Advertisement

Digestive Diseases and Sciences

, Volume 63, Issue 10, pp 2687–2694 | Cite as

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

  • Aymeric Becq
  • Saik Urien
  • Maximilien Barret
  • Christophe Faisy
Original Article
  • 131 Downloads

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.

Keywords

Epinephrine dose Stress ulcer Critically ill patients Gastrointestinal bleeding Enteral nutrition 

Notes

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.

Author’s contribution

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.

Compliance with ethical standards

Conflict of interest

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

Supplementary material

10620_2018_5155_MOESM1_ESM.docx (368 kb)
Supplementary material 1 (DOCX 368 kb)

References

  1. 1.
    Tryba M, Cook D. Current guidelines on stress ulcer prophylaxis. Drugs. 1997;54:581–596.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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.CrossRefPubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 5.
    Harris SK, Bone RC, Ruth WE. Gastrointestinal hemorrhage in patients in a respiratory intensive care unit. Chest. 1977;72:301–304.CrossRefPubMedGoogle Scholar
  6. 6.
    Spirt MJ. Stress-related mucosal disease: risk factors and prophylactic therapy. Clin Ther. 2004;26:197–213.CrossRefPubMedGoogle Scholar
  7. 7.
    Stollman N, Metz DC. Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients. J Crit Care. 2005;20:35–45.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedGoogle Scholar
  9. 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.PubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 11.
    Cain SM, Curtis SE. Experimental models of pathologic oxygen supply dependency. Crit Care Med. 1991;19:603–612.CrossRefPubMedGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 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. 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. 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.CrossRefPubMedGoogle Scholar
  16. 16.
    Levy B. Bench-to-bedside review: is there a place for epinephrine in septic shock? Crit Care Lond Engl. 2005;9:561–565.CrossRefGoogle Scholar
  17. 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.CrossRefGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 20.
    Forrest JA, Finlayson ND, Shearman DJ. Endoscopy in gastrointestinal bleeding. Lancet Lond Engl. 1974;2:394–397.CrossRefGoogle Scholar
  21. 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. 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.CrossRefPubMedGoogle Scholar
  23. 23.
    Skillman JJ, Silen W. Stress ulceration in the acutely ill. Annu Rev Med. 1976;27:9–22.CrossRefPubMedGoogle Scholar
  24. 24.
    Le Gall JR, Mignon FC, Rapin M, et al. Acute gastroduodenal lesions related to severe sepsis. Surg Gynecol Obstet. 1976;142:377–380.PubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Gastroenterology and EndoscopySaint Antoine Hospital, Assistance Publique – Hôpitaux de ParisParisFrance
  2. 2.Department of GastroenterologyCochin Hospital, Assistance Publique – Hôpitaux de ParisParisFrance
  3. 3.Clinical Investigations Center-1419 INSERMEA7323 - University Paris-Descartes Sorbonne-Paris CitéParisFrance

Personalised recommendations