Pathophysiology of the upper gastrointestinal tract in the critically ill patient: rationale for the therapeutic benefits of acid suppression

Abstract

Gastric mucosal damage occurs in critically ill patients in intensive care units and develops in the setting of severe physiologic stress. Within 24 hrs of admission to the intensive care unit, 75% to 100% of critically ill patients demonstrate evidence of stress-related mucosal disease. Stress ulcers present a risk of clinically important bleeding, which is associated with alterations in physiology, such as hypotension or tachycardia, or results in anemia or the need for transfusion. Clinically important bleeding occurs in approximately 1% to 4% of critically ill patients. The pathophysiology of stress-related mucosal disease is complex. Major factors responsible for stress ulcer are decreased blood flow, mucosal ischemia, and hypoperfusion and reperfusion injury. Acid-suppressive regimens that elevate the intragastric pH and maintain the pH over time have the potential to prevent stress-related mucosal disease. Intragastric pH studies have demonstrated that, whereas a pH of >4 may be adequate to prevent stress ulceration, a pH of >6 may be necessary to maintain clotting in patients at risk of rebleeding from peptic ulcer. Studies comparing the ability of intravenous administrations of histamine-2-receptor antagonists and proton pump inhibitors to raise and maintain intragastric pH suggest that, although both can raise the pH to >4, proton pump inhibitors are much more likely to maintain this pH. Unlike histamine-2-receptor antagonists, proton pump inhibitors can elevate and maintain the intragastric pH at >6. This is relevant for patients in the intensive care unit at risk for rebleeding from peptic ulcers after hemostasis.