Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Octreotide after endoscopic variceal ligation reduced recurrent bleeding

ACP J Club. 1996 May-June;124:66. doi:10.7326/ACPJC-1996-124-3-066


Source Citation

Sung JJ, Chung SC, Yung MY, et al. Prospective randomised study of effect of octreotide on rebleeding from oesophageal varices after endoscopic ligation. Lancet. 1995 Dec 23/30;346: 1666-9.


Abstract

Objective

To determine the effectiveness of octreotide combined with endoscopic variceal ligation for treating patients with esophageal varices.

Design

Randomized controlled trial with 1-year follow-up.

Setting

Hospital in Hong Kong.

Patients

94 patients (mean age 57 y, 71% men) who were ≥ 16 years of age and had esophageal varices that were bleeding during endoscopy or had recently hemorrhaged. Exclusion criteria were previous endoscopic treatment of esophageal varices or shunting surgery, other reason for upper gastrointestinal bleeding, or history of hepatocellular carcinoma. Follow-up was 96%.

Intervention

Patients were allocated to variceal ligation alone (n = 47) or variceal ligation plus octreotide, 50 µg, given as an intravenous bolus during endoscopy and then as a continuous infusion at 50 µg/h for 5 days (n = 47). Varices were ligated with single elastic bands on the end of an end-viewing endoscope, applied at or near the gastroesophageal junction and 4 to 5 cm up the esophagus. Balloon tamponade was used if patients had hematemesis of ≥ 500 mL, hemodynamic instability, or a requirement for ≥ 6 units of blood to sustain blood pressure.

Main Outcome Measures

Rebleeding in hospital, use of balloon tamponade, success rate of initial hemostasis, requirement for blood transfusion, in-hospital mortality, 30-day mortality, and 1-year survival.

Main Results

Treatment with variceal ligation plus octreotide for 5 days led to fewer patients with recurrent bleeding than did variceal ligation alone (9% vs 38%, P < 0.001). {This absolute risk reduction (ARR) of 29% means that 3 patients would need to be treated (NNT) with variceal ligation plus octreotide for 5 days (rather than ligation alone) to prevent 1 additional patient from having recurrent bleeding, 95% CI 2 to 7; the relative risk reduction (RRR) was 78%, CI 43% to 92%.}* Variceal ligation plus octreotide also led to fewer patients who required balloon tamponade (2% vs 21%, P = 0.004) {ARR 19%, NNT 5, CI 3 to 14; RRR 90%, CI 43% to 98%}*. No difference was detected between patients who received variceal ligation plus octreotide and patients who received variceal ligation alone for success of initial hemostasis (96% vs 94%, P = 1.0); requirement for blood transfusion (mean blood transfusion 3 vs 4 units, P = 0.06); in-hospital deaths (9% vs 19%, P = 0.14); deaths at 30 days (11% vs 23%, P = 0.09); or cumulative survival at 1 year.

Conclusion

The addition of octreotide for 5 days after endoscopic variceal ligation reduced recurrent bleeding and the need for balloon tamponade in patients with esophageal varices.

Source of funding: Sandoz Pharmaceuticals, Basel, Switzerland.

For article reprint: Dr. J.J. Sung, Department of Medicine, Chinese University of Hong Kong, Shatin, Hong Kong. FAX 852-263-73852.

*Numbers calculated from data in article.


Commentary

Somatostatin and octreotide (a synthetic octapeptide analog of somatostatin) have been widely studied for the treatment of variceal bleeding. 2 placebo-controlled trials of somatostatin showed no benefit, and 1 showed a significant decrease in further bleeding and transfusions with somatostatin (1, 2). Trials that compared somatostatin or octreotide with vasopressin or tamponade showed that the newer agents are at least as effective as the "standard" therapies, with fewer side effects (2). Other trials suggest that octreotide or somatostatin control bleeding at a rate similar to endoscopic sclerotherapy during the first 48 hours of hospitalization (2).

Sung and colleagues found less recurrent bleeding, fewer massive rebleeding episodes that required tamponade, and a suggestion of lower transfusion requirements when octreotide was combined with endoscopic ligation (a therapy more effective than sclerotherapy). Although the attending physicians were unblinded, Sung and colleagues used objective criteria for rebleeding, and the massive episodes of rebleeding were markedly decreased in the combined therapy group (2% vs 21%). Furthermore, a recent double-blind trial of sclerotherapy with or without octreotide in 199 patients also showed less rebleeding and less blood transfused with combination therapy (3).

Although most trials of octreotide and somatostatin do not show a substantial increase in efficacy when compared with placebo or standard medical therapies, 2 large trials now indicate that octreotide given with endoscopic therapy decreases further bleeding. If medical therapy is desired, I suggest octreotide for the first 48 hours of hospitalization because of its safety and potential efficacy. Early endoscopy is still required to document that the patient is bleeding from varices and to provide endoscopic therapy to decrease further bleeding.

Loren Laine, MD
University of Southern California School of MedicineLos Angeles, California, USA


References

1. Gotzsche PC, Gjorup I, Bonnen H, et al. BMJ. 1995;310:1495-8.

2. Burroughs AK. Gut. 1994;Suppl 3:S23-7.

3. Besson I, Ingrand P, Person B, et al. N Engl J Med. 1995;333:555-60.