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Epinephrine Dose Has a Preventive Effect on the Occurrence of Stress Ulcer-Induced Gastrointestinal Bleeding in Critically Ill Patients

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Abstract

Background

Epinephrine may impair splanchnic blood flow, but the impact of epinephrine dose on the occurrence of clinically significant gastrointestinal bleeding (CSGB) caused by stress ulcer remains unclear. We investigated the effect of epinephrine dose on the occurrence of stress ulcer-related CSGB in intensive care unit (ICU) patients.

Methods

In this prospective, observational, cohort study conducted in a French teaching hospital, 40 consecutive ICU patients receiving epinephrine infusion in whom a stress ulcer was diagnosed by an upper gastrointestinal endoscopy were included, from February 2010 to July 2015. The effects of epinephrine dose, and other covariates, on the occurrence of stress ulcer-related CSGB were analyzed using a multiple logistic regression model for repeated measures: At each observation, each patient serves as his own control.

Results

A total of 1484 time-dependent epinephrine dose modifications were available for analysis. The median epinephrine dose rate was 0.8 (0–9.5) mg/h, and the median epinephrine cumulative dose was 44.8 (2.6–2343) mg. Epinephrine, expressed as the average dose per day at time t, had a significant protective effect on the occurrence of stress ulcer (odds ratio 0.22; 95% confidence interval (CI), 0.12–0.38; p < 0.0001, for a log10 increase of epinephrine dose). Enteral feeding had also a protective effect (odds ratio 0.55; 95% CI 0.41–0.72; p < 0.0001, for a log10 increase of kcal/day). Only renal replacement therapy increased the occurrence of stress ulcer in the model.

Conclusions

An increase in the average dose of epinephrine per day increased the time to occurrence of stress ulcer in critically ill patients.

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References

  1. Tryba M, Cook D. Current guidelines on stress ulcer prophylaxis. Drugs. 1997;54:581–596.

    Article  CAS  PubMed  Google Scholar 

  2. Buendgens L, Koch A, Tacke F. Prevention of stress-related ulcer bleeding at the intensive care unit: risks and benefits of stress ulcer prophylaxis. World J Crit Care Med. 2016;5:57–64.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cook DJ, Fuller HD, Guyatt GH, et al. Risk factors for gastrointestinal bleeding in critically ill patients. Canadian Critical Care Trials Group. N Engl J Med. 1994;330:377–381.

    Article  CAS  PubMed  Google Scholar 

  4. Krag M, Perner A, Wetterslev J, et al. Prevalence and outcome of gastrointestinal bleeding and use of acid suppressants in acutely ill adult intensive care patients. Intensive Care Med. 2015;41:833–845.

    Article  CAS  PubMed  Google Scholar 

  5. Harris SK, Bone RC, Ruth WE. Gastrointestinal hemorrhage in patients in a respiratory intensive care unit. Chest. 1977;72:301–304.

    Article  CAS  PubMed  Google Scholar 

  6. Spirt MJ. Stress-related mucosal disease: risk factors and prophylactic therapy. Clin Ther. 2004;26:197–213.

    Article  PubMed  Google Scholar 

  7. Stollman N, Metz DC. Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care. 2005;20:35–45.

    Article  PubMed  Google Scholar 

  8. Schuster DP, Rowley H, Feinstein S, McGue MK, Zuckerman GR. Prospective evaluation of the risk of upper gastrointestinal bleeding after admission to a medical intensive care unit. Am J Med. 1984;76:623–630.

    Article  CAS  PubMed  Google Scholar 

  9. Michida T, Kawano S, Masuda E, et al. Endothelin-1 in the gastric mucosa in stress ulcers of critically ill patients. Am J Gastroenterol. 1997;92:1177–1181.

    CAS  PubMed  Google Scholar 

  10. Björne H, Govoni M, Törnberg DC, Lundberg JO, Weitzberg E. Intragastric nitric oxide is abolished in intubated patients and restored by nitrite. Crit Care Med. 2005;33:1722–1727.

    Article  CAS  PubMed  Google Scholar 

  11. Cain SM, Curtis SE. Experimental models of pathologic oxygen supply dependency. Crit Care Med. 1991;19:603–612.

    Article  CAS  PubMed  Google Scholar 

  12. Dahn MS, Lange MP, Wilson RF, Jacobs LA, Mitchell RA. Hepatic blood flow and splanchnic oxygen consumption measurements in clinical sepsis. Surgery. 1990;107:295–301.

    CAS  PubMed  Google Scholar 

  13. Nelson DP, Samsel RW, Wood LD, Schumacker PT. Pathological supply dependence of systemic and intestinal O2 uptake during endotoxemia. J Appl Physiol Bethesda Md. 1985;1988:2410–2419.

    Google Scholar 

  14. Wang P, Ba ZF, Chaudry IH. Hepatic extraction of indocyanine green is depressed early in sepsis despite increased hepatic blood flow and cardiac output. Arch Surg Chic Ill. 1960;1991:219–224.

    Google Scholar 

  15. De Backer D, Creteur J, Silva E, Vincent J-L. Effects of dopamine, norepinephrine, and epinephrine on the splanchnic circulation in septic shock: which is best? Crit Care Med. 2003;31:1659–1667.

    Article  CAS  PubMed  Google Scholar 

  16. Levy B. Bench-to-bedside review: is there a place for epinephrine in septic shock? Crit Care Lond Engl. 2005;9:561–565.

    Article  Google Scholar 

  17. Abboud I, Lerolle N, Urien S, et al. Pharmacokinetics of epinephrine in patients with septic shock: modelization and interaction with endogenous neurohormonal status. Crit Care Lond Engl. 2009;13:R120.

    Article  Google Scholar 

  18. Faisy C, Guerot E, Diehl J-L, Iftimovici E, Fagon J-Y. Clinically significant gastrointestinal bleeding in critically ill patients with and without stress–ulcer prophylaxis. Intensive Care Med. 2003;29:1306–1313.

    Article  PubMed  Google Scholar 

  19. Ekpe K, Novara A, Mainardi J-L, Fagon J-Y, Faisy C. Methicillin-resistant Staphylococcus aureus bloodstream infections are associated with a higher energy deficit than other ICU-acquired bacteremia. Intensive Care Med. 2014;40:1878–1887.

    Article  CAS  PubMed  Google Scholar 

  20. Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet Lond Engl. 1974;2:394–397.

    Article  CAS  Google Scholar 

  21. Therneau TM. Modeling Survival Data: Extending the Cox Model. Springer. [cited 2017 Mar 16]. Available from: http://www.springer.com/gp/book/9780387987842.

  22. Lafont E, Urien S, Salem J-E, Heming N, Faisy C. Modeling for critically ill patients: an introduction for beginners. J Crit Care. 2015;30:1287–1294.

    Article  PubMed  Google Scholar 

  23. Skillman JJ, Silen W. Stress ulceration in the acutely ill. Annu Rev Med. 1976;27:9–22.

    Article  CAS  PubMed  Google Scholar 

  24. Le Gall JR, Mignon FC, Rapin M, et al. Acute gastroduodenal lesions related to severe sepsis. Surg Gynecol Obstet. 1976;142:377–380.

    PubMed  Google Scholar 

  25. Zandstra DF, Stoutenbeek CP. The virtual absence of stress-ulceration related bleeding in ICU patients receiving prolonged mechanical ventilation without any prophylaxis. A prospective cohort study. Intensive Care Med. 1994;20:335–340.

    Article  CAS  PubMed  Google Scholar 

  26. Krag M, Perner A, Wetterslev J, Wise MP, Hylander Møller M. Stress ulcer prophylaxis versus placebo or no prophylaxis in critically ill patients. A systematic review of randomised clinical trials with meta-analysis and trial sequential analysis. Intensive Care Med. 2014;40:11–22.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We are indebted to Hélène Owczarek, from the medical intensive care unit of the European Georges Pompidou Hospital, for managing intensive care unit database.

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Author notes

  1. Aymeric Becq and Saik Urien have contributed equally as first authors.

Authors and Affiliations

  1. Department of Gastroenterology and Endoscopy, Saint Antoine Hospital, Assistance Publique – Hôpitaux de Paris, 184 rue du Faubourg Saint Antoine, 75012, Paris, France

    Aymeric Becq

  2. Department of Gastroenterology, Cochin Hospital, Assistance Publique – Hôpitaux de Paris, Paris, France

    Maximilien Barret

  3. Clinical Investigations Center-1419 INSERM, EA7323 - University Paris-Descartes Sorbonne-Paris Cité, Paris, France

    Saik Urien & Christophe Faisy

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  1. Aymeric Becq
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  2. Saik Urien
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  4. Christophe Faisy
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Contributions

AB is the guarantor of article. AB, SU, MB, and CF contributed to conception and study design, data collection and analysis, and drafting and revising of the manuscript. AB, SU, MB, and CF approved the final version of the article.

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Correspondence to Aymeric Becq.

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None. This work was not sponsored by gifts or fellowships.

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Becq, A., Urien, S., Barret, M. et al. Epinephrine Dose Has a Preventive Effect on the Occurrence of Stress Ulcer-Induced Gastrointestinal Bleeding in Critically Ill Patients. Dig Dis Sci 63, 2687–2694 (2018). https://doi.org/10.1007/s10620-018-5155-8

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  • DOI: https://doi.org/10.1007/s10620-018-5155-8

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