Methodologies in health services research for critical care
Pathophysiology and prophylaxis of stress ulcer in intensive care unit patients

https://doi.org/10.1016/j.jcrc.2004.10.003Get rights and content

Abstract

Gastrointestinal complications frequently occur in patients admitted to the intensive care unit. Of these, ulceration and bleeding related to stress-related mucosal disease (SRMD) can lengthen hospitalization and increase mortality. The purpose of this review is to discuss the many risk factors and underlying illnesses that have a role in the pathophysiology of SRMD and evaluate the evidence pertaining to SRMD prophylaxis in the intensive care unit population. Suppressing acid production is fundamental to preventing stress-related mucosal ulceration and clinically important gastrointestinal bleeding. Traditional prophylactic options for SRMD in critically ill patients include antacids, sucralfate, histamine2-receptor antagonists (H2RAs), and proton pump inhibitors. Many clinicians prescribe intermittent infusions of H2RAs for stress ulcer prophylaxis, a practice that has not been approved for this indication and may not provide the necessary degree or duration of acid suppression required to prevent stress ulcer–related bleeding. New data suggest that proton pump inhibitors suppress acid production more completely in critically ill patients, but more studies are required to assess their clinical effectiveness and safety for this indication. The prophylactic regimen chosen to prevent stress ulcer bleeding should take into account the risk factors and underlying disease state of individual patients to provide the best therapy to those most likely to benefit.

Introduction

An estimated 4.4 million patients are admitted to intensive care units (ICUs) each year. Of these, about 12%, or 500 000 patients, die in the ICU [1]. Gastrointestinal (GI) complications (eg, gastric and intestinal motor dysfunction as well as stress-related mucosal disease [SRMD]) frequently occur in these patients and adversely affect patient outcomes. Gastrointestinal motor dysfunction may predispose patients to impaired enteral nutrition and pulmonary aspiration of gastric contents [2]. Stress-related mucosal damage—an acute erosive gastritis—occurs in many critically ill patients in ICUs and may develop within 24 hours of admission [3]. The incidence of clinically important GI bleeding, defined as overt bleeding complicated by hemodynamic instability, decrease in hemoglobin, and/or need for blood transfusion, from SRMD in the ICU population was 1.5% in a prospective study of 2252 patients [4]. In addition, the morbidity associated with this type of severe ulceration and bleeding can increase the length of stay in the ICU by up to 8 days, and mortality is as much as 4-fold higher than it is in ICU patients without this complication [5].

Section snippets

Pathophysiology and pathogenesis of SRMD

Several factors have a role in the pathogenesis of SRMD, including gastric acid secretion, mucosal ischemia (as a result of splanchnic hypoperfusion), and reflux of upper intestinal contents into the stomach (Fig. 1) [6], [7]. Gastric hypoperfusion leads to an imbalance between oxygen supply and demand that may induce mucosal damage. Moreover, reperfusion after prolonged hypoperfusion may itself result in nonocclusive mesenteric ischemia and mucosal damage. As a result of ischemia, there is

Complications associated with SRMD

Mortality rates increase proportionately with the incidence and severity of SRMD. In 2 prospective multicenter studies, Cook et al [4], [5] found significant differences in mortality between clinically important GI bleeding and nonbleeding patients (Fig. 2). In these studies, patients who bled as a result of SRMD had mortality rates of 49% and 46%. In contrast, mortality rates for nonbleeding patients were 9% and 21% (P < .001 and P < .0001, respectively) [4], [5]. These findings are consistent

Risk factors for stress ulcer–related bleeding

As noted, critically ill patients admitted to ICUs are at risk for developing stress ulceration and subsequent bleeding as a result of both underlying disease and therapeutic interventions. Prophylaxis against stress ulcers can significantly minimize bleeding, but such therapy may be costly and can have adverse effects. Therefore, it is important to identify risk factors that would substantiate the need for prophylaxis and target interventions to those at highest risk. A study involving more

Stress ulcer prophylaxis options

Prevention of stress-related bleeding is clearly the most effective strategy for patients at risk for SRMD in the ICU. This can be accomplished by preventing gastric ischemia or acid injury. Although high acid concentrations are not the only factor that contributes to SRMD, controlling acid production in at-risk patients seems to be protective against bleeding episodes [9]. A metaanalysis of clinical trials by Cook et al [30] reported that various prophylactic therapies such as antacids,

Cost of prophylaxis

When evaluating the cost of regimens used for prevention of stress ulcer–related bleeding, it is important to recognize that acquisition cost is only one of several factors that need to be considered. Other factors include cost of preparing and administering the agent, as well as the potential for overuse, adverse effects, and risk of bleeding.

Evidence strongly suggests that stress ulcer prophylaxis should be limited to patients with established risk factors for clinically significant GI

Conclusions

The etiology of SRMD is multifactorial, but 2 conditions that seem to be necessary are intraluminal acid and gastric mucosal ischemia. Therefore, prophylaxis and treatment require maintenance of perfusion and protection against acid damage through elevation of gastric pH. Underlying disease and risk factors including surgery, burns, trauma, respiratory failure requiring mechanical ventilation, and coagulopathy predispose patients to SRMD. Gastrointestinal bleeding exacerbates the underlying

Acknowledgment

This work is supported by Wyeth Pharmaceuticals, Philadelphia, PA, with editorial support provided by Accel Medical Education, New York, NY.

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