0016-5107/92/3804-0421$03.00 GASTROINTESTINAL ENDOSCOPY Copyright © 1992 by the American Society for Gastrointestinal Endoscopy
Injection sclerotherapy preceded by esophageal tamponade versus immediate sclerotherapy in arresting active variceal bleeding: a prospective randomized trial Gin-Ho Lo, MD, Kwok-Hung Lai, MD Wai-Wah Ng, MD, Tseng-Nip Tam, MD Shou-Dong Lee, MD, Yang-Te Tsai, MD Kwang-Juei Lo, MD Taiwan, Republic of China
To investigate whether Sengstaken-Blakemore tube tamponade is needed before emergency sclerotherapy, 60 patients with active esophageal variceal bleeding were randomized to receive either immediate injection sclerotherapy (group A) or sclerotherapy preceded by balloon tamponade (group B). Three patients in group A (10%) were completely inaccessible to sclerotherapy. Initial success in stopping bleeding at 24 hours after sclerotherapy was 76% in group A and 81% in group B (p = 0.89). Re-bleeding rate was 27% in group A versus 50% in group B (p = 0.11). Blood requirement was significantly less in group A (3.7 ± 2.5 units vs. 6.2 ± 3.2 units, p < 0.01). Major complications were also significantly less frequently encountered in group A than in group B (14% vs. 39%, P < 0.05). In-hospital mortality was 24% in group A and 42% in group B (p = 0.14). We conclude that the efficacy of immediate sclerotherapy is comparable to that of delayed sclerotherapy preceded by balloon tamponade. Additionally, significantly less blood requirement and fewer complications were noted in the immediate sclerotherapy group. Thus, emergency sclerotherapy without prior balloon tamponade is feasible and recommended in most patients with acute esophageal variceal hemorrhage. (Gastrointest Endosc 1992;38:421-424)
Hemorrhage from esophageal varices is a serious complication of portal hypertension. Medical treatments including vasopressin, somatostatin infusion, Sengstaken-Blakemore tube (S-B tube) insertion/-5 and surgical intervention6 do not substantially increase survival. In recent years, endoscopic injection sclerotherapy (EIS) has received increasing attention as a valuable modality in arresting acute esophageal variceal bleeding. 7- 15 Controlled studies have shown that EIS is superior to the SoB tube and vasopressin in cessation of active variceal bleeding. 9 , 12-15 However, Received September 30,1991. For revision January 8,1992. Accepted February 10, 1992. From the Department of Medicine, Division of Gastroenterology, Veterans General Hospital-Kaohsiung, Taipei & Taichung, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China. Reprint requests: Kwok-Hung Lai, MD, Department of Medicine, Division of Gastroenterology, Veterans General Hospital-Kaohsiung, 386 Ta-Chung 1st Rd, Kaohsiung 813, Taiwan, Republic of China. VOLUME 38, NO.4, 1992
use of the S-B tube before sclerotherapy has been widely adopted in most studies. 7, 8, 10-12, 14 Other uncontrolled and retrospective studies have compared the efficacy of emergency versus delayed sclerotherapy,1618 but it is still unknown whether prior SoB tube tamponade is mandatory before EIS during brisk variceal bleeding. This prospective, randomized study investigated the role of SoB tube tamponade and immediate EIS in controlling active esophageal variceal hemorrhage, re-bleeding, and outcome. MATERIALS AND METHODS
Between July 1988 and June 1990,60 consecutive patients admitted to the Veterans General Hospital-Taipei for acute variceal bleeding were enrolled in the trial. All of the patients were proven to be actively bleeding from esophageal varices by emergency endoscopy within 12 hours of admission. Active variceal bleeding was diagnosed when blood was 421
directly seen by endoscopy to issue from a varix or when fresh blood was seen in the esophagus of patients with red color signs on varices and no other potential site of bleeding was discovered. 3 Another 27 patients with acute variceal bleeding were excluded: 15 were associated with hepatocellular carcinoma, 4 were associated with peptic ulcers, 2 had bleeding from fundal varices, and 6 had stopped bleeding on endoscopic examination. Patients included in the trial were randomized to receive either immediate sclerotherapy (group A) or S-B tube followed by sclerotherapy (group B). Randomization was performed after endoscopy by a system of random numbers. Informed consent was obtained from all patients. Standard therapy, including blood and frozen plasma transfusion, fluid and electrolytes replacement, and lactulose, was administered to patients in both groups as necessary. The severity of liver disease was stratified by the Pugh modification of Child's classification. 19 Evaluation of variceal size was based on Beppu's criteria. 20 Sclerotherapy was performed with the free-hand technique under premedication with 20 mg of buscopan intramuscularly. In rare instances, 5 mg of diazepam were administered intravenously. Oblique-viewing flexible fiberscopes (Olympus XK 10) and the Olympus NM-IK injector were utilized. 21 In patients with active bleeding, water instillation and suction was performed as soon as possible to clear the visual field. The sclerosing agent was a mixture of 3% sodium tetradecyl sulfate and 50% dextrose in water to a total concentration of 1.5% sodium tetradecyl sulfate. All injections were intended to be intravariceal. Approximately 3 to 6 ml of sclerosant were injected just below the bleeding point. Subsequently, other varices were injected circumferentially above the gastroesophageal junction with 3 to 4 ml of sclerosant per varix, with a total dose not more than 25 ml during each session. In group B, a Minnesota 4-lumen S-B tube was passed through the nose immediately after diagnostic endoscopy. Before passage, the balloons were checked for leaks and were lubricated with xylocaine jelly. The gastric balloon was slowly inflated with 150 ml of air and the tube was gradually withdrawn until firm resistance was encountered against the esophagogastric junction. The esophageal balloon was filled with an air pressure of 30 to 40 mm Hg. Nasal fixation was used but without traction. The correct position of the gastric balloon was confirmed by chest x-ray. After 12 to 24 hours, the S-B tube was removed immediately prior to sclerotherapy. The technique of sclerotherapy was the same as that used in group A. Each varix was injected with 3 to 4 ml of sclerosant. After sclerotherapy, patients in both groups were followed with vital signs and aspiration of gastric contents every 2 hours until clear aspirates were obtained and then every 4 hours until 24 hours elapsed. If clear aspirates appeared for 24 hours, then the nasogastric tube was removed and feeding was resumed. Initial success was defined as the absence of blood in the gastric aspirate and stabilization of vital signs and hematocrit for 24 hours after completion of sclerotherapy. Rebleeding was defined as the reappearance of hematemesis and/or melena with unstable vital signs during the same hospitalization, and the bleeding source was endoscopically proven to be from esophageal varices. Re-bleeding patients 422
were treated with the same protocol as the original treatment if their families agreed. Patients in whom initial success could not be achieved were subsequently treated with vasopressin or somatostatin infusion or by insertion of an S-B tube. After successful control of active variceal bleeding by sclerotherapy, patients in either group received another session of elective sclerotherapy at a I-week interval. They were then discharged and received subsequent sclerotherapy every 2 weeks until complete obliteration of varices. The mean observation period in this study was 17 ± 5 days in group A and 20 ± 6 days in group B. Data were analyzed by the chi-square test, Fisher's exact test, and Student's t test when appropriate. Statistical significance is defined as p < 0.05.
RESULTS
Group A consisted of 29 patients and group B COnsisted of 31 patients. Both groups were comparable with respect to age (60 ± 7 vs. 58 ± 8 years), sex (24 vs. 27 males), etiologies of cirrhosis (post-hepatitic 20 vs. 21, alcoholic 4 vs. 5, primary biliary cirrhosis 2 vs. 1, cryptogenic 3 vs. 4), variceal grading, amount of prior blood transfusion (2.8 ± 1.8 vs. 3.0 ± 1.6 units), and grades of Child-Pugh classification. There were 5 Child's A, 12 Child's B, and 12 Child's C patients in group A. Group B consisted of 4 Child's A, 12 Child's B, and 15 Child's C individuals. In group A, 9 patients had fresh blood in the esophagus and 20 patients had spurting or active oozing of fresh blood from varices immediately before sclerotherapy. Among them, three cases were completely inaccessible due to severe hemorrhage and an obscured visual field. They were considered to be treatment failures. One was then treated with pitressin but exsanguinated. The other two were subsequently treated by the S-B tube. In contrast, in group B, 25 patients had complete cessation of variceal bleeding after removal of the S-B tube (mean duration of S-B tube insertion was 16 hours). Six patients bled continuously in spite of insertion of an S-B tube that was readjusted by experienced medical staff. One patient bled incessantly even after 24 hours of S-B tube tamponade. His bleeding was later controlled by EIS. One patient died of uncontrolled variceal bleeding after the 10-hr placement of an S-B tube (before EIS was done). The others received sclerotherapy after 12 hours of S-B tube tamponade to prevent further bleeding. Initial success was achieved in 22 patients (76%) in group A and in 24 patients (81%) in group B (p = 0.89). Six patients (27%) in group A had 8 episodes of re-bleeding, whereas 12 of 24 patients (50%) in group B re-bled (p = 0.11). In group A, six of seven episodes of re-bleeding were controlled by immediate EIS again. One episode was later controlled by vasopressin infusion and the other one died SOOn after re-bleeding GASTROINTESTINAL ENDOSCOPY
occurred. In group B, 8 of 10 episodes were controlled by the same treatment again. Two patients died of rebleeding. The other two were controlled by vasopressin. The mean volumes of sclerosant used during initial sclerotherapy were comparable between both groups. However, the amount of blood component requirement after randomization was significantly lower in group A (Table 1). In group A, initial success was achieved in 14 of 20 (70%) patients with brisk bleeding, as compared with 8 of 9 (89%) patients without brisk bleeding (p = 0.92). In group B, the initial success rate with subsequent EIS was 80% in patients who stopped bleeding with the use of an S-B tube, the same as in those who bled continuously despite the use of an S-B tube. Major complications and mortality are shown in· Table 2. Major complications including deep esophageal ulcers, aspiration pneumonia, and septicemia were more frequently encountered in group B than in group A (39% vs. 14%, p < 0.05). Seven patients in group A (24%) and 13 patients in group B (42%) died during hospitalization (p = 0.14). The major causes of death were uncontrolled variceal bleeding and hepatic failure. It is of note that 16% in group Band 3% in group A died of infection (p = 0.15). DISCUSSION
Prior S-B tube tamponade before sclerotherapy is commonly used because it provides a better visual Table 1. Results of treatment Initial success Re-bleeding Definite control Sclerosant consumption (ml) Blood transfusion (units)
Group A
Group B
p
22/29 (76%) 6/22 (27%) 20/29 (72%) 16 ± 3 b
24/31 (81 %) 12/24 (50%) 20/31 (64%) 13 ± 4
NS· NS NS NS
3.7 ± 2.5
6.2 ± 3.2
Injection sclerotherapy preceded by esophageal tamponade versus immediate sclerotherapy in arresting active variceal bleeding: a prospective randomized trial Gin-Ho Lo, MD, Kwok-Hung Lai, MD Wai-Wah Ng, MD, Tseng-Nip Tam, MD Shou-Dong Lee, MD, Yang-Te Tsai, MD Kwang-Juei Lo, MD Taiwan, Republic of China
To investigate whether Sengstaken-Blakemore tube tamponade is needed before emergency sclerotherapy, 60 patients with active esophageal variceal bleeding were randomized to receive either immediate injection sclerotherapy (group A) or sclerotherapy preceded by balloon tamponade (group B). Three patients in group A (10%) were completely inaccessible to sclerotherapy. Initial success in stopping bleeding at 24 hours after sclerotherapy was 76% in group A and 81% in group B (p = 0.89). Re-bleeding rate was 27% in group A versus 50% in group B (p = 0.11). Blood requirement was significantly less in group A (3.7 ± 2.5 units vs. 6.2 ± 3.2 units, p < 0.01). Major complications were also significantly less frequently encountered in group A than in group B (14% vs. 39%, P < 0.05). In-hospital mortality was 24% in group A and 42% in group B (p = 0.14). We conclude that the efficacy of immediate sclerotherapy is comparable to that of delayed sclerotherapy preceded by balloon tamponade. Additionally, significantly less blood requirement and fewer complications were noted in the immediate sclerotherapy group. Thus, emergency sclerotherapy without prior balloon tamponade is feasible and recommended in most patients with acute esophageal variceal hemorrhage. (Gastrointest Endosc 1992;38:421-424)
Hemorrhage from esophageal varices is a serious complication of portal hypertension. Medical treatments including vasopressin, somatostatin infusion, Sengstaken-Blakemore tube (S-B tube) insertion/-5 and surgical intervention6 do not substantially increase survival. In recent years, endoscopic injection sclerotherapy (EIS) has received increasing attention as a valuable modality in arresting acute esophageal variceal bleeding. 7- 15 Controlled studies have shown that EIS is superior to the SoB tube and vasopressin in cessation of active variceal bleeding. 9 , 12-15 However, Received September 30,1991. For revision January 8,1992. Accepted February 10, 1992. From the Department of Medicine, Division of Gastroenterology, Veterans General Hospital-Kaohsiung, Taipei & Taichung, National Yang-Ming Medical College, Taipei, Taiwan, Republic of China. Reprint requests: Kwok-Hung Lai, MD, Department of Medicine, Division of Gastroenterology, Veterans General Hospital-Kaohsiung, 386 Ta-Chung 1st Rd, Kaohsiung 813, Taiwan, Republic of China. VOLUME 38, NO.4, 1992
use of the S-B tube before sclerotherapy has been widely adopted in most studies. 7, 8, 10-12, 14 Other uncontrolled and retrospective studies have compared the efficacy of emergency versus delayed sclerotherapy,1618 but it is still unknown whether prior SoB tube tamponade is mandatory before EIS during brisk variceal bleeding. This prospective, randomized study investigated the role of SoB tube tamponade and immediate EIS in controlling active esophageal variceal hemorrhage, re-bleeding, and outcome. MATERIALS AND METHODS
Between July 1988 and June 1990,60 consecutive patients admitted to the Veterans General Hospital-Taipei for acute variceal bleeding were enrolled in the trial. All of the patients were proven to be actively bleeding from esophageal varices by emergency endoscopy within 12 hours of admission. Active variceal bleeding was diagnosed when blood was 421
directly seen by endoscopy to issue from a varix or when fresh blood was seen in the esophagus of patients with red color signs on varices and no other potential site of bleeding was discovered. 3 Another 27 patients with acute variceal bleeding were excluded: 15 were associated with hepatocellular carcinoma, 4 were associated with peptic ulcers, 2 had bleeding from fundal varices, and 6 had stopped bleeding on endoscopic examination. Patients included in the trial were randomized to receive either immediate sclerotherapy (group A) or S-B tube followed by sclerotherapy (group B). Randomization was performed after endoscopy by a system of random numbers. Informed consent was obtained from all patients. Standard therapy, including blood and frozen plasma transfusion, fluid and electrolytes replacement, and lactulose, was administered to patients in both groups as necessary. The severity of liver disease was stratified by the Pugh modification of Child's classification. 19 Evaluation of variceal size was based on Beppu's criteria. 20 Sclerotherapy was performed with the free-hand technique under premedication with 20 mg of buscopan intramuscularly. In rare instances, 5 mg of diazepam were administered intravenously. Oblique-viewing flexible fiberscopes (Olympus XK 10) and the Olympus NM-IK injector were utilized. 21 In patients with active bleeding, water instillation and suction was performed as soon as possible to clear the visual field. The sclerosing agent was a mixture of 3% sodium tetradecyl sulfate and 50% dextrose in water to a total concentration of 1.5% sodium tetradecyl sulfate. All injections were intended to be intravariceal. Approximately 3 to 6 ml of sclerosant were injected just below the bleeding point. Subsequently, other varices were injected circumferentially above the gastroesophageal junction with 3 to 4 ml of sclerosant per varix, with a total dose not more than 25 ml during each session. In group B, a Minnesota 4-lumen S-B tube was passed through the nose immediately after diagnostic endoscopy. Before passage, the balloons were checked for leaks and were lubricated with xylocaine jelly. The gastric balloon was slowly inflated with 150 ml of air and the tube was gradually withdrawn until firm resistance was encountered against the esophagogastric junction. The esophageal balloon was filled with an air pressure of 30 to 40 mm Hg. Nasal fixation was used but without traction. The correct position of the gastric balloon was confirmed by chest x-ray. After 12 to 24 hours, the S-B tube was removed immediately prior to sclerotherapy. The technique of sclerotherapy was the same as that used in group A. Each varix was injected with 3 to 4 ml of sclerosant. After sclerotherapy, patients in both groups were followed with vital signs and aspiration of gastric contents every 2 hours until clear aspirates were obtained and then every 4 hours until 24 hours elapsed. If clear aspirates appeared for 24 hours, then the nasogastric tube was removed and feeding was resumed. Initial success was defined as the absence of blood in the gastric aspirate and stabilization of vital signs and hematocrit for 24 hours after completion of sclerotherapy. Rebleeding was defined as the reappearance of hematemesis and/or melena with unstable vital signs during the same hospitalization, and the bleeding source was endoscopically proven to be from esophageal varices. Re-bleeding patients 422
were treated with the same protocol as the original treatment if their families agreed. Patients in whom initial success could not be achieved were subsequently treated with vasopressin or somatostatin infusion or by insertion of an S-B tube. After successful control of active variceal bleeding by sclerotherapy, patients in either group received another session of elective sclerotherapy at a I-week interval. They were then discharged and received subsequent sclerotherapy every 2 weeks until complete obliteration of varices. The mean observation period in this study was 17 ± 5 days in group A and 20 ± 6 days in group B. Data were analyzed by the chi-square test, Fisher's exact test, and Student's t test when appropriate. Statistical significance is defined as p < 0.05.
RESULTS
Group A consisted of 29 patients and group B COnsisted of 31 patients. Both groups were comparable with respect to age (60 ± 7 vs. 58 ± 8 years), sex (24 vs. 27 males), etiologies of cirrhosis (post-hepatitic 20 vs. 21, alcoholic 4 vs. 5, primary biliary cirrhosis 2 vs. 1, cryptogenic 3 vs. 4), variceal grading, amount of prior blood transfusion (2.8 ± 1.8 vs. 3.0 ± 1.6 units), and grades of Child-Pugh classification. There were 5 Child's A, 12 Child's B, and 12 Child's C patients in group A. Group B consisted of 4 Child's A, 12 Child's B, and 15 Child's C individuals. In group A, 9 patients had fresh blood in the esophagus and 20 patients had spurting or active oozing of fresh blood from varices immediately before sclerotherapy. Among them, three cases were completely inaccessible due to severe hemorrhage and an obscured visual field. They were considered to be treatment failures. One was then treated with pitressin but exsanguinated. The other two were subsequently treated by the S-B tube. In contrast, in group B, 25 patients had complete cessation of variceal bleeding after removal of the S-B tube (mean duration of S-B tube insertion was 16 hours). Six patients bled continuously in spite of insertion of an S-B tube that was readjusted by experienced medical staff. One patient bled incessantly even after 24 hours of S-B tube tamponade. His bleeding was later controlled by EIS. One patient died of uncontrolled variceal bleeding after the 10-hr placement of an S-B tube (before EIS was done). The others received sclerotherapy after 12 hours of S-B tube tamponade to prevent further bleeding. Initial success was achieved in 22 patients (76%) in group A and in 24 patients (81%) in group B (p = 0.89). Six patients (27%) in group A had 8 episodes of re-bleeding, whereas 12 of 24 patients (50%) in group B re-bled (p = 0.11). In group A, six of seven episodes of re-bleeding were controlled by immediate EIS again. One episode was later controlled by vasopressin infusion and the other one died SOOn after re-bleeding GASTROINTESTINAL ENDOSCOPY
occurred. In group B, 8 of 10 episodes were controlled by the same treatment again. Two patients died of rebleeding. The other two were controlled by vasopressin. The mean volumes of sclerosant used during initial sclerotherapy were comparable between both groups. However, the amount of blood component requirement after randomization was significantly lower in group A (Table 1). In group A, initial success was achieved in 14 of 20 (70%) patients with brisk bleeding, as compared with 8 of 9 (89%) patients without brisk bleeding (p = 0.92). In group B, the initial success rate with subsequent EIS was 80% in patients who stopped bleeding with the use of an S-B tube, the same as in those who bled continuously despite the use of an S-B tube. Major complications and mortality are shown in· Table 2. Major complications including deep esophageal ulcers, aspiration pneumonia, and septicemia were more frequently encountered in group B than in group A (39% vs. 14%, p < 0.05). Seven patients in group A (24%) and 13 patients in group B (42%) died during hospitalization (p = 0.14). The major causes of death were uncontrolled variceal bleeding and hepatic failure. It is of note that 16% in group Band 3% in group A died of infection (p = 0.15). DISCUSSION
Prior S-B tube tamponade before sclerotherapy is commonly used because it provides a better visual Table 1. Results of treatment Initial success Re-bleeding Definite control Sclerosant consumption (ml) Blood transfusion (units)
Group A
Group B
p
22/29 (76%) 6/22 (27%) 20/29 (72%) 16 ± 3 b
24/31 (81 %) 12/24 (50%) 20/31 (64%) 13 ± 4
NS· NS NS NS
3.7 ± 2.5
6.2 ± 3.2
