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


Therapeutics

Early somatostatin helped control acute variceal hemorrhage in cirrhosis

ACP J Club. 1991 Mar-Apr;114:52. doi:10.7326/ACPJC-1991-114-2-052


Source Citation

Burroughs AK, McCormick PA, Hughes MD, et al. Randomized, double-blind, placebo-controlled trial of somatostatin for variceal bleeding. Emergency control and prevention of early variceal rebleeding. Gastroenterology. 1990;99:1388-95.


Abstract

Objective

To evaluate the efficacy of early administration of somatostatin in controlling bleeding varices in patients with hematemesis or melena.

Design

Randomized, double-blind, placebo-controlled trial of 5 days' duration.

Setting

The liver unit in a tertiary care hospital in London, England.

Patients

All patients admitted to the unit with hematemesis or melena were included if they were > 16 years of age; systolic blood pressure was ≥ 100/min; and cirrhosis was known or likely. Referred patients were not included if they had had vasoactive drugs, balloon tamponade, or sclerotherapy, or if there had been failure to control bleeding with blood and plasma transfusions. 120 admissions (92 patients) of 242 were included in the study. Patients were stratified by severity of liver disease.

Interventions

Diagnostic endoscopy was done after initial resuscitation. Immediately after admission and randomization, patients were administered either placebo (n = 59) or somatostatin, 250 µg, (n = 61) as a single bolus; continuous infusion of 250 µg/h of somatostatin or placebo diluted in 50 mL of 5% dextrose was given every 12 hours for 5 days. Blood and plasma were transfused to attain a hemoglobin concentration of 10 g/dL.

Main outcome measures

Failure of the treatment was defined as death; necessity for invasive therapy, such as surgery; necessity for transfusion of ≥ 6 units of blood in 6 hours; hematemesis or melena with a change in vital signs; and a 2 g/dL decrease in hemoglobin with melena.

Main results

Patients in the treatment groups were similar in age, sex, and clinical condition. Of 61 patients receiving somatostatin, 22 (36%) failed on treatment, compared with 35 of 59 (59%) receiving placebo (P < 0.01). {This absolute risk reduction of 23% means that 4 patients would need to be treated with somatostatin (compared with placebo) to prevent 1 additional failure, 95% CI 3 to 18; the relative risk reduction was 39%, CI 11% to 60%.}* The median number of units of blood or plasma transfused was 3 compared with 6 for patients receiving somatostatin and placebo, respectively, P = 0.005. 1 patient died 16 hours after starting somatostatin infusion. 9 patients receiving somatostatin (15%) and 7 patients receiving placebo (12%) died within 30 days of admission. {Absolute risk difference 3%, CI -10% to 16%, P = 0.6.}* After adjustment for severity of liver disease, somatostatin was associated with a 41% reduction in the hazard of failure (95% CI -1% to 65%, P = 0.055).

Conclusion

Control of acute variceal bleeding in patients with cirrhosis was less likely to fail if patients were assigned to early infusion of somatostatin than if they received placebo.

Sources of funding: Not stated.

Address for article reprint: Dr. A.K. Burroughs, Academic Department of Medicine, Royal Free Hospital, Pond Street, London NW3 2QG, England, UK.


Commentary

Vasoconstrictor therapy in the management of variceal bleeding is controversial. Trials evaluating vasopressin remain inconclusive, with small trial sizes and different outcome criteria giving conflicting results.

Somatostatin is a peptide that reduces gastric acid secretion, lowers serum gastrin, increases gastric mucosal protection, and decreases splanchnic blood flow. Randomized trials have shown that somatostatin was at least as effective (1) or more effective (2) than vasopressin and as effective as vasopressin and nitroglycerin combined.

The first randomized placebo-controlled trial that evaluated somatostatin for variceal hemorrhage did not show any difference between somatostatin and placebo (3). The study by Valenzuela and colleagues has been criticized for its highly selective and unrepresentative patient population with a placebo response rate of 83%. In contrast, this study by Burroughs and colleagues found somatostatin to be more effective than placebo in the control of variceal bleeding in patients with cirrhosis over a 5-day period; 64% success in the somatostatin-treated group compared with 41% in the placebo-treated group. The study is well-designed and executed in a single tertiary-care liver unit.

Although somatostatin appears to be an effective alternative to vasopressin, the routine use of any vasoconstrictor is controversial; vasoconstrictor therapy is generally considered adjunctive to endoscopic variceal sclerotherapy, ligation, or surgery. Further supportive evidence of the benefit of vasoconstrictors is needed before widespread clinical application ensues.

Bruno J. Salena, MD
McMaster UniversityHamilton, Ontario, Canada


References

1. Kravetz D, Bosch J, Teres J, et al. Comparison of intravenous somatostatin and vasopressin infusions in the treatment of acute variceal haemorrhage. Hepatology. 1984;4:422-46.

2. Jenkins SA, Baxter JN, Corbett W, et al. A prospective randomised controlled clinical trial comparing somatostatin and vasopressin in controlling acute variceal haemorrhage. Br Med J [Clin Res]. 1985: 290:275-8.

3. Valenzuela JE, Schubert T, Fogel MR, et al. A multicentre, randomised, double-blind trial of somatostatin in the management of acute haemorrhage from esophageal varices. Hepatology. 1989;10:958-61.