A Multicenter, Randomized, Double–Blind Trial of Somatostatin in the Management of Acute Hemorrhage From Esophageal Varices

Abstract

A prospective, randomized, placebo-controlled, double-blind, multicenter clinical trial of intravenous somatostatin (Stilamin; Serono Laboratories, Inc., Randolph, MA) was performed in 102 patients with actively bleeding esophageal varices from August, 1985, to November, 1986. Patients had major hemorrhage indicated by hematemesis or melena and evidence of significant blood loss. For entry, patients had to have endoscopic demonstration of active bleeding from esophageal varices or stigmata of recent hemorrhage and bright red blood in the gastric aspirate with no other source of bleeding found. Randomized patients received identical-appearing somatostatin or placebo for a 30-hr study period. Those given somatostatin received a 250-micrograms bolus and a 250-micrograms per hr infusion with repeat bolus and doubling of the infusion if the bleeding was not controlled. In retrospect, 18 patients could not be evaluated. Of the 84 evaluable patients, 48 received somatostatin and 36 placebo. They were comparable in age, gender, severity of liver disease and history of variceal bleeding. Transfusion requirements were similar in both groups. Bleeding stopped for 12 consecutive hr during 30 hr of the study period in 31 (65%) of the somatostatin group vs. 30 (83%) of the placebo group (p = 0.06). The median time to cessation of bleeding was 2 hr in the placebo group and 3 hr in the somatostatin group. Deaths following the study period were nine (25%) in the placebo group and 15 (31%) in the somatostatin group. Within the limitations of the present study, we conclude that somatostatin was ineffective in the management of active bleeding of esophageal varices.

Somatostatin alone or combined with emergency sclerotherapy in the treatment of acute esophageal variceal bleeding: A prospective randomized trial

“…However, the rate of cases in which active bleeding was completely arrested using SMT alone was lower than that reported in previous randomized trials. 5,11,15 This could be the result of the fact that in this study, but not in previous trials, SMT infusion was started immediately after the admission of patients, several hours before diagnostic endoscopy was performed. Thus, the identification of an active hemorrhage during endoscopy could reflect, at least in some cases, the failure of SMT in the initial arrest of active bleeding that could have selected a group of patients with a higher risk of therapeutic failure than those evaluated in previous studies.…”

“…3 Somatostatin (SMT) was introduced for the treatment of acute variceal hemorrhage because of its capacity to decrease portal pressure and collateral splanchnic blood flow, without the adverse effects of vasopressin on the systemic circulation. 4 One placebo-controlled trial failed to show any beneficial effect with SMT, 5 although the high spontaneous success rate observed with placebo suggests that some inadvertent bias could occur in this study. 5 Furthermore, several randomized, controlled trials have shown that SMT is more effective than placebo, 6 and as effective as vasopressin, 7,8 vasopressin associated with nitroglycerin, 9 terlipressin, 10,11 and balloon tamponade, 12,13 with fewer side-effects in most of these studies.…”

“…4 One placebo-controlled trial failed to show any beneficial effect with SMT, 5 although the high spontaneous success rate observed with placebo suggests that some inadvertent bias could occur in this study. 5 Furthermore, several randomized, controlled trials have shown that SMT is more effective than placebo, 6 and as effective as vasopressin, 7,8 vasopressin associated with nitroglycerin, 9 terlipressin, 10,11 and balloon tamponade, 12,13 with fewer side-effects in most of these studies. Both SMT and octreotide, a synthetic SMT analogue, have shown an efficacy similar to that of EST for the control of acute variceal bleeding, [14][15][16][17] and for the prevention of early rebleeding, 18 while morbidity significantly decreased.…”

Escleroterapia versus somatostatina na hemorragia digestiva alta por ruptura de varizes esofágicas

“…Causa uma vasoconstrição esplâncnica seletiva, provavelmente devido à inibição de peptídios vasodilatadores esplâncnicos, como o glucagon, peptídio intestinal vasoativo e substância P (8,14) . Além disso, por inibir a secreção gástrica, poderia evitar a dissolução do coágulo no local da hemostasia das varizes, que depende de um pH ácido (34,38) . Dois trabalhos clássicos da literatura comparando a eficácia da somatostatina com placebo no sangramento agudo de VGE, obtiveram resultados conflitantes; o primeiro, um estudo multicêntrico americano (38) , não mostrou efeito benéfico da somatostatina, ressalvado o fato de ter apresentado índice muito elevado de controle do sangramento no grupo placebo (83%).…”

“…Além disso, por inibir a secreção gástrica, poderia evitar a dissolução do coágulo no local da hemostasia das varizes, que depende de um pH ácido (34,38) . Dois trabalhos clássicos da literatura comparando a eficácia da somatostatina com placebo no sangramento agudo de VGE, obtiveram resultados conflitantes; o primeiro, um estudo multicêntrico americano (38) , não mostrou efeito benéfico da somatostatina, ressalvado o fato de ter apresentado índice muito elevado de controle do sangramento no grupo placebo (83%). Já o trabalho inglês, do Royal Free Hospital (11) , demonstrou que a somatostatina é significativamente mais eficaz que o placebo no controle da HDA por VGE.…”