Ascites

Background

The word ascites is of Greek origin (askos) and means bag or sac. Ascites describes the condition of pathologic fluid accumulation within the abdominal cavity. Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL depending on the phase of the menstrual cycle. This article focuses only on ascites associated with cirrhosis.

Pathophysiology

The accumulation of ascitic fluid represents a state of total-body sodium and water excess, but the event that initiates the unbalance is unclear. Three theories of ascites formation have been proposed.

The underfilling theory suggests that the primary abnormality is inappropriate sequestration of fluid within the splanchnic vascular bed due to portal hypertension and a consequent decrease in effective circulating blood volume. This activates the plasma renin, aldosterone, and sympathetic nervous system, resulting in renal sodium and water retention.

The overflow theory suggests that the primary abnormality is inappropriate renal retention of sodium and water in the absence of volume depletion. This theory was developed in accordance with the observation that patients with cirrhosis have intravascular hypervolemia rather than hypovolemia.

The most recent theory, the peripheral arterial vasodilation hypothesis, includes components of both of the other theories. It suggests that portal hypertension leads to vasodilation, which causes decreased effective arterial blood volume. As the natural history of the disease progresses, neurohumoral excitation increases, more renal sodium is retained, and plasma volume expands. This leads to overflow of fluid into the peritoneal cavity. According to the vasodilation theory, the underfilling theory is proposed to be operative early and the overflow theory is proposed to be operative late in the natural history of cirrhosis.

Although the sequence of events that occurs between the development of portal hypertension and renal sodium retention is not entirely clear, portal hypertension apparently leads to an increase in nitric oxide levels. Nitric oxide mediates splanchnic and peripheral vasodilation. Patients with ascites have greater hepatic artery nitric oxide synthase activity compared to patients without ascites.

Regardless of the initiating event, a number of factors contribute to the accumulation of fluid in the abdominal cavity. Elevated levels of epinephrine and norepinephrine are well-documented factors. Hypoalbuminemia and reduced plasma oncotic pressure favor the extravasation of fluid from the plasma to the peritoneal fluid, and, thus, ascites is infrequent in patients with cirrhosis unless both portal hypertension and hypoalbuminemia are present.

Mortality/Morbidity

Ambulatory patients with an episode of cirrhotic ascites have a 3-year mortality rate of 50%. The development of refractory ascites carries a poor prognosis, with a 1-year survival rate of less than 50%.

Sex

Healthy men have little or no intraperitoneal fluid, but women may normally have as much as 20 mL depending on the phase of the menstrual cycle.

Treatment

Medical Care

Sodium restriction (20-30 mEq/d) and diuretic therapy constitute the standard medical management for ascites and are effective in approximately 95% of patients.

• Water restriction is used only if persistent hyponatremia is present.

• Therapeutic paracentesis should be reserved for patients who need rapid symptomatic relief of tense ascites.

• TIPS is an interventional radiologic technique that reduces portal pressure and may be the most efficacious for treatment of patients with diuretic-resistant ascites. This procedure consists of inserting a long metal needle from the right jugular vein into the hepatic vein. This is slowly becoming the standard of care in patients with diuretic-refractory ascites.

Surgical Care

The peritoneovenous shunt is an alternative for patients with medically intractable ascites. This is a megalymphatic shunt that returns the ascitic fluid to the central venous system. Beneficial effects of these shunts include increased cardiac output, renal blood flow, glomerular filtration rate, urinary volume, and sodium excretion and decreased plasma renin activity and plasma aldosterone concentration. No evidence indicates that these shunts improve patient survival. With the advent of the TIPS procedure, this form of therapy is almost obsolete.

Consultations

Consultation with a gastrointestinal specialist and/or hepatologist should be considered for all patients with ascites, particularly if the ascites is refractory to medical treatment.

Diet

Sodium restriction of 500 mg/d (22 mmol/d) is feasible in a hospital setting; however, it is unrealistic in most outpatient settings. A more appropriate sodium restriction is 2000 mg/d (88 mmol). Indiscriminate fluid restriction is inappropriate. Fluids need not be restricted unless the serum sodium level drops below 120 mmol/L.

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Drug Category: Diuretics

Mainstay of medical therapy in ascites.

Drug Name	Spironolactone (Aldactone)
Description	For management of edema resulting from excessive aldosterone excretion. Competes with aldosterone for receptor sites in distal renal tubules, increasing water excretion while retaining potassium and hydrogen ions. The peak effect of Aldactone is approximately 3 d.
Adult Dose	25-200 mg/d PO qd or divided bid
Pediatric Dose	1.5-3.5 mg/kg/d PO in divided doses q6-24h
Contraindications	Documented hypersensitivity; anuria; renal failure; hyperkalemia
Interactions	May decrease effect of anticoagulants; potassium and potassium-sparing diuretics may increase toxicity
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in renal and hepatic impairment; may cause gynecomastia and impotence in men

Drug Name	Furosemide (Lasix)
Description	Increases excretion of water by interfering with chloride-binding cotransport system, which, in turn, inhibits sodium and chloride reabsorption in ascending loop of Henle and distal renal tubule. Dose must be individualized to patient. Depending on response, administer at increments of 20-40 mg, no sooner than 6-8 h after the previous dose, until desired diuresis occurs. When treating infants, titrate in increments of 1 mg/kg/dose until a satisfactory effect is achieved.
Adult Dose	20-80 mg/d PO/IV/IM; titrate up to 600 mg/d for severe edematous states
Pediatric Dose	1-2 mg/kg/dose PO; not to exceed 6 mg/kg/dose; do not administer >q6h 1 mg/kg IV/IM slowly under close supervision; not to exceed 6 mg/kg
Contraindications	Documented hypersensitivity; hepatic coma; anuria; state of severe electrolyte depletion
Interactions	Metformin decreases concentrations; interferes with hypoglycemic effect of antidiabetic agents and antagonizes muscle-relaxing effect of tubocurarine; auditory toxicity appears to be increased with coadministration of aminoglycosides, hearing loss of varying degrees may occur; anticoagulant activity of warfarin may be enhanced when taken concurrently; increased plasma lithium levels and toxicity are possible when taken concurrently
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Perform frequent serum electrolyte, carbon dioxide, glucose, creatinine, uric acid, calcium, and BUN determinations during first few months of therapy and periodically thereafter

Drug Name	Amiloride (Midamor)
Description	A pyrazine-carbonyl-guanidine unrelated chemically to other known antikaliuretic or diuretic agents. Potassium-conserving (antikaliuretic) drug which, compared with thiazide diuretics, possesses weak natriuretic, diuretic, and antihypertensive activity.
Adult Dose	5-20 mg PO qd
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; elevated serum potassium levels (>5.5 mEq/L); impaired renal function, acute or chronic renal insufficiency, and evidence of diabetic nephropathy; monitor electrolytes closely if evidence of renal functional impairment is present, BUN is >30 mg/100 mL, or serum creatinine level is >1.5 mg/100 mL
Interactions	Concomitant therapy with potassium supplementation may increase serum potassium levels; if concomitant use of these agents is indicated because of demonstrated hypokalemia, use caution and monitor serum potassium level frequently; generally, lithium should not be administered with diuretics because may reduce renal clearance and add a high risk of lithium toxicity; administration of NSAIDs can reduce diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing, and thiazide diuretics; when used concomitantly, observe patient closely to determine if desired effect of diuretic obtained Indomethacin and potassium-sparing diuretics, including amiloride, may be associated with increased serum potassium levels; consider potential effects on potassium kinetics and renal function
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Potassium retention associated with use of an antikaliuretic agent accentuated in presence of renal impairment and may result in rapid development of hyperkalemia; monitor serum potassium level; mild hyperkalemia usually not associated with abnormal ECG findings

Drug Name	Metolazone (Mykrox, Zaroxolyn)
Description	Helps treat edema in congestive heart failure. Increases excretion of sodium, water, potassium, and hydrogen ions by inhibiting reabsorption of sodium in distal tubules. May be more effective in those with impaired renal function.
Adult Dose	5-20 mg/dose PO q24h
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; hepatic coma or anuria
Interactions	Thiazides may decrease effect of anticoagulants, sulfonylureas, and gout treatments; anticholinergics and amphotericin B may increase toxicity of thiazides; effects of thiazides may decrease when used concurrently with bile acid sequestrants, NSAIDs, or methenamine; when administered concurrently, thiazides increase toxicity of anesthetics, diazoxide, digitoxin, lithium, loop diuretics, antineoplastics, allopurinol, calcium salts, vitamin D, and nondepolarizing muscle relaxants
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Caution in hepatic or renal disease, diabetes mellitus, gout, or lupus erythematosus

Drug Name	Mannitol (Osmitrol)
Description	Inhibits tubular reabsorption of electrolytes by increasing osmotic pressure of glomerular filtrate. Increases urinary output.
Adult Dose	0.5-2 g/kg IV over 30-60 min as a 15-25% solution; repeat q6-8h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; anuria, severe pulmonary congestion, progressive renal damage, severe dehydration, active intracranial bleeding, and progressive heart failure
Interactions	May decrease serum lithium levels
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Carefully evaluate cardiovascular status before rapid administration because a sudden increase in extracellular fluid may lead to fulminating CHF; avoid pseudoagglutination; when blood given simultaneously, add at least 20 mEq of sodium chloride to each liter of mannitol solution; do not give electrolyte-free mannitol solutions with blood