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Gøtzsche PC, Hróbjartsson A. Somatostatin analogues for acute bleeding oesophageal varices. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD000193.

Study Population: 2588 subjects with bleeding from esophageal varices

Efficacy Endpoints

All-cause mortality, rebleeding, transfused blood

Harm Endpoints

Not assessed

Narrative

Acute esophageal variceal bleeding is an important cause of morbidity and mortality in patients with cirrhosis. Pharmacological agents used to treat such hemorrhages include somatostatin, a vasoactive agent that reduces splanchnic blood flow and thus portal pressure.1

The systematic review discussed here2 included 21 randomized trials with 2588 subjects in aggregate and compared somatostatin analogues to placebo or no treatment for variceal bleeding. The review found adding somatostatin to routine care did not reduce all-cause mortality or the risk of rebleeding, but reduced the average units of blood transfused by 0.7 units (95% Confidence Interval [CI] 0.2-1.1) in trials with a low risk of bias and 1.5 units (95% Cl 0.9-2.0) in poor quality trials at moderate/high risk of bias.2

One additional systematic review and network meta-analysis, published in 2016, compared somatostatin to placebo, proton pump inhibitors, and histamine H2 receptor antagonists in patients with upper gastrointestinal hemorrhage (not limited to variceal bleeding). The authors included 47 randomized trials (n=9528), reporting no significant all-cause mortality benefit or the risk of rebleeding,3 similar to the Cochrane review. Somatostatin was not superior to other pharmacologic agents.

Caveats

Because variceal bleeding is uncommon, enrolling many patients in a consecutive manner is difficult. As expected, there was significant clinical and statistical heterogeneity within and between trials in the meta-analysis. Endoscopic confirmation of variceal bleeding was performed in less than half of trials. There were also marked differences in dosing and duration of somatostatin administration: boluses varied from 0 to 250 micrograms; infusions were up to 50 microgram/hour but sometimes not done; and duration was anywhere from 1 to 5 days. Finally, no harms were tracked or reported in most trials, and therefore were not included in this review. Somatostatin analogues are generally well tolerated but can have side effects such as transient gastrointestinal symptoms (diarrhea, abdominal discomfort, nausea and flatulence) attributed to inhibition of pancreatic exocrine secretions.4 Additionally, somatostatin analogues inhibit gallbladder contractions and may increase the risk of gallbladder sludge and gallstones.5 Exposing already ill patients to these side effects should be weighed in any clinical or summary recommendations.

Among somatostatin analogues, only octreotide is available in the United States and it has been recommended as an initial IV bolus of 50 μg followed by a continuous infusion of 50 μg/hour for 3-5 days.6 Currently, one vial of Octreotide (5 ml, 200 mcg/ml) costs approximately $30.7

Lastly, while the modest reduction in blood transfusion requirements is an important finding, especially in terms of costs, resource utilization, and risk of transfusion-related adverse events, this endpoint is not a patient-centered outcome. In case of somatostatin, a reduction in blood transfusion requirements did not translate into a survival benefit, which is the most important patient-centered outcome in clinically significant gastrointestinal bleeding.

In summary, in this update of a prior NNT summary6 we find no change in the nature or findings of existing trial data. Adding somatostatin or its analogues to routine care does not reduce mortality or rebleeding, and likely reduces blood transfusion by less than one unit. Therefore, we have assigned a color recommendation of red (no benefit) to this treatment for variceal bleeding.

The original manuscript was published in Academic Emergency Medicine as part of the partnership between TheNNT.com and AEM.

See theNNT.com's previous reviews of this topic:
Somatostatin Analogues (Octreotide) for Acute Variceal Bleeding, October 6, 2010

Author

Jia Jian Li; Priscilla Chao, MD; Joel Gernsheimer, MD; Rajesh Verma, MD
Supervising Editor: Kabir Yadav, MD

Published/Updated

December 16, 2019