Oral vs Intravenous and Proton Pump Inhibitor (PPI）for Peptic Ulcer Bleeding (PUB)

Overview

A bleeding peptic ulcer remains a serious medical problem with significant morbidity and mortality. Endoscopic therapy significantly reduces further bleeding, surgery, and mortality in patients with bleeding peptic ulcers and is now recommended as the first hemostatic modality for these patients. In the past few years, adjuvant use of a high-dose proton pump inhibitor (PPI) after endoscopic therapy has been endorsed in some studies. Laine and Javid et al found that oral PPI and IV PPI had a similar intragastric pH response in the past two years. Therefore, whether oral can replace IV in the management of peptic ulcer bleeding is the objective in this study. The investigators enrolled 130 patients with active bleeding or nonbleeding visible vessels（NBVV） in this study. They are randomly assigned as oral lansoprazole or IV nexium group. All patients receive successful endoscopic therapy with heater probe or hemoclip placement. In the lansoprazole group (N=65), 30 mg four times daily is given orally for three days. Thereafter, the patients receive 30 mg lansoprazole orally daily for two months. In the nexium group, 160 mg/day continuous infusion is given for three days. Thereafter, the patients receive 40 mg nexium orally daily for two months. The primary end point is recurrent bleeding before discharge and within 14 days. At day 14, volume of blood transfused, number of surgeries performed, and the mortality rates of the two groups are compared as well.

A bleeding peptic ulcer remains a serious medical problem with significant morbidity and mortality. Endoscopic therapy significantly reduces further bleeding, surgery, and mortality in patients with bleeding peptic ulcers (1) and is now recommended as the first hemostatic modality for these patients (1, 2). In the past few years, adjuvant use of a high-dose proton pump inhibitor (PPI) after endoscopic therapy has been endorsed in some studies, two consensus statements and two meta-analysis (3-8). To sustain a high intragastric pH, a high dose of omeprazole has been used in previous studies concerning high-risk peptic ulcer bleeding. In our study, the investigators used 40 mg omeprazole intravenous bolus followed by 160 mg/day continuously infusion for three days. The mean intragastric pH rose to 6.0 one hour after the initial bolus of omeprazole in the omeprazole group; it persisted around this value for the rest of the 24 hours.7 The rebleeding rates were much lower in the PPI as compared with H2RA group (Day 3: 0/50 vs 8/50, p\<0.01; Day 14: 2/50 vs 12/50, p\<0.01) (4). How about the route of PPI usage? Oral or IV is the preferred route? Laine et al used oral lansoprazole in patients with peptic ulcer bleeding.9 They were randomly assigned to intravenous lansoprazole (90-mg bolus followed by 9-mg/h infusion) or oral lansoprazole (120-mg bolus followed by 30 mg every 3 hours). A pH was recorded for 24 hours. Mean pH rose above 6 after 2-3 hours of intravenous PPI and 3-4 hours of oral PPI. They concluded that frequent oral PPI may be able to replace the currently recommended intravenous bolus plus infusion PPI therapy in patients with bleeding ulcers. In one recent article, Javid et al also proved that there was no significant difference among various PPIs (omeprazole, pantoprazole, and rabeprazole) given through different routes (IV and oral routes) on raising intragastric pH above 6 for 72 h after successful endoscopic hemostasis in bleeding peptic ulcer.10 In our recent study, the investigators have proved that oral rabeprazole and IV omeprazole are equally effective in preventing rebleeding (13/78 in rabeprazole vs 12/78 in omeprazole, p\>0.1) in high-risk bleeding peptic ulcers.11 All secondary outcomes between the two groups were similar, including the amount of blood transfusion, hospital stay, need for surgery and mortality. The objectives of this study are to assess the outcomes of two different regimens of oral lansoprazole vs high dose of intravenous nexium after endoscopic therapy in patients with peptic ulcer bleeding.