COMMON CAUSES OF GI HEMORRHAGE AND TREATMENT

Upper GI Hemorrhage

Peptic Ulcer Disease

Peptic ulcer disease is the most common cause of acute UGI hemorrhage, accounting for nearly 40% of

cases in most series although this proportion may be decreasing.89 About 15% to 20% of patients with

peptic ulcer disease experience bleeding during the course of their disease and as many as 20% of these

patients will have bleeding as the initial manifestation. Hemorrhage is the principal cause of death from

peptic ulcer disease and has replaced intractable pain as the most frequent indication for surgery.

Complications of peptic ulcer disease occur more commonly in older patients who often have coexisting

medical problems, which profoundly influence their risk of morbidity and mortality.

Duodenal ulcers occur slightly more frequently than gastric ulcers. Penetration of the ulcer through

the posterior wall of the duodenal bulb is associated with erosion into the gastroduodenal artery or one

of its branches, resulting in brisk hemorrhage. Patients may present with hematemesis of bright red

blood and clots or with melena alone. Between 80% and 90% of patients stop bleeding spontaneously

during the initial stages of therapy with volume resuscitation.

In general, patients with gastric ulcers tend to be older and have coexisting medical problems that

increase morbidity and mortality compared with duodenal ulcers. Bleeding may occur from any site in

the stomach, although ulcers occurring at the incisura are most common. At this site, involvement of the

branches of the left gastric artery may result in brisk, if not torrential, hemorrhage. The clinical

presentation of patients bleeding from gastric ulcers is similar to that of duodenal ulcers, with

hematemesis, melena, and hematochezia.

6 An important risk factor for the development of GI hemorrhage and gastroduodenal ulcer formation

is the use of NSAIDs. NSAID use has been associated with a continuum of mucosal injury ranging from

small acute mucosal hemorrhages to large chronic ulcers. It has been estimated that 10% to 15% of

regular NSAID users have chronic gastric ulcers.90 Symptoms correlate poorly with the degree of

mucosal injury since as many as 20% of ulcers penetrating the muscularis are asymptomatic.91 Case

control and cohort studies have suggested that NSAIDs are associated with a relative risk of GI

hemorrhage and ulceration ranging from about 2 to 9.1.92 Ketorolac, in particular, has been associated

with a high risk of GI bleeding (relative risk approaches 25).93 The risk of NSAID-associated

complications is highest in patients with a history of UGI bleeding, the elderly, those patients taking

oral anticoagulants,94 or corticosteroids. Patients with a prior history of peptic ulcer disease also appear

to be at increased risk of NSAID-associated GI hemorrhage and tend to have a significantly worse

outcome when compared to individuals not using NSAIDs.95

The tremendous frequency with which NSAIDs are used by the elderly underscores the magnitude of

this problem. Individuals with a history of NSAID-induced hemorrhage may benefit from the

prostaglandin E1 analog, misoprostol, which has been shown to prevent NSAID-induced gastric erosions

and ulcers.96 Histamine (H2

)-receptor blockers (ranitidine and cimetidine) are effective in preventing

NSAID-induced duodenal ulcers, but appear to have little effect on the occurrence of gastric lesions.91,97

Proton pump inhibitors (PPIs) have also been shown to be protective in patients on NSAIDs, with

greater efficacy than H2 blockers.98 NSAIDs are also associated with lower GI bleeding, including lesions

not generally considered related to NSAID-induced ulcers such as diverticulosis.99,100 Selective COX-2

inhibitors have been marketed as being safer than nonselective NSAIDs, although some of these have

been withdrawn from the U.S. market for other safety concerns. It appears that these selective

inhibitors cause fewer UGI problems overall than traditional NSAIDs, the main benefit being fewer

uncomplicated ulcers. Various studies have shown no decrease in complicated events, including

clinically significant bleeding episodes.101,102 However, in a Cochrane systematic review of the GI safety

of COX-2 inhibitors, COX-2 inhibitors produced significantly fewer gastroduodenal ulcers (relative risk,

0.26; 95% CI = 0.23–0.30) and ulcer complications (relative risk, 0.39; 95% CI = 0.31–0.50), as well

as fewer withdrawals caused by GI symptoms when compared to nonselective NSAIDs.103

Medical Treatment

7 Once bleeding from the UGI tract is confirmed, treatment with a PPI should be initiated. Acute use of

a PPI has been shown in several studies to decrease rebleeding.43,104–107 Although the Scottish

Intercollegiate Guidelines Network (SIGN) recommended withholding PPI therapy until after

endoscopy,108,109 in our opinion the balance of evidence would suggest no harm and perhaps a benefit

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