Octreotide for esophageal variceal bleeding treated with endoscopic sclerotherapy: a randomized, placebo-controlled trial

BACKGROUND/AIMS: 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. METHODOLOGY: 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. RESULTS: 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. CONCLUSIONS: 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.     

Comparative trial of three different schedules for endoscopic esophageal variceal sclerotherapy

We analyzed our experience in 125 patients with variceal bleeding to compare the efficacy and complications of various schedules of endoscopic variceal sclerotherapy. The schedules for the first three injections were as follows: (A) 3-5 ml of aqueous phenol injected at intervals of three weeks (Group I, n = 28), one week (Group II, n = 30) and three days (Group IIIa, n = 33), and (B) 2-3 ml of phenol at each site at intervals of 3 days (Group IIIb, n = 34). Subsequent injections were given at four week intervals for all groups. Varices could be obliterated significantly earlier (p less than 0.001) in patients injected at 3-day intervals (mean +/- SD 9.12 +/- 5.95 weeks) as compared with those injected at 1-week (13.50 +/- 10.28 weeks) and 3-week (20.55 +/- 7.77 weeks) intervals. The rebleeding rate was not significantly less in the 3-day interval group (Group IIIa--16.66% and Group IIIb--17.64%) as compared with the 1-week (23.3%) and 3-week (28.5%) groups. However the mortality due to rebleed was significantly less (p less than 0.05) in patients injected at 3-day interval (nil), as compared with those injected at 1-week (13.3%) and 3-week (10.7%) intervals. Mucosal ulcerations and stricture formation were observed significantly (p less than 0.001) more frequently in patients undergoing sclerotherapy at 3-day intervals (Group IIIa--51.5% and 18.18%) with 3-5 ml of phenol as compared with those injected similar volume at 1-week (16.66% and 3.3%) and 3-week (7.1% and 3.5%) intervals respectively.(ABSTRACT TRUNCATED AT 250 WORDS)     

肝硬化食管静脉曲张破裂出血序贯治疗的临床应用价值

目的 评价曲张静脉套扎术(EVL)+不同硬化剂曲张静脉硬化术(EVS)序贯治疗肝硬化食管静脉曲张破裂出血的疗效及安全性.方法 回顾性总结314例肝硬化食管静脉曲张破裂出血内镜治疗患者的临床资料,包括单纯EVL治疗者112例(EVL组)、单纯鱼肝油酸钠硬化治疗者48例(EVS1组)、单纯聚桂醇硬化治疗者40例(EVS2组)、套扎+鱼肝油酸钠硬化序贯治疗者26例(EVLS1组)、套扎+聚桂醇硬化序贯治疗者88例(EVLS2组),统计各组曲张静脉治疗有效率、静脉曲张复发率、并发症发生率并进行对比分析.结果 EVL组、EVS1组、EVS2组、EVIS1组、EVLS2组曲张静脉治疗有效率比较差异均无统计学意义[85.7％ (96/112)、83.3％ (40/48)、92.5％ (37/40)、92.3％(24/26)、94.3％ (83/88),P＞0.05],但EVLS1组和EVLS2组曲张静脉完全消失率均明显高于其他3组[88.5％(23/26)和87.5％(77/88)比58.0％(65/112)、62.5％(30/48)、70.0％(28/40),P＜0.05],而EVLS1组与EVLS2组比较差异无统计学意义(P＞0.05).EVS1组再出血率最高(18.8％,9/48) (P ＜0.05),其次是EVL组(11.6％,13/112),均高于EVS2组、EVLS1组和EVLS2组[7.5％(3/40)、7.7％ (2/26)、6.8％ (6/88),P＜0.05],后3组再出血率相似(P＞0.05).治疗后随访6 ～18个月,EVL组静脉曲张复发26例(23.2％,26/112),EVS1组复发8例(16.7％,8/48),EVS2组复发6例(15.0％,6/40),EVLS1组复发4例(15.4％,4/26),EVLS2组复发9例(10.2％,9/88);EVL组复发率最高(P＜0.05),EVLS2组复发率最低(P＜0.05),EVS1组、EVS2组和EVLS1组复发率相似(P＞0.05).EVS1组总体并发症发生率(32.2％,49/152)明显高于其他4组(P＜0.05),而EVL组(14.5％,32/220)、EVLS2组(19.6％,22/112)、EVLS1组(22.7％,25/110)、EVLS2组(15.8％,34/229)4组间比较差异无统计学意义(P＞0.05).结论 EVL+鱼肝油酸钠EVS或+聚桂醇EVS序贯治疗肝硬化食管静脉曲张破裂出血是安全而有效的,尤以EVL+聚桂醇EVS序贯治疗效果显著,有可能成为治疗食管静脉曲张出血并防止再出血的最佳选择.     

Controlled clinical trial of injection sclerotherapy for active variceal bleeding

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.     

A prospective, randomized controlled trial of chronic esophageal variceal sclerotherapy

The results of a prospective, randomized controlled trial of chronic esophageal variceal sclerotherapy conducted over a 38-month period are presented. One-hundred twenty patients were randomized following variceal bleeding, 63 to esophageal variceal sclerotherapy and 57 to control. Mean follow-up was similar in both groups (esophageal variceal sclerotherapy, 12.5 +/- 8.8 months; control, 14.9 +/- 6.6 months). Twenty-one percent of the patients in each group were lost to follow-up. Esophageal variceal sclerotherapy decreased rebleeding as evidenced by a decrease in the mean bleeding risk factor, transfusion requirement and by an increase in bleeding free interval; differences between the treated and control groups in these parameters were especially significant after variceal obliteration. A high incidence of asymptomatic ulceration and low frequency of strictures were notable effects of esophageal variceal sclerotherapy. Cumulative life table analysis revealed no differences in survival between esophageal variceal sclerotherapy and control groups. However, when patients who received portal-systemic shunt surgery (esophageal variceal sclerotherapy, 6%; control, 28%) were removed from the analysis at the time the shunt surgery was performed (defining the shunt as an endpoint, a significant difference in survival (p less than 0.05, F ratios) in favor of esophageal variceal sclerotherapy was observed.     

急诊内镜下套扎与硬化治疗食管静脉曲张破裂出血的比较

目的比较食管静脉曲张破裂出血急诊内镜下套扎与硬化治疗的疗效和安全性。方法对210例食管静脉曲张破裂出血患者,急诊情况下行内镜下套扎或硬化治疗,并分析比较两组急诊止血成功率、近期再出血率、急诊治疗曲张静脉消失率、不良反应、并发症、病死率等情况。结果急诊止血成功率套扎组达95.4%,硬化组达96.0%;近期再出血率分别为4.8%和4.1%;套扎组急诊治疗曲张静脉消失率明显优于硬化组（P〈0.01）。两组不良反应、并发症及病死率无差别。临床疗效与肝功能呈正相关。结论急诊内镜下套扎与硬化治疗食管静脉曲张出血均为有效、安全的止血方法。临床上可结合患者实际情况综合考虑后选择。     

Cardiorespiratory effects of endoscopic esophageal variceal sclerotherapy

Endoscopic variceal sclerotherapy (EVS) is an effective means of controlling variceal hemorrhage, which develops as a consequence of portal hypertension. While esophageal perforation, ulceration, strictures, and mediastinitis are potential complications associated with this procedure, it is not clear whether isolated pleuropulmonary events such as pleuritis, pneumonitis, and adult respiratory distress syndrome are causally related to the EVS. Endoscopy and sedation with the attendant risk of aspiration, particularly in the background of hepatic encephalopathy, may account for some of these events. Recent controlled studies of respiratory function demonstrate that EVS as such results in minor changes in gas exchange, lung volumes, and pulmonary and systemic hemodynamics. Most pulmonary complications have been reported with the use of sodium morrhuate sclerosant. Comparative studies among different sclerosants are necessary to evaluate relative safety. Finally, there have been rare reports of myocardial ischemia and pericarditis reported in association with EVS, but these are of a transient nature. Chest symptoms, roentgenographic pleuropulmonary changes, pulmonary hemodynamics, and cardiac perturbations are transient and should not preclude offering EVS to patients with variceal hemorrhage.     

A randomized controlled trial comparing ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin in acute variceal bleeding

BACKGROUND/AIMS: The currently recommended treatment for acute variceal bleeding is the association of vasoactive drugs and endoscopic therapy. However, which emergency endoscopic treatment combines better with drugs has not been clarified. This study compares the efficacy and safety of variceal ligation and sclerotherapy as emergency endoscopic treatment added to somatostatin. METHODS: Patients admitted with acute gastrointestinal bleeding and with suspected cirrhosis received somatostatin infusion (for 5 days). Endoscopy was performed within 6h and those with esophageal variceal bleeding were randomized to receive either sclerotherapy (N=89) or ligation (N=90). RESULTS: Therapeutic failure occurred in 21 patients treated with sclerotherapy (24%) and in nine treated with ligation (10%) (RR=2.4, 95% CI=1.1-4.9). Failure to control bleeding occurred in 15% vs 4%, respectively (P=0.02). Treatment group, shock and HVPG >16 mmHg were independent predictors of failure. Side-effects occurred in 28% of patients receiving sclerotherapy vs 14% with ligation (RR=1.9, 95% CI=1.1-3.5), being serious in 13% vs 4% (P=0.04). Six-week survival probability without therapeutic failure was better with ligation (P=0.01). CONCLUSIONS: The use of variceal ligation instead of sclerotherapy as emergency endoscopic therapy added to somatostatin for the treatment of acute variceal bleeding significantly improves the efficacy and safety.     

内镜下套扎与硬化夹心联合法治疗食管静脉曲张出血的研究

目的　了解套扎与硬化夹心联合法 (套扎 硬化 套扎 )能否获得优于单纯内镜下食管静脉曲张结扎 (EVL)的疗效。方法　对 98例肝硬化食管静脉曲张伴活动性出血或近期出血的患者随机采用单纯EVL或夹心法治疗 (EVL组 5 0例 ,夹心法组 4 8例 )。EVL组每条曲张静脉结扎皮圈不超过 3个 ,夹心法组每条曲张静脉结扎 2个皮圈 ,并在两个结扎点之间的曲张静脉内注射 1～ 3ml硬化剂。夹心法组 7例在首次内镜治疗时接受食管静脉造影检查。 7～ 10d重复 1次内镜治疗 ,直至静脉曲张消除。结果　 7例行静脉造影检查 ,其中 6例硬化剂在曲张静脉内滞留时间超过 4 5min。两种方法控制活动性食管静脉曲张出血 (EVB)的止血成功率相同 (10 0 .0 % ) ;两组间静脉曲张消除率相似 (夹心法组 93.8% ,EVL组 90 .2 % ,P >0 .0 5 ) ,但夹心法组一次治疗后静脉曲张消除率明显高于EVL组 (6 6 .7%比10 .0 % ,P <0 .0 0 1) ,达到消除的平均治疗次数明显减少 (1.2± 0 .4比 3.8± 1.5 ,P <0 .0 1) ,所需时间显著缩短 [(13.1± 4 .3)d比 (42 .5± 16 .7)d ,P <0 .0 1];与EVL组相比 ,夹心法组再出血率较低 (8.3%比2 8.0 % ,P <0 .0 5 ) ,随访期内静脉曲张复发率明显下降 (8.3%比 4 4 .0 % ,P <0 .0 0 5 ) ;两组间并发症发生率相似 (夹心法组 1     

A new technique of combined endoscopic sclerotherapy and ligation for variceal bleeding

AIM: To develop a technique of combined endoscopic sclerotherapy and ligation (ESL) in which both techniques of endoscopic sclerotherapy (ES) and endoscopic variceal ligation (EVL) can be optimally used. METHODS: ESL was performed in 10 patients (age 46.4+/-7.9; 9 males, 1 female) with cirrhosis of liver using sclerotherapy needle and Speedband, Superview multiple band ligater (Boston Scientific, Microvasive, Watertown, MA). A single band was placed 5-10 cm proximal to the gastro-esophageal junction over each varix from proximal to distal margin, followed by intravariceal injection of 1.5 % ethoxysclerol (4 ml each) 2 to 3 cm proximal to the gastroesophageal junction on the ligated varices distal to deployed band. EVL was then performed at the injection site. Similarly other varices were also injected and ligated from distal to proximally. In the subsequent sessions, ES alone was performed to sclerose small varices at the gastroesophageal junction. RESULTS: ESL was successfully performed in all patients. A median of 3 (ESL 1, ES 2) sessions (ranged 1-4) were required to eradicate the varices in 9 (90 %) of 10 patients. Recurrence of varices without bleed was seen in 1 patient during a mean follow-up of 10.3 months (ranged 6-15). Two patients died of liver failure. None died of variceal bleeding. None of the patients had procedure related complications. CONCLUSION: ESL may be useful in the fast eradication of esophageal varices. However, randomised controlled trials are required to find out its relative efficacy and impact on variceal recurrence in comparison to ES or EVL.     

Comparison of endoscopic variceal injection sclerotherapy and ligation for the treatment of esophageal variceal hemorrhage: A prospective randomized trial

To determine the efficacy of endoscopic variceal sclerotherapy (EVS) and ligation (EVL) in the management of esophageal variceal bleeding, 134 cirrhotic patients were randomized to receive either treatment. The clinical and endoscopic characteristics were similar in both groups. Active bleeding was controlled with ligation (20 of 20) as efficiently as with sclerotherapy (14 of 16). Elective sclerotherapy consumed less time than ligation (7.9 ± 1.8 minutes vs. 11.5 ± 2.7 minutes, P <.001), but there was no difference between emergent sclerotherapy (14.5 ± 5.8 minutes) and ligation (14.9 ± 4.1 minutes). Ligation reduced one grade of variceal size more quickly than sclerotherapy (1.1 ± 0.4 vs. 2.0 ± 1.7 session, P < .001). The rebleeding rate was lower with ligation (13 of 67 vs. 28 of 67, P < .01). Esophageal ulcer was the most common source of rebleeding. Recurrence of varices appears more probable with ligation (P = .079). The complication rate was higher with sclerotherapy (15 of 67 vs. 3 of 67, P < .01), with esophageal stricture being the most common cause. Survival rate was the same in both groups even after stratifying patients into good and poor hepatic reserve groups. Hepatic failure was the major cause of death, followed by exsanguination. In summary, EVL was superior to EVS regarding rebleeding and complications but not in other aspects such as time consumption in elective treatment and recurrence of varices. Substantial results for long-term follow-up are required before conclusion of the treatment of choice.     

A meta-analysis of endoscopic variceal ligation for primary prophylaxis of esophageal variceal bleeding

Despite publication of several randomized trials of prophylactic variceal ligation, the effect on bleeding-related outcomes is unclear. We performed a meta-analysis of the trials, as identified by electronic database searching and cross-referencing. Both investigators independently applied inclusion and exclusion criteria, and abstracted data from each trial. Standard meta-analytic techniques were used to compute relative risks and the number needed to treat (NNT) for first variceal bleed, bleed-related mortality, and all-cause mortality. Among 601 patients in 5 homogeneous trials comparing prophylactic ligation with untreated controls, relative risks of first variceal bleed, bleed-related mortality, and all-cause mortality were 0.36 (0.26-0.50), 0.20 (0.11-0.39), and 0.55 (0.43-0.71), with respective NNTs of 4.1, 6.7, and 5.3. Among 283 subjects from 4 trials comparing ligation with beta-blocker therapy, the relative risk of first variceal bleed was 0.48 (0.24-0.96), with NNT of 13; however, there was no effect on either bleed-related mortality (relative risk [RR], 0.61; confidence interval [CI], 0.20-1.88) or all-cause mortality (RR, 0.95; CI, 0.56-1.62). In conclusion, compared with untreated controls, prophylactic ligation reduces the risks of variceal bleeding and mortality. Compared with beta-blockers, ligation reduces the risk for first variceal bleed but has no effect on mortality. Prophylactic ligation should be considered for patients with large esophageal varices who cannot tolerate beta-blockers. Subsequent research should further compare ligation and beta-blockers to determine the effect on mortality, and measure ligation's cost-effectiveness.     

Endoscopic variceal sclerotherapy as primary treatment for bleeding esophageal varices

In this study of 75 patients with bleeding esophageal varices we confirm not only the ability of endoscopic variceal sclerotherapy (EVS) to control acute bleeding episodes but to effect variceal obliteration that confers a significant survival advantage, regardless of initial Child's classification. Survival correlates directly with the degree of hepatic dysfunction, although all patients regardless of Child's status have a statistically significant survival advantage when treated until esophageal variceal obliteration is achieved. All patients treated with EVS should be followed for life, but virtually all follow-up can be done on an outpatient basis. Shunt surgery should be reserved for: (a) patients whose acute bleeding cannot be controlled with EVS at the time of index bleed; and (b) patients who rebleed repeatedly or uncontrollably from gastric or duodenal varices. EVS is more cost-effective than other available treatments. It also effectively stabilizes potential candidates for orthotopic liver transplantation. Despite a progressive increase in the admissions for bleeding varices at our institution, the introduction of EVS has been associated with a significant decline in portosystemic shunt therapy. We believe that EVS is now the first-line treatment for all patients with bleeding esophageal varices.     

A controlled trial of oral propranolol compared with injection sclerotherapy for the long-term management of variceal bleeding

This trial was carried out to assess the value of propranolol for the prevention of recurrent variceal bleeding in patients with well-compensated cirrhosis. We also compared propranolol therapy to long-term injection sclerotherapy. One hundred and eight patients, in whom the original variceal hemorrhage stopped spontaneously (before diagnostic endoscopy) and without sclerotherapy or surgical intervention, were included. All were Pugh grade A or B; 55% had alcoholic cirrhosis. Patients were chosen randomly to receive oral propranolol (in a dosage to reduce resting pulse rate by 25%) or to undergo long-term injection sclerotherapy. In both groups, episodes of repeat bleeding that did not stop spontaneously were managed with sclerotherapy. Patients considered to have failed propranolol therapy were treated with long-term sclerotherapy. Follow-up ranged from 12 to 64 mo. In the propranolol group, 28 (54%) of the 52 patients had repeat bleeding from varices with a total of 57 episodes; 14 received long-term sclerotherapy. In the sclerotherapy group, 25 (45%) of the 56 patients had repeat bleeding, with a total of 40 episodes (p less than 0.20). On an intention-to-treat basis, the risk of bleeding expressed per patient-month of follow-up was similar for the two groups, at 0.05 and 0.037, respectively. Survival as assessed by cumulative life analysis was also similar, with 55% and 66% alive at 3 yr (p less than 0.40). Stepwise regression analysis of possible factors predicting further bleeding in patients taking propranolol selected only two variables--the pretreatment pulse rate and the extent of pulse-rate reduction in response to propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of endoscopic variceal ligation in prophylactic therapy for bleeding of oesophageal varices: a prospective, controlled trial compared with endoscopic injection sclerotherapy

BACKGROUND: To evaluate the efficacy of endoscopic variceal ligation (EVL) in prophylactic therapy for oesophageal varices, we performed a randomized prospective trial to compare the recurrence of oesophageal varices treated by EVL with those treated by endoscopic injection sclerotherapy. METHODS: Fifty patients with liver cirrhosis were divided into two groups at random, after informed consents were obtained, to receive prophylactic therapy for bleeding of oesophageal varices. Group 1 patients underwent sessions of sclerotherapy with 5% ethanolamine oleate used as the sclerosant. Group 2 patients underwent EVL followed by one or two sessions of sclerotherapy. RESULTS: During the 18 month follow-up period, both the recurrence rate in group 2 (56%) and the incidence of bleeding (20%) were significantly higher compared with group 1 (recurrence rate 16%, bleeding 0%). CONCLUSIONS: This result indicates that EVL is not effective for prophylactic therapy for oesophageal varices in liver cirrhosis.     

食管静脉曲张出血硬化治疗十三年回顾

目的评价食管静脉曲张出血硬化治疗疗效.方法对我院1987年4月至2000年5月行食管静脉曲张硬化治疗(EVS)的1010例门脉高压食管静脉曲张出血患者,进行回顾分析.肝硬化患者850例,肝癌160例,共行EVS3203例次,急诊602例次,择期2601例次,追加治疗502例次,710例肝硬化患者首次进行EVS(3.18±1.1)次,对579例肝硬化患者进行了3～157个月的随访,平均随访时间为(42.47±32.78)个月.肝硬化患者850例,其中治疗结束时706例行胃镜检查.结果1.全组急诊止血率为970%,治疗并发症为13.4%,死亡率为1.8%.2.肝硬化患者食管静脉曲张消失和基本消失率为84.1%,远期再发出血率为23.7%,生存率按Kaplan-Meier法计算,1、3、5、10年分别为(95.8±0.8)%、(86.1±1.6)%、(745±2.4)%和(53.6±3.8)%.结论EVS对食管静脉曲张出血仍是一重要治疗方法.