Stress ulcer refers to an ulcer or, more often, multiple ulcers that develop during the severe physiologic stress of serious illness.
1. The pathogenesis of stress ulcer is unclear but probably is related to a reduction in mucosal blood flow or a breakdown in other normal mucosal defense mechanisms in conjunction with the injurious effects of acid and pepsin on the gastroduodenal mucosa.
- The ulcerations may be superficial and confined to the mucosa, in which case they are more appropriately called erosions, or they may penetrate deeper into the submucosa. The former may cause diffuse mucosal oozing of blood, whereas the latter may erode into a submucosal vessel and produce frank hemorrhage.
- Location. Stress ulcerations may develop anywhere within the stomach and proximal duodenum but are more likely to occur in fundic mucosa, which lines the body and fundus of the stomach. This is in contradistinction to the location of ordinary peptic ulcers, which typically are found in the gastric antrum and the duodenum.
- The clinical setting is usually one of severe and often multisystem illness. For example, elderly patients in a surgical intensive care unit with heart and lung disease have a high postoperative prevalence of stress ulcers. Similarly, patients in a medical intensive care unit, particularly those who require respirators, are at high risk of development of stress ulcers. Although not proved, it is possible that poor mucosal oxygenation, differences in acid-base balance, and elevated circulating corticosteroids may contribute to the formation of these ulcers.
Upper gastrointestinal bleeding is the usual clinical manifestation of stress ulceration. In the appropriate clinical setting, the onset of bleeding makes the diagnosis likely. The diagnosis can be confirmed and the extent of involvement documented by upper gastrointestinal endoscopy, after the initial management of gastrointestinal bleeding has been started.
Treatment of stress ulceration usually begins with prevention. Careful attention to respiratory status, acid-base balance, and treatment of other illnesses helps prevent the conditions under which stress ulcers occur.
Patients who develop stress ulcers typically do not secrete large quantities of gastric acid; however, acid does appear to be involved in the pathogenesis of the lesions. Thus, it is reasonable either to neutralize acid or to inhibit its secretion in patients at high risk. In patients admitted to surgical intensive care units, hourly antacid titration to keep the intragastric pH above 4 has been shown to reduce markedly the frequency of acute bleeding. With regard to the use of histamine-2 (H2) antagonists, famotidine 20 mg intravenous (intravenous) q12h or ranitidine 50 mg intravenous q8h appears to control pH and prevent gastric stress ulcers better than cimetidine 300 mg intravenous q6h in intensive care unit patients after coronary artery bypass graft surgery. Some studies indicate that continuous intravenous infusion of H2 antagonists control intragastric pH better than does bolus delivery.
Proton-pump inhibitors have not been available in a parenteral formulation in the United States. However, pantoprazole sodium (Protonix) has recently been released by the Food and Drug Administration in an intravenous formulation. Because gastric-acid suppression with proton-pump inhibitors is much more profound allowing the gastric pH to rise to 5 or 6, Protonix intravenous is expected to be more effective in the prevention of stress ulcers and stress ulcer bleeding.
Although maintenance of intragastric pH above 4 may prevent clinically significant stress ulceration, it also may predispose to bacterial colonization of the stomach and pharynx and subsequent development of pneumonia with the same organisms. Treatment with sucralfate is reported to be as effective as treatment with antacids or H2 antagonists in preventing bleeding and in some studies, appears to have a lower risk of development of pneumonia.
Not all patients in an intensive care unit require acid suppressive prophylaxis. Patients who should be considered for a prophylactic regimen include those who are on respirators and have multisystem disorders and those with a history of peptic ulcer or upper gastrointestinal bleeding. Once bleeding has occurred, however, intravenous acid suppressive therapy with a proton-pump inhibitor to control intragastric pH above 5 remains the most appropriate therapy.