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Therapeutics

Somatostatin did not increase survival or decrease blood transfusions in bleeding esophageal varices

ACP J Club. 1996 Jan-Feb;124:12. doi:10.7326/ACPJC-1996-124-1-012


Source Citation

Gøtzsche PC, Gjørup I, Bonnén H, et al. Somatostatin v placebo in bleeding oesophageal varices: randomised trial and meta-analysis. BMJ. 1995 Jun 10;310:1495-8.


Abstract

Objective

To compare, using meta-analysis, the effectiveness of somatostatin or its derivative octreotide with that of placebo in patients with cirrhosis and bleeding esophageal varices.

Data Sources

Studies were identified by searching MEDLINE from 1966 to January 1995 using the term explode somatostatin/all subheadings or the text words somatostatin or octreotide combined with any of the following: variceal, varices, bleed:, hemorrhage, haemorrhage, oesophag:, esophag:, haematemesis, hematemesis, melaena, or melena. To identify additional studies, the company that markets octreotide was contacted; reference lists of relevant articles, reviews, and editorials were scanned; and experts were contacted. Original data from a randomized controlled trial done by the authors were reported and added to the meta-analysis.

Study Selection

All randomized trials that compared somatostatin or octreotide with placebo or no treatment in patients suspected of bleeding from esophageal varices were eligible for inclusion.

Data Extraction

Data on the number of patients randomly assigned, deaths, randomization and blinding procedures, number of dropouts, and exclusions after randomization were extracted. Additional information was sought by writing to the authors. Survival, number of blood transfusions, and number of patients needing balloon tamponade were weighted by the inverse variance; median values were used for blood transfusions.

Main Results

3 studies of somatostatin involving 290 patients met the selection criteria. Somatostatin had no effect on survival; 40 patients (26.5%) in the somatostatin group died compared with 33 (23.7%) in the placebo group {95% CI for the 2.8% absolute difference -7.3% to 12.7%, P = 0.59}*. For blood transfusions and use of balloon tamponade, heterogeneity existed among the trials (P ≤ 0.05). When heterogeneity was ignored, patients in the somatostatin group received a mean of 1.6 (CI -0.1 to 3.2, P = 0.06) fewer transfusions than patients in the placebo group.

Conclusion

Compared with placebo, somatostatin did not increase survival or decrease the number of blood transfusions in patients with bleeding esophageal varices.

Source of funding: None.

For article reprint: Dr. P.C. Gøtzsche, Director of the Nordic Cochrane Centre, Research and Development Secretariat, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. FAX 45-35-45-6528.

*Numbers calculated from data in article.


Commentary

Nonsurgical methods for the management of variceal hemorrhage include balloon tamponade, vasoactive drugs (vasopressin or glypressin, nitroglycerin, somatostatin or octreotide), endoscopic sclerotherapy, or variceal ligation and transjugular portosystemic shunts. The use of these treatments varies depending on their availability, safety, and efficacy and the urgency and severity of hemorrhage. Unfortunately, all controlled studies evaluating the effectiveness of these treatments for variceal hemorrhage have small sample sizes. To date, no treatment has significantly reduced the high mortality (10% to 40%) associated with variceal hemorrhage.

The absence of benefit of somatostatin over placebo in the emergency treatment of variceal bleeding should be viewed in the context of other trials. Some of these trials show that both somatostatin (250 µg/h) and its long-acting synthetic analog octreotide (25 to 50 µg/h) are as effective, without major side effects, as vasopressin or glypressin with or without nitroglycerin (1) or endoscopic sclerotherapy (2). Somatostatin might also be useful if given early to allow improved technical performance of endoscopic hemostasis. Further large-scale trials of combination therapy (e.g., vasoactive drugs plus endoscopic hemostasis), however, will be needed to provide more definitive answers. Thus, the book is not closed on somatostatin for variceal hemorrhage despite its apparent lack of benefit against placebo.

George Triadafilopoulos, MD
Stanford UniversityPalo Alto, California, USA


References

1. Silvain C, Carpentier S, Sautereau D, et al. Terlipressin plus transdermal nitroglycerin vs. octreotide in the control of acute bleeding from esophageal varices: a multi-center randomized trial. Hepatology. 1993;18:61-5.

2. Sung JJ, Chung SC, Lai CW, et al. Octreotide infusion or emergency sclerotherapy for variceal haemorrhage. Lancet. 1993;342:637-41.