ManageMent probleMs in liver diseaseAscitesMara e baccaro

Mnica guevara

Juan rods

Abstractascites is the abnormal accumulation of fluid in the peritoneal cavity.

the most frequent cause of ascites is portal hypertension related to

cirrhosis. ascites in patients with cirrhosis is the consequence of the

homeostatic activation of vasoconstrictor systems and sodium reten-

tion. these mechanisms are triggered by a decrease in effective arterial

blood volume due to a severe arterial vasodilatation located mainly in

the splanchnic circulation. the ascitic fluid of patients with cirrhosis is

generally low in proteins and albumin. since the presence of ascites

is associated with poor prognosis and low survival, the patients with

ascites should be evaluated for liver transplantation. the treatment con-

sists basically of a negative sodium balance that is obtained by decreas-

ing the sodium intake and increasing its excretion by the administration

of diuretic agents. the patients in whom these drugs are not effective

or cannot be administered (because they develop adverse effects, a

condition well known as refractory ascites), should be treated with large-

volume paracentesis plus albumin.

Keywords ascites; cirrhosis; diuretic; paracentesis

Ascites is defined as the accumulation of fluid in the peritoneal cavity exceeding the normal maximum volume of 25 ml. Cirrhotic ascites accounts for over 75% of patients who present with ascites, the remaining 25% being due to malignancy (10%), cardiac failure (3%), pancreatitis (1%), tuberculosis (2%) or other rarer causes.1 Ascites occurs in more than 50% of patients within 10 years of the diagnosis of cirrhosis.

Pathogenesis

The peripheral vasodilatation theory is currently the most accepted hypothesis to explain ascites formation in cirrhotic patients.2 This hypothesis suggests that cirrhosis and portal

Mara E Baccaro MD is Fellow of the Liver Unit at the Hospital Clinic-Barcelona, Barcelona, Spain. Competing interests: none declared.

Mnica Guevara MD is Associate Investigator of IDIBAPS at the Liver Unit at the Hospital Clinic-Barcelona, Barcelona, Spain. Competing

interests: none declared.

Juan Rods FRCP is Professor of Medicine and General Manager at Hospital Clinic-Barcelona, Barcelona, Spain. Competing interests: MediCine 35:2 10

none declared.hypertension induce progressive splanchnic vasodilatation leading to an effective decreased plasma volume, which results in overactivity of endogenous vasoconstrictor systems and renal sodium and water retention (hyperdynamic circulation). In the early stages of cirrhosis, splanchnic arterial vasodilatation is moderate and the effective arterial blood volume is maintained within normal limits through increases in plasma volume and cardiac output. In the later stages of cirrhosis, splanchnic arterial vasodilatation is more important, the effective arterial blood volume decreases markedly, and arterial pressure decreases. Arterial pressure is maintained by activation of vasoconstrictor and antinatriuretic factors, determining sodium and fluid retention and ascites formation. As the disease progresses, there is impairment in sodium and water excretion followed by renal vasoconstriction that determines dilutional hyponatremia at first and hepatorenal syndrome later (Figure 1).24

Classification

Uncomplicated ascites is ascites that is not infected and that is not associated with the development of the hepatorenal syndrome (HRS). Grade 1 ascites is mild ascites only detectable by ultrasound examination. Grade 2 ascites, or moderate ascites, is manifest by moderate symmetrical distension of the abdomen. Grade 3 ascites is large or gross ascites with marked abdominal distension.

Refractory ascites in 1996, the International Ascites Club defined refractory ascites as ascites that cannot be mobilized or the early recurrence of which cannot be satisfactorily prevented by medical therapy.4 It occurs in approximately 510% of cases of ascites.5 Refractory ascites can be divided into

Proposed pathogenesis of ascites formation in cirrhosis according to the arterial vasodilatation hypothesis

Portal hypertension

Cirrhosis

Splanchnic arterial vasodilatation

Effective blood volume

Sodium and water retention

Ascites

Stimulation of:

Reninangiotensin system

Sympathetic nervous systems

Arginine vasopressin

Figure 14 2006 elsevier ltd. all rights reserved.

ManageMent probleMs in liver diseasetwo subgroups: diureticresistant ascites and diureticintractable ascites.4

General evaluation of patients with cirrhosis and ascites

The evaluation of patients with cirrhosis and ascites should include, not only the evaluation of liver function, but also the evaluation of renal and circulatory function (Table 1).6

DiagnosisDiagnosis of ascites is simple when a large amount of fluid is accumulated in the peritoneal cavity. On physical examination, the abdomen is distended, the flanks bulge and a fluid wave may be demonstrable. If the volume of ascitic fluid is small, an abdominal ultrasound scan is useful; it can detect as little as 100 ml of abdominal fluid and may suggest the cause. The diagnosis is confirmed by fluid aspiration by paracentesis. The procedure should be performed by inserting a needle into the left lower abdominal quadrant under strict sterile conditions.

Characteristics of cirrhotic ascites biochemical and cytological analysis of ascitic fluid provides important information. Traditionally, ascites in patients with cirrhosis was considered to have the characteristics of a transudate, with a total protein concentration of less than 2.5 g/dL and relatively few cells. It is helpful to subtract the concentration of the ascites fluid albumin from serum albumin; a serumascites albumin gradient of more than 1.1 g/dL predicts portal hypertension with great accuracy (Table 2).7,8 The ascitic fluid in cirrhosis usually contains fewer than 300500 white blood cells/mm3. More than 70% of these

Evaluation of patients with cirrhosis and ascites6

evaluation of liver disease

liver function and coagulation tests

standard haematological tests

abdominal ultrasonography or computed tomography

endoscopy of the upper gastrointestinal tract

liver biopsy in selected patients

evaluation of renal and circulatory function

Measurement of serum creatinine and electrolytes

Measurement of urinary sodium (preferably from a 24-hour

urine collection)*

Measurement of urinary protein (from a 24-hr urine

collection)

arterial blood pressure

evaluation of ascitic fluid

Cell count

bacterial culture

Measurement of total protein

other tests (measurement of albumin, glucose, lactate

dehydrogenase, amylase, and triglycerides; an acid-fast

smear; and cytological examination)

*if possible, patients should be evaluated when they are not receiving diuretic drugs, since some variables related to these drugs may alter renal function.MediCine 35:2 10

Table 1cells are mononuclear leucocytes. When the ascitic fluid contains more than 250 neutrophils/mm3, a diagnosis of spontaneous bacterial peritonitis is made.9

Differential diagnosisThe most frequent causes of ascites due to nonhepatic diseases are cardiac failure and neoplasm.1 In the first case, the protein content of the ascites is usually elevated and the abdominal ultrasound shows expansion of suprahepatic veins. The existence of jugular ingurgitation suggests cardiac ascites.10 The neoplasic invasion of the peritoneum causes the exudation of liquid that is usually rich in proteins (generally superior to 25 g/litre).11 The diagnosis is made through the cytology of the ascitic fluid, which is positive in 6090% of the cases. If the cytological examinations are repeatedly negative, the last option is to perform laparoscopy and biopsy of the peritoneum.

Other less frequent causes of ascites are peritoneal tuberculosis and pancreatic ascites. Ascitic fluid in peritoneal tuberculosis contains abundant lymphocytes, has a high concentration of the adenosindeaminase enzyme and is generally rich in proteins.12 The culture of ascitic fluid is frequently negative. The diagnostic confirmation must be made by means of laparoscopy and biopsy of the peritoneum looking for granulomas. In pancreatic ascites, the ascitic fluid is very rich in amylase and lipase, making the diagnosis relatively easy.13 Abdominal computerized tomography is useful to define the cause of ascites.

Managment of ascites

General measuresAll patients with ascites should be evaluated as if they were possible candidates for liver transplantation because the presence of large ascites is associated with poor longterm survival.7,14

Reduction of sodium intake is beneficial in patients with ascites, particularly those with severe sodium retention who do not respond, or respond poorly, to diuretics.15 A lowsodium diet

Differential diagnosis of ascites by the serumascites albumin gradient*

High gradient (1.1 g/dl) low gradient (

ManageMent probleMs in liver diseasedelay the reaccumulation of fluid.15,16 More strict restriction of sodium intake is not recommended because it is poorly tolerated.16 Fluid intake should be restricted only in patients with dilutional hyponatremia (serum sodium concentration lower than 130 mEq/L in the presence of ascites, oedema, or both) to avoid a further decrease in serum sodium concentration.17

Specific measuresGrade II ascites (moderate volume)Patients with moderate ascites can be treated as outpatients and do not require hospitalization unless they have other complications of cirrhosis. In most cases, a negative sodium balance and loss of ascitic fluid are quickly achieved with low doses of diuretics.16,18,19 The diuretic of choice is either spironolactone (50200 mg/day) or amiloride (510 mg/day). Low doses of furosemide (2040 mg/day) may be added during the first few days to increase natriuresis, especially in patients with peripheral oedema. Furosemide should be used with caution because of the risk of excessive diuresis, which may lead to prerenal failure. The recommended weight loss is 300500 g/day in patients without peripheral oedema and 8001000 g/day in those with peripheral oedema.20

Grade III ascites (large volume)The treatment of choice for largevolume ascites is largevolume paracentesis followed by intravenous albumin (8 g/litre of ascitic fluid removed) whenever the total volume of ascites is eliminated. The administration of albumin prevents paracentesisinduced circulatory dysfunction (PICD). PICD is characterized by a reduction in effective arterial blood volume and is associated with a high rate of recurrence of ascites, development of hepatorenal syndrome or dilutional hyponatremia, and decreased survival.2124 In patients where less than 5 litres of ascites has been removed, the incidence of PICD is very low. In these cases synthetic plasma expanders are effective in preventing this complication.21,22 The complications associated with the paracentesis procedure are extremely low and these include: abdominal wall haematomas, infection or bleeding in the puncture site, leakage of ascitic fluid, haemoperitoneum, and intestinal perforation.

The practice guideline of the American Association for the Study of Liver Diseases states that routine correction of prolonged prothrombin time or thrombocytopenia (common alterations in patients with cirrhosis) is not required when experienced personnel carry out paracentesis.25 However, most clinical trials evaluating paracentesis complications have included patients with an international normalized ratio around 1.7, or a platelet count around 50,000/mm.3,21,24,2630

Refractory ascitesThere are two therapeutic strategies for largevolume refractory ascites: largevolume paracentesis with intravenous albumin and transjugular intrahepatic portosystemic shunts (TIPS). The peritoneovenous shunt was abandoned because of significant rates of complications.30 Although several studies have demonstrated that TIPS is more effective in the control of the ascites compared to paracentesis, it increases the risk of developing hepatic encephalopathy, has a greater cost, and it does not improve survival compared to paracentesis.3134 For this reason, the treatment of choice in patients with refractory ascites is MediCine 35:2 1paracentesis plus albumin. TIPS should probably be reserved for patients without severe liver failure or encephalopathy who have loculated fluid that cannot be treated with paracentesis and for those who are unwilling to undergo repeated paracentesis.

Prognosis of patients with cirrhosis and ascites

The development of ascites in patients with cirrhosis indicates a poor prognosis. The probability of death in cirrhotic patients hospitalized with ascites is 40% at 2 years.5 The prognosis is worse for those with refractory ascites and those who develop spontaneous bacterial peritonitis or hepatorenal syndrome.9,35

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Acknowledgements

supported in part by grants from Fondo de investigacin

sanitaria (Fis 05/0273 and 05/0246), instituto de salud Carlos iii

(Co3/2) and instituto reina sofia de investigacin nefrolgica.07 2006 elsevier ltd. all rights reserved.

AscitesPathogenesisClassificationGeneral evaluation of patients with cirrhosis and ascitesDiagnosisDifferential diagnosis

Managment of ascitesGeneral measuresSpecific measures

Prognosis of patients with cirrhosis and ascitesReferencesAcknowledgements