Stress-related Mucosal Disease Research Articles

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

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.

Switching Between Intravenous and Oral Pantoprazole

Proton pump inhibitors (PPIs) are the most effective antisecretory drugs available for controlling gastric acid acidity and volume. They are the drugs of choice in the treatment of moderate-to-severe gastroesophageal reflux disease, hypersecretory disorders, and peptic ulcers. Currently in the United States, they are only available in an oral formulation. However, pantoprazole will soon be available in an intravenous formulation and will extend the power of PPIs to inpatient hospital settings. Intravenous pantoprazole has been shown to be effective and safe in clinical trials. Intravenous pantoprazole is indicated for the treatment of patients who require PPI therapy but who are unable to take oral medication. Intravenous pantoprazole has been shown to maintain acid suppression in patients switched from oral PPIs, so no change in dosage is required when switching from one formulation to the other. Potential hospital-based uses for intravenous PPI therapy include perioperative use as prophylaxis for acid aspiration syndrome during induction of anesthesia, prophylaxis for stress-related mucosal disease, and management of gastrointestinal bleeding from stress or acid peptic disease.

Stress-Related Mucosal Disease: Pathophysiology, Prevention, and Treatment

The advent of gastrointestinal endoscopy has allowed us to follow the morphologic results of severe stress on the gastrointestinal mucosa. It has become clear, however, that the presence of mucosal abnormalities does not always correlate with the presence of overt bleeding, or with the effect of bleeding on the overall outcome of such patients. In fact, the incidence of severe gastrointestinal hemorrhage, secondary to stress-related mucosal disease, has been decreasing over the past decade, as the care of these critically ill patients has improved. In patients who do have overt hemorrhage, however, the mortality rate is extremely high. It therefore remains the duty of the clinician to identify patients who are at high risk of having overt hemorrhage, and ensure that they receive adequate prophylactic therapy.