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Intravenous PPI Therapy Before Endoscopy for UGI Bleeding

Early omeprazole therapy lowered the prevalence of high-risk stigmata, but it did not affect other clinical outcomes.

High-dose proton-pump inhibitor (PPI) therapy lowers risk for rebleeding in patients who have bleeding peptic ulcers with high-risk stigmata (active bleeding or nonbleeding visible vessels; Cochrane Database Syst Rev 2006; 1:CD002094). In patients with low-risk stigmata (i.e., clean ulcer base, flat pigmented lesions), PPI therapy has no effect. In most of the world, high-dose PPI therapy after endoscopic therapy for high-risk ulcer lesions is the standard of care; however, the value of PPI therapy before endoscopy is less clear, because most patients will not exhibit high-risk lesions at the time of endoscopy. A recent meta-analysis suggested that pre-endoscopy PPI therapy could lower the prevalence of high-risk stigmata at index endoscopy but that it did not change meaningful clinical outcomes, such as rebleeding rates, mortality rates, or need for surgery (Cochrane Database Syst Rev 2006; 4:CD005415).

Investigators in Hong Kong randomized 638 patients with acute upper gastrointestinal bleeding (UGIB) to receive either intravenous omeprazole (80-mg bolus, followed by 8 mg/hour) or placebo from the time of stabilization until endoscopy. Patients taking low-dose aspirin were excluded from the study. Endoscopy was performed an average of 15 hours after initiation of therapy. Patients whose high-risk stigmata were identified by index endoscopy received endoscopic therapy (using dilute epinephrine injection and heater-probe coagulation) and continued IV omeprazole therapy (8 mg/hour) for 72 hours. When present, Helicobacter pylori infections were treated. All endoscopic-therapy patients received daily oral omeprazole (40 mg) for 8 weeks after discharge.

The requisite endoscopic therapy rate was lower in the omeprazole group than in the placebo group (19.1% vs. 28.4%; P=0.007). However, other clinical endpoints (rebleeding, transfusions, surgery, 30-day mortality rate, and length of hospital stay) were similar in the groups. The authors concluded that high-dose omeprazole, prior to endoscopy, accelerated resolution of bleeding and lowered the need for endoscopic therapy.

Comment: These data are similar to the results of the meta-analysis cited above, which showed that early omeprazole therapy lowered the prevalence of high-risk stigmata and, thus, lowered the need for endoscopic therapy but did not affect other clinical outcomes. In this study, the difference in the percentages of patients who required endoscopic therapy was due to fewer actively bleeding lesions and more clean-based ulcers in the omeprazole group. Although peptic ulcers were the most common cause of bleeding in this study (approximately 60% in each group), many patients had other causes of bleeding, including varices, cancer, erosive disease, and other mucosal lesions. No cause of bleeding could be identified in approximately 10% of patients in each group. Whether omeprazole affects rebleeding from nonulcer lesions is unclear, although the mechanism of clot stabilization (raising gastric pH) suggests that it could be beneficial. The exclusion of patients who took low-dose aspirin prevents us from assessing whether aspirin therapy lowers the efficacy of omeprazole in this situation. The beneficial effect of omeprazole on ulcer rebleeding is more prominent in Asia than in Western Europe or North America, and these results might not be generalizable to other areas.

Perhaps the most important factor not evaluated in this study was the time between initial omeprazole therapy and endoscopy. Other researchers have shown that urgent endoscopy (performed within a few hours) leads to identification of more high-risk lesions than does endoscopy that is delayed until the next day (Gastrointest Endosc 2004; 60:1). In the current study, urgent endoscopy was performed in only 13 patients who displayed persistent evidence of bleeding; all others waited until the following day. Omeprazole’s effect on endoscopic stigmata might increase with duration of therapy prior to endoscopy. Unfortunately, this delay eliminates the benefit of earlier endoscopy in selecting patients for more cost-effective outpatient therapy. PPI therapy is not a substitute for endoscopic therapy in patients with high-risk stigmata (Ann Intern Med 2003; 139:237), but these data suggest that IV omeprazole therapy in patients with UGIB who are awaiting endoscopy decreases the number of patients who will undergo endoscopic therapy. Further studies are needed to determine the duration of therapy required to achieve this effect, whether this effect occurs in non-Asian populations, and if PPI therapy is cost-effective compared with urgent endoscopy when other clinically significant outcomes are not affected.

— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)

Published in Journal Watch Gastroenterology April 18, 2007

Citation(s):

Lau JY et al. Omeprazole before endoscopy in patients with gastrointestinal bleeding. N Engl J Med 2007 Apr 19; 356:1631-40.

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