Hospital Universitari Germans Trias i Pujol Ascitis refractaria Ramon Planas i Vilà Hospital Universitari Germans Trias i Pujol Badalona XXVI Jornadas de la Sociedad Canaria de Patología Digestiva. Tenerife, 3 de diciembre de 2005

Ascitis refractaria. Definición Ascitis que no puede movilizarse o su recurrencia precoz que no puede evitarse con tratamiento diurético. ascitis resistente a los diuréticos: ausencia de respuesta a la dieta hiposódica y al tratamiento diurético intensivo (Esp 400 mg/día + F 160 mg/día)). ascitis intratable con diuréticos: desarrollo de complicaciones inducidas por los diuréticos que impiden el uso de dosis adecuadas de diuréticos. Accordingly to the International Ascites Club, refractory ascites was defined as the ascites that cannot be mobilized or the early recurrence of which cannot be satisfactorily prevented by medical therapy. The term refractory ascites includes the following two subtypes: a) diuretic-resistance ascites due to a lack of response to dietary sodium restriction and intensive diuretic therapy (spironolactone 400 mg/day plus furosemide 160 mg/day); and b) diuretic-intractable ascites due to the development of diuretic-induced complications, such as encephalopathy, renal failure, hyponatremia and hypo- or hyperkalemia, that preclude the use of an effective diuretic dosage. International Consensus Conference Ascites Club

Ascitis intratable con diuréticos Cuando aparecen complicaciones que impiden la administración de la dosis necesaria de diuréticos. Aparición de encefalopatía, en ausencia de otros factores precipitantes Elevación de la creatinina sérica del 100% (siempre que sea > 2mg/dl) Descenso de la concentración sérica de sodio >10 mEq (siempre que sea < 125 mEq/l) Cambios de la concentración de potasio sérico (que superen las concentraciones entre 3 y 6 mEq/l) International Consensus Conference Ascites Club

Hospital del Mar, Hospital Germans Tries i Pujol 2005 n = 263 C-ascitis (41 ± 3 meses) Probabilidad AR ,2 ,4 ,6 ,8 1 20 40 60 80 100 Meses 1 año: 5,1 5 años: 16,7 Ascitis refractaria 93 % Supervivencia ,2 ,4 ,6 ,8 1 20 40 60 80 100 Ascitis sin complicaciones Ascitis refractaria Meses 1 año: 31,6% 5 años: 79,3% 5 años: 15,3% 30 (11,4 %) 7 % resistente intratable Hospital del Mar, Hospital Germans Tries i Pujol 2005

Características de los pacientes con ascitis y con ascitis refractaria Ascitis (n= 263) Ascitis refractaria (n= 30) Child-Pugh MELD Bilirrubina (mg/dL) BUN (mg/dL) Creatinina (mg/dL) MAP (mmHg) Sodio plasma Sodio orina 8,3 ± 0,7 10,6 ± 0,01 2,5 ± 0,1 20 ± 0,9 0,9 ± 0,03 89 ± 0,9 136 ± 0,2 48 ± 2 10,3 ± 0,3 17,8 ± 1 3,5 ± 0,5 41 ± 4 1,7 ± 0,1 74 ± 2 132 ± 1 15 ± 2

WORSENING OF CIRRHOSIS LEADS TO WORSENING OF ASCITES AND HEPATORENAL SYNDROME deterioro hepatopatía Cirrosis Resistencia intrahepática Resistencia arteriolar sistémica Presión sinusoidal Volumen arterial efectivo Ascitis refractaria Retención sodio y agua Ascitis Activación sistemas neurohumorales Cirrhosis leads to increased intrahepatic resistance and thereby to an increased sinusoidal pressure. In addition, portal hypertension leads to splanchnic and systemic arteriolar vasodilation, decreased effective arterial blood volume, upregulation of sodium-retaining hormones, sodium and water retention and consequently, plasma volume expansion. With progression of cirrhosis and portal hypertension, the systemic arteriolar resistance is more pronounced, leading to further activation of the renin-angiotensin-aldosterone and sympathetic nervous systems. The resulting increase in water and sodium retention can lead to refractory ascites while the increase in renal vasoconstriction can lead to a functional renal failure, the hepatorenal syndrome. Síndrome Hepatorrenal Vasoconstricción renal

Ascitis refractaria. Tratamiento Diuréticos Anastomosis peritoneovenosa Paracentesis total Derivación portosistémica percutánea intrahepática Trasplante hepático Until the last decade peritoneovenous shunting was the only therapeutic alternative in cirrhotic patients with refractory ascites. However, peritoneovenous shunting does not improve survival in these patients, has serious complications, and it is associated with a high rate of obstruction of the shunt. More recently, large-volume paracentesis, the transjugular intrahepatic portosystemic shunt (TIPS), and liver transplantation have been used in the treatment of refractory ascites.

Tratamiento diurético en pacientes con ascitis refractaria ¿Debe suspenderse el tratamiento diurético en pacientes con ascitis refractaria? Ausencia de datos objetivos. El consenso de la AEEH 2003 consideró, aceptable su uso si Sodio orina >30mEq, en ausencia de HE o hiponatremia grave. Consenso Español AEEH. Gastroenterol Hepatol 2004;27:535-44

MECHANISMS OF ACTION OF LARGE VOLUME PARACENTESIS IN THE MANAGEMENT OF Cirrosis Resistencia arteriolar (vasodilatación) Resistencia intrahepática Parac Volumen arterial efectivo Ascitis + Effective arterial blood volume Presión sinusoidal Albúmina Large volume paracentesis (LVP) is a local therapy that does not act on the mechanisms that lead to ascites formation. Therefore, ascites recurrence is the rule. LVP consists of the direct removal of ascitic fluid from the peritoneal cavity through a needle. It is performed in association with albumin as a plasma volume expander in order to increase the effective arterial blood volume. Activación sistemas vasoactivos Retención sodio y agua Ascites

Paracentesis total con albúmina ev Tratamiento estándar en la ascitis refractoria al ser eficaz y segura en la eliminación de la ascitis. Puede producir DCP: mayor recurrencia de la ascitis y reducción de la supervivencia. Tratamiento local que no modifica los mecanismos responsables de la formación de ascitis, por lo que la recidiva de la ascitis es muy frecuente. Currently, the treatment of choice for refractory ascites in most centers, both for patients awaiting liver transplantation and patients who are not candidates to transplantation, is repeated large-volume paracentesis associated with intravenous albumin since this treatment is effective and safe in the elimination of ascites. Albumin is intented to correct the decreased effective arterial blood volume that drives sodium retention in cirrhosis and maintains ascites formation. Large volume paracentesis can lead to postparacentesis circulatory dysfunction, mainly when paracentesis is performed without plasma expansion with albumin. This vascular complication is associated with faster recurrence of ascites and reduction in survival. Since therapeutic paracentesis is a local therapy that does not modify the mechanisms that lead to ascites formation, ascites will always recur in patients with refractory ascites unless there is an improvement in liver disease (i.e.alcoholic hepatitis).

POST-PARACENTESIS CIRCULATORY DYSFUNCTION (PCD) DEPENDS ON THE TYPE OF PLASMA VOLUME EXPANDER AND THE AMOUNT OF ASCITES REMOVED La disfunción circulatoria post-paracentesis (DCP) depende del tipo de espansor plasmático y del volumen de ascitis extraído Desarrollo de DCP % Ascitis extraída Global <5-6 L >5-6 L 70 60 50 40 30 20 10 No espansor Fisiológico Espansor sintético Albúmina Two factors have been shown to be independently predictive of the development of PCD: the amount of ascites extracted and the type of plasma volume expander used at the time of large volume paracentesis (LVP). The incidence of PCD can be as high as 80% if no plasma expander is given at the time of LVP. If less than 5 liters of ascites are removed, the incidence of PCD is the same (~10%) using albumin, synthetic expanders or saline solution. However, if more than 5 liters are removed, the lowest rate of PCD is observed with albumin (~18) with significantly higher rates observed with the administration of synthetic plasma expanders (~40%) or saline solution (~55%). Therefore, albumin should be used with LVP when 5 of more liters of ascites are removed. Gines A, et al., Gastroenterology 1996; 111: 1002 Sola-Vera J, et al., Hepatology 2003; 37: 1147 Gines et al., Gastroenterology 1988; 94:1493; Gines et al., Gastroenterology 1996; 111:1002; Sola-Vera et al., Hepatology 2003; 37:1147

Anastomosis peritoneovenosa en la ascitis refractaria PERITONEO-VENOUS SHUNT (PVS) IS USEFUL IN THE TREATMENT OF REFRACTORY ASCITES Anastomosis peritoneovenosa en la ascitis refractaria Válvula uni-direccional The peritoneovenous shunt (PVS) consists of a silicone tube system with a distal fenestrated limb that is placed in the peritoneal cavity and is connected through a one-way pressure-sensitive valve to a tube that is tunneled under the skin and placed into the right atrium. The shunt can be placed under local anesthesia and has been shown to eliminate ascites, increase diuresis and the response to diuretics and to markedly suppress renin, aldosterone, norepinephrine and antidiuretic hormone, indicative of an improvement in the circulatory state. Unfortunately, PVS becomes obstructed at a high rate (50% in the first year). Placement of a PVS may hinder future placement of TIPS and may complicate liver transplant surgery given its ability to produce peritoneal adhesions. Therefore, PVS is mostly indicated in patients who require LVP frequently and who are not candidates for TIPS or for transplant.

Paracentesis vs. anastomosis peritoneovenosa 170 pacientes cirróticos con ascitis refractoria Paracentesis + Albúmina (8 g/L) 83 pacientes LeVeen Shunt 48 pacientes LeVeen Shunt + Punta titanio 39 pacientes At present, two randomized controlled trials have been performed comparing therapeutic paracentesis with peritoneovenous shunting in cirrhotic patients with refractory ascites. The first one was published in N Engl J Med in 1991 and the second in Hepatology in 1985. The design of both studies was almost identical. A total of 170 cirrhotic patients with refractory ascites were included in both trials. 83 of them were treated with total or repeated paracentesis associated with iv albumin (8 g per liter of ascites removed) and 87 with LeVeen shunt. In 39 of them, a titanium-tip was inserted at the venous end of the prosthesis to prevent obstruction at that level. Alta con diuréticos N Engl J Med 1991; Hepatology 1995

Paracentesis vs. anastomosis peritoneovenosa N Engl J Med 1991; Hepatology 1995 Probabilidad de obstrucción del shunt APV Mejora el control a largo plazo de la ascitis, pero..... no mejora la supervivencia y requiere reintervenciones frecuentes global The results of these studies demonstrate that peritoneovenous shunting improves the long-term control of ascites since it markedly increased the time to first readmission for ascites, and significantly decreased the number of readmissions for ascites, but…. It does not prolong survival, and it requires frequent reopearation because of shunt obstruction (approximately 45% at 1-year of follow-up), which was not prevented by the insertion of a titanium-tip at the venous end of the prosthesis. In fact, the probability of obstruction attributable to clotting at the venous end of the shunt was approximately 20% a 1-year of follow-up in the Hepatology study, a figure very similar when the titanium tip was not used. In summary, the results of these studies indicate that paracentesis is an alternative treatment to peritoneovenous shunting in refractory ascites. With the advent of alternative therapies for refractory ascites, and with progressively fewer and fewer surgeons trained in the surgical procedure, peritoneovenous shunting is now no longer the treatment of choice for refractory ascites. Extremo venoso meses

Anastomosis peritoneovenosa en la ascitis refractaria PERITONEO-VENOUS SHUNT (PVS) IS USEFUL IN THE TREATMENT OF REFRACTORY ASCITES Anastomosis peritoneovenosa en la ascitis refractaria El uso de la vena yugular puede dificultar una DPPI posterior Válvula uni-direccional The peritoneovenous shunt (PVS) consists of a silicone tube system with a distal fenestrated limb that is placed in the peritoneal cavity and is connected through a one-way pressure-sensitive valve to a tube that is tunneled under the skin and placed into the right atrium. The shunt can be placed under local anesthesia and has been shown to eliminate ascites, increase diuresis and the response to diuretics and to markedly suppress renin, aldosterone, norepinephrine and antidiuretic hormone, indicative of an improvement in the circulatory state. Unfortunately, PVS becomes obstructed at a high rate (50% in the first year). Placement of a PVS may hinder future placement of TIPS and may complicate liver transplant surgery given its ability to produce peritoneal adhesions. Therefore, PVS is mostly indicated in patients who require LVP frequently and who are not candidates for TIPS or for transplant. Las adherencias intraabdominales pueden dificultar el trasplante hepático

THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT Derivación portosistémica percutánea intrahepática (DPPI) Vena hepática DPPI Vena esplénica Portal hypertension can be corrected by creating a communication between the hypertensive portal system and low-pressure systemic veins, bypassing the liver, i.e., the site of increased resistance. This communication can be created surgically or by the transjugular placement of an intrahepatic stent that connects a branch of the portal vein with a branch of an hepatic vein, a procedure designated transjugular intrahepatic porto-systemic shunt (TIPS). TIPS is performed by advancing a catheter introduced through the jugular vein into a hepatic vein and into a main branch of the portal vein. An expandable stent is then introduced connecting hepatic and portal systems, and blood from the hypertensive portal vein and sinusoidal bed is shunted to the hepatic vein. The procedure is highly effective in correcting portal hypertension but can be associated with complications related to diversion of blood flow away from the liver, namely portal-systemic encephalopathy and liver failure. Vena porta Vena mesentérica

Resultados morfológicos y hemodinámicos de la DPPI 20.8±5.5 10.5±2.7 Portacaval gradient (mmHg)

Resistencia arteriolar Resistencia intrahepática MECHANISMS OF ACTION OF THE TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT IN THE MANAGEMENT OF ASCITES Cirrosis Resistencia arteriolar (vasodilación) Resistencia intrahepática Presión sinusoidal Volumen arterial efectivo Volumen arterial efectivo Presión sinusoidal DPPI The transjugular intrahepatic portosystemic shunt (TIPS) acts as a side-to-side portocaval shunt thereby decompressing the hepatic sinusoids. In addition, it also increases the effective arterial blood volume by shunting portal venous blood into the systemic circulation. However, by bypassing the liver this therapy can lead to other complications such as encephalopathy and liver failure. Activación sistemas vasoactivos Retención sodio y agua Ascitis

Principales inconvenientes de la DPPI Encefalopatía hepática (15-30%) Deterioro de la función hepática Estenosis-obstrucción de la prótesis (30-60%) Aumento mortalidad en pacientes Child C Despite its potentital advantages for the treatment of ascites, TIPS has important limitations. Like surgical portosystemic shunts, TIPS can lead to liver failure and hepatic encephalopathy in 15 to 30% of cases as a result of diversion of blood away from the liver into the systemic circulation. Another important problem of TIPS is its high rate of dysfunction/occlusion, which occurs in 50-70% of patients during the first year. This is an important limitation of TIPS requiring frequent retreatments. Finally, an increased mortality rate was reported in Child C patients treated with TIPS.

Paracentesis frente a DPPI en la ascitis refractaria Paracentesis frente a DPPI en la ascitis refractaria. Estudios publicados Lebrec D, et al. J Hepatol 1996;25:135-44 Rössle M, et al. N Engl J Med 2000;342:1701-7 Ginès P, et al. Gastroenterology 2002;123:1839-47 Sanyal AJ, et al. Gastroenterology 2003;124:634-41 Salerno F, et al. Hepatology 2004;40:629-35 Meta-análisis Deltenre P, et al. Liver International 2005;25:349-56 D’Amico G, et al. Gastroenterology 2005;129:1282-93 Abillos A, et al. J Hepatol 2005;43:990-6

DPPI vs paracentesis. Características de los pacientes incluidos en 5 estudios controlados Lebrec D DPPI/P (13/12) Rössle M DPPI/P (29/31) Ginès P DPPI/P (35/35) Sanyal A DPPI/P (52/57) Salerno F DPPI/P (33/33) Alcohol Child C 76/83 31/33 83/74 38/22 51/60 37/43 62/58 -- 58/60 79/73 Sodio orina Ascitis <5/<5 refractaria 45/61 refractaria/recidivante 9/7 refractaria NR refractaria 38/38 refractaria/recidivante Although numerous studies suggest that TIPS is an effective therapy of refractory ascites, only three randomized controlled trials on the efficacy of TIPS or large-volume paracentesis with alumin in refractory ascites has been performed to date: the French study by Lebrec et al, the German study by Rössle et al, and the study by the Interhospital group for the study of the Ascites performed in 9 universitary hospitals (seven from Spain and 2 from USA). This table summarizes the main characteristics of the patients included in these trials. Please note that in the study by Lebrec et al only 25 patients were included, 13 in the TIPS group an 12 in the paracentesis one, a sample size too small to allow for valid conclusions. On the other hand, the trial of Rössle et al. was not made in a population of patients with true refractory ascites. In this study a significant proportion of patients had recidivant or recurrent ascites instead of true refractory ascites. This is clearly illustrated by a very high mean baseline urine sodium of patients included (greater than 45 mmol/d), a feature not compatible with the existance of true refractory ascites which is characterized by extremely low urine sodium, ussually lower than 10 mmol/d.

Resultados técnicos de la DPPI en los 5 estudios controlados Lebrec Rössle Ginès Sanyal Salerno Colocación correcta (%) 77 100 97 94 89 GPP post DPPI 14 10 8,7 8,3 Reducción GPP 6 14 10,4 11,5 13,8 Disf DPPI (%) 30 45 38 73 41 Perm asist/ aleat (%) 46 93 91 >90 82

Supervivencia DPPI frente a paracentesis en la ascitis refractaria Lebrec 1996 Rossle 2000 Salerno 2004 DPPI Paracentesis Ginès 2002 Sanyal 2003

Efecto del tratamiento sobre la mortalidad. Análisis univariado Covariable Año publicación Edad media Bilirrubina media Albúmina media Creatinina EH aleatoriazación Child-Pugh score % DPPI satisfactoria Coeficiente -0,16 -0,22 4,99 -0,15 -2,33 -0,02 1,41 -6,42 Valor de p 0,29 0,006 0,001 0,30 0,36 0,28 0,57 0,14 D’Amico et al. Gastroenterology 2005;129:1282-93

D’Amico et al. Gastroenterology 2005;129:1282-93 Efecto del tratamiento sobre la mortalidad. Análisis uni y multivariado Covariable Año publicación Edad media Bilirrubina media Albúmina media Creatinina EH aleatoriazación Child-Pugh score % DPPI satisfactoria Coeficiente Valor de p -0,16 -0,22 4,99 -0,15 -2,33 -0,02 1,41 -6,42 0,29 0,006 0,001 0,30 0,36 0,28 0,57 0,14 No incluida -0,07 4,44 -5,40 0,19 0,002 0,048 D’Amico et al. Gastroenterology 2005;129:1282-93

D’Amico et al. Gastroenterology 2005;129:1282-93 Log-OR para la mortalidad en los 5 estudios según las 2 variables significativas en el análisis multivariado Lebrec Lebrec D’Amico et al. Gastroenterology 2005;129:1282-93

Efecto del tratamiento sobre la recurrencia de ascitis OR (IC 95%) Lebrec (1996) 0,30 (0,03-3,41) Rössle (2000) 0,18 (0,05-0,6) Ginès (2003) 0,20 (0,06-0,59) Sanyal (2003) 0,14 (0,06-0,34) Salerno (2004) 0,02 (0,00-0,17) Global (IC95%) 0,14 (0,08-0,26) Excluyendo Lebrec 0,14 (0,07-0,27) ,01 ,5 1 10 Mejor DPPI Mejor paracentesis D’Amico et al. Gastroenterology 2005;129:1282-93

Efecto del tratamiento sobre la encefalopatía hepática OR (IC 95%) Lebrec (1996) 8,33 (0,39-180,3) Rössle (2000) 2,43 (0,55-10,8) Ginès (2003) 1,76 (0,61-5,05) Sanyal (2003) 2,48 (1,08-5,68) Salerno (2004) 2,37 (0,88-6,35) Global (IC95%) 2,34 (1,41-3,87) Excluyendo Lebrec 2,26 (1,35-3,76) 10 ,2 1 2 Mejor DPPI Mejor paracentesis D’Amico et al. Gastroenterology 2005;129:1282-93

Efecto del tratamiento sobre la mortalidad OR (IC 95%) Lebrec (1996) 4,50 (0,84-24,8) Rössle (2000) 0,37 (0,13-1,10) Ginès (2003) 1,26 (0,49-3,23) Sanyal (2003) 1,16 (0,54-2,51) Salerno (2004) 0,42 (0,16-1,13) Global (IC95%) 0,90 (0,44-1,81) Excluyendo Lebrec 0,74 (0,40-1,37) 10 ,1 ,5 1 5 Mejor DPPI Mejor paracentesis D’Amico et al. Gastroenterology 2005;129:1282-93

D’Amico et al. Gastroenterology 2005;129:1282-93 Conclusiones La DPPI mejora el control de la ascitis, pero su uso se asocia con un aumento de la frecuencia y gravedad de la encefalopatía No mejora la supervivencia, pero existe una tendencia favorable En futuros estudios con DPPI, seleccionar pacientes según bilirrubina y evitar los que presentan riesgo elevado de encefalopatía post-DPPI ¿Coste del tratamiento? ¿Calidad de vida? In conclusion, although TIPS improves the control of ascites and prevents the occurrence of hepatorenal syndrome in patients with cirrhosis and refractory ascites, its use is associated with an increased frequency and severity of hepatic encephalopathy, does not improve survival, and has a higher cost compared with repeated paracentesis and albumin. Therefore, repeated total paracentesis with albumin should be considered the first treatment option of refractory ascites. D’Amico et al. Gastroenterology 2005;129:1282-93

Coste del tratamiento (dólares EEUU) Hospitales EEUU Hospitales España DPPI PARA TOTALES Coste/paciente Diferencias 972,450 27,784 837,116 23,917 318,151 9,090 221,675 6,333 16% 43% Total costs as well as the average cost of treatment of ascites per patient in the TIPS group was greater than that in the paracentesis and albumin group both in USA and in Spain. Differences in cost were 16% and 43%, respectively, yet the cost in the former country was higher than in the latter. Costes calculados según análisis de intención de tratar Ginès P, et al . Gastroenterology 2002;123:1839-47

Campbell MS, et al . Hepatology 2005;42:635-40 Calidad de vida en la ascitis refractaria: DPPI frente a paracentesis (SF-36) Basal 6 meses* 12 meses* p** Comp. físico Comp. Mental Grupo DPPI Parac 28 ± 8 27 ± 9 48 ± 12 41 ± 10 7 ± 8,4 6,3 ± 9,3 3,7 ± 8,3 3,4 ± 13 5 ±10,5 2 ± 11,7 3,3 ± 12,6 0,5 ± 12 0,29 0,06 Total costs as well as the average cost of treatment of ascites per patient in the TIPS group was greater than that in the paracentesis and albumin group both in USA and in Spain. Differences in cost were 16% and 43%, respectively, yet the cost in the former country was higher than in the latter. * Cambio respecto basal ** Cambio DPPI frente a paracentesis Campbell MS, et al . Hepatology 2005;42:635-40

Campbell MS, et al . Hepatology 2005;42:635-40 Calidad de vida en la ascitis refractaria: DPPI frente a paracentesis. Análisis multivariado Mejora componente físico ausencia de confusión mejora ascitis ausencia de hospitalización no diferencia según tratamiento Mejora componente mental DPPI Campbell MS, et al . Hepatology 2005;42:635-40

POLYTETRAFLUOROETHYLENE (e-PTFE)-COVERED TIPS DPPI cubierta con Politetrafluoroetileno POLYTETRAFLUOROETHYLENE (e-PTFE)-COVERED TIPS

Las DPPI cubiertas permanecen más funcionantes que las no cubiertas COVERED STENTS ARE MORE LIKELY TO REMAIN FUNCTIONAL THAN UNCOVERED STENTS Las DPPI cubiertas permanecen más funcionantes que las no cubiertas 100 Cubierta 80 % Libre de disfunción 60 p=0.0005 40 No cubierta 20 6 12 18 24 Meses Bureau et al. Gastroenterology 2004; 126:469

COVERED TIPS STENTS ARE ASSOCIATED TO LESS ENCEPHALOPATHY WITH EQUIVALENT SURVIVAL La DPPI cubierta produce menos encefalopatía sin modificar la supervivencia? Encefalopatía Mortalidad 100 Cubierta 80 Cubierta % Libres p = 0,0586 60 No cubierta No cubierta 40 p = 0,17 20 6 12 18 24 6 12 18 24 Meses Meses Bureau et al. Gastroenterology 2004; 126:469

Sumario (I) En todo paciente con ascitis refractaria ha de evaluarse la posibilidad de un trasplante hepático. La paracentesis total repetida con albúmina ev es actualmente el primer tratamiento de elección. Los pacientes pueden continuar con tratamiento diurético si lo toleran y es algo efectivo. In summary, since the development of refractory ascites is associated with a poor prognosis, the possibility of a liver transplantation should be considerer in every cirrhotic patients with refractory ascites. Currently, the first line treatment of refractory ascites is repeated total paracentesis associated with intravenous albumin administration. To reduce the frequency of repeated paracentesis, patients may continue to receive diuretics as long as they tolerate. However, diuretics should be stopped if there are significant complications or the urine sodium is below 30 mmols/day.

Sumario (II) La DPPI puede recomendarse en pacientes que no toleran la paracentesis total repetida (3 o más paracentesis por mes?), o si la paracentesis no puede evacuar la ascitis. La DPPI está contraindicada en pacientes con un Child-Pugh de 13 o más puntos, encefalopatía crónica o cardiopatía. En los no candidatos a trasplante, la anastomosis peritoneovenosa en caso de fracaso de la paracentesis o contraindicaciones a la DPPI. TIPS could be recommended in patients who do not tolerate repeated total paracentesis. This is generally agreed at 3 or more paracentesis per month, but may vary depending on patient tolerance. TIPS is also indicated if paracentesis fails to adequately remove ascitic fluid (I.e. loculated ascites). By contrast, TIPS is contraindicated in patients with a Child Pugh score of 12 or more, overt or chronic hepatic encephalopathy, or preexisting cardiac disease. Finally, in non-transplant candidates, peritoneovenous shunting may be considered after failure of total paracentesis or contraindications to TIPS.

Ascitis refractaria. Tratamiento Falta de respuesta a : Esp 400mg/día + Fur 160 mg/día o complicaciones con dosis menores Paracentesis total más albúmina ( 8 g/L) Dieta hiposódica (<80mEq/día) Tratamiento diurético si sodio urinario > 30mEq/día Recidiva de la ascitis Paracentesis repetidas más albúmina TIPS Indicaciones Recidiva muy frecuente Ascitis tabicada Contraindicaciones Child Pugh >13 Encefalopatía crónica Consenso Español AEEH. Gastroenterol Hepatol 2004;27:535-44