Stress-related mucosal damage: review of drug therapy. The increased awareness of stress-related mucosal damage (SRMD) that accompanied the widespread use of fiberoptic endoscopy and the increased incidence of SRMD that accompanied the advances in caring for critically ill patients resulted in the recognition that the majority of patients in the intensive care unit (ICU) setting wil develop mucosal damage. Complications of gastrointestinal hemorrhage in these patients may contribute significantly to their morbidity and mortality, and the consequences of this bleeding may be more severe than the underlying predisposing conditions. Because of the importance of gastric acid in the pathogenesis of SRMD, therapy has focused on reduction of the intraluminal acid concentration. Acid neutralization, while effective, is laborious and associated with side effects. H2-receptor antagonists have been used successfully in the prophylaxis and treatment of SRMD and offer the potential for an effective parenteral as well as oral agent. They obviate the need for frequent antacid administration and eliminate some of the troubles and side effects that accompany an intensive antacid regimen. Of the available H2-receptor antagonists, cimetidine has been the most thoroughly evaluated. It is equivalent to antacids in the prevention of overt bleeding and offers the advantage of dosing flexibility, ease of administration, and a remarkable safety profile. Cimetidine has also been shown to be effective when administered by intermittent bolus infusions given every 8, 6, or 4 h or by primed continuous infusion, which has proven to be the most successful method of controlling intragastric pH. 