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Ascites occurs in 50% of patients within 10 years of diagnosis of compensated cirrhosis. [1]It is a poor prognostic

indicator, with a 50% 2-year survival, [2]worsening significantly to 20% to 50% at 1 year when the ascites becomes

refractory to medical therapy.[3,4]Ascites also predisposes patients to life-threatening complications such asspontaneous bacterial peritonitis and hepatorenal syndrome, and therefore is a major indication for liver

transplantation. Effective management of ascites requires a thorough understanding of the pathophysiology of ascites

formation and the rationale for various treatment modalities.

The pathophysiology leading to ascites formation is complex. Subtle sodium and water retention develops early in

cirrhosis, and this becomes more avid as the cirrhotic process progresses. The presence of cirrhosis is associated

with hemodynamic changes. Systemic and splanchnic vasodilatation occurs due to an imbalance of vasoactive

substances, favoring vasodilators. The latter results in a decrease in effective circulating blood volume. The perceived

hypovolemia in turn activates various vasoconstrictor systems, including the sympathetic nervous system, the renin-

angiotensin-aldosterone system, and arginine vasopressin, producing renal vasoconstriction with a decrease in

glomerular filtration rate (GFR), as well as an increase in renal sodium and water reabsorption. [5]Independent of the

hemodynamic changes, hepatic dysfunction also enhances renal sodium retention through some yet undefined

mechanism, as sodium excretion has been shown to be related to a threshold of hepatic function. [6,7]The presence

of portal hypertension then preferentially localizes the excess fluid to the peritoneal cavity.

In 1997, alcoholic liver disease accounted for 40% of deaths from cirrhosis in the United States.[8]One prospective

study[9]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, al

patients should be advised to abstain from alcohol completely, including avoidance of alcohol-containing medications

and so-called "nonalcoholic" beers.[10]

Bedrest has traditionally been recommended for patients with ascites on the basis that upright posture increases

aldosterone levels, which is associated with sodium retention. [11]Although bedrest has been shown to increase

natriuresis in cirrhotics,[12]there are no data available to support improvement in clinically relevant outcomes in

ascites.[10]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.[13]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. Adiet containing

88 mmol/day is currently recomm ended for patients with ascites.[14]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 alone may be

adequate in the control of ascites.[14]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

The Management of Cirrhotic AscitesElaine Yeung, MD, Florence S. Wong, MD, FRCP(C)

Medscape General Medicine. 2002;4(4)
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shown to decrease the time to complete resolution of ascites. [15]One study has shown that compliance with a low-

sodium diet can significantly decrease diuretic requirements.[16]

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 ofhyperaldosteronism 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.[17]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. [18]

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 1-2hours and a duration of action of 4 hours. It is a potent diuretic but is not as effective as spironolactone alone. [19]

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. [14]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. [10]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.[22]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.[23]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).[10]

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).[24]The use of 225 mg/day of spironolactone was

shown to be effective and safe in most cases, without increased incidence of postparacentesis circulatory


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dysfunction. Patients should also continue to observe sodium restriction.

Refractory ascites is subdivided into diuretic-resistant and diuretic-intractable ascites ( ). [25]Diuretic-resistant ascites

usually requires a period of observation on maximal medical therapy to ensure diuretic resistance, which may take up

to several weeks. A recent study showed that a single dose of 80 mg of intravenous furosemide and a subsequent

random urine sodium of < 50 mmol/L is indicative of refractory ascites, compared with those cases of diuretic-

responsive ascites, where the serum sodium is always > 80 mmol/L, with no overlap between the 2 groups. [26]

Refractory ascites portends a poor prognosis and requires second-line therapy, such as large-volume paracentesis,

transjugular intrahepatic portosystemic shunts (TIPS), or liver transplantation.

Table 1. Definitions of Refractory Ascites

Diuretic-resistant ascites:

Lack of response (weight loss < 200 g/day and urinary sodium

excretion < 50 mmol/day) on a 50-mmol sodium/day diet and maximal

doses of diuretics (spironolactone 400 mg/day and furosemide 160 mg/day

for 2 weeks).

Diuretic-intractable ascites:

Development of diuretic-induced complications such as severe electrolyte

disturbances, renal impairment, or hepatic encephalopathy, precluding the

use of an effective diuretic dose.

Several large randomized, controlled trials have shown that repeated large-volume paracentesis (4 L-6 L) is safer and

more effective for the treatment of tense ascites compared with larger-than-usual doses of diuretics. [27-30]Incidence

of systemic and hemodynamic disturbance, electrolyte abnormalities, renal impairment, and encephalopathy is lower

in patients treated with repeated large-volume paracentesis compared with diuretic therapy.[27]Improvement in

cardiac output[31]; lung volumes[32]; and reductions in intra-abdominal, portal, [33]intra-thoracic, and pulmonary

pressures[32]was also observed. Shortened duration of hospitalization was observed with large-volume paracentesis,

but the rates of hospital readmission and survival were similar to those associated with use of diuretic therapy.[27]

Total paracentesis has also been shown to be as safe as repeated partial paracentesis and to shorten the period of

hospitalization -- and may even be performed on an outpatient basis. [34]However, even in the most sodium-avid of all

ascitic patients, paracentesis > 10 L should not be performed more often than every 2 weeks. More frequent need for

paracentesis implies dietary noncompliance.

Procedure-associated risks include a 1% chance of significant abdominal-wall hematoma, 0.01% chance of

hemoperitoneum, and a 0.01% chance of iatrogenic infection related to paracentesis. [35,36]The only absolute

contraindication to paracentesis is clinically evident fibrinolysis and disseminated intravascular coagulation.[10]


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Severe coagulopathy and thrombocytopenia (INR > 2 or platelet count < 50) may need correction prior to the

procedure to minimize the risk of bleeding, although there are no data supporting specific cut-offs. Leakage of ascitic

fluid occasionally occurs and can be managed by placing a purse-string suture around the opening and by instructing

the patient to lie on the side opposite to the puncture site. [37]Permanent indwelling catheters should not be left in the

peritoneal cavity, as this significantly increases the risk of peritonitis. The attachment of a colostomy bag to collect

the ascit ic fluid is also not recommended.

An important potential complication of paracentesis is postprocedure circulatory dysfunction characterized by renal

impairment and activation of neurohormonal factors.[38]

In one randomized, controlled study of patients with tenseascites, intravenous albumin infusion was shown to lower the rates of hyponatremia, elevations in serum creatinine,

and activation of neurohormonal factors (increased levels of renin and aldosterone) after paracentesis. [39]However,

the group that did not receive albumin did not suffer any greater morbidity or mortality. Another study found that

patients with postparacentesis rise in plasma renin had decreased survival at 1 year,[38]but it is unclear whether

circulatory dysfunction is a consequence of the procedure or merely a marker of more advanced disease. Runyon, [14

in his recent review of ascites, suggests that there are no adequate survival data to justify the expense of routine

human albumin infusion and the possibility of infection with noneradicated and undefined viruses.

Despite the lack of evidence, albumin is still commonly used for intravenous plasma expansion after large-volume

therapeutic paracentesis (> 5 L-6 L). Six to 8 g of albumin/L of ascitic fluid removed is administered intravenously

during or after the procedure to prevent relative hypovolemia, which usually occurs 3-6 hours later. [40]Another area ofcontroversy relates to the use of nonalbumin plasma expanders. Four studies have compared nonalbumin plasma

expanders with albumin. Although 3 of the 4 studies[41-43]showed that synthetic plasma expanders were as effective

in preventing hyponatremia and renal impairment, Gines and coworkers[38]showed that postparacentesis circulatory

dysfunction was more frequent in patients treated with dextran 70 or polygeline than in patients receiving albumin.

Once again, more studies are necessary before definite recommendations can be made regarding the use of plasma

expanders after paracentesis.

A peritoneovenous shunt is a surgically inserted tube that connects the peritoneal cavity to the superior vena cava

along subcutaneous tissue, allowing one-way passage of ascitic fluid from the peritoneal cavity back into the

circulation.

Poor long-term patency and other technical problems such as shunt dislodgement and kinking, and the lack of a

survival advantage, have all led to near abandonment of this procedure. Furthermore, shunt-fibrous adhesions and so-

called "cocoon" formation can make subsequent liver transplantation difficult. [44]The most recent guidelines from the

American Association for the Study of Liver Diseases recommend peritoneovenous shunting only for diuretic-resistan

patients who are not transplant candidates and who are not candidates for serial therapeutic paracentesis because of

multiple abdominal surgical scars, or when a physician is unavailable to perform serial paracentesis.[14]

TIPS is a side-to-side portocaval shunt initially designed to relieve portal hypertension for patients with refractory

variceal bleeding.[45]Because patients who had ascites were noted to have a reduction or disappearance of ascites

after TIPS insertion, TIPS has become another option for the treatment of refractory ascites. A flexible metal

prosthesis is used to bridge a branch of the hepatic and portal veins and is effective in reducing sinusoidal pressure.[46]The procedure is performed percutaneously under radiologic guidance and obviates the need for surgery. It is

recommended that coagulopathy (INR > 2 and platelet count < 50 x109/L) be corrected first if indicated, and that

paracentesis be performed in patients with tense ascites prior to the procedure.

Four randomized, controlled studies have compared TIPS with large-volume paracentesis in refractory ascites. [47-50]

All 4 studies showed better control of ascites with TIPS, but only 1 study showed a survival benefit.[48]The

mechanism for improvement in ascites with TIPS begins with decompression of portal circulation with improvement in

splanchnic hemodynamics.[51]The resulting refilling of the circulatory volume and decrease in plasma levels of renin

and aldosterone results in an increase in creatinine clearance and natriuresis. Without diuretic therapy, the onset of


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natriuresis is delayed for up to 4 weeks.[51]Once begun, natriuresis continues to improve, so that at 6 months after

TIPS insertion, most patients are in a negative sodium balance on a 22-mmol/day diet, allowing elimination of

ascites.[52]Natriuretic response correlated significantly with baseline pre-TIPS renal function[53-56]and inversely with

the patient's age.[51]Child-Pugh class C patients with ascites are less likely to respond to TIPS, and are generally

not recommended for TIPS insertion. [57-59]

Procedure-related complications and long-term difficulties with TIPS have prevented TIPS from being recommended in

all patients with refractory ascites. [56]The rate of procedure-related complications is 10% and of procedure-related

mortality is 2%.[59]

Procedure-related complications include neck hematomas, hemobilia, puncture of the livercapsule causing intra-abdominal bleeding, and shunt occlusion. Reported rates of shunt occlusion range from 23% to

87% within the first year.[57]It is recommended that ultrasonographic screening be performed at 24 hours after TIPS

insertion, at 6 weeks, 3 months, 6 months, and every 6 months thereafter.[46]In patients with a successful TIPS

placement, there is resolution of ascites, improved renal function, patient well-being, and positive nitrogen balance

during long-term follow-up.[60]

In the early post-TIPS period, deterioration of liver function may occur as blood flow is shunted away from the liver.

Deterioration in renal function may occur in patients with prior renal dysfunction (creatinine > 2.5 x upper limit of

normal) and may be exacerbated by exposure to radiographic dye. In patients with pre-existing cardio-pulmonary

disease, sudden portal decompression with return of the splanchnic volume to the systemic circulation can lead to an

immediate and significant increase in cardiac output precipitating cardiac failure and pulmonary hypertension. [61]Thepresence of a metal stent may also cause hemolysis. [62]

Late TIPS complications include encephalopathy in 30% of cases, [63]endothelial hyperplasia causing shunt stenosis

in 40%, and reappearance of ascites in noncompliant patients. Encephalopathy is more frequent in patients older

than age 60 years and in patients with a history of spontaneous encephalopathy. [63]In most patients, chronic

encephalopathy improves with time and can be controlled with lactulose. Chronic incapacitating encephalopathy can

be reversed by balloon occlusion of the stent. [64]Shunt infection is uncommon but may be difficult to eradicate.

Therefore, dental clearance and treatment of spontaneous bacterial peritonitis are recommended before considering

patients for TIPS insertion.

Absolute contraindications[56]for TIPS insertion include serum bilirubin > 85 mcmol/L (5 mg/dL), INR > 2, functional

renal disorder with serum creatinine > 250 mcmol/ (2.8 mg/dL), intrinsic renal disease with urine protein > 500 mg/24

hr or active urinary sediment, Grade III or IV hepatic encephalopathy, cardiac disease, portal vein thrombosis,

noncompliance with sodium restriction, or the presence of carcinoma that is likely to limit the patient's lifespan to

less than 1 year. Relative contraindications include dental sepsis, spontaneous bacterial peritonitis, and active

infection (pneumonia or urinary tract infection).

Liver transplantation is the only definitive treatment for ascites and the only treatment that has been clearly shown to

improve survival.[65]Patients with cirrhosis who develop ascites should be assessed for possible liver transplantation

because of their poor prognosis. Patients who develop renal dysfunction (GFR < 50 mL/min) do much worse after liver

transplantation (80% vs 50% survival at 15 months, P< .05).[66,67]Therefore, given the latter, every effort should be

made to transplant patients prior to the onset of renal dysfunction. Other poor prognostic indicators include mean

arterial pressure < 82 mmHg, urinary sodium excretion of < 1.5 mEq/day, plasma norepinephrine levels of > 570

pg/mL, poor nutritional state, presence of hepatomegaly, and serum albumin < 25 g/L. [68]Long waiting lists for

cadaveric organs mean that only a small proportion of patients can benefit from this therapy. Living-related donor

transplants are offered at a few centers, but careful selection of both donor and recipient is necessary because of

significant risks to the donor.[69]

Spontaneous bacterial peritonitis (SBP) is defined as an ascitic fluid infection associated with a posit ive bacterial

culture and an ascitic fluid polymorphonuclear cell count of > 250/mm3, in the absence of a surgically treatable

abdominal source of infection.[70]In hospitalized patients with cirrhosis, 10% to 25% will have an episode of SBP with


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a mortality rate of 17% to 50%,[71]with outcome dependent on the association with a recent gastrointestinal bleed,[72]the severity of infection, and degree of renal and liver failure. [73]Clinically, certain factors predispose patients with

cirrhosis to developing ascites ( ).[70,74]Patients who already have had 1 episode of SBP are at high risk for

recurrence, with rates of 43% at 6 months, 69% at 1 year, and 74% at 2 years.[75]Patients with SBP are also at

particularly high risk for renal complications,[76,77]likely related to systemic hemodynamic changes and the

increased cytokine levels that are part of the systemic inflammatory response to infection.

Table 2. Factors Predisposing to SBP

Severity of liver disease (70% of all SBP episodes are in patients with Child-Pugh class C cirrhosis)

Ascitic fluid total protein level of < 1 g/dL and/or ascitic fluid complement factor C3 < 13 mg/dL

Gastrointestinal bleeding

Urinary tract infections

Intestinal bacterial overgrowth

Iatrogenic sources of bacteremia such as urinary bladder and intravascular catheters

One or more previous SBP episodes

Serum bilirubin of > 2.5 mg/dL

Cirrhotic patients often have bacteremia and high levels of endotoxin levels without clinically significant infection. [78]

Bacteremia is most often from intestinal bacterial overgrowth, [79]but may also result from bacteriuria or intravascular

catheters.[70]Intestinal permeability from vascular congestion and edema secondary to portal hypertension and

malnutrition can cause increased bacterial translocation from the intestinal lumen to the bloodstream and seeding of

ascit ic fluid. Despite this, infection occurs only in those patients with decreased levels of complement factors (ascit ic

fluid third component of complement [C3] < 13 mg/dL and/or protein level < 1g/dL), severely impaired neutrophil

chemotaxis, and poor phagocytic activity of neutrophils and macrophages. [74,80]Deficiency in complements may be

due to decreased synthesis or increased consumption.[74,80]In addition, neutrophil response is worse in ascitic fluid

than in serum, and worse in patients with Child-Pugh class C cirrhosis and in those with previous episodes of

bacterial infections, including SBP. Furthermore, intrahepatic and extrahepatic shunts that prevent circulating

bacteria from encountering Kupffer cells in the reticuloendothelial system also contribute to the development of SBP.[70]In cirrhotic rats with hemorrhagic shock, [81]increased bacterial translocation and intestinal permeability, as well

as decreased effectiveness of the reticuloendothelial system, have been demonstrated, which could explain the

higher rates of SBP among patients hospitalized with gastrointestinal bleeds.[80,82]

The most common form of SBP involves ascitic fluid with a positive bacterial culture and a polymorphonuclear (PMN)

cell count of 250/mm3. About two thirds of ascitic fluid infections belong to this subgroup and are almost invariably

monomicrobial. [83]Other variants of SBP include culture-negative neutrocytic ascites (CNNA) characterized by PMN

cell count of 250/mm3with negative ascitic fluid cultures, and monomicrobial nonneutrocytic bacterascites (MNB),

characterized by isolation of bacteria in cultures but with a PMN cell count of 250 mm 3. The differential diagnosis o


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Table 4. Indications for Diagnostic Paracentesis in Hospitalized Patients With Ascites

Symptoms or signs of peritoneal infection

-abdominal pain, rebound tenderness, vomiting, diarrhea, ileus

Systemic signs of infection

-fever, leukocytosis, septic shock

Hepatic encephalopathy or rapid impairment in renal function without clear precipitant

Gastrointestinal bleeding before starting prophylactic antibiotics

Treatment should be started empirically if SBP is suspected clinically, regardless of the availability of laboratory

results. In community-acquired SBP and in patients not on SBP prophylaxis, Escherichia coli and Klebsiella

pneumoniae are seen in up to 60% of isolates. About 25% are Gram-positive cocci, mostly streptococcal species.

Anaerobes are rarely seen. Intravenous cefotaxime is the empiric antibiotic of choice and has been shown to cure

SBP episodes in 85% of patients compared with in 56% of those receiving ampicillin and tobramycin. The optimal

cost-effective dosage is 2 g every 12 hours for a minimum of 5 days. [84]Intravenous amoxicillin-clavulanic acid

followed by oral therapy has been shown to be as effective as cefotaxime, but may not be widely available. [86]

Intravenous ciprofloxacin followed by oral treatment has also been shown to be effective. [87]Trials of oral ofloxacin vs

intravenous cefotaxime in patients without septic shock, encephalopathy, azotemia, gastrointestinal bleed, or ileus

showed an SBP resolution rate of 84% in the ofloxacin group vs 85% in the cefotaxime group. Survival rate was 81%

in both groups.[88]Although oral antibiotics are promising as a form of outpatient therapy, monitoring of patient

compliance is necessary and the duration of therapy must be evaluated before this option can be recommended.Once culture results are available, antibiotic modifications may be necessary, but aminoglycosides should still be

avoided because of the risk of renal failure. Patients who develop SBP while on norfloxacin prophylaxis are more

likely to have infections caused by Gram-positive cocci or quinolone-resistant Gram-negative bacilli.[89,90]Cefotaxime

is effective even in these latter cases.[90,91]See .

Table 5. Treatment Regimens for SBP

Cefotaxime 2 g intravenously every 12 hours x minimum of 5 days

Other cephalosporins (cefonicid, ceftriaxone, ceftizoxime, ceftazidime)

Amoxicillin (1 g) and clavulanic acid (200 mg) intravenously 3 times daily x ~5 days, then orally 500 mg/125

mg 3 times daily x ~3 days

Ciprofloxacin 200 mg intravenously every 12 hours x 7 days

Ciprofloxacin 200 mg intravenously every 12 hours x 2 days then 500 mg orally every 12 hours x 5 days


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In terms of other adjunctive therapies, one randomized trial of intravenous albumin in addition to antibiotics reduced

renal impairment from 33% to 10% and hospital mortality from 29% to 10%.[92]Despite these impressive results, the

high cost of using albumin would require further studies to confirm efficacy before intravenous albumin can be

recommended.

Prevention of SBP involves treatment of the ascites and underlying liver disease, prophylaxis in high-risk patients, and

eliminating potential sources of bacteremia.[70]Patients should be counseled to avoid alcohol. Diuretics, by

decreasing the amount of ascites, have been shown to lead to improved ascitic fluid opsonic activity.[93]

Gastrointestinal bleeding should be treated aggressively, including consideration for TIPS. Treatment and eradication

of local infections should be undertaken before dissemination. Bacteriuria is common, especially in women. All

patients should be screened and treated for urinary tract infections even in the absence of symptoms. Urinary

catheters should be avoided. Intravascular catheters cause between 4% and 20% of bacteremic episodes and their

use should also be minimized.[70]

Patients who have had previous episodes of SBP should receive long-term antibiotic prophylaxis because of high

rates of recurrence. It has been shown that norfloxacin 400 mg once daily decreases the recurrence rate of SBP at 1year (from 68% to 20%).[89]In a group of patients with low ascitic fluid protein concentration, with or without previous

episodes of SBP, ciprofloxacin 750 mg weekly has been shown to decrease the incidence of SBP from 22% to 4% a

6 months.[94]One meta-analysis of 4 randomized, controlled trials for SBP prophylaxis using quinolones or

trimethoprim-sulfamethoxazole suggested increased survival at 5 months (82% with SBP prophylaxis vs 73% with

placebo), but the analysis included patients with and without prior episodes of SBP.[95]Economic analyses also

suggest that SBP prophylaxis is associated with reduced cost compared with a "diagnose and treat" strategy in high

risk patients, and even reduces total antibiotic burden.[96,97]Indications for SBP prophylaxis and various

recommended antibiotic regimens are listed in . [84]

Table 6. Recommendations for SBP Prophylaxis

In nonbleeding cirrhotic patients with ascites:

Recovering from an SBP episode

-continuous oral administration of norfloxacin 400 mg daily or ciprofloxacin 750 mg weekly

-consider liver transplantation

Without past history of SBP and with

-high ascitic fluid protein (> 10 g/dL): no prophylaxis necessary

-low ascitic fluid protein (< 10 g/dL): no consensus on the necessity of prophylaxis

In cirrhotics with upper gastrointestinal hemorrhage:

Exclusion of SBP and other infections before prophylaxis

Oral administration of norfloxacin 400 mg every 12 hours x minimum of 7 days


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Alternative regimens:

-ofloxacin 400 mg/day x 10 days (first intravenously, then orally) and with each endoscopy 1 g of

amoxicillin/200 mg clavulanic acid

-ciprofloxacin 500 mg twice daily x 7 days orally or via nasogastric tube after endoscopy

-amoxicillin/clavulanic acid 1 g/200 mg 3 times daily and ciprofloxacin 200 mg twice daily intravenously then

orally until 3 days after cessation of bleeding

In patients who have active gastrointestinal bleeding, norfloxacin is traditionally recommended for SBP prophylaxis

because of its ability to selectively eliminate Gram-negative intestinal bacteria without having an impact on anaerobic

flora; therefore, it can prevent problems with bacterial overgrowth. In a randomized, controlled trial, norfloxacin 400 mg

twice daily administered for 7 days significantly reduced the incidence of bacteremia and/or SBP in patients with

gastrointestinal hemorrhage.[82]Other antibiotic regimens that have been investigated include ofloxacin 400 mg/day

(initially intravenously then orally) plus amoxicillin-clavulanic acid (1 g intravenous, before each endoscopy), [98]

ciprofloxacin plus amoxicillin-clavulanic acid (first intravenously and then orally once bleeding is controlled), [99]and

oral ciprofloxacin (500 mg twice daily for 7 days).[100]The incidence of bacterial infections was significantly lower

among patients in the treated groups (10% to 20%) compared with those in the control groups (45% to 66%).

Furthermore, a meta-analysis has shown that short-term survival is improved significantly with antibiotic prophylaxis

in patients with cirrhosis and gastrointestinal hemorrhage, with no difference between oral vs intravenous antibiotics.[101]Regardless of the antibiotic regimen used, SBP must be ruled out before starting prophylaxis.

Long-term norfloxacin administration reduces the risk of Gram-negative infections but increases the risk of severe

hospital-acquired staphylococcal infections and resistance to antibiotics. [102]There is currently insufficient evidence

to use prophylaxis in low-protein ascites (< 1 g/dL), but some groups advocate the use of norfloxacin 400 mg once

daily during hospitalization to reduce the incidence of SBP and extraperitoneal infections. [70]However, others have

routinely stopped norfloxacin prophylaxis in patients who are admitted to hospital.[102]At present, quinolone-resistan

bacteria do not seem to be a problem because there is no cross-resistance between quinolones and third-generation

cephalosporins.[70]

Despite effective antibiotic therapy for episodes of SBP, long-term prognosis is still extremely poor, with probabilitiesof survival at 1 and 2 years of 30% and 20%, respectively. [70]An episode of SBP is an indication for liver

transplantation. Previous SBP, however, is associated with greater incidence of infectious complications and higher

mortality rate after liver transplantation.[103]

Effective treatment of ascites remains one of the most important aspects in the management of patients with

decompensated cirrhosis, especially in those who are not candidates for liver transplantation. Currently existing

therapies, aside from liver transplantation, have not been shown to have a significant impact on survival. Living-related

organ donation may be an attractive option for many patients, but can only be performed in specialized centers. As

our understanding of the pathophysiology of ascites improves, new therapies may become available to enhance

survival while awaiting liver transplantation.


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