Treatment of Cirrhotic Ascites
In 1997, alcoholic liver disease accounted for 40% of deaths from cirrhosis in the United States. One prospective study has shown reduction of portal pressures in some patients following a period of abstinence from alcohol, with possible resolution of ascites or greater responsiveness to medical therapy. Irrespective of the etiology of cirrhosis, all patients should be advised to abstain from alcohol completely, including avoidance of alcohol-containing medications and so-called "nonalcoholic" beers.
Bedrest has traditionally been recommended for patients with ascites on the basis that upright posture increases aldosterone levels, which is associated with sodium retention. Although bedrest has been shown to increase natriuresis in cirrhotics, there are no data available to support improvement in clinically relevant outcomes in ascites. Furthermore, prolonged bedrest is impractical, expensive, and difficult to enforce.
Sodium retention is central to the formation of ascites. The typical North American diet contains 200-300 mmol of sodium per day, whereas a no-added-salt diet contains 100-150 mmol of sodium per day. Nonurinary sodium excretion in afebrile cirrhotic patients without diarrhea is approximately 10 mmol/day. Patients with ascites on no diuretics commonly have renal sodium excretion of < 20 mmol/day. Such a patient on a no-added-salt diet will retain at least 100 mmol of sodium per day and 10 L of fluid in 2 weeks (100 mmol/day x 14 days/140 mmol/L = 10 L).
All patients with ascites should receive counseling regarding the importance of a low-sodium diet. A diet containing 88 mmol/day is currently recomm ended for patients with ascites. Diets that have even lower salt contents are not well tolerated. Potassium-containing salt substitutes should be avoided because of the risk of hyperkalemia, especially in those receiving potassium-sparing diuretics. In 10% of patients, sodium restriction sbp prophylaxis with ciprofloxacin alone may be adequate in the control of ascites. Only patients who have urinary excretions of > 78 mmol/day should be treated with sodium restriction alone. In patients with severely impaired natriuresis and difficult-to-control ascites, sodium restriction of 44 mmol per day or even 22 mmol per day may be required.
Most experts believe that dietary sodium restriction is essential to the effective management of ascites. Trials of sodium restriction vs unrestricted diet among patients on diuretics have not shown significant benefits, but have been shown to decrease the time to complete resolution of ascites. One study has shown that compliance with a low-sodium diet can significantly decrease diuretic requirements.
Fluid loss usually follows sodium loss; therefore, fluid restriction in patients with ascites is usually not required. Cirrhotic patients with ascites often have hyponatremia, which is a reflection of severe intravascular volume contraction. In most instances, hyponatremia responds to volume replacement with colloid, and fluid restriction should only be used in patients with serum sodium < 120 mmol/L.
Diuretics that block aldosterone receptors in the distal convoluted tubule are preferred because of the presence of hyperaldosteronism in patients with cirrhosis. Loop diuretics may be used in combination, but are ineffective when used alone. The initial starting dose of spironolactone is 100 mg once daily and can be titrated up to a maximum of 400 mg once a day. Absorption of spironolactone is improved if administered with food. The diuretic effect can be seen within 48 hours, but the peak onset of action is 2 weeks, due to impaired metabolism in cirrhotic persons and a half-life of up to 5 days. Therefore, the dose should be adjusted only once a week. Side effects include hyperkalemia and painful gynecomastia. Amiloride can be used instead of spironolactone, starting at 5 mg per day. The latter is sometimes preferred because of its shorter half-life and quicker onset of action. However, it is much more expensive than spironolactone and has also been shown to be less effective in a randomized, controlled trial.
Both spironolactone and amiloride are weak diuretics and often require the addition of a loop diuretic such as furosemide. Furosemide effects are evident within 30 minutes of oral administration, with a peak effect within 1-2 hours and a duration of action of 4 hours. It is a potent diuretic but is not as effective as spironolactone alone. Furosemide prevents reabsorption of sodium in the loop of Henle; without spironolactone, however, sodium delivered to the distal collecting duct is rapidly reabsorbed due to unopposed aldosterone action. Side effects of furosemide include hypokalemia, hypovolemia, hyponatremia, and increased renal ammonia production. Hypokalemia is usually not a problem when furosemide is combined with a potassium-sparing diuretic. Intravenous administration of furosemide is not recommended because of good oral availability and because of the potential for causing acute reductions in GFR.[20,21] There is no advantage to using other loop diuretics. The usual starting doses of diuretics are 100 mg of spironolactone and 40 mg furosemide. Doses can be titrated up to a maximum of 400 mg of spironolactone and 160 mg of furosemide. A ratio of 100:40 usually maintains normokalemia.
Compliance with and response to sodium restriction and diuretics can be evaluated by daily weights and 24-hour urine collection for sodium. Completeness of urine collection is indicated by urinary creatinine levels of 15-20 mg/kg in males and 10-15 mg/kg in females. Weight loss should be limited to 0.5 kg per day. More rapid weight loss can cause hypovolemia and renal insufficiency, as fluid resorption from the peritoneal cavity is limited to 700 mL per day. Patients with massive edema can tolerate more rapid fluid loss until the edema has resolved.
In order for a patient with a serum sodium concentration of 140 mmol/L on an 88-mmol/day diet to lose 0.5 kg/day or 0.5 L of fluid, the 24-hour urine collection should contain approximately 150 mmol of sodium (140 mmol/Lx 0.5 L + 78 mmol/day). If a 24-hour urine collection is not possible, a random urine sodium-to-potassium ratio of > 1 predicts a > 78-mmol/day sodium excretion in 90% of patients. Noncompliance with a low-sodium diet is reflected by an adequate sodium excretion but with the patient not losing weight. Inadequate sodium excretion, on the other hand, necessitates increasing the doses of diuretics as tolerated up to the maximum recommended level. Diuretics should be discontinued and consideration should be given to the use of second-line therapy if there is evidence of encephalopathy, if serum sodium is < 120 mmol/L despite fluid restriction, or if serum creatinine is > 2.0 mg/dL (180 micromoles [mcmol]/day).
Large-volume paracentesis, if performed for tense nonrefractory ascites, should be followed by diuretics to prevent reaccumulation of fluid. In a study of 36 patients treated by total paracentesis plus intravenous albumin randomized to receive spironolactone 225 mg/day vs placebo, only 18% of those receiving spironolactone had recurrence of ascites compared with 93% of those in the placebo group (P <.0001). The use of 225 mg/day of spironolactone was shown to be effective and safe in most cases, without increased incidence of postparacentesis circulatory dysfunction. Patients should also continue to observe sodium restriction.
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