A prospective randomized trial from Turkey comparing octreotide versus injection sclerotherapy in acute variceal bleeding. Endoscopic variceal sclerosis compared with distal splenorenal shunt to prevent recurrent variceal bleeding in cirrhosis. A prospective, randomized trial. Multicenter randomized controlled trial of terlipressin versus sclerotherapy in the treatment of acute variceal bleeding: the TEST study. Controlled clinical trial of injection sclerotherapy for active variceal bleeding. Endoscopic sclerotherapy versus portacaval shunt in patient with severe cirrhosis and acute variceal hemorrhage. Long-term follow-up. Shunt surgery versus endoscopic sclerotherapy for long-term treatment of variceal bleeding. Early results of a randomized trial. Transjugular intrahepatic portosystemic shunts compared with endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage. A randomized, controlled trial. Endoscopic sclerotherapy compared with percutaneous transjugular intrahepatic portosystemic shunt after initial sclerotherapy in patients with acute variceal hemorrhage. A randomized, controlled trial. Octreotide for esophageal variceal bleeding treated with endoscopic sclerotherapy: a randomized, placebo-controlled trial.
Bleeding from gastroesophageal varices continues to be a life threatening complication of chronic liver diseases and portal hypertension. The purpose of this randomized prospective study is to compare the efficacy of octreotide administration and emergency injection sclerotherapy for the control of actively bleeding esophageal varices and prevention of early rebleeding in patients with cirrhosis.
                A total of 66 episodes of endoscopically proven active variceal bleeding in 52 patients were included in this study. Following admission to the hospital, the patients were resuscitated with blood and plasma, and fiberoptic endoscopy was performed within 2 hours. Thirty-six bleeds in 28 patients and 30 bleeds in 24 patients were randomized to endoscopic variceal sclerotherapy (1% polidocanol) and to octreotide infusion (at 50 micrograms/h for 12 hours following the initial 50 micrograms i.v. bolus), respectively.
                Bleeding was initially controlled within 6 hours in 75% of episodes by endoscopic variceal sclerotherapy and in 73.3 by octreotide infusion (P > 0.05). There were no significant differences between the 2 groups in early rebleeding (within 72 hours of randomization) (22% vs. 22.7%), blood transfusion (4.2 +/- 1.8 units vs. 4.8 +/- 2.9 units), or hospital mortality (3.6% vs. 3.3%). Treatment failed in 9 episodes (25%) in the sclerotherapy group and in 8 episodes (26.7%) in the octreotide group.
                We consider that Octreotide would appear to be as effective as sclerotherapy in both the early control of variceal hemorrhage and in the prevention of early recurrent bleeding and should therefore be considered the treatment of choice in those centers where 24-hour endoscopy is not available. Furthermore, even in hospitals that do have a 24-hour endoscopy service there is good evidence that octreotide therapy should be commenced as soon as a patient enters hospital with a suspected variceal bleed to achieve rapid homeostasis. When initial hemostasis is achieved, elective endoscopic therapies can be undertaken with greater success. To define the roles of endoscopic variceal sclerosis and distal splenorenal shunt in the prevention of recurrent variceal bleeding in patients with cirrhosis.
                A prospective, randomized clinical trial with crossover for those failing therapy. The median follow-up was 61 months.
                A private, tertiary-referral university hospital.
                Seventy-two patients fulfilling inclusion criteria were drawn from a total of 420 patients treated during a 4.5-year interval.
                Endoscopic variceal sclerosis or distal splenorenal shunt. MEASUREMENTS and
                Survival was significantly (P = 0.02) improved in patients randomly assigned to receive sclerotherapy: 13 of these 37 (35%) patients failed sclerotherapy and required surgical rescue. A survival advantage (P = 0.01) was seen in patients with alcoholic cirrhosis who had this combined therapy; however, in patients with nonalcoholic cirrhosis, survival for those receiving sclerotherapy and surgical rescue was not significantly (P = 0.36) different from that of patients receiving distal splenorenal shunt. Control of variceal bleeding was significantly (P less than 0.001) better in the distal splenorenal shunt group (34 of 35 [97%] compared with 15 of 37 [41%] in the sclerotherapy group). Using death, uncontrolled rebleeding, or shunt thrombosis as the endpoints resulted in no significant difference between treatment groups. Hepatocyte function and portal perfusion were significantly better maintained in patients with alcoholic cirrhosis who were managed by sclerotherapy rather than shunt (P = 0.01 and P = 0.001, respectively).
                Endoscopic sclerotherapy with surgical rescue for uncontrolled bleeding is the optimum therapy for patients with alcoholic cirrhosis and variceal bleeding. Survival is similar in nonalcoholic patients treated with either distal splenorenal shunt or endoscopic sclerotherapy, but shunting provides better control of variceal bleeding. Failure to control bleeding and early rebleeding account for the high mortality associated with variceal hemorrhage in cirrhosis. We compared endoscopic sclerotherapy to terlipressin, a drug that effectively controls acute bleeding while reducing in-hospital mortality. This multicenter randomized controlled trial included 219 cirrhotic patients admitted for endoscopy-proven acute variceal bleeding and randomized to receive repeated injections of terlipressin during 6 days (n = 105) or emergency sclerotherapy (n = 114). Success was defined as obtaining control of bleeding (24-hour bleeding-free period during the first 48 hours) and lack of early rebleeding (any further bleeding from initial control to 5 days later) and survival during the study. Both groups were similar at inclusion. Failure rate for terlipressin was 33% and 32% for sclerotherapy (not significant [NS]). Early rebleeding was responsible for 43% and 44% of failures, respectively. This high efficacy was observed in both Child-Pugh class A + B and Child-Pugh class C patients. Both treatments were similar regarding transfusion requirements, in-hospital stay, and 6-week mortality (26 vs. 19 patients). Side effects appeared in 20% of patients receiving terlipressin and in 30% of those on sclerotherapy (P =.06); being serious in 4% and 7%, respectively (NS). In conclusion, terlipressin and sclerotherapy are equally highly effective therapies achieving the initial control of variceal bleeding and preventing early rebleeding. Both treatments are safe, but terlipressin is better tolerated. Therefore, terlipressin may represent a first-line treatment in acute variceal bleeding until the administration of elective therapy, especially in hospitals where a skilled endoscopist is not available 24 hours a day. In a prospective, randomized clinical trial, immediate injection sclerotherapy was compared with treatment by a combined infusion of vasopressin (0.4 unit per min) and nitroglycerin (40 to 400 micrograms per min) in 50 consecutive patients with 64 episodes of endoscopy-proven variceal hemorrhage. Control of bleeding was assessed over a 12-hr period following entry into the trial. Patients in the vasopressin + nitroglycerin group were then treated by sclerotherapy, as were those in the sclerotherapy group who continued to bleed. At 12 hr, bleeding was controlled in 29 (88%) of the 33 episodes treated by sclerotherapy compared with 20 (65%) of 31 episodes treated by vasopressin + nitroglycerin (p less than 0.05). Recurrence of variceal bleeding occurred at the same frequency (31%). Although admission mortality was less in those initially treated by sclerotherapy compared to those managed by vasopressin + nitroglycerin, this did not reach statistical significance (27 and 39%, respectively, p greater than 0.20). Sclerotherapy carried out as the first treatment of the active variceal hemorrhage proved both safe and effective, even in the presence of major hemorrhage, and as compared to combined vasopressin and nitroglycerin it proved superior. In a continuation of a trial for which preliminary results were reported in the Journal two years ago, a total of 64 patients with Child Class C cirrhosis and variceal hemorrhage requiring six or more units of blood were randomly assigned to receive either a portacaval shunt (32 patients) or endoscopic sclerotherapy (32 patients). The duration of initial hospitalization and the total amount of blood transfused during hospitalization were significantly less in the patients receiving sclerotherapy (P less than 0.001). There was no difference in short-term survival (50 percent of the sclerotherapy group were discharged alive, as compared with 44 percent of the shunt-surgery group). Both groups were followed for a mean of 530 days after randomization. Rebleeding from varices, the duration of rehospitalization for hemorrhage, and transfusions received after discharge were all significantly greater in the sclerotherapy group (P less than 0.001). Forty percent of the sclerotherapy-treated patients discharged alive (7 of 16 patients) ultimately required surgical treatment for bleeding varices, despite a mean of 6.1 treatment sessions. Health care costs and long-term survival did not differ significantly between the groups (P greater than 0.05). We conclude that although endoscopic sclerotherapy is as good as surgical shunting for the acute management of variceal hemorrhage in poor-risk patients with massive bleeding, sclerotherapy-treated patients in whom varices are not obliterated and bleeding continues should be considered for elective shunt surgery. In September 1982, a prospective randomized trial comparing shunt surgery and endoscopic sclerotherapy for the elective management of variceal hemorrhage in patients with cirrhosis was initiated. Twenty-seven patients have received shunts (distal splenorenal = 23, nonselective = 4) and 30 patients have had chronic sclerotherapy. Eighty-six per cent of patients had alcoholic cirrhosis and 33% were Child's class C. After a mean follow-up of 25 months, 19% of shunt and 57% of sclerotherapy patients have had rebleeding (p = 0.003). Kaplan-Meier survival analysis reveals similar 2-year survival rates for shunt (65%) and sclerotherapy (61%) groups. Only two of 10 sclerotherapy failures have been salvaged by surgery. Posttherapy quantitative hepatic function, frequency of encephalopathy, and cumulative medical costs were similar for both groups. Hepatic portal perfusion and portal pressure at 1 year were better maintained by sclerotherapy than by distal splenorenal shunt. In conclusion, endoscopic sclerotherapy and shunt surgery provide similar results with respect to survival, hepatic function, frequency of encephalopathy, and costs. Sclerotherapy is an acceptable, but not superior, alternative to shunt surgery for treatment of variceal hemorrhage. Transjugular intrahepatic portosystemic shunts (TIPS) have widened the use of portal decompression as therapy for variceal hemorrhage. However, no controlled studies have examined the efficacy of TIPS compared with that of other treatments.
                To compare the efficacy and safety of TIPS with those of endoscopic sclerotherapy for the prevention of recurrent variceal hemorrhage.
                Randomized, controlled trial.
                Tertiary-care academic medical center.
                100 patients with cirrhosis were evaluated a mean of approximately 10 days after an episode of acute variceal bleeding; 20 patients were excluded because of portal venous thrombosis (n = 6), hepatoma (n = 3), florid alcoholic hepatitis (n = 6), and refusal to give consent (n = 5).
                TIPS (n = 41) or sclerotherapy (n = 39). The latter was performed by freehand injections of 5% Na morrhuate at 2- to 3-week intervals. Recurrent variceal hemorrhage was managed by sclerotherapy followed by angiographic assessment of TIPS and dilatation of the stents (TIPS group) or crossover to TIPS (sclerotherapy group).
                Rebleeding and survival were the primary end points. Complications and rates of rehospitalization were secondary end points.
                During a mean follow-up of approximately 1000 days, recurrent gastrointestinal bleeding resulted from variceal hemorrhage (9 patients in the TIPS group and 8 in the sclerotherapy group), portal gastropathy (1 patient in each group), and gastric lipoma (0 and 1 patients, respectively). A higher mortality rate was seen with TIPS (P = 0.03). Death resulted from variceal bleeding (5 patients in the TIPS group and 3 in the sclerotherapy group), sepsis (3 and 2 patients, respectively), liver failure (2 patients in each group), hepatoma (1 and 0 patients, respectively), and hemoperitoneum (1 and 0 patients, respectively). Encephalopathy was the most common complication in the TIPS group (n = 12), and pain developing after sclerotherapy was the most common in the sclerotherapy group (n = 10). The two groups had similar rates of rehospitalization.
                Endoscopic sclerotherapy and TIPS are equivalent with respect to rebleeding developing over the long term. However, sclerotherapy may be superior to TIPS with respect to survival. Hemorrhage from esophageal varices remains a substantial management problem. Endoscopic sclerotherapy was preferred for more than a decade, but fluoroscopically placed intrahepatic portosystemic stents have recently been used with increasing frequency.
                To compare sclerotherapy with transjugular intrahepatic portosystemic shunt (TIPS) in patients with bleeding from esophageal varices.
                Randomized, controlled clinical trial.
                Three teaching hospitals.
                49 adults hospitalized with acute variceal hemorrhage from November 1991 to December 1995: 25 assigned to sclerotherapy and 24 assigned to TIPS.
                Patients assigned to repeated sclerotherapy had the procedure weekly. In those assigned to TIPS, an expandable mesh stent was fluoroscopically placed between an intrahepatic portal vein and an adjacent hepatic vein.
                Pretreatment measures included demographic and laboratory data. Postrandomization data included index hospitalization survival, duration of follow-up, successful obliteration of varices, rebleeding from varices, number of variceal rebleeding events, total days of hospitalization for variceal bleeding, blood transfusion requirements after randomization, prevalence of encephalopathy, and total health care costs.
                Mean follow-up (+/-SE) was 567 +/- 104 days in the sclerotherapy group and 575 +/- 109 days in the TIPS group. Varices were obliterated more reliably by TIPS than by sclerotherapy (P < 0.001). Patients having TIPS were significantly less likely to rebleed from esophageal varices than patients receiving sclerotherapy (3 of 24 compared with 12 of 25; P = 0.012). No other follow-up measures differed significantly between groups. A trend toward improved survival, which was not statistically significant, was noted in the TIPS group (hazard ratio, 0.53 [95% CI, 0.18 to 1.5]).
                In obliterating varices and reducing rebleeding events from esophageal varies, TIPS was more effective than sclerotherapy. However, TIPS did not decrease morbidity after randomization or improve health care costs. It seemed to produce better survival, but the increase in survival was not statistically significant. Endoscopic sclerotherapy is considered a first line therapy to stop bleeding from esophageal varices, but acute variceal bleeding is still associated with high risk of rebleeding and death. We compared the use of octreotide with endoscopic sclerotherapy versus sclerotherapy alone to control acute variceal bleeding and prevent rebleeding in patients with cirrhosis.
                In a prospective controlled trial, 68 patients with cirrhosis and acute variceal bleeding who underwent emergency sclerotherapy were randomly assigned to receive a continuous infusion of octreotide or placebo for two days. The primary outcome measure was 7-day mortality.
                After seven days the overall mortality was 19.1%, and the proportion of patients who died in octreotide group (8 of 40, or 20%) was similar to the placebo group (5 of 28, or 17.85%; p = 0.74). Rebleeding occurred in 20.6% (14 of 68 patients), being 20% (8 of 40) in the octreotide group vs. 21.4% (6 of 28) in the placebo group (p = 0.88). The mean number of units of blood transfused after sclerotherapy was 2.05 units in the octreotide group vs. 2.08 units in the placebo group (p = 0.96). Thirty patients needed intensive care support (20 of 40 in the octreotide group vs. 10 of 28 in the placebo group; p = 0.24). The differences remained without statistical significance even after adjustment for hepatic function and endoscopic bleeding stigmata by a linear regression model analysis test.
                In patients with cirrhosis, octreotide intravenous per 48h associated with sclerotherapy is not superior to sclerotherapy alone in terms of 7-day mortality, frequency of rebleeding, number of units of packet red blood cell transfusion and length of stay in intensive care setting.
We found no convincing evidence to support the use of emergency sclerotherapy for variceal bleeding in cirrhosis as the first, single treatment when compared with vasoactive drugs. Vasoactive drugs may be safe and effective whenever endoscopic therapy is not promptly available and seems to be associated with less adverse events than emergency sclerotherapy. Other meta-analyses and guidelines advocate that combined vasoactive drugs and endoscopic therapy is superior to either intervention alone.