The ascites that recurs at least on three occasions within a 12-month period despite

dietary sodium restriction and adequate diuretic dosage is defined as recidivant

Grade 1. Mild ascites: it is only detectable by ultrasound examination

Grade 2. Moderate ascites: it is manifest by moderate symmetrical distension of abdomen
Grade 3. Large or gross ascites: it provokes marked abdominal distension

Diagnostic paracentesis is indicated in all patients with new onset of grade 2 or 3 ascites
and in those admitted to the hospital for any complication of cirrhosis.

Ascitic cholesterol determination followed by cytology and carcinoembryonic antigen

(CEA) determination in samples where cholesterol concentration exceeds 45 mg/dl
appears to be a cost-effective method for the differential diagnosis between malignancy-
related and non-malignant ascites.

Ascites is uncomplicated when it is not infected, refractory or associated with HRS.

The negative fluid balance induced by diuretics should not lead to a body weight loss
exceeding 0.5 kg/day in patients without peripheral oedema and 1 kg/day in the
presence of peripheral oedema to avoid plasma volume contraction, ultimately leading
to renal failure and hyponatraemia.

Hyponatraemia is another common diuretic-induced side effect in cirrhosis. It mostly,

but not exclusively, occurs with loop diuretics, as they inhibit Na-K-Cl transporter and,
therefore, solute-free water generation. Plasma volume contraction can also enhance
arginine-vasopressin release. Thus, hyponatraemia can also ensue with anti-
mineralocorticoid administration, albeit infrequently. Most experts agree on at least
temporarily withdrawing diuretics when serum sodium concentration decreases below
120–125 mmol/L
Hyponatremia is common in patients with advanced cirrhosis, and has been arbitrarily
defined as serum sodium concentration lower than 130 mmol/L. 141 142 However,
according to guidelines on hyponatremia in the general patient population reductions
below 135 mmol/L should also be considered.

Both hypovolaemic and hypervolaemic hyponatremia can occur in patients with

cirrhosis. The second, most common, is characterised by an expansion of the
extracellular fluid volume, with ascites and oedema.

The main drivers are non-osmotic hypersecretion of vasopressin and enhanced proximal
nephron sodium reabsorption, which impair free water generation and are both caused
by effective hypovolaemia. hypervolaemic hyponatremia, hypovolaemic hyponatremia is
characterised by the frequent absence of ascites and oedema. It is caused by a prolonged
negative sodium balance with marked loss of extracellular fluid often due to excessive
diuretic therapy. The management of hypervolemic hyponatremia requires attainment
of a negative water balance

Vaptans are selective antagonists of the V2-receptors of arginine-vasopressin in the

principal cells of the collecting ducts that enhance solute-free water excretion. Namely,
tolvaptan, satavaptan and lixivaptan lead to an increased urine volume, a solute-free
water excretion, and an improvement of hyponatremia in 45–82% of cases
Dietary sodium restriction and oral diuretics are mainstays of treatment for patients
with cirrhosis and ascites. Negative sodium balance leads to fluid and weight loss in
patients with cirrhosis and ascites. It is usually sodium restriction, not water restriction,
that induces weight loss, because water follows sodium passively. 50 Dietary sodium
should be restricted to 2000 mg/d (88 mmol/d). Nonurinary excretion of sodium is
about 10 mmol/d. One of the goals of treatment is to achieve negative sodium balance.

In order to achieve negative sodium balance, urinary sodium excretion should be greater
than 78 mmol/d. Sodium restriction is effective in reducing the dose of diuretics,
providing faster solution for ascites, and a shorter hospital stay. 52 53 However, dietary
sodium restriction is successful in achieving a negative sodium balance in only about
10% to 15% of patients with cirrhosis and ascites.
Most experts believe fluid restriction has no role in the management of patients with
uncomplicated ascites. 15 17 Water restriction is recommended only when the serum
sodium decreases to values below 130 mEq/L.

Decreased oral intake and absorption of nutrients, increased energy expenditure, and
altered fuel metabolism with a starvation pattern of metabolism are the underlying
mechanisms for malnutrition in patients with cirrhosis and ascites.

Diuretics have been the mainstay of treatment for patients with cirrhosis and ascites
since they first became available. Patients with grade 1 ascites have mild ascites that can
only be detected by ultrasound. These patients should have a sodium-restricted diet but
do not require diuretics. Patients with grade 2 or higher severity require diuretics to
reduce edema and ascites. Activation of RAAS plays an important role in the
development of ascites. Spironolactone is the diuretic of choice because it is an
aldosterone antagonist that acts on the distal tubules in the kidney to increase sodium
excretion and conserve potassium. As a single agent, spironolactone has been shown to
be more efficacious than furosemide in a randomized clinical trial. 62 However, it is used
as a single agent mostly in patients with minimal fluid overload.
Furosemide is a loop diuretic that causes marked natruresis and diuresis. It is less
efficacious than spironolactone as a single agent in the treatment of patients with
cirrhosis and ascites. 62 It is usually used as an adjunct to spironolactone treatment. It
should be used with caution because it can cause hyponatremia, hypokalemia, and
prerenal renal failure. Because of its good oral availability and intravenous
administration–induced acute reduction in renal glomerular filtration rate, furosemide
is usually used as an oral agent. 64 65 Simultaneous use of spironolactone and furosemide
increases the natriuretic effect and prevents hypokalemia. 15 Furosemide 40 mg and
spironolactone 100 mg daily are usually started as an initial dose in patients with
moderate to severe ascites. It usually takes 3 to 5 days for the diuretics to show their
maximal effects. 66 The doses of spironolactone and furosemide can be increased
simultaneously in a stepwise manner until the maximal doses of 400 mg spironolactone
and 160 mg furosemide every day are reached if desired weight loss and natriuresis are
not attained.

Efforts should be made to avoid overdiuresis that can lead to decreased intravascular
volume, prerenal kidney impairment, hepatic encephalopathy, and
hyponatremia. 69 Serum creatinine greater than 2.0 mg/dL, or serum sodium less than
120 mmol/L indicate that diuretics should be discontinued and alternative treatment
considered.