Download Cirrhotic Ascites

Cirrhotic Ascites
Definition
Accumulation of peritoneal fluid
Symptoms
1. Small amount of Ascites
1. Asymptomatic
2. Large amount of Ascites
1. Abdominal distention and discomfort
2. Anorexia
3. Nausea
4. Early satiety
5. Heartburn (Gastroesophageal Reflux)
6. Flank pain
7. Respiratory distress
2. Signs
1. Umbilicus may evert
2. Bulging flanks with patient lying supine
1. Weight of ascitic fluid pushes against side walls
3. Tympany at the top of the abdominal curve
1. Patient lies supine
2. Gas filled bowel floats upward over Ascites
4. Fluid Wave Test
5. Shifting Dullness Test
6. Puddle Sign
3. Causes
1. See Ascites Causes
2. Most common etiologies
1. Cirrhosis (Cirrhotic Ascites): 85% of cases
2. Cancer (Malignant Ascites)
3. Congestive Heart Failure
4. Tuberculosis
4. Labs
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1. Diagnostic abdominal Paracentesis in all cases
2. Ascites Fluid: Serum Ascites albumin gradient (SAAG)
1. Serum Albumin and Ascites albumin
2. Exudate (Serum to Ascites albumin gradient <1.1)
1. Peritonitis
2. Neoplasm (Malignant Ascites)
3. Pancreatitis
4. Vasculitis
3. Transudate (Serum to Ascites albumin gradient
>1.1)
1. Cirrhosis (Cirrhotic Ascites)
1. Secondary to Portal Hypertension
2. Congestive Heart Failure
3. Budd-Chiari Syndrome
5. Ascites Fluid: Cell Count with Differential
1. Ascites Red Blood Cells (RBC) elevated
1. Neoplasm (Malignant Ascites)
2. Tuberculous Peritonitis (variably elevated)
3. Pancreatitis (variably elevated)
2. Ascites White Blood Cells <250 cells/mm3
1. Serum to Ascites Albumin Gradient (SAAG)
< 1.1 g/dl
1. Fluid total protein >2.5: Cardiac Ascites
2. Fluid total protein <2.5: Cirrhotic
Ascites
2. Serum to Ascites Albumin Gradient (SAAG)
> 1.1 g/dl
1. Fluid total protein <2.5: Nephrotic
Ascites
3. Ascites White Blood Cells >500 (or PMNs >250)
1. WBC Differential <50% Neutrophils (PMNs)
1. Peritoneal carcinomatosis (>50%
Lymphocytes)
1. Search for primary tumor
2. Tuberculous Peritonitis (>70%
Lymphocytes)
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6.
7.
8.
9.
1. Culture fluid for Tuberculosis
2. WBC Differential >50% Neutrophils (PMNs)
1. Pancreatic Ascites (Fluid amylase >100
U/L)
1. Evaluate with abdominal CT
2. Spontaneous Bacterial Peritonitis (single
colony)
1. Fluid total protein <1 g/dl
2. Fluid glucose >50 mg/dl
3. Fluid LDH <225 U/L
3. Bacterial peritonitis (polymicrobial)
1. White Blood Cell count often >
10,000
2. Fluid total protein >1 g/dl
3. Fluid glucose <50 mg/dl
4. Fluid LDH >225 U/L
Ascites fluid color
1. Transparent to cloudy yellow or clear (typical)
2. Dark brown: Obtain quantitative fluid Bilirubin
3. Milky: Obtain Triglyceride concentration
4. Bloody: Adjust Leukocyte count
1. Subtract 1 White Blood Cell per 750 Red
Blood Cells
2. Subtract 1 Neutrophil (PMN) per 250 Red
Blood Cells
Ascites fluid assorted labs
1. Lactate Dehydrogenase
2. Amylase
3. pH
4. Lipids
5. Culture and cytology
Diagnostics: Diagnostic Paracentesis
1. Identify site at linea alba, 2 cm below Umbilicus
2. Use 22 gauge needle with catheter
Radiology
1. Ultrasound abdomen or CT Abdomen
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10.
1. Very sensitive for ascitic fluid
Management
1. Cirrhosis
1. Check Cirrhotic Ascites
2. Malignant Ascites
1. Paracentesis offers symptomatic relief as needed
2. Medication Management
1. Spironolactone and
2. Thiazide or Loop Diuretic
Treatment of Cirrhotic Ascites
Treating Reversible Causes of Cirrhosis
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.
Bed rest
Bed rest has traditionally been recommended for patients with ascites
on the basis that upright posture increases aldosterone levels, which
is associated with sodium retention. Although bed rest has been
shown to increase natriuresis (excessive loss of cations esp. sodium in
the urine) in cirrhotics, there are no data available to support
improvement in clinically relevant outcomes in ascites. Furthermore,
prolonged bed rest is impractical, expensive, and difficult to enforce.
Sodium Restriction
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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. Non-urinary sodium excretion in afebrile (without fever)
cirrhotic patients without diarrhea is approximately 10 mmol/day.
Patients with ascites on 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 recommended 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 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 Restriction
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
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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
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 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 Henley; 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
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because of good oral availability and because of the potential for
causing acute reductions in GFR. 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.
Monitoring Response to Sodium Restriction and Diuretics
Compliance with and response to sodium restriction and diuretics
can be evaluated by taking the weight daily and checking the 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 non-refractory
ascites, should be followed by diuretics to prevent re-accumulation of
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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 post-paracentesis circulatory dysfunction. Patients
should also continue to observe sodium restriction.
Cirrhosis is the late result of any disease that causes
scarring of the liver. Patients with cirrhosis are
susceptible to a variety of complications that include
ascites, hepatic encephalopathy, and portal hypertensive
bleeding. Quality of life and survival are often improved
by the prevention and treatment of these complications.
This chapter will review the general principles in the
diagnosis and treatment of cirrhotic ascites. (See
separate Disease Management chapters for overviews of
hepatic encephalopathy and portal hypertensive
bleeding).
DEFINITION
Ascites is defined as the accumulation of fluid in the
peritoneal cavity. It is a common clinical finding with a
variety of both extra-peritoneal and peritoneal etiologies
(Table 1), but it is most often caused by liver cirrhosis.
The development of ascites in a cirrhotic patient
generally heralds deterioration in clinical status and
portends a poor prognosis.
PREVALENCE
Ascites is the most common major complication of
cirrhosis and is an important landmark in the natural
history of chronic liver disease. If observed for 10 years,
approximately 60% of patients with cirrhosis will
develop ascites requiring therapy and/or orthotopic liver
transplantation.2
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PATHOPHYSIOLOGY
The currently accepted theory of ascites formation is the
"peripheral arterial vasodilation hypothesis" (Figure 1).
This hypothesis does not directly refute older
hypotheses, but rather incorporates them into one
uniform theory that most matches actual hemodynamic
data.
According to this theory, development of portal
hypertension is the first abnormality to occur in cirrhotic
patients who develop ascites. Cirrhosis itself increases
the resistance to blood flow within the liver, thereby
causing the development of portal hypertension and
shunting of blood to the systemic circulation. Portal
pressures >12 mm Hg are generally required for the
accumulation of fluid in cirrhosis. This concept is
important, since reducing portal pressure to <12 mm Hg
is the goal of many modern therapeutic maneuvers.
As portal hypertension develops, vasodilators are
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released
locally. These vasodilators affect splanchnic
arteries and thereby decrease the effective arterial blood
flow and arterial pressures. The precise agent (or agents)
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Mechanisms involved include the renin-angiotensin
system, sympathetic nervous system, and antidiuretic
hormone (vasopressin). The ultimate effect is sodium
and water retention. In the late stages of cirrhosis, free
water accumulation is more pronounced than the sodium
retention and leads to a dilutional hyponatremia.
Cirrhotic patients with ascites may therefore demonstrate
urinary sodium retention, increased total body sodium,
and dilutional hyponatremia, a challenging concept to
many physicians.
SIGNS AND SYMPTOMS
The symptoms of ascites vary from patient to patient and
depend largely on the quantity of fluid. If trace ascites is
present, the patient may be asymptomatic, and fluid is
detected only on physical or radiological examination. If
a large amount of fluid is present, the patient may
complain of abdominal fullness, early satiety, abdominal
pain, or shortness of breath.
Physical examination findings are equally variable. The
accuracy of detecting ascites depends on the amount of
fluid present and the body habitués of the patient
(detecting ascites may be more technically difficult in
obese patients). If ascites is present, typical findings
include generalized abdominal distention, flank fullness,
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and
shifting dullness. If the physical examination is not
definitive, abdominal ultrasonography can be used to
confirm the presence or absence of ascites.
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established.
Table 2:
Grading Systems for Ascites
Sleisinger International
and
Ascites
3
Fordtran
Club11
Minimal
1+
Grade 1
Moderate
2+
Grade 2
Severe
3+
Grade 3
Tense
4+
''
DIAGNOSIS
If a non-cirrhotic patient develops ascites, diagnostic
paracentesis with ascites fluid analysis is an essential part
of the medical evaluation. In a patient with welltablished
cirrhosis, the exact role of a diagnostic paracentesis is
less clear. Our opinion is that for a highly functional
outpatient with documented cirrhosis, the new
development of ascites does not routinely require
paracentesis. Cirrhotic patients should, however,
undergo paracentesis in cases of (1) unexplained fever,
abdominal pain, or encephalopathy, or (2) admission to
the hospital for any cause. It is common for hospitalized
cirrhotic patients to have infected ascites fluid
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(spontaneous
bacterial peritonitis), even if no symptoms
are present. This is particularly true in the event of a
significant gastrointestinal hemorrhage.
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the paracentesis needle is most commonly performed in
the left or right lower quadrants but can also be
performed safely in the midline. To minimize bleeding
complications, care should be taken to avoid any
engorged and/or superficial blood vessels. The course of
the inferior hypogastric artery (along the mid portion of
the rectus abdominal muscle) should also be avoided.
Abdominal ultrasound can guide the procedure if the
fluid is difficult to localize or if initial attempts to obtain
fluid are unsuccessful.
Valuable clinical information can often be obtained by
gross examination of the ascitic fluid (Table 3).
Uncomplicated cirrhotic ascites is usually translucent and
yellow. If the patient is deeply jaundiced, the fluid may
appear brown. Turbidity or cloudiness of the ascitic fluid
suggests that infection may be present, and further
diagnostic testing should be performed. Pink or bloody
fluid is most often caused by mild trauma, with
subcutaneous blood contaminating the sample. Bloody
ascites is also associated with hepatocellular carcinoma or
any malignancy-associated ascites. Milky fluid usually has
an elevated triglyceride concentration. Such fluid,
commonly referred to as "chylous ascites," can be related
to thoracic duct injury or obstruction or to lymphoma,
but it is often related primarily to cirrhosis.
Table 3:
Gross Appearance of Ascites
Color
Association
Translucent or
Normal/sterile
yellow
Brown
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Hyperbilirubinemia
(most common)
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Cloudy or tubid
Pink or blood
tinged
Grossly bloody
Milky ("chylous")
Gallbladder or
biliary perforation
Infection
Mild trauma at the
site
Malignancy
Abdominal trauma
Cirrhosis
Thoracic duct injury
Lymphoma
Many ascitic fluid tests are currently available, yet the
optimal testing strategy has not been well established.
Generally, if uncomplicated cirrhotic ascites is suspected,
only an albumin concentration test and a cell count with
differential are performed (Table 4). Less than 10 mL of
fluid placed in a "purple top" tube (containing an
anticoagulant) is required to perform these basic tests.
The albumin concentration test is used to confirm the
presence of portal hypertension by calculating the serumto-ascites albumin gradient, (SAAG), which is
determined by subtracting the ascites albumin value from
a serum albumin value obtained on the same day (ie.,
Albumin serum - Albuminascites = SAAG). The SAAG has
been proven in prospective studies to categorize ascites
better than any previous criteria. The presence of a
gradient >1.1 g/dL indicates with 97% accuracy that the
patient has portal hypertension-related ascites. Portal
hypertension is usually caused by liver cirrhosis or, less
commonly, outflow obstruction from right-sided heart
failure or Budd-Chiari syndrome. A SAAG of <1.1 g/dL
indicates that the patient does not have portal
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hypertension-related ascites, and another cause should be
sought. The SAAG does not need to be repeated after
the initial measurement.
Table 4:
Ascites Fluid Testing
Sometimes
Rarely
Routine
Useful
Helpful
Cell count
with
Total protein pH
differential
Lactose
Albumin
Lactate
dehydrogenase
Ascites
Glucose
Gram stain
culture*
Amylase
Triglycerides
Bilirubin
Cytology
TB smear and
culture
*Suspected infection and/or corrected
PMN count
is >250
The cell count and differential are used to determine
whether the patient is likely to have spontaneous
bacterial peritonitis. Patients with an ascitic
polymorphonuclear (PMN, or absolute neutrophil) count
greater >250 cells/mm3 should receive empiric
antibiotics, and additional fluid should be inoculated into
blood culture bottles to be sent for culture. The PMN
count is calculated by multiplying the white cells/mm3 by
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the percentage of neutrophils in the differential. In a
"bloody" sample that contains a high concentration of
red blood cells, the PMN count must be corrected: one
PMN is subtracted from the absolute PMN count for
every 250 red cells/mm3 in the sample. It is imperative
that these results be made available within 1 hour, so that
important diagnostic and therapeutic decisions can be
made.
Based on clinical judgment, additional testing can be
performed on ascites fluid including total protein, lactose
dehydrogenase, glucose, amylase, triglycerides, bilirubin,
cytology or tuberculosis smear and culture. These tests
are generally useful only when there is suspicion of
something other than sterile cirrhotic ascites. Tests that
are not routinely helpful include pH, lactate, and a Gram
stain. A Gram stain is of particular low yield unless a
large concentration of bacteria, such as in a free gut
perforation, is suspected.
THERAPY
It is important to know the cause of ascites before the
appropriate treatment can be determined. For example,
ascites related to cancer and/or carcinomatosis responds
best to therapies directed at the underlying malignancy.
Likewise, ascites related to myxedema generally improves
with aggressive thyroid hormone replacement. This
chapter
will focus specifically on the treatment of ascites
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related to cirrhosis.
Successful treatment of ascites is defined as the
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of ascites fluid may decrease infection-related morbidity.
Furthermore, treating ascites can dramatically improve
quality of life by decreasing abdominal discomfort
and/or dyspnea. General ascites management in all
patients should include minimizing consumption of
alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs),
and dietary sodium. The use of more aggressive
interventions depends on the severity of ascites and nonresponse to these general measures. This includes use of
oral diuretics, therapeutic (or large-volume) paracentesis,
trans-jugular intra-hepatic portosystemic shunt (TIPS),
and orthotopic liver transplantation (Figure 2).
General Management
All patients with cirrhotic ascites should be encouraged
to minimize consumption of alcohol. Even if alcohol is
not the cause of their liver disease, cessation may lead to
decreased fluid and improved response to medical
therapies. Patients with ascites should also minimize use
of all NSAIDs. NSAIDs inhibit the synthesis of renal
prostaglandin and can lead to renal vasoconstriction,
decreased diuretic response, and acute renal failure.
Lastly, ascites patients should be counseled to limit their
sodium consumption to no more than 2 g/day. Avoiding
frozen or canned foods in combination with "throwing
away the salt shaker" (using other spices or saltsubstitutes to season freshly prepared foods) can usually
accomplish this restriction. Since fluid passively follows
sodium, a salt restriction without a fluid restriction is
generally all that is required to decrease the amount of
ascites. In patients with minimal fluid, the restriction of
alcohol, NSAIDs, and salt may be all that is needed to
adequately control ascites formation.
Moderate-Volume Ascites
Patients with moderate fluid overload who do not
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respond to the above measures should be considered for
the addition of pharmacologic therapy. A rapid reduction
of ascites is often accomplished simply with initiation of
low-dose oral diuretics. In general, patients with
moderate ascites do not need to be admitted to the
hospital unless there are other, accompanying
complications. First-line diuretic therapy for cirrhotic
ascites is dual use of oral spironolactone (Aldactone) and
furosemide (Lasix). Beginning daily doses are 100 mg of
spironolactone and 40 mg of furosemide orally. If weight
loss and natriuresis are inadequate, both drugs can be
simultaneously increased after 3 to 5 days to 200 mg of
spironolactone and 80 mg of furosemide. To maintain
normal electrolyte balance, the use of the 100:40-mg
ratio of spironolactone to furosemide is generally
recommended. Maximum accepted doses are 400 mg
and 160 mg daily of spironolactone and furosemide,
respectively.
The response to diuretics should be carefully monitored
on the basis of changes in body weight, laboratory tests,
and clinical assessment. Patients taking diuretics should
be weighed daily, and the rate of weight loss should not
exceed >0.5 kg/day in the absence of edema and >1
kg/day when edema is present. Serum potassium, blood
urea nitrogen (BUN) and creatinine should be serially
followed. In the event of marked hyponatremia, hyperor hypokalemia, renal insufficiency, dehydration, or
encephalopathy, diuretics should be reduced or
discontinued. Routine measurement of urinary sodium is
not necessary but can be helpful in identifying noncompliance with dietary sodium restriction. Patients
excreting >78 mmol/day of sodium (88 mmol dietary
intake—10 mmol non-urinary excretion) detected on a
24-hour urinary collection should be losing weight. If
not, they are noncompliant with their diet and should be
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referred to a dietician. The spot urine sodium-topotassium ratio may ultimately replace the cumbersome
24-hour collection: a random urine sodium concentration
that is greater than the potassium concentration has been
shown to correlate with a 24-hour sodium excretion >
78 mmol per day with approximately 90% accuracy.
Because of the potential severe complications associated
with diuretic use, patients with ascites should be assessed
by a health care provider at least once weekly until they
are clinically stable.
Large-Volume Ascites
Large-volume ascites is defined as intra-peritoneal fluid
in an amount that significantly limits the activities of
daily life. With additional fluid retention, the abdomen
can become progressively distended and painful. This is
commonly referred to as "massive" or "tense" ascites.
Large-volume ascites can usually be managed in the
outpatient setting as long as no additional complications
are present.
Therapeutic (or large-volume) paracentesis is a wellestablished therapy for large-volume ascites. However,
the use of post-procedural colloid, usually albumin,
continues to be a controversial issue. Studies have shown
that patients who do not receive intravenous albumin
after large-volume paracentesis develop significantly
more changes in their serum electrolytes, creatinine, and
renin levels. The clinical relevance of these findings,
however, is not well established. In fact, no study to date
has been able to demonstrate decreased morbidity or
mortality in patients given no plasma expanders
compared with patients given albumin after paracentesis.
In view of the high cost of albumin and its uncertain
clinical role, more studies certainly need to be conducted.
In the meanwhile, current practice guidelines of the
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American Association for the Study of Liver Diseases
(AASLD) state that it is reasonable, although not
mandatory, to give albumin for paracentesis greater that
5 L. Although no direct comparisons have ever been
studied, 25% albumin at doses of 5 to 10 grams per liter
of ascites removed is generally used.
In order to prevent re-accumulation of ascites fluid,
patients with large-volume ascites should be counseled
on limiting consumption of alcohol, NSAIDs, and
sodium. They should also be placed on an aggressive
diuretic regimen. Diuretic-sensitive patients are generally
treated with lifestyle modifications and medications, not
serial paracentesis.
Refractory Ascites
Refractory ascites occurs in 5% to 10% of cirrhotic
ascites patients and portends a poor prognosis. The
definition of refractory ascites is (1) lack of response to
high-dose diuretics (400 mg of spironolactone and 160
mg of furosemide per day) while remaining compliant
with a low-sodium diet, or (2) frequent ascites recurrence
shortly after therapeutic paracentesis. Patients with
recurrent side effects from diuretic therapy, including
symptomatic hyponatremia, hyper- or hypokalemia, renal
insufficiency, or hepatic encephalopathy, are also
considered to have refractory ascites. Treatment options
include frequent large-volume paracentesis with or
without albumin infusion, placement of a trans-jugular
intra-hepatic portosystemic shunt (TIPS) or liver
transplantation. Surgical peritoneovenous shunts (ie,
LeVeen or Denver) have essentially been abandoned
since controlled trials showed poor long-term patency,
an excessive number of complications, and no survival
advantage over medical therapy.
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Frequent therapeutic paracentesis with or without
albumin infusion is the most widely accepted treatment
for patients with refractory ascites (see Large-Volume
Ascites section above for controversy and dosing
regarding albumin use). For those who have loculated
fluid or are unwilling or unable to receive frequent
paracentesis, TIPS placement can also be considered. In
the appropriately selected patient, TIPS is highly
effective for preventing ascites recurrence by decreasing
the activity of sodium-retaining mechanisms and
improving renal function. Ongoing studies will
determine if TIPS may also provide a survival benefit.
In the United States, TIPS is most commonly performed
under conscious sedation by an interventional
radiologist. The portal system is accessed through the
jugular vein, and the operator inserts a self-expanding
shunt between the portal (high-pressure) and hepatic
(low-pressure) veins. The ultimate goal of the procedure
is to lower portal pressures to <12 mm Hg, the level at
which ascites begins to accumulate. Complications are
common and include hemorrhage (intra-hepatic or intraabdominal) and stent stenosis or thrombosis. Other
important complications include hepatic encephalopathy
and decompensation of liver or cardiac function. It is for
these reasons that TIPS is generally not recommended
for patients with preexisting encephalopathy, an ejection
fraction <55%, or a Child-Pugh score >12 (Table 5).
Additional disadvantages of the procedure are its high
cost and lack of availability at some medical centers.
Liver transplantation is the ultimate treatment of
cirrhosis and cirrhotic ascites. Appropriate timing for
referral is debated, but should be considered when a
cirrhotic patient first presents with a complication from
cirrhosis, such as ascites. Because refractory ascites
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portends a particularly poor prognosis, immediate
referral to an experienced liver transplantation center is
recommended.
OUTCOMES
Two-year survival for a patient with cirrhotic ascites is
approximately 50%. Once patients become refractory to
routine medical therapy, 50% die within 6 months and
75% within 1 year. Because liver transplantation is
associated with 2-year survival rates of almost 85%, it
should be considered an important treatment option in
all appropriate patients.
Classification
Ascites exists in three grades:
•
•
•
Grade 1: mild, only visible on ultrasound
Grade 2: detectable with flank bulging and shifting dullness
Grade 3: directly visible, confirmed with fluid thrill
Causes
Causes of high SAAG ("transudate") are:
•
•
•
•
Cirrhosis - 81% (alcoholic in 65%, viral in 10%, cryptogenic in
6%)
Heart failure - 3%
Budd-Chiari syndrome or veno-occlusive disease
Constrictive pericarditis
Causes of low SAAG ("exudate") are:
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•
•
•
•
•
Cancer (primary peritoneal carcinomatosis and metastasis) 10%
Tuberculosis - 2%
Pancreatitis - 1%
Serositis
Nephrotic syndrome
Pathophysiology
Ascitic fluid can accumulate as a transudate or an exudate. Amounts
of up to 25 liters are fully possible.
Roughly, transudates are a result of increased pressure in the portal
vein (>8 mmHg, usually around 20 mmHg), e.g. due to cirrhosis,
while exudates are actively secreted fluid due to inflammation or
malignancy. As a result, exudates are high in protein, high in lactate
dehydrogenase, have a low pH (<7.30), a low glucose level, and more
white blood cells. Transudates have low protein (<30g/L), low LDH,
high pH, normal glucose, and fewer than 1 white cell per 1000 mm³.
Clinically, the most useful measure is the difference between ascitic
and serum albumin concentrations. A difference of less than 1 g/dl
(10 g/L) implies an exudate.
Portal hypertension plays an important role in the production of
ascites by raising capillary hydrostatic pressure within the splanchnic
bed.
Regardless of the cause, sequestration of fluid within the abdomen
leads to additional fluid retention by the kidneys due to stimulatory
effect on blood pressure hormones, notably aldosterone. The
sympathetic nervous system is also activated, and renin production is
increased due to decreased perfusion of the kidney. Extreme
disruption of the renal blood flow can lead to the feared hepatorenal
syndrome. Other complications of ascites include spontaneous
bacterial peritonitis (SBP), due to decreased antibacterial factors in
the ascitic fluid such as complement.
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Spontaneous chylous ascites of cirrhosis
The spontaneous development of chylous ascites in patients with
cirrhosis is documented, but its clinical features are not well defined.
The incidence of this complication of chronic liver disease was 0.5%
in ascitic patients in our liver unit. These patients were older than a
control group with non-chylous cirrhotic ascites and, despite better
liver tests, appeared to have a higher diuretic requirement. Several
had disabling, recurrent spontaneous encephalopathy. The
mechanism of chylous ascites in cirrhosis is probably portal
hypertension causing lymphatic rupture; however, the fact that
serum-to-ascites albumin gradients were similar in the two groups,
indicating similar degrees of portal hypertension, suggests that other
factors also play a role. Spontaneous transformation of previously
clear ascites appeared to be associated with a poor prognosis. In
contrast, the appearance of chylous ascites de novo in a cirrhotic
patient appeared to have a more favorable outcome. Conservative
management is recommended for most patients, as the degree of
their liver disease appears to be the most important factor
determining prognosis.
Respiratory mechanics in patients with tense cirrhotic ascites
Lung volumes are decreased by tense ascites and increase after large
volume paracentesis (LVP). The overall effect of ascites and LVP on
the respiratory function is poorly understood. We studied eight
cirrhotic patients with tense ascites before and after LVP. Inspiratory
muscle force (maximal trans-diaphragmatic pressure (Pdi, max), and
the lowest pleural pressure (Pp1, min)) was assessed while the
patients were seated. Rib cage and abdominal volume displacements,
as well as pleural and gastric pressures were measured during quiet
breathing while the patients were supine. Pdi, max and Ppl, min were
normal and did not change after LVP (from 84.2+/-19.7 to 85.2+/17.0 cmH2O and from 68.3+/-19.7 to 74+/-15.9 cmH2O,
respectively). The abdominal contribution to the generation of tidal
volume was greater than that of the rib cage (79 vs 21%), a pattern
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which did not change after LVP (73 and 27%). Before LVP, tidal
swings both of pleural pressure (Ppl, sw) and trans-diaphragmatic
pressure (Pdi, sw) were large (15.3+/-4.3 and 18.5+/-3.9 cmH2O,
respectively) and the load on inspiratory muscles was increased as a
consequence of elevated dynamic elastance of the lung (El, dyn)
(11.4+/-2.6 cmH2O x L(-1)) and ("intrinsic") positive end-expiratory
pressure (PEEPi) (4.3+/-3.5 cmH2O). LVP reduced the load on the
inspiratory muscles, as shown by the significant decrease in Ppl, sw
(10.6+/-2.0 cmH2O), Pdi, sw (12.8+/-3.0 cmH2O), El, dyn (10.0+/2.0 cmH2O x L(-1)) and PEEPi (1.1+/-1.3 cmH2O). The amount of
fluid removed was closely related to changes in Ppl, sw and PEEPi.
We conclude that the strength of the inspiratory muscles is normal or
reduced in seated cirrhotic patients. In the supine position, tense
ascites results in an increase in lung elastic load and development of
positive end-expiratory pressure, with a consequent overload and
increased activation of inspiratory muscles. Large volume
paracentesis decreases overloading and activation, but does not
change the strength of the inspiratory muscles.
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