Peptic ulcer bleeding. Towards improved outcome

Abstract

Bleeding from a peptic ulcer is a common and life threatening event. To reduce the risk for further bleeding, normal coagulation and a stable clot formation are pivotal factors. In vitro studies have shown that neither coagulation nor platelet aggregation can take place if pH is below 5.4. Efforts have therefore been made to improve intragastric hemostasis by administrating antacids or histamine-2-receptor antagonists to raise intragastric pH to or above this level. The effect of these treatments has, however, been limited. In vivo studies have shown that if omeprazole is given as a primed continuous infusion a stable intragastric pH above 5.4 can be reached. The aims of the present study were: 1) To determine the dose regimens for intravenous omeprazole infusion and subsequent per oral administration to stabilize intragastric pH at a levels alleged to allow hemostasis and facilitate further ulcer healing. 2) To study if this omeprazole dose regimen improved the outcome for high risk patients with peptic ulcer bleeding (PUB). 3) To identify risk factors for fatal outcome in both short and long term perspective in patients with PUB.Healthy volunteers and duodenal ulcer patients in remission were included in the dose-finding study. An omeprazole infusion, 80 mg + 8 mg/h for 72 hours, followed by omeprazole 20 mg orally once daily fulfilled the requirements set up based upon intragastric pH measurements. This dose regimen was evaluated in two separate clinical studies enrolling patients with acute PUB. One study included patients 60 years or over (n = 322), while the other study included patients in hemorrhagic shock (n = 265). Both studies showed consistently better outcomes in the groups treated with omeprazole when either assessed by a defined overall outcome score, blood transfusions requirements or need for surgical/endoscopic interventions. The cumulative mortality was approximately 1% after the first three days of admission but rose almost linearly during the subsequent three weeks reaching about 6% at day 21. Most deaths were caused by cardiovascular events.In a multiple logistic regression analysis performed on a subset of the data, age, coronary heart disease, blood pressure on admission and absence of previous ulcer were significantly associated with mortality.Patients above 60 years admitted to hospital due to a PUB in Göteborg during 1989 to 1993 (n=687) were found to have a 5.5% cumulative mortality at 30 days. Age and Forrest class significantly influenced mortality during this period. During the subsequent 5 year follow-up mortality was significantly higher in women compared to matched controls while no significant difference was found in men.Finally, 1020 patients with a PUB were selected from the General Practitioners Research Database in the UK. Day 30 mortality was 4.4% and again high age and absence of previous ulcer had a significant impact upon mortality.In conclusion, an omeprazole infusion 80 mg + 8 mg/h for 72 hours significantly improved clinical outcome in high risk patients with PUB. Mortality occurred almost linearly over the first month of admission and most patients died due to cardiovascular events. High age and absence of previous ulcer significantly increased the mortality risk.