Elsevier

Journal of Critical Care

Volume 43, February 2018, Pages 108-113
Journal of Critical Care

Clinical Potpourri
Enteral nutrition as stress ulcer prophylaxis in critically ill patients: A randomized controlled exploratory study

https://doi.org/10.1016/j.jcrc.2017.08.036Get rights and content

Highlights

  • GI bleeding has low incidence in the critically ill mechanically ventilated patients.

  • Adding PPI to enteral nutrition may not offer an added prophylaxis against stress-related GI bleeding.

  • Our study supports the protective role of enteral nutrition in ICU.

Abstract

Purpose

We investigated whether early enteral nutrition alone may be sufficient prophylaxis against stress-related gastrointestinal (GI) bleeding in mechanically ventilated patients.

Materials and methods

Prospective, double blind, randomized, placebo-controlled, exploratory study that included mechanically ventilated patients in medical ICUs of two academic hospitals. Intravenous pantoprazole and early enteral nutrition were compared to placebo and early enteral nutrition as stress-ulcer prophylaxis. The incidences of clinically significant and overt GI bleeding were compared in the two groups.

Results

124 patients were enrolled in the study. After exclusion of 22 patients, 102 patients were included in analysis: 55 patients in the treatment group and 47 patients in the placebo group. Two patients (one from each group) showed signs of overt GI bleeding (overall incidence 1.96%), and both patients experienced a drop of > 3 points in hematocrit in a 24-hour period indicating a clinically significant GI bleed. There was no statistical significant difference in the incidence of overt or significant GI bleeding between groups (p = 0.99).

Conclusion

We found no benefit when pantoprazole is added to early enteral nutrition in mechanically ventilated critically ill patients. The routine prescription of acid-suppressive therapy in critically ill patients who tolerate early enteral nutrition warrants further evaluation.

Introduction

As early as 1969, Skillman et al. described lethal gastric bleeding in patients with a triad of hypotension, respiratory failure, and sepsis [1]. We now know that splanchnic hypoperfusion and mucosal ischemia play a major role in stress-related mucosal disease, a form of erosive gastritis [2], [3]. Coagulopathy and respiratory failure have been identified as important risk factors in the pathogenesis of stress-related mucosal disease [4]. Endoscopic studies have shown that up to 25% of patients have gastric erosions on admission to the intensive care unit (ICU) and up to 90% on the third ICU day [5], [6]. Despite the high incidence of endoscopic findings, clinically important bleeding has a much lower incidence reported between 0.1 and 8.5% [4], [7], [8], [9]. When clinically important GI bleeding occurs, it may result in hemodynamic instability, an increased need for blood transfusions, prolonged ICU stay, and an increased mortality [10].

Stress ulcer prophylaxis (SUP) in ICUs has become the standard of care with up to 70% of mechanically ventilated patients admitted to the ICU receiving SUP [11], [12]. Pharmacologic prophylaxis has traditionally involved medications such as histamine-2 receptor blockers (H2RB) and proton pump inhibitors (PPI). The widespread use of gastric acid suppressing agents has raised concern over loss of the protective bacteriostatic effect of gastric acid leading to a greater incidence of ventilator-associated pneumonias [13], [14], [15]. The increasing use of gastric acid suppressive therapy together with the use of broad-spectrum antibiotics has also been associated with an increased risk of Clostridium difficile infection (CDI) [16], [17], [18], [19], [20]. Suppression of gastric acid may facilitate the growth of pathogenic flora in the gastrointestinal (GI) tract, in addition to permitting the conversion from spores to vegetative cells that ultimately produce toxins [21].

Animal studies have shown enteral nutrition (EN) to increase GI blood flow without increasing cardiac output [22], [23], [24], and provide protection against stress related GI bleeding [25]. Two studies using a murine model suggested that continuous enteral administration of elemental formulas significantly reduced the occurrence of macroscopic mucosal lesions, compared with enteral administration of an antacid or intravenous (IV) administration of an H2RB [26], [27]. It has been proposed that continuous enteral nutrition is more likely to raise gastric pH above 3.5 than H2RBs and PPIs, and that early enteral nutrition is more effective in preventing overt GI bleeding than H2RB and antacids [14].

Some early reports supported the idea that early EN may be as effective as pharmacologic SUP agents [28], [29]. More recently, a retrospective cohort analysis in trauma and surgical ICU patients disclosed no added benefit of PPIs once patients were tolerating enteral feeding [30]. This finding was confirmed by the POP-UP exploratory study in medical and surgical ICU patients that revealed no added benefit with the addition of PPIs to patients on enteral feeding [31]. Definitive recommendations regarding the role of EN for SUP are deficient, and most prospective trials are limited by design flaws and lack of consistency surrounding details of the EN feeding regimen [14].

We hypothesized that early enteral feeding could potentially play a preventative role for stress-related GI bleeding and conducted a prospective randomized controlled trial to determine if early-enteral nutrition alone suffices as GI prophylaxis in critically ill patients on mechanical ventilation. We also intended to investigate the difference in incidence of CDI.

Section snippets

Study population

The study was conducted over a period of three years. The study started in July 2013 in the medical ICU of University of Louisville Hospital. In July 2014, a second recruitment site (medical ICU at Jewish Hospital) was added as a site for recruitment to enhance enrollment rate. The study was completed in September 2016. The University Hospital team included an academic ICU physician, a fellow, and internal medicine residents. The Jewish Hospital team included an academic ICU physician, a

Results

Patients admitted to the medical ICU who were expected to need mechanical ventilation for > 48 h were assessed for eligibility. Between July 2013 and September 2016, 320 patients were screened for eligibility and 124 patients were consented and enrolled in the study. Of the enrolled patients, 22 had one day or less of data (tube feed was not started in most of these patients who were extubated soon after the study enrolment) and these patients were excluded (none of these patients developed any

Discussion

This was a prospective, randomized, double blind, exploratory study conducted over a period of three years in critically ill, mechanically ventilated patients who were admitted to the medical ICU and were expected to receive mechanical ventilation for > 48 h. All patients received enteral nutrition within 24 h of intubation. Results indicated a low incidence of overt or clinically significant GI bleeding in our study (1.96%, n = 2) without a statistically significant difference between the treatment

Conclusions

This study did not find an additional benefit of pharmacologic SUP when early EN is initiated in critically ill, mechanically ventilated patients in the medical ICU. These results add to the growing evidence supporting the protective role of early enteral nutrition in ICU. Larger clinical trials are necessary to corroborate our findings.

Conflict of interest

None.

Acknowledgment

This work was supported by a grant from Abbott Nutrition (ANUS1107). The funder of the trial had no active role in the design, methodology, data collections, analysis, preparation of this manuscript, or the decision to submit the manuscript for publication.

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