Alimentary tract and pancreas

           Alimentary trakt i pankreas

           ARCH GASTROENTEROHEPATOLOGY 2000; 19 ( No 3 - 4 ):



                               We read it for You


                               Journal:    The New England Journal of Medicine 2000; 343: 310-6.


                               Title:        Effect of intravenous omeprazole  on recurrent

                                        bleeding after endoscopic treatment of bleeding

                                        peptic ulcers


                                       Efekat intravenskog omeprazola na ponovljeno krvarenje

                                               posle endoskopske terapije krvarecih peptickih ulkusa


                              Authors:   Lau JYW, Sung JJY, Lee Kenneth KKC, et al.  


                             Institution: Departments of Surgery and Medicine, Chinese University

                                               Hong Kong, China.




                                              Background: After endoscopic treatment of bleeding peptic

                                              ulcers, bleeding recur in 15 to 20 percent of patients.

                                              Methods: We assessed whether the use of a high dose of proton-

                                              pump inhibitor would reduce the frequency of recurrent bleeding

                                              after endoscopic treatment of bleeding peptic ulcers. Patients with

                                             actively bleeding ulcers or ulcers with nonbleeding visible

                                             vessels were treated with an epinephrine injection followed by

                                             thermocoagulation. After hemostasis had been achieved, they were

                                             randomly assigned in a double-blind fashion to receive omeprazole

                                             ( given as a bolus intravenous injection of 80mg followed by an

                                              infusion of 8 mg per hour for 72 hours ) or placebo. After the

                                              infusion, all patients were given 20mg of omeprazole orally per

                                              day for eight weeks. The primary end point was recurrent bleeding

                                              within 30 days after endoscopy.

                                              Results: We enrolled 240 patients, 120 in each group. Bleeding

                                              recurred within 30 days in 8 patients ( 6.7% ) in the omeprazole

                                              group, as compared with 27 ( 22.5% ) in the placebo group

                                              ( hazard ratio, 3.9; 95% confidence interval, 1.7 to 9.0 ). Most

                                              episodes of recurrent bleeding occurred during the first three

                                              days, which made up the infusion period ( 5 in the omeprazole

                                              group and 24 in the placebo group, P< 0.001 ). Three patients

                                              in the omeprazole group and nine in the placebo group underwent

                                              surgery ( P=0.14 ). Five patients ( 4.2% ) in the omeprazole

                                            group and 12 ( 10% ) in the placebo group died within 30 days

                                            after endoscopy ( P=0.13 )

                                            Conclusions: After endoscopic treatment of bleeding peptic

                                            ulcers, a high-dose infusion of omeprazole substantially reduces

                                            the risk of recurrent bleeding.





The management of peptic ulcer disease has changed during the past three decades. Infection with Helicobacter pylori is now recognized as the cause of most ulcers, the endoscopy improved diagnosis, antisecretory drugs are available to suppress the production of gastric acid, and the majority of patients with peptic ulcer disease can be treated medically without having to undergo surgery.

Despite the remarkable advances, haemorrhage from gastric or duodenal ulcers remains a common reason for hospitalization with significant morbidity and mortality. Bleeding occurs when ulcers erode deeply into the wall of the stomach or duodenum, disrupting the integrity of nearby vessels. Most ulcers stop bleeding spontaneously as a result of intrinsic hemostatic mechanisms. In about 25% of cases, however, these mechanisms fail and bleeding continues, further contributing to the morbidity associated with haemorrhagic ulcers.


Current medical therapy for bleeding peptic ulcers includes volume restoration, hemodynamic stabilization, and correction of coagulopathy. Endoscopic examination is an important part of treatment in most cases. Patients with active bleeding or a nonbleeding visible vessel on endoscopy have a greatly increased risk of further bleeding. In approximately 20% of such patients, bleeding recurs within 72h after it is controlled by endoscopic therapy.


Acid is essential to the pathogenesis of peptic ulcer disease. Histamine H2- receptor antagonist suppress acid secretion and are remarkable effective at speeding ulcer healing. One might assume that this effect would improve the outcomes of treatment for bleeding ulcers. Unfortunately, numerous studies of effect of H2- receptor antagonist on bleeding have had disappointing results.  The introduction of proton pump inhibitors raised expectations that antisecretory drugs could make a difference in the rates of recurrent bleeding. However, even these more potent acid inhibitors have not been consistently shown to benefit patients with acute gastrointestinal bleeding.


In this article Lau et al. reported results of a large, double-blind trial conducted in Hong Kong in which omeprazole  was compared with placebo in patients who were receiving endoscopic therapy for bleeding ulcers. Patients with Forrest IA,IB and IIA bleeding ulcers were treated with high dose omperazole intravenously ( see  abstract for doses ! ) or placebo. Recurrent bleeding occurred in 6.7% of the patients in the ( i.v ) omeprazole group, as compared with 22.5% of the patients in the placebo group. The patients who received intravenous omepazole had significantly shorter hospital stay and required fewer bood transfusions. This study indicates that aggressive acid suppression with intravenous omeprazole reduces the rate of recurrent bleeding in patients with high-risk ulcers, after successful endoscopic therapy.


Why does omeprazole prevent recurrent bleeding when H2-receptor antagonist dos not? Its beneficial effect results from protecting the clot rather than healing the ulcer. Clot formation is highly sensitive to pH. It appears that a pH > 6.0 is required for platelet aggregation and fibrin formation, whereas a pH < 5.0 is associated with lysis of clots. The H2-receptor antagonist may initially raise intragastric pH rapidly, but this effect is short- lived, and the pH typically returns to levels between 3.0 and 5.0 within 24 hours thus allowing clot lysis and recurrent ulcer bleeding. When taken orally, omeprazole suppress acid production but it takes several days before the pH is consistently > 6.0. On the contrary an intravenous infusion of omeprazole maintains intragastric pH > 6.0 more effectively than intravenous administration of H2-receptor antagonists and much quicker when the same drug is orally given. In this article Lau et al demonstrated that intraveous omaprazole raise intragastric pH> 6.0 within 3 hours and maintains this level. They further showed that after endoscopic therapy of bleeding peptic ulcers ( thermocoagulation or injection of a hemostatic agent ) aggressive acid suppression with proton-pump inhibitors further reduce the rate of recurrent bleeding, the need for transfusions and  the need for surgery.


Although omeprazole is available for intravenous use in many countries, it is not available in Serbia and Yugoslavia.  The results of Chinese study from Hong Kong implies that the influence of medical experts and medical audience have to be stronger on market suppliers, drug promoters, and in particular on the members of Federal Drug Committee, shadowed assembly lacking vivid ties and responsibility toward Serbian medical corps.













































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