Are there studies about whether infusion of omeprazole has a better effect than injection (1-2 per

Fråga: Are there studies about whether infusion of omeprazole has a better effect than injection (1-2 per day) in the treatment of acute upper GI-bleeding?

Sammanfattning: Theoretically it is expected that sufficient amount of omeprazole can inhibit proton pumps in parietal cells. Continuous infusion rather than injection will supply this concentration in parietal cells. On the other hand there is only one clinical study found in the literature showing superiority of omeprazole infusion treatment.

Since there are conflicting results about use of proton pump inhibitors and H2 receptor antagonists, this data should be confirmed by further studies.

Svar: Acute GI-bleeding usually occurs because of acid-related lesions. The aim of the acute treatment is to raise the intragastric pH above 4.0 (1).

Although intravenous H2 receptor antagonists and proton pump inhibitor drugs are commonly used in patients with acute GI-bleeding, clinical trials have shown conflicting results with no clear evidence of a treatment benefit between these two classes of drugs (1, 2). In a study including 1147 patients with acute upper GI-bleeding no significant differences were found between the placebo and omeprazole groups for rates of transfusion, rebleeding, surgery and death (3). On the other hand, in a recent study including 220 patients with bleeding peptic ulcers, treatment with omeprazole decreased the rate of further bleeding and the need for surgery (4).

Omeprazole injection was recently compared with omeprazole infusion in the treatment of acute GI-bleeding (1). Effects of repeated injections and continuous infusion of omeprazole and ranitidine were investigated on intragastric pH over 72 hours (1). This is the only study found in the literature, comparing infusion and injection of omeprazole. The major findings of the study were that omeprazole infusion was superior to all other regimens over the entire 72 hours. Only omeprazole infusion was able to keep median pH > 6 on each day. Intraindividual variation of the antisecretory effect of omeprazole infusion was very low in contrast to that of the other regimens (1).

The superiority of continuous omeprazole infusion over omeprazole injection therapy was more clear on the first day of the treatment. Thereafter, the median pH and percentage of time with pH > 6 did not change statistically (1).

Omeprazole is a prodrug and needs the acidity in the secretory canaliculi of parietal cells with activated proton pumps. Parietal cells reserve proton pumps which will be activated by gastrin levels in the hours after the injection. It is necessary to have enough omeprazole level during the following hours of the treatment. The steady state is reached after the third injection (5). After reaching this level remaining proton pumps will be inactivated. Consequently, more frequent injections rather than higher may help to reach this steady state earlier. That may be the theoretical explanation of superiority of omeprazole infusion during the first day of treatment. 1 Netzer P, Gaia C, Sandoz M, Huluk T, Gut A, Halter F, Husler J, Inauen W: Effect of repeated injection and continuous infusion of omeprazole and ranitidine on intragastric pH over 72 hours. Am J Gastroenterol 1999; 94: 351-7 2 Kiilerich S, Rannem T, Elsborg L: Effect of intravenous infusion of omeprazole and ranitidine on twenty-four-hour intragastric pH in patients with a history of duodenal ulcer. Digestion 1995; 56: 25-30 3 Daneshmend TK, Hawkey CJ, Langman MJ, Logan RF, Long RG, Walt RP: Omeprazole versus placebo for acute upper gastrointestinal bleeding: randomised double blind controlled trial. Br Med J 1992; 304: 143-7 4 Khuroo MS, Yattoo GN, Javid G, Khan BA, Shah AA, Gulzar GM, Sodi JS: A comparison of omeprazole and placebo for bleeding peptic ulcer. N Engl J Med 1997; 336: 1054-8 5 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1998. p. O16