefold, \{Joerg C\} and J{\o}rn Wetterslev and Anders Perner and M{\o}ller, \{Morten Hylander\}",

note = "{\textcopyright} 2024 The Author(s). Acta Anaesthesiologica Scandinavica published by John Wiley \& Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.",

year = "2024",

month = oct,

doi = "10.1111/aas.14471",

language = "English",

volume = "68",

pages = "1244--1253",

journal = "Acta Anaesthesiologica Scandinavica",

issn = "0001-5172",

publisher = "Blackwell Munksgaard",

number = "9",

}

TY - JOUR

T1 - Associations between enteral nutrition and outcomes in the SUP-ICU trial

T2 - Results of exploratory post hoc analyses

AU - Borthwick, Mark

AU - Granholm, Anders

AU - Marker, Søren

AU - Krag, Mette

AU - Lange, Theis

AU - Wise, Matt P

AU - Bendel, Stepani

AU - Keus, Frederik

AU - Guttormsen, Anne Berit

AU - Schefold, Joerg C

AU - Wetterslev, Jørn

AU - Perner, Anders

AU - Møller, Morten Hylander

PY - 2024/10

Y1 - 2024/10

N2 - BACKGROUND: Enteral 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.METHODS: Extended 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.RESULTS: Enteral 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).CONCLUSIONS: Enteral 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.

AB - BACKGROUND: Enteral 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.METHODS: Extended 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.RESULTS: Enteral 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).CONCLUSIONS: Enteral 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.

KW - 2-Pyridinylmethylsulfinylbenzimidazoles/therapeutic use

KW - Aged

KW - Critical Illness

KW - Enteral Nutrition/methods

KW - Female

KW - Gastrointestinal Hemorrhage

KW - Humans

KW - Intensive Care Units

KW - Male

KW - Middle Aged

KW - Pantoprazole/therapeutic use

KW - Pneumonia/epidemiology

KW - Proportional Hazards Models

KW - Proton Pump Inhibitors/therapeutic use

KW - Treatment Outcome

UR - https://www.scopus.com/pages/publications/85195954890

U2 - 10.1111/aas.14471

DO - 10.1111/aas.14471

M3 - Journal article

C2 - 38867404

SN - 0001-5172

VL - 68

SP - 1244

EP - 1253

JO - Acta Anaesthesiologica Scandinavica

JF - Acta Anaesthesiologica Scandinavica

IS - 9

ER -

Associations between enteral nutrition and outcomes in the SUP-ICU trial: Results of exploratory post hoc analyses

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this