Journal of Gastroenterology and Hepatology (1990) 5, 549-553
LIVER AND BILIARY
A controlled study of glypressin versus vasopressin in the control of bleeding from oesophageal varices KING-WAH CHIU, I-SHYAN SHEEN AND YUN-FAN LIAW
Liver Unit, Chang Gung Memorial Hospital and Chang Gung Medical College, Taipei, Taiwan, Republic of China
Abstract To evaluate the therapeutic effect of glypressin (triglycyl-lysine-vasopressin,C,,H,,N,, O,,S,. 2C,H,O,. 5H20)in the treatment of oesophageal variceal bleeding, a randomized controlled trial of glypressin and vasopressin was conducted in 54 cirrhotic patients with oesophageal varices bleeding. Bleeding ceased within 24 h in 50% (13/26) of patients treated with glypressin and in 53.6% (15/28) of patients given vasopressin. Re-bleeding within 7 days occurred in 30.8% (4/13) of the glypressin group and in 20.0% (3/15) of the vasopressin group. There was no statistically significant difference in the therapeutic effect between glypressin and vasopressin. In the glypressin group, bleeding was more easily stopped in non-hepatocellular carcinoma (HCC) cirrhotic patients of Pugh's criteria A or B than in patients of Pugh's criterion C or HCC. We conclude that glypressin and vasopressin have similar therapeutic effect. In considering the application convenience, glypressin is an alternative to vasopressip in the treatment of bleeding varices in patients of good liver function reserve.
Key wards: glypressin, oesophageal varices, vasopressin,
INTRODUCTION Approximately half of cirrhotic patients die, directly or indirectly, of haemorrhage from gastrooesophageal varices.' Stopping the bleeding as soon as possible is the major goal in the management of such patients. In the past 30 years, intravenous or superior mesenteric arterial infusion of vasopressin, balloon tamponade with the Sengstaken-Blakemore tube, transhepatic obliteration of oesophageal varices, devascularization and oesophageal transection, surgical intra-abdominal shunting, endoscopic injection sclerotherapy and beta-blocker have been advocated as the treatment or preventive measure of choice for bleeding oesophageal varices.2-8Vasopressin infusion will control gastro-oesophageal haem-
orrhage in about 50% of the bleeding episodes and is currently recommended as the first therapeutic a p p r ~ a c hHowever, .~ angina, arrhythmia, arterial spasm, releasing plasminogen activator and increasing fibrinolysis hindering local haemostasis, and retention of water impairing the electrolytes balance, are potential adverse effects.'O Glypressin (triglycyl-lysine vasopressin) is a long-acting vasopressin analogue hormonogen that is slowly broken down by enzymes into lysine-vasopressin after intravenous administration. Haemodynamically, glypressin decreases portal venous and collateral blood flow and thus decreases portal pressure as vasopressin does in patients with portal hypertension due to liver Besides, hepatic blood flow is decreased less by glypressin than by vasopressin.12
Correspondence: Yun-Fan Liaw, MD, Liver Unit, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei 10591, Taiwan. Accepted for publication 4 February 1990.
K-W.Chiu et al.
550
Therefore, a longer therapeutic effect and fewer untoward effects are expected.I3 In addition, the study of Freeman et al. has shown a higher rate of control of bleeding oesophageal varices in cirrhotic patients by intermittent intravenous bolus of glypressin than by continuous infusion of vasopressin (70% vs 9%).14However, conflicting results were reported later by Walker et al. and others.ls-17 We therefore conducted a prospective, randomized controlled study to compare the effectiveness and adverse effects of glypressin with those of vasopressin in the treatment of bleeding from oesophageal varices.
METHODS Fifty-four patients with actively bleeding oesophageal varices entered the randomized controlled study by random number table as soon as the diagnosis was established. Diagnosis of active oesophageal bleeding was made by the endoscopic findings of blood issuing from a varix, or blood in the stomach and nearby varices in the absence of any other bleeder.* All the varices were of a moderate or severe form with redcolour signs.’* Patients with any of the following were excluded from this study: (i) previous treatment with endoscopic sclerotherapy or surgery; (ii) vasopressin had been used before the endoscopic diagnosis; (iii) heart and lung disease. Cirrhosis was diagnosed either by histology or by the findings of liver biochemistry and sonography. Alcoholism was diagnosed by a history of longterm alcoholic consumption (over 60 g/ day). Hepatocellular carcinoma (HCC) was diagnosed by pathology or alpha-fetal protein (AFP) level greater than 10 000 ng/mL plus positive image studies.(ultrasonography, celiac angiography or CAT scan). Patients in the glypressin group were treated with 2 mg glypressin intravenously (i.v.) every 4 h for 12 h. If there was no more active bleeding, the dose was changed to 1 mg i.v. every 4 h for another 20 h. Patients in the vasopressin group were treated with 0.4 u/min, continuous vasopressin infusion (IVAC pump, IVAC Corp., San Diego, CA.), for 12 h, then 0.2 unitlmin for another 20 h.19No S-B tube or sclerotherapy was added during the study. Initial control of bleeding was determined by clear gastric lavage, stable vital signs and no active bloody stool passage at
the end of 12 h of therapy. Successful control of bleeding was defined as the initial control of bleeding followed by no rebleeding in the subsequent 12 h. Re-bleeding was defined as haematemesis or active bloody stool again within 7 days after successful contro1.2*22 In the initial 12 h, if bleeding was active and vital signs were unstable despite blood transfusion, we defined this as failure and changed therapy. All treatments and observations were conducted in the intensive care unit. Parenteral nutrition, lactulose, neomycin, enemas, fluid and electrolytes, dnd transfusions of blood and fresh frozen plasma or platelets, were supplied according to the clinical conditions. There were 26 cases in the glypressin group and 28 cases in vasopressin group. Patients in both groups had comparable clinical and laboratorial data at admission (Table 1). Student’s t-tests and Chi-square test with Yates’ correction were used in the statistical analysis.
RESULTS The variceal bleeding was successfully controlled within 24 h in 13 of the 26 patients (50%) of the glypressin group and in 15 of the 28 patients (53.6%) of the vasopressin group (Table 2). The difference in failure rates was not statistically significant (50.0% vs 46.4%, P > 0.05).As to the influence of liver function on the effect of treatment, there was no statistically significant difference between the bleeding control rate and Pugh’s classification in vasopressin group, while in the glypressin group, haemorrhage control rate was significantly higher in Pugh’s A or B patients than Pugh’s C patients (72.7% vs 33.3%; Table 2). Twelve patients in the glypressin group and 10 patients in the vasopressin group died of bleeding during their hospital stay. The overall hospital mortality rates of the glypressin and vasopressin groups (46.2% vs 35.7%) was also similar. Re-bleeding within 7 days occurred in four of 13 patients of the glypressin group and three of 15 patients of the vasopressin group. When the association with HCC was compared, no relation was present either in the glypressin group (25% ers 6l%, P > O.OS), or in the Vasopressin group (50% vs 54.5%, P > 0.1). No adverse effect was observed using present dosage of glypressin and vasopressin.
55 1
Glypressin vs vasopressin in oesophageal bleeding Table 1 Pretreatment patient data profile Glypressin
Vasopressin
(n= 26)
(n= 28)
52.6+ 11.5 80.7 80.8 50.5
48.6+ 10.2 67.8 67.9 46.2
NS NS
19.2 80.8 30.8 8.3+ 2.6 13.1+ 10.2
32.1 67.9 21.4 8.1k 2.1 9.9+ 5.8
NS NS NS NS NS
9 . 3 5 7.9 9 . 6 5 8.0
9.8+ 7.3 9.8+ 7.3
NS NS
2 9 15
1 10 17
NS NS NS
Characteristics Age (years) Male (YO) Time Lapse < 24 hrs (YO) First bleeding (%) Aetiology (%) Alcoholic Post-necrotic HCC Haemoglobin (g/dL) Platelet (x lo4) Blood transfusion PRBC (units) Plasma (units) hgh’s classification Grade A (5-6) B (7-9)
c (1cb15)
P
NS NS
NS = no statistical significance.
Table 2 Results of bleeding control
Result Success Pugh’s A + B C Re-bleeding
Glypressin
Vasopressin
(n= 26)
(n= 28)
13 (50.0%)* 15 (53.6%)* 8 (72.7%)’” 6 (54.5%)b.c 5 (33.3%)”,d 9 (52.9%)b.d 4 (30.8%)** 3 (20.0%)** ~
**no statistical significance. ‘ P < 0.05, b*c*dP> 0.05.
DISCUSSION The results of the present study concur with the observation of Burroughs et al. that glypressin has no better haemostatic effect than vasopressin in the control of variceal bleeding.15This contradicts the observation of Freeman et a l l 4 The latter was a small, randomized, controlled study with wide confidence limits on the observed treatment difference. In addition, most of their patients were graded as Child A and B.14 In contrast, most of our patients, as well as those of Burroughs et al., were graded Pugh’s C.16 Although our study showed glypressin and vasopressin stop variceal bleeding in 50% of patients,
as in Conn’s report, however, glypressin achieved 72.7% haemostatic rate in Pugh’s A or B patients, a difference which was not observed in the vasopressin group. In addition, glypressin showed a higher control rate than vasopressin in Pugh’s A or B patients, though the difference was not statistically significant, probably due to the small number of patients (Table 2). It is possible that in patients with poor liver function reserve, gradual conversion of glypressin to lysine-vasopressin enzymatically could not take place efficiently enough to maintain the effective and sustained concentration in the body.13 The biotransformation and haemodynamic effects of glypressin in patients with different liver function reserves await further study. However, the results of the present study suggest that either glypressin or vasopressin will be beneficial in patients with good liver function reserve, while it is better to choose vasopressin for patients with poor liver function reserve. Variceal bleeding is more difficult to control by vasopressin and less benefit is derived from endoscopic injection sclerotherapy (EIS) in HCC patients than in non-HCC patients.z0In our study, no statistically significant therapeutic difference could be demonstrated between patients in vasopressin and glypressin group who had associated
K-W. Chiu et al.
552
HCC (25% vs 50%). In addition, glypressin arterial and intravenous infusions of vasopressin in hemorrhage from esophageal varices. Gasshowed a lower response rate than vasopressin troenterology 1979; 77: 5 4 M . (16.7% vs 49.0%) in Pugh's C patients associated 3. MALLORY A., SCHEEFER J. W., COHENJ. R. et al. with HCC, though, the difference was not statistSelective intra-arterial vasopressin infusion for upically significant, probably due to the small numper gastrointestinal tract hemorrhage. Arch. Surg. ber of patients. This awaits further study. 1980; 115: 30-2. Many side effects, such as ischaemic heart, 4. HUNTP. S., FRACSM. S., KORMAN M. K. et al. ischaemic bowel or acute renal insufficiency have An 8-year prospective experience with ballon tambeen reported during the continuous intravenous ponade in emergency control of bleeding esophaginfusion of vasopressin.z1 Abdominal cramps, eal varices. Dig. Dis. Sci. 1982; 27: 4134. chest pain, transient elevation of blood pressure, 5. TERBLANCHE J., NORTHOVER J. M. A., BORNMAN P. et al. A prospective controlled trial of sclerothertransient bradycardia, angina and left ventricular failure have been observed ~ c c a s i o n a l l y . ~ ~ * ~ ~apy * ~in~the long term management of patients after esophageal variceal bleeding. Surg. Gynecol. Obstet. During treatment with glypressin, no significant 1979; 148: 323-33. arrhythmias, skin necrosis or bowel necrosis were G., SCOTTJ., LONGR. G. et al. 6. SMITH-LAING seen.a1 However, no adverse effects were obRole of percutaneous transhepatic obliteration of served in either the vasopressin or glypressin varices in the management of hemorrhage from groups in the present study. It has been shown gastro-esophageal varices. Gastroenterology 1981; that the side effects of vasopressin are dose-de81: 1031-6. pendent." Vasopressin at a dose of 0.66 unit/min D., NOUELO., BERNUAU J. et aJ. Pro7. LEBREC resulted in the above adverse effects, while the pranolol in prevention of recurrent gastrointestinal bleeding in cirrhotic patients. Lancet 1981; i: dose of vasopressin in the present study was only 920-1. 0.4 ~ n i t / m i n . l ~ Perhaps * ~ ~ the smaller dose of 8. SHEENI. S., CHENT. Y . 81LIAWY. F. Randomvasopressin we used is the reason for few side ized controlled study of propranolol for prevention effects. of recurrent esophageal varices bleeding in patients In conclusion, glypressin appears as effective with cirrhosis. Liwer 1989; 9: 1-5. as vasopressin, and might be more effective in 9. CONNH. 0. Vasopressin and nitroglycerin in the Pugh's A and B patients, in the control of oesotreatment of bleeding varices: The bottom line. phageal variceal bleeding. In addition, no conHepatology 1986; 6: 523-5. J. G., FORREST J. A. H., PROWSE C. V. 10. DOUGLAS tinuous intravenous infusion is required. Thereet aJ.Effects of lysine vasopressin and glypressin on fore, it is a good choice for patients with good the fibrinolytic system in cirrhosis. Gut 1979; 20: liver function reserve. 565-7. A. et al. The effect of 11. RABOLA., JUHL E., SCHMIDT
ACKNOWLEDGEMENTS The authors thank the medical and nursing staff of the acute care unit of gastroenterology for their excellent assistance, Miss Judy Perry for her kind editorial assistance and Kelu Trading Company Limited for the generous supply of glypressin.
REFERENCES 1. GRAHAM D. Y.,SMITHJ. L. The course of patients after variceal hemorrhage. Gastroenterology 1981; 80: 800-9. M., GROSZMANN J., ATTERBURY et al. 2. CHOJKIER
A controlled comparison of continuous intra-
vasopressin and triglycyl lysine vasopressin (glypressin) on the splanchnic circulation in cirrhotic patients with portal hypertension. Digestion 1976; 14: 285-9. 12. VOSMIKJ., JEDDICKA K., MULDERJ. L. et al.
Action of the triglycyl hormonogen of vasopressin (glypressin) in patients with liver cirrhosis and bleeding esophageal varices. Gastroenterology 1977; 72: 605-9. M. L., Azrz L. A., MILLER et aJ. Conver13. FORSING
sion of triglycylvasopressinto lysine-vasopressinin man. 3. Endomiwl. 1980; 110: 2 3 7 4 . J. G., COBDEN I., LISHMAN A. H. et al. 14. FREEMAN Controlled trial of terlipressin (glypressin) versus vasopressin in the early treatment of esophageal varices. Lancet 1982; ii: 66-8. 15. WALKERS. et al. Terlipressin in bleeding esophageal varices: A placebo controlled. Double blind study. Hepatology 1986, 6: 112-5. A. K., SHERLOCK S. et al. Prospective 16. BURROUGHS
Glypressin vs vasopressin in oesophageal bleeding evaluation of Glypressin in the treatment of bleeding varices in cirrhotic patients. Vasopressin analogs and portal hypertension. In: D. Lebrec and A. T. Blei, eds, Vasopressin A ~ o and ~ Portal s Hypertenswn. John Libbey Eurotext, 1987; 143-6. Y. T., LAIK. H. et al. A random17. LEEF. Y., TSAI ized controlled study of triglycyl-vasopressin and vasopressin plus nitroglycerin in the control of acute esophageal variceal hemorrhage. Chin. 3. Gastroenterol. 1988; 5: 131-8. 18. BEPPUK., INOKUCHI K., KOYANAGI K. et al. Prediction of variceal hemorrhage by esophageal endoscopy. Gastrointest. Endosc. 1981; 27: 213-8. 19. JOHNSON W. C., WIDRICHW.C., ANSELLJ. E. et al. Control of bleeding varices by vasopressin: A prospective randomized study. Ann. Surg. 1977; 168: 369-76. 20. LAIK. H., CHIANG T. T., TSAI Y .T. et al. Follow
553 up study after endoscopic injection sclerotherapy. Chin.3. Gastroenterol. 1985; 2: 164-70. 21. SODERLUND C. Vasopressin and glypressin in upper gastrointestinal bleeding. Scand. J. Gastroenterol. 1987; 22 (suppl 137): 50-5. 22. TSAI Y. T., LAYC. S., LAI K. H. et al. Controlled trial of vasopressin plus nitroglycerin vs. vasopressin alone in the treatment of bleeding esophageal varices. Hepatology 1986; 6: 410. J. et 41. 23. GIMSONA. E. S.,WESTABYD., HEGARTY A randomized trial of vasopressin and vasopressin plus nitroglycerin in the control of acute variceal hemorrhage. Hepatology 1986; 6: 410-3. 24. RIGBERGL. A., UFBERGM. H., BROOKSC. M. et al. Continuous low dose peripheral vein pitressin infusion in the control of variceal bleeding. Amer. 3. Gastroenterol. 1977; 68: 481-4.
LIVER AND BILIARY
A controlled study of glypressin versus vasopressin in the control of bleeding from oesophageal varices KING-WAH CHIU, I-SHYAN SHEEN AND YUN-FAN LIAW
Liver Unit, Chang Gung Memorial Hospital and Chang Gung Medical College, Taipei, Taiwan, Republic of China
Abstract To evaluate the therapeutic effect of glypressin (triglycyl-lysine-vasopressin,C,,H,,N,, O,,S,. 2C,H,O,. 5H20)in the treatment of oesophageal variceal bleeding, a randomized controlled trial of glypressin and vasopressin was conducted in 54 cirrhotic patients with oesophageal varices bleeding. Bleeding ceased within 24 h in 50% (13/26) of patients treated with glypressin and in 53.6% (15/28) of patients given vasopressin. Re-bleeding within 7 days occurred in 30.8% (4/13) of the glypressin group and in 20.0% (3/15) of the vasopressin group. There was no statistically significant difference in the therapeutic effect between glypressin and vasopressin. In the glypressin group, bleeding was more easily stopped in non-hepatocellular carcinoma (HCC) cirrhotic patients of Pugh's criteria A or B than in patients of Pugh's criterion C or HCC. We conclude that glypressin and vasopressin have similar therapeutic effect. In considering the application convenience, glypressin is an alternative to vasopressip in the treatment of bleeding varices in patients of good liver function reserve.
Key wards: glypressin, oesophageal varices, vasopressin,
INTRODUCTION Approximately half of cirrhotic patients die, directly or indirectly, of haemorrhage from gastrooesophageal varices.' Stopping the bleeding as soon as possible is the major goal in the management of such patients. In the past 30 years, intravenous or superior mesenteric arterial infusion of vasopressin, balloon tamponade with the Sengstaken-Blakemore tube, transhepatic obliteration of oesophageal varices, devascularization and oesophageal transection, surgical intra-abdominal shunting, endoscopic injection sclerotherapy and beta-blocker have been advocated as the treatment or preventive measure of choice for bleeding oesophageal varices.2-8Vasopressin infusion will control gastro-oesophageal haem-
orrhage in about 50% of the bleeding episodes and is currently recommended as the first therapeutic a p p r ~ a c hHowever, .~ angina, arrhythmia, arterial spasm, releasing plasminogen activator and increasing fibrinolysis hindering local haemostasis, and retention of water impairing the electrolytes balance, are potential adverse effects.'O Glypressin (triglycyl-lysine vasopressin) is a long-acting vasopressin analogue hormonogen that is slowly broken down by enzymes into lysine-vasopressin after intravenous administration. Haemodynamically, glypressin decreases portal venous and collateral blood flow and thus decreases portal pressure as vasopressin does in patients with portal hypertension due to liver Besides, hepatic blood flow is decreased less by glypressin than by vasopressin.12
Correspondence: Yun-Fan Liaw, MD, Liver Unit, Chang Gung Memorial Hospital, 199 Tung Hwa North Road, Taipei 10591, Taiwan. Accepted for publication 4 February 1990.
K-W.Chiu et al.
550
Therefore, a longer therapeutic effect and fewer untoward effects are expected.I3 In addition, the study of Freeman et al. has shown a higher rate of control of bleeding oesophageal varices in cirrhotic patients by intermittent intravenous bolus of glypressin than by continuous infusion of vasopressin (70% vs 9%).14However, conflicting results were reported later by Walker et al. and others.ls-17 We therefore conducted a prospective, randomized controlled study to compare the effectiveness and adverse effects of glypressin with those of vasopressin in the treatment of bleeding from oesophageal varices.
METHODS Fifty-four patients with actively bleeding oesophageal varices entered the randomized controlled study by random number table as soon as the diagnosis was established. Diagnosis of active oesophageal bleeding was made by the endoscopic findings of blood issuing from a varix, or blood in the stomach and nearby varices in the absence of any other bleeder.* All the varices were of a moderate or severe form with redcolour signs.’* Patients with any of the following were excluded from this study: (i) previous treatment with endoscopic sclerotherapy or surgery; (ii) vasopressin had been used before the endoscopic diagnosis; (iii) heart and lung disease. Cirrhosis was diagnosed either by histology or by the findings of liver biochemistry and sonography. Alcoholism was diagnosed by a history of longterm alcoholic consumption (over 60 g/ day). Hepatocellular carcinoma (HCC) was diagnosed by pathology or alpha-fetal protein (AFP) level greater than 10 000 ng/mL plus positive image studies.(ultrasonography, celiac angiography or CAT scan). Patients in the glypressin group were treated with 2 mg glypressin intravenously (i.v.) every 4 h for 12 h. If there was no more active bleeding, the dose was changed to 1 mg i.v. every 4 h for another 20 h. Patients in the vasopressin group were treated with 0.4 u/min, continuous vasopressin infusion (IVAC pump, IVAC Corp., San Diego, CA.), for 12 h, then 0.2 unitlmin for another 20 h.19No S-B tube or sclerotherapy was added during the study. Initial control of bleeding was determined by clear gastric lavage, stable vital signs and no active bloody stool passage at
the end of 12 h of therapy. Successful control of bleeding was defined as the initial control of bleeding followed by no rebleeding in the subsequent 12 h. Re-bleeding was defined as haematemesis or active bloody stool again within 7 days after successful contro1.2*22 In the initial 12 h, if bleeding was active and vital signs were unstable despite blood transfusion, we defined this as failure and changed therapy. All treatments and observations were conducted in the intensive care unit. Parenteral nutrition, lactulose, neomycin, enemas, fluid and electrolytes, dnd transfusions of blood and fresh frozen plasma or platelets, were supplied according to the clinical conditions. There were 26 cases in the glypressin group and 28 cases in vasopressin group. Patients in both groups had comparable clinical and laboratorial data at admission (Table 1). Student’s t-tests and Chi-square test with Yates’ correction were used in the statistical analysis.
RESULTS The variceal bleeding was successfully controlled within 24 h in 13 of the 26 patients (50%) of the glypressin group and in 15 of the 28 patients (53.6%) of the vasopressin group (Table 2). The difference in failure rates was not statistically significant (50.0% vs 46.4%, P > 0.05).As to the influence of liver function on the effect of treatment, there was no statistically significant difference between the bleeding control rate and Pugh’s classification in vasopressin group, while in the glypressin group, haemorrhage control rate was significantly higher in Pugh’s A or B patients than Pugh’s C patients (72.7% vs 33.3%; Table 2). Twelve patients in the glypressin group and 10 patients in the vasopressin group died of bleeding during their hospital stay. The overall hospital mortality rates of the glypressin and vasopressin groups (46.2% vs 35.7%) was also similar. Re-bleeding within 7 days occurred in four of 13 patients of the glypressin group and three of 15 patients of the vasopressin group. When the association with HCC was compared, no relation was present either in the glypressin group (25% ers 6l%, P > O.OS), or in the Vasopressin group (50% vs 54.5%, P > 0.1). No adverse effect was observed using present dosage of glypressin and vasopressin.
55 1
Glypressin vs vasopressin in oesophageal bleeding Table 1 Pretreatment patient data profile Glypressin
Vasopressin
(n= 26)
(n= 28)
52.6+ 11.5 80.7 80.8 50.5
48.6+ 10.2 67.8 67.9 46.2
NS NS
19.2 80.8 30.8 8.3+ 2.6 13.1+ 10.2
32.1 67.9 21.4 8.1k 2.1 9.9+ 5.8
NS NS NS NS NS
9 . 3 5 7.9 9 . 6 5 8.0
9.8+ 7.3 9.8+ 7.3
NS NS
2 9 15
1 10 17
NS NS NS
Characteristics Age (years) Male (YO) Time Lapse < 24 hrs (YO) First bleeding (%) Aetiology (%) Alcoholic Post-necrotic HCC Haemoglobin (g/dL) Platelet (x lo4) Blood transfusion PRBC (units) Plasma (units) hgh’s classification Grade A (5-6) B (7-9)
c (1cb15)
P
NS NS
NS = no statistical significance.
Table 2 Results of bleeding control
Result Success Pugh’s A + B C Re-bleeding
Glypressin
Vasopressin
(n= 26)
(n= 28)
13 (50.0%)* 15 (53.6%)* 8 (72.7%)’” 6 (54.5%)b.c 5 (33.3%)”,d 9 (52.9%)b.d 4 (30.8%)** 3 (20.0%)** ~
**no statistical significance. ‘ P < 0.05, b*c*dP> 0.05.
DISCUSSION The results of the present study concur with the observation of Burroughs et al. that glypressin has no better haemostatic effect than vasopressin in the control of variceal bleeding.15This contradicts the observation of Freeman et a l l 4 The latter was a small, randomized, controlled study with wide confidence limits on the observed treatment difference. In addition, most of their patients were graded as Child A and B.14 In contrast, most of our patients, as well as those of Burroughs et al., were graded Pugh’s C.16 Although our study showed glypressin and vasopressin stop variceal bleeding in 50% of patients,
as in Conn’s report, however, glypressin achieved 72.7% haemostatic rate in Pugh’s A or B patients, a difference which was not observed in the vasopressin group. In addition, glypressin showed a higher control rate than vasopressin in Pugh’s A or B patients, though the difference was not statistically significant, probably due to the small number of patients (Table 2). It is possible that in patients with poor liver function reserve, gradual conversion of glypressin to lysine-vasopressin enzymatically could not take place efficiently enough to maintain the effective and sustained concentration in the body.13 The biotransformation and haemodynamic effects of glypressin in patients with different liver function reserves await further study. However, the results of the present study suggest that either glypressin or vasopressin will be beneficial in patients with good liver function reserve, while it is better to choose vasopressin for patients with poor liver function reserve. Variceal bleeding is more difficult to control by vasopressin and less benefit is derived from endoscopic injection sclerotherapy (EIS) in HCC patients than in non-HCC patients.z0In our study, no statistically significant therapeutic difference could be demonstrated between patients in vasopressin and glypressin group who had associated
K-W. Chiu et al.
552
HCC (25% vs 50%). In addition, glypressin arterial and intravenous infusions of vasopressin in hemorrhage from esophageal varices. Gasshowed a lower response rate than vasopressin troenterology 1979; 77: 5 4 M . (16.7% vs 49.0%) in Pugh's C patients associated 3. MALLORY A., SCHEEFER J. W., COHENJ. R. et al. with HCC, though, the difference was not statistSelective intra-arterial vasopressin infusion for upically significant, probably due to the small numper gastrointestinal tract hemorrhage. Arch. Surg. ber of patients. This awaits further study. 1980; 115: 30-2. Many side effects, such as ischaemic heart, 4. HUNTP. S., FRACSM. S., KORMAN M. K. et al. ischaemic bowel or acute renal insufficiency have An 8-year prospective experience with ballon tambeen reported during the continuous intravenous ponade in emergency control of bleeding esophaginfusion of vasopressin.z1 Abdominal cramps, eal varices. Dig. Dis. Sci. 1982; 27: 4134. chest pain, transient elevation of blood pressure, 5. TERBLANCHE J., NORTHOVER J. M. A., BORNMAN P. et al. A prospective controlled trial of sclerothertransient bradycardia, angina and left ventricular failure have been observed ~ c c a s i o n a l l y . ~ ~ * ~ ~apy * ~in~the long term management of patients after esophageal variceal bleeding. Surg. Gynecol. Obstet. During treatment with glypressin, no significant 1979; 148: 323-33. arrhythmias, skin necrosis or bowel necrosis were G., SCOTTJ., LONGR. G. et al. 6. SMITH-LAING seen.a1 However, no adverse effects were obRole of percutaneous transhepatic obliteration of served in either the vasopressin or glypressin varices in the management of hemorrhage from groups in the present study. It has been shown gastro-esophageal varices. Gastroenterology 1981; that the side effects of vasopressin are dose-de81: 1031-6. pendent." Vasopressin at a dose of 0.66 unit/min D., NOUELO., BERNUAU J. et aJ. Pro7. LEBREC resulted in the above adverse effects, while the pranolol in prevention of recurrent gastrointestinal bleeding in cirrhotic patients. Lancet 1981; i: dose of vasopressin in the present study was only 920-1. 0.4 ~ n i t / m i n . l ~ Perhaps * ~ ~ the smaller dose of 8. SHEENI. S., CHENT. Y . 81LIAWY. F. Randomvasopressin we used is the reason for few side ized controlled study of propranolol for prevention effects. of recurrent esophageal varices bleeding in patients In conclusion, glypressin appears as effective with cirrhosis. Liwer 1989; 9: 1-5. as vasopressin, and might be more effective in 9. CONNH. 0. Vasopressin and nitroglycerin in the Pugh's A and B patients, in the control of oesotreatment of bleeding varices: The bottom line. phageal variceal bleeding. In addition, no conHepatology 1986; 6: 523-5. J. G., FORREST J. A. H., PROWSE C. V. 10. DOUGLAS tinuous intravenous infusion is required. Thereet aJ.Effects of lysine vasopressin and glypressin on fore, it is a good choice for patients with good the fibrinolytic system in cirrhosis. Gut 1979; 20: liver function reserve. 565-7. A. et al. The effect of 11. RABOLA., JUHL E., SCHMIDT
ACKNOWLEDGEMENTS The authors thank the medical and nursing staff of the acute care unit of gastroenterology for their excellent assistance, Miss Judy Perry for her kind editorial assistance and Kelu Trading Company Limited for the generous supply of glypressin.
REFERENCES 1. GRAHAM D. Y.,SMITHJ. L. The course of patients after variceal hemorrhage. Gastroenterology 1981; 80: 800-9. M., GROSZMANN J., ATTERBURY et al. 2. CHOJKIER
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