Scandinavian Journal of Gastroenterology
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Propranolol May Prevent Recurrence of Oesophageal Varices after Obliteration by Endoscopic Sclerotherapy L. S. Jensen & N. Krarup To cite this article: L. S. Jensen & N. Krarup (1990) Propranolol May Prevent Recurrence of Oesophageal Varices after Obliteration by Endoscopic Sclerotherapy, Scandinavian Journal of Gastroenterology, 25:4, 352-356, DOI: 10.3109/00365529009095498 To link to this article: http://dx.doi.org/10.3109/00365529009095498
Published online: 08 Jul 2009.
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Date: 23 April 2016, At: 17:49
Propranolol May Prevent Recurrence of Oesophageal Varices after Obliteration by Endoscopic Sclerotherapy L. S. JENSEN & N. KRARUP Surgical Gastroenterological Dept. L, Aarhus Kommunehospital, Aarhus, Denmark
Downloaded by [UNSW Library] at 17:49 23 April 2016
Jensen LS, Krarup N. Propranolol may prevent recurrence of oesophageal varices after obliteration by endoscopic sclerotherapy. Scand J Gastroenterol1990,25,352356
In 29 patients admitted with their first bleeding episode from oesophageal varices the varices were obliterated within 6 months by treatment with serial endoscopic sclerotherapy and propranolol or with sclerotherapy only. The patients were checked regularly during 18 months after the varices had been obliterated. Variceal recurrence was found in 11 patients (73%; 95% confidence limits, 4 5 9 2 %) treated with sclerotherapy only and in 2 patients (15%; 95% confidence limits, 2 4 3 % ; p < 0.01) treated with sclerotherapy and propranolol. In nine patients (69%) with recurrence significant variceal bleeding occurred. All recurrences were observed within 12 months after the initial obliteration. Variceal recurrence occurred in 3 Child A patients and in 10 Child B or C patients. All bleeding occurred in Child B or C patients. It is concluded that obliteration of oesophageal varices by endoscopic sclerotherapy and propranolol may be more effective in the long-term control of variceal recurrence than treatment with sclerotherapy only. Key words: Oesophageal varices; propranolol; recurrence; sclerotherapy Lone S . Jensen, M . D . , Ph.D., Dept. of Surgery I , Aarhus amtssygehus, DK-8000 Aarhus C, Denmark
Recurrence of oesophageal varices after initial obliteration by endoscopic sclerotherapy occurs in about 60% of patients (1-3). The recurrence is nearly always observed within 12 months after initial obliteration, which emphasizes the importance of regular follow-up examination in this period (2). Long-term administration of propranolol has been found to reduce the risk of recurrent gastrointestinal bleeding and to improve the 2-year survival rate (4).However, in another study (5) no such effect of propranolol was found. In a previous study (6) we found that administration of oral propranolol reduced the frequency of variceal rebleeding until variceal obliteration was obtained by means of endoscopic sclerotherapy. The aim of the present study was to investigate the recurrence rate of oesophageal varices after primary obliteration by means of endoscopic sclerotherapy and propranolol.
MATERIALS AND METHODS Patients The investigated group consisted of 29 patients primarily admitted with their first bleeding episode from oesophageal varices and in whom the varices were successfully obliterated (6). The index bleed was controlled by emergency endoscopic sclerotherapy. Thereafter the patients were treated every 4th week with sessions of paravariceal sclerotherapy until complete obliteration of the varices had occurred. Furthermore, the patients were randomized in a double-blind manner to receive either 160 mg oral propranolol per day (given as a slow-release preparation of Indera]@)for 6 months or matching placebo for the same period. During the next year the patients were checked every 3rd month and in the case of bleeding episodes and, finally, after a further 6 months. Thus the patients were followed up for 2 years after their first bleeding episode. The
Downloaded by [UNSW Library] at 17:49 23 April 2016
Propranolol and Variceal Recurrence
patients gave oral informed consent, and the study protocol was approved by the official ethical committee. Endoscopy was performed with a flexible endoscope, and variceal obliteration was defined as absence of variceal columns in the oesophageal lumen. When recurrence of variceal columns was observed, either at routine follow-up examination or after a new bleeding episode, these were injected with paravariceal depots of 0.5-1.0 ml Aethoxysclerol@2 % . Injection sclerotherapy was repeated every month until obliteration was achieved again, and the patients then continued the follow-up in accordance with the protocol. Patients were classified at entry into the trial and at the 2-year follow-up examination, in accordance with Pugh‘s modification of Child’s classification (7). Statistical unulysis Results are expressed in median and ranges. Differences between the groups were tested with Fisher’s exact test or the Mann-Whitney test. Results are considered significant at p < 0.05; 95% confidence limits for differences were calculated.
RESULTS Fourteen patients were treated with sclerotherapy and propranolol, and 15 with sclerotherapy and placebo. The age of the patients was 47 (range, 27-71) years at entry, with no differences between the groups. There were four women in the trial, all of whom were allocated to the placebo group.
353
Variceal recurrence after initial obliteration was observed in 13 patients (48%). In patients given propranolol during the first 6 months variceal recurrence was found in two (15%; 95% confidence limits, 2 4 3 % ) . In 11 of the patients treated with sclerotherapy only (73%; 95% confidence limits, 45-92%) variceal recurrence occurred. This beneficial effect of propranolol was significant (p < 0.01), and the difference in variceal recurrence between the two groups was 0.58 0.37. In nine patients (69%) the variceal recurrence presented as an episode of variceal bleeding, whereas four patients had their recurrence diagnosed at routine follow-up examination (Table I). All the recurrences occurred within 12 months after primary obliteration (Table I). Three patients treated with sclerotherapy only had a total of two, two. and three bleeding episodes from recurrent varices. In all rebleeding episodes haemostasis was achieved by means of emergency endoscopic sclerotherapy. The transfusion requirements during the rebleeding episodes were 3 (@8) units for the patients in the placebo group and 2 units for the patient in the propranolol group. The recurrent varices were obliterated by two (one to five) sessions of sclerotherapy. No gastric varices were seen at the control investigations. In three patients (one propranolol and two placebo) recurrent varices occurred at a second occasion 6, 6, and 10 months, respectively, after the previous recurrence. None of these varices caused clinical bleeding episodes, and they were eradicated after a single session of sclerotherapy. None of the patients developed ulcerations or strictures after sclerotherapy .
*
Recurrence of varices
Primary variceal obliteration was achieved in 5 (range, 1-6) months in patients treated with sclerotherapy and propranolol and in 5 (range, 47) months in patients treated with sclerotherapy only. In both treatment groups two-thirds of the patients had large varices at entry, and one-third medium-sized varices. During the follow-up period before obliteration of the varices 3 patients receiving propranolol had variceal rebleeding, whereas 12 patients receiving placebo had episodes of rebleeding (p c 0.05).
Clinical course One patient treated with sclerotherapy and propranolol died of a subdural haemorrhage 20 months after his first bleeding episode. A t autopsy no recurrent varices were found. O n e patient treated with sclerotherapy only died of hepatic insufficiency 12 months after inclusion in the study. At that time there was no variceal recurrence. The Child classification for the other patients at entry t o the study and after 2 years is shown in
354
L. S. Jensen & N . Krarup
Table I. Recurrence of oesophageal varices after primary obliteration Months
Sclerotherapy propranolol Sclerotherapy placebo
@3
3-6
6-12
12-18
1 (1B)*
1
0
0
2 (2B)
6 (3B)
0
+
+
3 (3B)
* B = the number of patients presenting with variceal bleeding. Table 11. Child classification
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Sclerotherapy + propra noioI
Sclerotherapy placebo
+
Child’s grade
I*
11*
I
I1
A
3 7 3
7 6 0
4 6 4
5 8
B C
1
* I = the primary bleeding episode; I1 = the 2-year follow-up examination.
Table 111. Alcohol consumption Sclerotherapy propranolol
Abstinence Moderate drinkers Heavy drinkers
I
=
+
Sclerotherapy placebo
+
I*
11*
I
I1
2 7 4
6 5 2
1
4
5 8
5 5
the primary bleeding episode; I1 = the 2-year follow-up examination.
Table 11. At entry to the trial seven of the patients who completed the study belonged to Child C, whereas only one patient was still Child C after 2 years. Furthermore, Child A included 7 patients at entry and 12 after 2 years, indicating that patients had changed from Child C to B and from B to A. Ten of the patients with recurrent varices were classified as Child B or C at follow-up. AU patients with recurrent varices and rebleeding episodes belonged to Child group B or C. The patients’ alcohol consumption at randomization and at the 2-year follow-up examination is demonstrated in Table 111. Recurrence of varices was found in 3 patients with alcohol abstinence (Child A) and in 10 who were still drinking (Child B and C).
DISCUSSION The present study indicates that recurrence of oesophageal varices after primary obliteration by sclerotherapy may be prevented when the sclerotherapy is combined with propranolol medication. All patients in this study were admitted with their first bleeding episode from oesophageal varices. Primary obliteration of the varices was completed after a median of five sessions of sclerotherapy both in patients treated with sclerotherapy and propranolol and in those treated with sclerotherapy only. However, in the group treated with sclerotherapy only there were significant more rebleeding episodes before obliteration was obtained (6).
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Propranolol and Variceal Recurrence
The recurrence of oesophageal varices in 73% of the patients treated with sclerotherapy only is in accordance with the findings in some other studies ( 1 , 3 ) . In contrast. Sarin et al. (8) reported recurrences in only 19% of patients, with rebleeding in only 2.9%. which may be due to the close follow-up examinations with monthly endoscopies after initial obliteration. In the present study 72% of the variceal recurrences caused manifest bleeding episodes. All bleeding episodes from recurrent varices were stopped by endoscopic sclerotherapy without the use of a Sengstaken tube. The varices were obliterated by fewer sessions of sclerotherapy than used after the bleeding at entry to the study, indicating that recurrent varices were of smaller size. The marked reduction in the variceal recurrence rate when sclerotherapy was combined with propranolol was maintained throughout the study (Table I). The haemodynamic effects of propranolol on variceal flow and pressure and the concomitant effect on vascular structure and compliance (9) probably cause a more effective occlusion of the varices than when sclerotherapy is used alone. Changes in vascular wall structure is also seen in other vessels when flow is decreased (10,ll). Recurrence and rebleeding were most pronounced in Child B and C patients, as only 25% of Child A patients had recurrence and no bleeding episodes. In Child B and C 66% had recurrence, and 90% of these presented as a bleeding episode. The improvement in the clinical condition was evident both in patients treated with sclerotherapy and propranolol and in patients treated with sclerotherapy only. This is in accordance with the findings of Warren et al. (12), who showed that hepatocyte function, as determined by the galactose elimination capacity, was improved after endoscopic sclerotherapy. Sarin et al. (8) also found a significant improvement of liver function in Child C patients after variceal obliteration by sclerotherapy. The efficacy of endoscopic sclerotherapy in improving liver function may be due to an increase in liver blood flow and a concomitant decrease in blood flow through the oesophageal varices, as previously demonstrated in an experimental study (9).
355
In the present study eleven patients had stopped drinking. W e had not performed any objective tests to monitor the patients’ alcohol consumption, but it was remarkable that recurrence only was seen in 3 patients who claimed to have stayed abstinent, whereas the remaining 10 recurrences were seen in patients still drinking. Furthermore, the patient with three bleeding episodes from recurrent varices was a patient with a great alcohol consumption and still belonging to Child C. There were no statistically significant differences in drinking habits between the two treatment groups, even though there was a tendency to more heavy drinkers in the placebo group both at entry and at follow-up examination. This effect of randomization can be explained by the small number of patients. The difference in both variceal rebleeding and variceal recurrence between the two treatment groups may then also to some extent be explained by differences in drinking habits. Therefore, it further appears that both alcohol abstinence and frequent endoscopic control examinations and treatment of recurrences may stabilize the liver disease and contribute to improvement in hepatic function. O n the basis of observations from the present study we consider it important to follow up patients intensively during the first year after primary obliteration. Only two patients died in the follow-up period after variceal obliteration. However. any possible effect on the overall survival cannot be judged from the present study. as deaths before variceal obliteration were excluded. Furthermore. a conservatively treated control group was not included in this trial. In conclusion, sclerotherapy is an effective treatment of oesophageal varices. but when sclerotherapy is combined with propranolol medication. two advantages seem to be obtained: 1) a decrease in the number of rebleeding episodes until the varices are obliterated; and 2) a reduction in the tendency for the varices to recur. Apparently, there is no indication that the propranolol treatment should be prolonged beyond initial variceal obliteration. The recurrence of oesophageal varices and rebleeding is also related to Child’s classification and drinking habits.
356
L. S. Jensen & N. Krarup
Downloaded by [UNSW Library] at 17:49 23 April 2016
REFERENCES 1. Westaby D, MacDougall B, Williams R. Improved survival following injection sclerotherapy for esophageal varices: Final analysis of a controlled trial. Hepatology 1985, 5, 827-830 2. Westaby D, Williams R. Follow-up study after sclerotherapy. Scand J Gastroenterol1984,19(suppl 102), 71-75 3. Terblanche J, Kahn D, Campbell JAH, et al. Failure of repeated injection sclerotherapy to improve long-term survival after oesophageal variceal bleeding. A five-year prospective controlled trial. Lancet 1983, 2, 1328-1332 4. Lebrec D, Poynard T. Bernuau J, et al. A randomized controlled study of propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis. A final report. Hepatology 1984, 4, 355-358 5. Villeneuve JP, Pomier-Layrargues G , InfanteRivard C, et al. Propranolol for the prevention of recurrent variceal hemorrhage: A controlled trial. Hepatology 1986, 6, 1239-1243 6. Jensen LS, Krarup N. Propranolol in prevention of rebleeding from oesophageal varices during the course of endoscopic sclerotherapy. Scand J Gastroenterol 1989, 24, 339-345 Received 11 August 1989 Accepted 12 October 1989
7. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus €or bleeding oesophageal varices. Br J Surg 1973, 60, 646-4549 8. Sarin SK, Sachdev G, Nanda R. Follow-up of patients after variceal eradication. Ann Surg 1986, 204.78-82 9. Jensen LS, Krarup N, Juhl CO, Nielsen TH, Larsen JA. Endoscopic, portographic, and hemodynamic evaluation of prolonged propranolol administration in pigs with experimental portal hypertension and esophageal varices. Scand J Gastroenteroll989,24, 2 13-222 10. Rodbard S. Vascular caliber. Cardiology 1975, 60, 4-49 11. Langille L, O’Donnell F. Reductions in arterial diameter produced by chronic decreases in blood flow are endothelium-dependent. Science 1986,231. 40.5407 12. Warren WD, Henderson JM, Millikan WJ. et al. Distal splenorenal shunt versus endoscopic sclerotherapy for long-term management of variceal bleeding. Ann Surg 1986, 203, 454-462 13. Jensen LS, Krarup N, Larsen JA, Juhl CO, Nielsen TH, Dybdahl H. Effect of endoscopic sclerotherapy of esophageal varices on liver blood flow and liver function. Scand J Gastroenterol 1987, 22, 619-626
ISSN: 0036-5521 (Print) 1502-7708 (Online) Journal homepage: http://www.tandfonline.com/loi/igas20
Propranolol May Prevent Recurrence of Oesophageal Varices after Obliteration by Endoscopic Sclerotherapy L. S. Jensen & N. Krarup To cite this article: L. S. Jensen & N. Krarup (1990) Propranolol May Prevent Recurrence of Oesophageal Varices after Obliteration by Endoscopic Sclerotherapy, Scandinavian Journal of Gastroenterology, 25:4, 352-356, DOI: 10.3109/00365529009095498 To link to this article: http://dx.doi.org/10.3109/00365529009095498
Published online: 08 Jul 2009.
Submit your article to this journal
Article views: 3
View related articles
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=igas20 Download by: [UNSW Library]
Date: 23 April 2016, At: 17:49
Propranolol May Prevent Recurrence of Oesophageal Varices after Obliteration by Endoscopic Sclerotherapy L. S. JENSEN & N. KRARUP Surgical Gastroenterological Dept. L, Aarhus Kommunehospital, Aarhus, Denmark
Downloaded by [UNSW Library] at 17:49 23 April 2016
Jensen LS, Krarup N. Propranolol may prevent recurrence of oesophageal varices after obliteration by endoscopic sclerotherapy. Scand J Gastroenterol1990,25,352356
In 29 patients admitted with their first bleeding episode from oesophageal varices the varices were obliterated within 6 months by treatment with serial endoscopic sclerotherapy and propranolol or with sclerotherapy only. The patients were checked regularly during 18 months after the varices had been obliterated. Variceal recurrence was found in 11 patients (73%; 95% confidence limits, 4 5 9 2 %) treated with sclerotherapy only and in 2 patients (15%; 95% confidence limits, 2 4 3 % ; p < 0.01) treated with sclerotherapy and propranolol. In nine patients (69%) with recurrence significant variceal bleeding occurred. All recurrences were observed within 12 months after the initial obliteration. Variceal recurrence occurred in 3 Child A patients and in 10 Child B or C patients. All bleeding occurred in Child B or C patients. It is concluded that obliteration of oesophageal varices by endoscopic sclerotherapy and propranolol may be more effective in the long-term control of variceal recurrence than treatment with sclerotherapy only. Key words: Oesophageal varices; propranolol; recurrence; sclerotherapy Lone S . Jensen, M . D . , Ph.D., Dept. of Surgery I , Aarhus amtssygehus, DK-8000 Aarhus C, Denmark
Recurrence of oesophageal varices after initial obliteration by endoscopic sclerotherapy occurs in about 60% of patients (1-3). The recurrence is nearly always observed within 12 months after initial obliteration, which emphasizes the importance of regular follow-up examination in this period (2). Long-term administration of propranolol has been found to reduce the risk of recurrent gastrointestinal bleeding and to improve the 2-year survival rate (4).However, in another study (5) no such effect of propranolol was found. In a previous study (6) we found that administration of oral propranolol reduced the frequency of variceal rebleeding until variceal obliteration was obtained by means of endoscopic sclerotherapy. The aim of the present study was to investigate the recurrence rate of oesophageal varices after primary obliteration by means of endoscopic sclerotherapy and propranolol.
MATERIALS AND METHODS Patients The investigated group consisted of 29 patients primarily admitted with their first bleeding episode from oesophageal varices and in whom the varices were successfully obliterated (6). The index bleed was controlled by emergency endoscopic sclerotherapy. Thereafter the patients were treated every 4th week with sessions of paravariceal sclerotherapy until complete obliteration of the varices had occurred. Furthermore, the patients were randomized in a double-blind manner to receive either 160 mg oral propranolol per day (given as a slow-release preparation of Indera]@)for 6 months or matching placebo for the same period. During the next year the patients were checked every 3rd month and in the case of bleeding episodes and, finally, after a further 6 months. Thus the patients were followed up for 2 years after their first bleeding episode. The
Downloaded by [UNSW Library] at 17:49 23 April 2016
Propranolol and Variceal Recurrence
patients gave oral informed consent, and the study protocol was approved by the official ethical committee. Endoscopy was performed with a flexible endoscope, and variceal obliteration was defined as absence of variceal columns in the oesophageal lumen. When recurrence of variceal columns was observed, either at routine follow-up examination or after a new bleeding episode, these were injected with paravariceal depots of 0.5-1.0 ml Aethoxysclerol@2 % . Injection sclerotherapy was repeated every month until obliteration was achieved again, and the patients then continued the follow-up in accordance with the protocol. Patients were classified at entry into the trial and at the 2-year follow-up examination, in accordance with Pugh‘s modification of Child’s classification (7). Statistical unulysis Results are expressed in median and ranges. Differences between the groups were tested with Fisher’s exact test or the Mann-Whitney test. Results are considered significant at p < 0.05; 95% confidence limits for differences were calculated.
RESULTS Fourteen patients were treated with sclerotherapy and propranolol, and 15 with sclerotherapy and placebo. The age of the patients was 47 (range, 27-71) years at entry, with no differences between the groups. There were four women in the trial, all of whom were allocated to the placebo group.
353
Variceal recurrence after initial obliteration was observed in 13 patients (48%). In patients given propranolol during the first 6 months variceal recurrence was found in two (15%; 95% confidence limits, 2 4 3 % ) . In 11 of the patients treated with sclerotherapy only (73%; 95% confidence limits, 45-92%) variceal recurrence occurred. This beneficial effect of propranolol was significant (p < 0.01), and the difference in variceal recurrence between the two groups was 0.58 0.37. In nine patients (69%) the variceal recurrence presented as an episode of variceal bleeding, whereas four patients had their recurrence diagnosed at routine follow-up examination (Table I). All the recurrences occurred within 12 months after primary obliteration (Table I). Three patients treated with sclerotherapy only had a total of two, two. and three bleeding episodes from recurrent varices. In all rebleeding episodes haemostasis was achieved by means of emergency endoscopic sclerotherapy. The transfusion requirements during the rebleeding episodes were 3 (@8) units for the patients in the placebo group and 2 units for the patient in the propranolol group. The recurrent varices were obliterated by two (one to five) sessions of sclerotherapy. No gastric varices were seen at the control investigations. In three patients (one propranolol and two placebo) recurrent varices occurred at a second occasion 6, 6, and 10 months, respectively, after the previous recurrence. None of these varices caused clinical bleeding episodes, and they were eradicated after a single session of sclerotherapy. None of the patients developed ulcerations or strictures after sclerotherapy .
*
Recurrence of varices
Primary variceal obliteration was achieved in 5 (range, 1-6) months in patients treated with sclerotherapy and propranolol and in 5 (range, 47) months in patients treated with sclerotherapy only. In both treatment groups two-thirds of the patients had large varices at entry, and one-third medium-sized varices. During the follow-up period before obliteration of the varices 3 patients receiving propranolol had variceal rebleeding, whereas 12 patients receiving placebo had episodes of rebleeding (p c 0.05).
Clinical course One patient treated with sclerotherapy and propranolol died of a subdural haemorrhage 20 months after his first bleeding episode. A t autopsy no recurrent varices were found. O n e patient treated with sclerotherapy only died of hepatic insufficiency 12 months after inclusion in the study. At that time there was no variceal recurrence. The Child classification for the other patients at entry t o the study and after 2 years is shown in
354
L. S. Jensen & N . Krarup
Table I. Recurrence of oesophageal varices after primary obliteration Months
Sclerotherapy propranolol Sclerotherapy placebo
@3
3-6
6-12
12-18
1 (1B)*
1
0
0
2 (2B)
6 (3B)
0
+
+
3 (3B)
* B = the number of patients presenting with variceal bleeding. Table 11. Child classification
Downloaded by [UNSW Library] at 17:49 23 April 2016
Sclerotherapy + propra noioI
Sclerotherapy placebo
+
Child’s grade
I*
11*
I
I1
A
3 7 3
7 6 0
4 6 4
5 8
B C
1
* I = the primary bleeding episode; I1 = the 2-year follow-up examination.
Table 111. Alcohol consumption Sclerotherapy propranolol
Abstinence Moderate drinkers Heavy drinkers
I
=
+
Sclerotherapy placebo
+
I*
11*
I
I1
2 7 4
6 5 2
1
4
5 8
5 5
the primary bleeding episode; I1 = the 2-year follow-up examination.
Table 11. At entry to the trial seven of the patients who completed the study belonged to Child C, whereas only one patient was still Child C after 2 years. Furthermore, Child A included 7 patients at entry and 12 after 2 years, indicating that patients had changed from Child C to B and from B to A. Ten of the patients with recurrent varices were classified as Child B or C at follow-up. AU patients with recurrent varices and rebleeding episodes belonged to Child group B or C. The patients’ alcohol consumption at randomization and at the 2-year follow-up examination is demonstrated in Table 111. Recurrence of varices was found in 3 patients with alcohol abstinence (Child A) and in 10 who were still drinking (Child B and C).
DISCUSSION The present study indicates that recurrence of oesophageal varices after primary obliteration by sclerotherapy may be prevented when the sclerotherapy is combined with propranolol medication. All patients in this study were admitted with their first bleeding episode from oesophageal varices. Primary obliteration of the varices was completed after a median of five sessions of sclerotherapy both in patients treated with sclerotherapy and propranolol and in those treated with sclerotherapy only. However, in the group treated with sclerotherapy only there were significant more rebleeding episodes before obliteration was obtained (6).
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Propranolol and Variceal Recurrence
The recurrence of oesophageal varices in 73% of the patients treated with sclerotherapy only is in accordance with the findings in some other studies ( 1 , 3 ) . In contrast. Sarin et al. (8) reported recurrences in only 19% of patients, with rebleeding in only 2.9%. which may be due to the close follow-up examinations with monthly endoscopies after initial obliteration. In the present study 72% of the variceal recurrences caused manifest bleeding episodes. All bleeding episodes from recurrent varices were stopped by endoscopic sclerotherapy without the use of a Sengstaken tube. The varices were obliterated by fewer sessions of sclerotherapy than used after the bleeding at entry to the study, indicating that recurrent varices were of smaller size. The marked reduction in the variceal recurrence rate when sclerotherapy was combined with propranolol was maintained throughout the study (Table I). The haemodynamic effects of propranolol on variceal flow and pressure and the concomitant effect on vascular structure and compliance (9) probably cause a more effective occlusion of the varices than when sclerotherapy is used alone. Changes in vascular wall structure is also seen in other vessels when flow is decreased (10,ll). Recurrence and rebleeding were most pronounced in Child B and C patients, as only 25% of Child A patients had recurrence and no bleeding episodes. In Child B and C 66% had recurrence, and 90% of these presented as a bleeding episode. The improvement in the clinical condition was evident both in patients treated with sclerotherapy and propranolol and in patients treated with sclerotherapy only. This is in accordance with the findings of Warren et al. (12), who showed that hepatocyte function, as determined by the galactose elimination capacity, was improved after endoscopic sclerotherapy. Sarin et al. (8) also found a significant improvement of liver function in Child C patients after variceal obliteration by sclerotherapy. The efficacy of endoscopic sclerotherapy in improving liver function may be due to an increase in liver blood flow and a concomitant decrease in blood flow through the oesophageal varices, as previously demonstrated in an experimental study (9).
355
In the present study eleven patients had stopped drinking. W e had not performed any objective tests to monitor the patients’ alcohol consumption, but it was remarkable that recurrence only was seen in 3 patients who claimed to have stayed abstinent, whereas the remaining 10 recurrences were seen in patients still drinking. Furthermore, the patient with three bleeding episodes from recurrent varices was a patient with a great alcohol consumption and still belonging to Child C. There were no statistically significant differences in drinking habits between the two treatment groups, even though there was a tendency to more heavy drinkers in the placebo group both at entry and at follow-up examination. This effect of randomization can be explained by the small number of patients. The difference in both variceal rebleeding and variceal recurrence between the two treatment groups may then also to some extent be explained by differences in drinking habits. Therefore, it further appears that both alcohol abstinence and frequent endoscopic control examinations and treatment of recurrences may stabilize the liver disease and contribute to improvement in hepatic function. O n the basis of observations from the present study we consider it important to follow up patients intensively during the first year after primary obliteration. Only two patients died in the follow-up period after variceal obliteration. However. any possible effect on the overall survival cannot be judged from the present study. as deaths before variceal obliteration were excluded. Furthermore. a conservatively treated control group was not included in this trial. In conclusion, sclerotherapy is an effective treatment of oesophageal varices. but when sclerotherapy is combined with propranolol medication. two advantages seem to be obtained: 1) a decrease in the number of rebleeding episodes until the varices are obliterated; and 2) a reduction in the tendency for the varices to recur. Apparently, there is no indication that the propranolol treatment should be prolonged beyond initial variceal obliteration. The recurrence of oesophageal varices and rebleeding is also related to Child’s classification and drinking habits.
356
L. S. Jensen & N. Krarup
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REFERENCES 1. Westaby D, MacDougall B, Williams R. Improved survival following injection sclerotherapy for esophageal varices: Final analysis of a controlled trial. Hepatology 1985, 5, 827-830 2. Westaby D, Williams R. Follow-up study after sclerotherapy. Scand J Gastroenterol1984,19(suppl 102), 71-75 3. Terblanche J, Kahn D, Campbell JAH, et al. Failure of repeated injection sclerotherapy to improve long-term survival after oesophageal variceal bleeding. A five-year prospective controlled trial. Lancet 1983, 2, 1328-1332 4. Lebrec D, Poynard T. Bernuau J, et al. A randomized controlled study of propranolol for prevention of recurrent gastrointestinal bleeding in patients with cirrhosis. A final report. Hepatology 1984, 4, 355-358 5. Villeneuve JP, Pomier-Layrargues G , InfanteRivard C, et al. Propranolol for the prevention of recurrent variceal hemorrhage: A controlled trial. Hepatology 1986, 6, 1239-1243 6. Jensen LS, Krarup N. Propranolol in prevention of rebleeding from oesophageal varices during the course of endoscopic sclerotherapy. Scand J Gastroenterol 1989, 24, 339-345 Received 11 August 1989 Accepted 12 October 1989
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