Stress-Induced Gastritis 

Updated: Apr 14, 2020
Author: Rohan C Clarke, MD; Chief Editor: BS Anand, MD 

Overview

Practice Essentials

Stress-induced gastritis—also referred to as stress-related erosive syndrome, stress ulcer syndrome, and stress-related mucosal disease—can cause mucosal erosions and superficial hemorrhages in patients who are critically ill or in those who are under extreme physiologic stress, resulting in minimal-to-severe gastrointestinal (GI) blood loss and leading to blood transfusion if not addressed in time.

Signs and symptoms

Stress-induced gastritis has a variable clinical presentation, but the following clues should raise the level of clinical suspicion for this entity:

  • Coffee ground vomitus

  • Melena

  • Hematemesis (in extreme cases)

  • Orthostasis (unusual)

See Presentation for more detail.

Diagnosis

A high degree of clinical awareness is the key to early diagnosis. Patients who may have an increased risk of stress gastritis are those with massive burn injury, head injury associated with raised intracranial pressure, sepsis and positive blood culture results, severe trauma, and multiple system organ failure.

Laboratory testing

  • Hematocrit

  • Coagulation profile

Procedures

  • Nasogastric tube and lavage: Useful test to confirm the presence of blood in the upper GI tract and to quantify the amount of blood if found (roughly assessed by the amount of normal saline needed before the aspirate becomes clear)

  • Endoscopy: Useful only in the diagnosis of stress-induced gastritis

See Workup for more detail.

Management

Prophylaxis of stress gastritis is the goal of management. Monitor the pH of the gastric contents (target: pH >4.0). If the pH level is below the target pH, consider doubling the dose of the agent used to reduce gastric acid levels if the patient was previously on prophylaxis therapy.

Pharmacotherapy

The following medications are used in the management of stress-induced gastritis:

  • Sucralfate: Primary agent for prophylaxis

  • Histamine 2 (H2) receptor blockers (eg, ranitidine, famotidine, cimetidine, nizatidine)

  • Proton pump inhibitors (eg, esomeprazole, pantoprazole)

See Treatment and Medication for more detail.

Background

Stress-induced gastritis, also referred to as stress-related erosive syndrome, stress ulcer syndrome, and stress-related mucosal disease, can cause mucosal erosions and superficial hemorrhages in patients who are critically ill or in those who are under extreme physiologic stress, resulting in minimal-to-severe gastrointestinal blood loss and leading to blood transfusion if not addressed expeditiously.[1]

Patients who may have an increased risk of stress gastritis are those with massive burn injury, head injury associated with raised intracranial pressure, sepsis and positive blood culture results, severe trauma, and multiple system organ failure.

Pathophysiology

Common sites for stress ulceration include the gastric body and fundus, antrum, and duodenum.[2]

Acid is secreted by the parietal cells of the gastric mucosa, which is under the influence of several biologic agents or activities (eg, histamine, gastrin, vagal nerve stimulation).[1] The mucosa is protected by the mucous gel layer, which is under the influence of prostaglandins, nitric oxide,[3] trefoil proteins, and vagal nerve stimulation. This mucous layer forms a barrier between the acidic pH of the stomach and the gastric epithelium. In the presence of noxious agents or conditions, this protective barrier is destroyed. When this occurs, the acid is able to diffuse backward to the epithelium and cause mucosal damage.[2]

Two entities are thought to normally play a role in the breakdown of the mucosal barrier: gastric acid secretion and defense mechanisms. With stress gastritis, gastric acid secretion is invariably either normal or decreased. Thus, acid hypersecretion is not a significant etiologic factor; instead, the breakdown of the mucosal defense mechanism is the primary cause. The defense mechanisms, particularly the mucous secretion, tend to have a decrease in bicarbonate concentration and, therefore, are unable to buffer the proton in the stomach.[4] Stress causes decreased blood flow to the mucosa, leading to ischemia with subsequent destruction of the mucosal lining.

Epidemiology

United States data

Of patients who are critically ill, 6% have overt bleeding, while fewer than 2%-3% have clinically significant hemorrhage. According to several studies, endoscopy has revealed evidence of intraepithelial hemorrhage in 52%-100% of patients in the intensive care unit within 24 hours of the onset of the stressor.[5]

Race-, sex-, and age-related demographics

No studies have shown any differences among the races with respect to the bleeding rates associated with stress gastritis.

No differences have been noted between the sexes with respect to stress gastritis.

With increasing age, atherosclerosis may play a role in the decreased blood supply to the gastric mucosa. This, in the setting of a stressor, may lead to decreased mucous production and, hence, greater susceptibility to erosions and ulcerations.

Etiology

Prolonged mechanical ventilation and coagulopathy increase the predisposition to stress gastritis. Causative factors include the following conditions:

  • Severe trauma (stress ulcers in the setting of acute traumatic brain injury are known as Cushing ulcers[2] )

  • Massive burns (stress ulcers due to systemic burns are known as Curling ulcers[2] )

  • Hypotension

  • Sepsis with positive blood culture results

  • Central nervous system injury with raised intracranial pressure

  • Mechanical ventilation[6]

  • Multiorgan failure

Prognosis

In general, the prognosis depends on the severity of the etiologic condition and timely recognition and management of stress-induced gastritis.[1] Gastrointestinal bleeding due to stress ulcerations range from 1.5% to 15%, depending on whether stress ulcer prophylaxis has been provided.[2] If stress gastritis is left untreated, life-threatening intestinal hemorrhage may occur, followed by perforation, with ensuing septic shock and, potentially, death.[1]

Morbidity/mortality

Gastrointestinal bleeding due to stress-related mucosal disease is itself an independent risk factor for greater morbidity/mortality.

Morbidity/mortality figures are high in older patients because of several factors, including atherosclerosis that leads to reduced blood supply and impaired host defenses. The severity of the injury leads to a further reduction in blood flow to the gastrointestinal tract, thereby resulting in a further compromise of the mucosal barrier and an increased risk of gastritis. The presence of Helicobacter pylori may also contribute to the mucosal barrier breakdown and lead to stress gastritis.

 

Presentation

History

The most common presenting sign/symptom of stress-induced gastritis is bleeding (hematemesis, melena) in a patient with an acute critical illness.[2, 1]

Patients who may have an increased risk of stress gastritis are those with severe illness,[1] major surgery,[1] massive burn injury, head injury associated with raised intracranial pressure, sepsis and positive blood culture results, severe polytrauma,[1] and multiple system organ failure.[2] The clinician should have a high index of suspicion in patients in these settings who are noted to have decreased hematocrit values and who are not receiving prophylaxis for stress gastritis.

Some types of psychiatric stressors (eg, major, untreated depression) can cause stress gastritis.[1]

The clinical presentation in patients with stress-induced gastritis is varied, but the following clues should raise the level of clinical suspicion for this entity:

  • Coffee ground vomitus

  • Melena

  • Hematemesis (in extreme cases)

  • Orthostasis (unusual)

 

DDx

Diagnostic Considerations

Important considerations

Hemodynamic stabilization of the patient should be prioritized before any diagnostic evaluation for stress gastritis.[2]

Timely prophylaxis with H2 blockers can lead to a significant reduction in the development of stress-induced gastritis and, hence, the avoidance of upper gastrointestinal hemorrhage.

Consider the possibility of blood product transfusions, which are dependent on the severity of a hemorrhage.[1, 2] This may expose the patient to the unnecessary risk of blood-borne infections, and the possible resultant hypotension could worsen any vascular compromise that is present, leading to cerebrovascular accidents, myocardial infarction, and renal failure. This could potentially leave the physician liable for lawsuits, if the patient does not receive prophylaxis earlier or in a timely manner.

The geriatric population may be more susceptible to the loss of blood, leading to a worsening of any underlying chronic vascular disease.

Other conditions to consider

The following conditions should also be considered in the differential diagnosis of stress-induced gastritis:

  • Peptic ulcer disease

  • Nonsteroidal anti-inflammatory drug (NSAID)–induced gastritis

  • Alcoholic gastropathy

  • Uremic gastropathy

 

Workup

Laboratory Studies

A high degree of clinical awareness is the key to early diagnosis of stress-induced gastritis. The presence of any of the previously discussed clinical features should alert the clinician to the presence of stress gastritis.

Useful investigations and diagnostic tools include the following:

  • Hematocrit level

  • Coagulation profile

  • Helicobacter pylori studies (eg, urea breath test, stool antigen test) for refractory stress ulceration

Procedures

Nasogastric tube and lavage

Gastric lavage is a useful test to confirm whether blood is present in the upper gastrointestinal tract[1] and to quantify the amount of blood if found. This is roughly assessed by how much normal saline it takes before the aspirate becomes clear.

Endoscopy

Endoscopy is useful only in the diagnosis of stress-induced gastritis.

For patients with burns, the presence of epigastric pain and major burns covering more than 20% of the total body surface area is significantly associated with the development of Curling ulcer, as revealed with endoscopy.[7]

 

Treatment

Medical Care

The goal of management for stress-induced gastritis is prophylaxis,[1, 2, 8] which has been shown to reduce the incidence by 50% when treatment is started at admission. Monitor the pH of the gastric contents. The target pH value should be greater than 4.0. Anything less should prompt the clinician to double the dose of the agent used to reduce gastric acid levels if the patient was previously on prophylaxis.

Sucralfate is the primary agent for prophylaxis of stress gastritis. It has long been used as a means of decreasing the incidence of gastritis. This drug is readily available, easy to administer, and inexpensive. Sucralfate (complex salt of sucrose aluminum hydroxide and sulfate) has a positive charge and binds to the negative charge of the ulcer base to form a gel, which acts to effectively plug the ulcer base and to prevent worsening of the gastritis. For patients on mechanical ventilation, this action has been shown to decrease the risk of nosocomial pneumonias by aspiration.

Histamine 2 (H2) receptor blockers (eg, ranitidine, famotidine) have also been used for prophylaxis. Their action selectively blocks H2 receptors on the parietal cells, thereby reducing the production of hydrogen ions. The H2 blockers are readily affordable and can be administered intravenously. For active hemorrhage, a continuous infusion of H2 blockers over a 24-hour period can be used because this delivers a constant concentration to the gastric mucosa, thus promoting healing. The major adverse effect of this class of drugs is the risk of nosocomial pneumonia, which is thought to result from the suppression of gastric acid and which leads to colonization by secondary organisms and subsequent aspiration pneumonia.

Although the role of proton pump inhibitors (PPIs) in prophylaxis has not been fully evaluated, these agents have been recommended as first-line agents for prophylaxis.[1, 2] However, PPIs are prodrugs and usually require an acidic medium to be activated. Hence, in the fasting stressed patient, or in a subset of critical care patients who present with overt GI bleeding but without stress ulceration or stress-related mucosal disease (eg, variceal bleeds, vascular anomalies, diverticulosis),[2] this may not be the case. PPIs block the final common pathway of acid secretion by blocking the H-K-ATPase enzyme. In addition, there appears to be a higher risk (38.6%) of hospital-acquired Clostridium difficile infection when PPIs are used for prophylaxis and treatment of stress ulcers than when H2RAs are used.[9, 10]

PPIs are available in various forms (eg, tablets, microspheres, liquid [IV]). In patients who are critically ill and intubated for nasogastric tube or percutaneous endoscopic gastrostomy (PEG) feeding, the administration of microspheres or intravenous preparations can be useful if the patients are thought to be bleeding from stress gastritis, especially if they have not responded to any of the previously discussed measures.

Small studies have shown the efficacy of PPIs in mechanically ventilated patients to reduce stress gastritis and have also found them to be safe and cost effective. In a comparison of PPIs and placebo, the superiority of PPIs over placebo was demonstrated in cases of bleeding peptic ulcer. PPIs were also shown to be more effective for rebleed prophylaxis versus H2 blockers.

In a review of studies from a MEDLINE search through August 2015, Barletta and colleagues found that PPIs appear to be the dominant drug class used worldwide. However, when the researchers evaluated only trials that were at low risk for bias, the evidence failed to clearly support lower bleeding rates with proton pump inhibitors over H2-receptor antagonists.[11]

In a search of the Cochrane library, MEDLINE, EMBASE, ACPJC, clinical trials registries, and conference proceedings through November 2015, Alshamsi et al reviewed randomized controlled trials of PPIs versus H2-receptor antagonists (H2RAs) for stress ulcer prophylaxis in critically ill adults. They found that in 19 trials enrolling 2117 patients, PPIs were more effective than H2RAs in reducing the risk of clinically important gastrointestinal (GI) bleeding and overt GI bleeding, without significantly increasing the risk of pneumonia or mortality.[12]

In a more recent meta-analysis with trial sequential analysis that included 34 randomized controlled trials comprising 3220 critically ill adults who received PPIs or H2RAs versus placebo, control, no therapy, or enteral nutrition, the strategy of stress ulcer prophylaxis was associated with significant reductions in bleeding but did not affect the mortality.[13]

In a retrospective study (2008-2013) of data from 200 patients at risk for stress gastropathy due to mechanical ventilation in a surgical trauma intensive care unit (ICU) at a single center, investigators noted that the incidence of clinically significant GI bleeding (CSGB) was low (0.50%) and that of stress gastropathy was rare in this population.[14] Moreover, pharmacologic stress gastropathy prophylaxis provided no benefit once at-risk surgical and trauma patients tolerated enteral nutrition, potentially secondary to sufficient gut blood flow rending the stress gastropathy prophylaxis unnecessary.[14]

A prospective observational study (2010-2015) of 40 ICU patients regarding the effects of 1484 time-dependent doses of epinephrine (average dose per day at time t) on the occurrence of stress ulcer-related CSBG found that an increase in the average daily epinephrine dose raised the time to occurrence of stress ulcer in these critically ill patients, as did enteral feeding.[15] However, renal replacement therapy increased the occurrence of stress ulcers.

Surgical Care

In general, surgical interventions are for life-saving measures—such as refractory bleeding despite endoscopic or angiographic therapy, or in individuals who are hemodynamically unstable to undergo these procedures.[2]

Surgical intervention may also be required in the setting of deep ulcers that lead to perforation of the gastric wall, resulting in acute peritonitis that necessitates urgent laparotomy.[2]

 

Medication

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Proton-pump inhibitors (PPIs) have not been fully evaluated in the role of prophylaxis for this disease.

Gastrointestinal agents

Class Summary

Shown to be effective in the prevention of stress-induced gastritis.

Sucralfate (Carafate)

Binds with positively charged proteins in exudates and forms a viscous adhesive substance that protects the GI lining against pepsin, peptic acid, and bile salts. Primary agent for prophylaxis of stress gastritis.

Histamine H2 antagonists

Class Summary

These agents block H2 receptor binding. The primary indication is to reduce symptoms and to accelerate healing of gastric ulcers. In the acutely bleeding patient, they are of limited benefit. Some have also been used for prophylaxis (eg, famotidine).

Famotidine (Pepcid)

Competitively inhibits histamine at H2 receptor of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Nizatidine (Axid)

Competitively inhibits histamine at H2 receptors of gastric parietal cells, resulting in reduced gastric acid secretion, gastric volume, and reduced hydrogen concentrations.

Cimetidine (Tagamet)

Inhibits histamine at H2 receptors of gastric parietal cells, which results in reduced gastric acid secretion, gastric volume, and hydrogen concentrations.

Ranitidine (Zantac)

Inhibits histamine stimulation of the H2 receptor in gastric parietal cells, which, in turn, reduces gastric acid secretion, gastric volume, and hydrogen ion concentrations.

Proton Pump Inhibitor

Class Summary

Proton pump inhibitors are inhibitors of the gastric H+/K+ -ATPase (proton pump) enzyme system, which catalyzes the exchange of H+ and K+.

Esomeprazole (Nexium)

S-isomer of omeprazole. Inhibits gastric acid secretion by inhibiting H+/K+ -ATPase enzyme system at secretory surface of gastric parietal cells.

Used in severe cases and in patients not responding to H2 antagonist therapy.

Used for up to 4 weeks to treat and relieve symptoms of active duodenal ulcers; may be used for up to 8 weeks to treat all grades of erosive esophagitis.

Pantoprazole (Protonix)

Pantoprazole suppresses gastric acid secretion by specifically inhibiting the H+/K+-ATPase enzyme system at the secretory surface of gastric parietal cells. Use of the intravenous preparation has only been studied for short-term use (ie, 7-10 days).