Cirrhotic Patients Refractory to Combination Diuretics

The massive ascites and edema of some cirrhotic patients cannot be reduced despite the above therapeutic interventions. In such patients large volume paracentesis (5-8 liters) can alleviate many of the symptoms associated with tense ascites. In the past, large volume paracentesis was discouraged for fear that it would produce severe intravascular volume depletion and cardiovascular collapse. However, recent studies show that large volume paracentesis can be safely carried out [11]. Indeed, several controlled studies suggest that the complication rate associated with this procedure is lower than that produced by aggressive diuretic therapy. Large volume paracentesis has become a relatively common outpatient procedure [8].

Intravenous expansion with albumin or nonprotein colloids is sometimes combined with paracentesis but the benefit of such adjunctive therapy generally remains unproven. If large volume paracentesis produces hemodynamic instability, or if more than 5 liters of ascitic fluid is to be removed, then postparacentesis azotemia and hyponatremia may be minimized by the administration of 40-60 g of albumin intravenously [9].

Ascites reinfusion simultaneously reduces the ascitic volume and expands the intravascular compartment. For selected patients, ascites reinfusion may correct the low EABV and reverse diuretic resistance. More recently, internal subcutaneous peritoneovenous shunts have been utilized for this purpose [ 14]. These internal shunts, inserted under local anesthesia, are associated with a relatively low incidence of infection, permit rapid ambulation and may contribute to earlier hospital discharge. However, peritoneovenous shunts are also associated with a number of complications including disseminated intravascular coagulation, variceal bleeding, and sepsis. Shunt failure due to canula occlusion also occurs commonly. When first introduced, these shunts were considered a major advance and were widely utilized. However, experience has tempered enthusiasm for this approach. Although peritoneovenous shunts reduce certain categories of morbidity, they simultaneously increase other forms of morbidity and have had little impact on overall mortality [27]. Peritoneovenous shunts are now considered a therapeutic option only when end-stage cirrhotic patients have become diuretic resistant.

The transjugular intrahepatic porta-systemic shunt is in an expandable metal mesh intravascular stent used to create a fistula between the hepatic venous and portal venous circulations. The device, inserted percutaneously, reduces portal pressures and was first deployed to treat variceal bleeding [3]. However, it was soon noted that coexistent ascites often improved or resolved after placement of such shunts. Apparently, the reduction in hepatic sinusoidal and splanchnic pressures together with increased cardiac return reduced the ascitic formation rate and increased renal salt excretion [34], This device has been most often used in patients with end-stage liver disease.


The authors acknowledge the secretarial support provided by Ann Drew in the preparation of the manuscript.


1. Arroyo, V., Rodes, J., Gutierrez-Lizarraga, M. A., and Revert, L. (1976). Prognostic values of spontaneous hyponatremia in cirrhotics with ascites. Am. J. Digest Dis. 21, 249-256.

2. Bomzon, A., and Blendis, L. M. (1994). The nitric oxide hypothesis and the hyperdynamic circulation in cirrhosis. Hepatology 20, 1343-1350.

3. Conn, H. O. (1993). Transjugular intrahepatic port-systemic shunts: The state of the art. Hepatology 17, 148-158.

4. Epstein, M. (1978). Renal effects of head-out water immersion in man: Implications for an understanding of volume homeostasis. Physiol. Rev. 58, 529-581.

5. Fogel, M. R., Sawhney, V. K., Neal, E. A., Miller, R. G., Knaver, C. M„ and Gregory, P. B. (1981). Diuresis in the ascitic patients: A randomized controlled trial of three regimes. J. Clin. Gastroenterol. 3, 73-80.

6. Fuller, R., Hoppel, C., and Ingalls, S. T. (1981). Furosemide kinetics in patients with hepatic cirrhosis with ascites. Clin. Pharmacol. Ther. 30,461 -467.

7. Gabuzda, G.J. (1970). Cirrhosis, ascites and edema. Gastroenterology 58, 546-553.

8. Gines, P., Arroyo, V., Quintero, E., Planas, R., Borg, F., Cabrera, J., Rimola, A., Vive, J., Camps, J., and Jimenez, W. (1987). Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites. Results of a randomized study. Gastroenterology 93, 234-241.

9. Gines, P., Tito, L. 1., Arroya, V., Planas, R., Panea, J., Rimola, A., Llach, J., Humbert, P., Badala-menti, S., and Jimenez, W. (1988). Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology 94, 1493-1502.

10. Inoue, M., Okajima, K., Itoh, K„ Ando, Y., Watanabe, N., Yasaka, T„ Nagase, S., and Morino, Y. (1987). Mechanism of furosemide resistance in analbuminemic rats and hypoalbuminemic patients. Kidney Int. 32, 198-203.

11. Kao, H. W., Rakov, N. E„ Savage, E., and Reynolds, T. B. (1985). The effect of large volume paracentesis on plasma volume: A cause of hypovolemia? Hepatology 5, 403-407.

12. Laffi, G„ Marra, F„ Buzzelli, G., Azzena, G., Meacci, E., DeFeo, M. L., LaVilla, G„ and Gentilini, P. (1991). Comparison of effects of torsemide and furosemide in nonazotemic cirrhotic patients with ascites: A randomized, double-blind study. Hepatology 13, 1101-1105.

13. Leevy, C. M., Zinke, M., Baber, J., and Chey, W. Y. (1985). Observations on the influence of medical therapy on portal hypertension in hepatic cirrhosis. Ann. Intern. Med. 49, 837-851.

14. LeVeen, H. H., Christoudias, G., Moon, J. P., Ip, M., Luft, R., Falk, G., and Grosberg, S. (1974). Peritoneovenous shunting for ascites. Ann. Surg. 180, 580-591.

15. Levy, M. (1977). Sodium retention in dogs with cirrhosis and ascites: Efferent mechanisms. Am. J. Physiol. 233, F586-F592.

16. Ito, S., and Reynolds, T. B. (1969). Effective plasma volume in cirrhosis with ascites. Evidence that a decreased value does not account for renal sodium retention, a spontaneous reduction in glomerular filtration rate (GFR) and a fall in GFR during drug-induced diuresis. J. Clin. Invest. 48, 975-981.

17. Marcantonio, L. A., Auld, W. H. R., Murdoch, W. R., Purohit, R„ Skellern, G. G., and Howes, C. A. (1983). The pharmacokinetics and pharmacodynamics of the diuretic bumetanide in hepatic and renal disease. Br. J. Clin. Pharmacol. 15, 245-252.

18. Naranjo, C. A., Pontigo, E., Valdenergo, C., Gonzalez, G., Ruiz, I., and Busto, U. (1979). Furosemide-induced adverse reactions in cirrhosis of the liver. Clin. Pharmacol Ther. 25, 154-160.

19. Oster, J. R„ Epstein, M., and Smoller, S. (1983). Combined therapy with thiazide-type and loop diuretic agents for resistant sodium retention. Ann. Intern. Med. 99, 405-406.

20. Perez-Ayuso, R. M., Arroyo, V., Planas, R., Goya, J., Bory, F„ Rimola, A., Rivera, F., andRodes,J. (1983). Randomized comparative study of efficacy of furosemide versus spironolactone in nonazotemic cirrhosis with ascites: Relationship between the diuretic response and the activity of the renin-aldosterone system. Gastroenterology 84, 961-968.

21. Pockros, P. J., and Reynolds, T. B. (1986). Rapid diuresis in patients with ascites from chronic liver disease: The importance of peripheral edema. Gastroenterology 90,1827-1833.

22. Runyon, B. A., Montano, A. A., Acriviadis, E. A., Antillon, M. R., Irving, M. A., and Mc-Hutchison, J. G. (1992). The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann. Intern. Med. 117, 215-220.

23. Salerno, F., Incerti, P., Badalamenti, S., Lorenzano, E., Graziana, G., Morganti, A., andGhirardi, P. (1990). Renal and humoral effects of ibopamine, a dopamine agonist in patients with liver cirrhosis. Arch. Intern. Med. 150, 65-69.

24. Salo, J., Gines, A., Anibarro, L., Jimenez, W., Bataller, R., Claria, J., Gines, P., Rivera, F., Arroyo, W., and Rodes, J. (1995). Effect of upright posture and physical exercise on endogenous neurohormonal systems in cirrhotic patients with sodium retention and normal supine plasma renin, aldosterone, and norepinephrine levels. Hepatology 22,479-487.

25. Schrier, R. W„ Arroyo, V., Bernardi, M„ Epstein, M„ Henriksen, J. H„ and Rodes, J. (1988). Peripheral arterial vasodilation hypothesis: A proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology 8, 1151 -1157.

26. Shear, L., Ching, S., and Gabuzda, G.J. (1970). Compartmentalization of ascites and edema in patients with hepatic cirrhosis. N. Engl.]. Med. 232, 1391-1396.

27. Stanley, M. M., Ochi, S„ Lee, K. K„ Nemchausky, B. A., Greenlee, H. B„ Allen,J. 1., Allen, M. J., Baum, R. A., Gadacz, T. R., and Camara, D. S. (1989). Peritoneovenous shunting as compared with medical treatment in patients with alcoholic cirrhosis and massive ascites. N. Engl. J. Med. 321, 1632-1638.

28. Sungaila, 1., Bartle, W. R., Walker, S. E., De Angelis, C., Uetrecht, J., Pappas, C., and Vidins, E. (1992). Spironolactone pharmacokinetics and pharmacodynamics in patients with cirrhotic ascites. Gastroenterology 102, 1680-1685.

29. Tristani, F. E., and Cohn, J. N. (1967). Systemic and renal hemodynamics in oliguric hepatic failure: Effect of volume expansion./ Clin. Invest. 46, 1894-1906.

30. Unikowsky, B., Wexler, M. J., and Levy, M. (1983). Dogs with experimental cirrhosis of the liver but without intrahepatic hypertension do not retain sodium or form ascites. J. Clin. Invest. 72, 1594-1604.

31. Vermeulen, L. C. Jr., Ratko, T. A., Erstad, B. L., Brecher, M. E., and Matuszewski, K. A. (1995). A paradigm for consensus. The University Hospital Consortium guidelines for the use of albumin, nonprotein colloid, and crystalloid solutions. Arch. Intern. Med. 155, 373-379.

32. Villeneuve, J. P., Verbeeck, R. K., Wilkinson, G. R„ and Branch, R. A. (1986). Furosemide kinetics and dynamics in patients with cirrhosis. Clin. Pharmacol. Ther. 40,14-20.

33. Witte, M. H., Witte, C. L., and Dumont, A. E. (1971). Progress in liver disease: Physiological factors involved in the causation of cirrhotic ascites. Gastroenterology 61, 742-750.

34. Wong, F., Sniderman, K., Liu, P., Allidina, Y., Sherman, M„ and Blendis, L. (1995). Transjug-ular intrahepatic portosystemic stent shunt: Effects on hemodynamics and sodium homeostasis in cirrhosis and refractory ascites. Ann. Intern. Med. 122, 816-822.


35. Aiza, L, Perez, G. O., and Schiff, E. R. (1994). Management of ascites in patients with chronic liver disease. Am. J. Gastroenterol. 89, 1949-1956.

36. Ellison, D. H. (1994). Diuretic drugs and the treatment of edema: From clinic to bench and back again. Am. J. Kidney Dis. 23, 623-643.

37. Rocco, V. K., and Ware, A.J. (1986). Cirrhotic ascites: Pathophysiology, diagnosis, and management. Ann. Intern. Med. 105, 573-585.

38. Runyon, B. A. (1993). Refractory ascites. Semin. Liver Dis. 13, 343-351.

39. Schrier, R. W. (1988). Pathogenesis of sodium and water retention in high-output and low-output cardiac failure, nephrotic syndrome, cirrhosis, and pregnancy (pt 1). N. Engl. J. Med. 319, 1065-1072.


Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

Get My Free Ebook

Post a comment