2. • Ascites is the pathologic accumulation of fluid within the peritoneal cavity.
• It is the most common complication of cirrhosis and occurs in about 50% of patient with
decompensated cirrhosis in 10 years.
• The development of ascites denotes the transition from compensated to decompensated cirrhosis.
3.
4. ASCITIC FLUID
? What is in the ascetic fluid : 1. Proteins ( Albumin)
2.WBC
3.Lipids
4. Bile acids
The main issues that arise regarding ascites are:
Is the fluid infected?
Is portal hypertension present?
5. • Initial tests that should be performed on the ascitic fluid
include :
1. Appearance assessment (eg, clear, bloody, cloudy, milky)
2. Serum-to-ascites albumin gradient determination (SAAG)
3.Cell count and differential
4.Total protein concentration
6. Appearance The gross appearance of the ascitic fluid can be helpful in the
differential diagnosis
1. Clear Uncomplicated ascites in the setting of cirrhosis is usually translucent
yellow;
it can be completely clear if the bilirubin is normal and the protein
concentration is very low.
2. Turbid or cloudy Spontaneously infected fluid is frequently turbid or cloudy.
3. Opalescent Infrequently, ascitic fluid in the setting of cirrhosis is "opalescent" and
has a slightly elevated TG concentration, misinterpreted as "pus.
4. Milky Milky fluid usually has a triglyceride concentration that exceeds the
serum concentration, is greater than 200 mg/dL (2.26 mmol/L),
and is often greater than 1000 mg/dL (11.3 mmol/L); such specimens
are referred to as "chylous ascites“
5. Pink or bloody (and corrected
neutrophil count)
Pink fluid usually has a red cell concentration of >10,000 per mm3.
Most bloody samples are due to a "traumatic tap"
7. SERUM-TO-ASCITES ALBUMIN GRADIENT — accurately
identifies the presence of portal hypertension
• ≥1.1 g/dL (≥11 g/L) predicts that the patient has portal
hypertension with 97 percent accuracy .
• <1.1 g/dL (<11 g/L) indicates that the patient does not have
portal hypertension
8.
9. • The total protein concentration may also help differentiate
uncomplicated ascites from cirrhosis from cardiac ascites, both of
which have a SAAG ≥1.1 g/dL (≥11 g/L).
• In the case of ascites from cirrhosis, the total protein is
<2.5 g/dL (<25 g/L), whereas in cardiac ascites it is
≥2.5 g/dL(≥25 g/L).
• In patients with nephrotic ascites, the SAAG is
<1.1 g/dL (<11 g/L), and the total protein in the ascites of
<2.5 g/dL (<25 g/L).
10. • Cell count with differential — the single most useful test
performed to evaluate for infection and should be ordered
on every specimen
• The cell count should be available within one hour, while
the culture takes several hours to days
• Antibiotic treatment should be considered in any patient
with a corrected neutrophil count ≥250/mm3
11. • The white blood cell and neutrophil counts need to be
corrected in patients with bloody samples.
• One white blood cell should be subtracted from the white blood cell count for every 750 red blood
cells to yield the "corrected white blood cell count," and one neutrophil should be subtracted from
the absolute neutrophil count for every 250 red blood cells to yield the "corrected neutrophil count"
• In bloody ascites, the corrected neutrophil count is frequently
<0 due to remote hemorrhage with lysis of neutrophils.
12. • Measurement of total protein, glucose, and lactate dehydrogenase
(LDH) in ascites may also be of value in distinguishing SBP from
bowel perforation into ascites
• Patients with ascitic fluid that has a corrected neutrophil count
≥250 cells/mm3 and meets two out of the following three criteria
are unlikely to have SBP and warrant immediate evaluation to
determine if bowel perforation into ascites has occurred :
• Total protein >1 g/dL
• Glucose <50 mg/dL (2.8 mmol/L)
• LDH greater than the upper limit of normal for serum
13.
14. Tests that may be performed to aid in confirming a diagnosis
include:
• Culture with bedside inoculation of aerobic and anaerobic blood culture bottles
(infection, bowel perforation)
• Glucose concentration (malignancy, infection, bowel perforation)
• Lactate dehydrogenase concentration (malignancy, infection, bowel perforation)
• Gram stain (suspected bowel perforation)
• Amylase concentration (pancreatic ascites or bowel perforation)
• Tuberculosis smear, culture, and adenosine deaminase activity (tuberculous
peritonitis)
• Cytology and possibly carcinoembryonic antigen level (malignancy)
• Triglyceride concentration (chylous ascites)
• Bilirubin concentration (bowel or biliary perforation)
• Serum pro-brain natriuretic peptide (heart failure)
15. • Total protein concentration — Ascitic fluid can be classified as
an exudate if the total protein concentration is ≥2.5 or
3 g/dL and a transudate if it is below this cutoff.
• However, the exudate/transudate system of ascitic fluid
classification has been replaced by the SAAG, which is a more
useful measure for determining whether portal hypertension is
present
16. • Culture — Cultures of ascitic fluid should be obtained on
specimens from patients who are being admitted to the hospital
with ascites and those who deteriorate with fever, abdominal
pain, azotemia, acidosis, or confusion.
• By comparison, therapeutic paracentesis samples in patients
without symptoms of infection do not need to be cultured.
• An adequate volume of ascitic fluid (generally 10 mL per bottle,
but the amount varies according to the manufacturer of the
bottle) should be inoculated into aerobic and anaerobic blood
culture bottles at the bedside.
17. • Cytology – Almost 100 percent of patients with peritoneal
carcinomatosis will have positive ascitic fluid cytology due to
the presence of viable malignant cells exfoliating into the
ascitic fluid .
• However, only about two-thirds of patients with
malignancy-related ascites have peritoneal carcinomatosis.
• As a result, the overall sensitivity of cytology smears for the
detection of malignant ascites is 58 to 75 percent.
18. • Carcinoembryonic antigen concentration –
• Measurement of carcinoembryonic antigen (CEA) in ascitic
fluid has been proposed as a helpful test in detecting
malignancy-related ascites.
• However, the study that validated CEA was small and did not
subgroup patients based on the type of cancer. CEA may be of
some utility in ascitic fluid analysis, but its precise value
remains unclear.
19. • Triglyceride concentration – A triglyceride concentration should
be obtained on ascitic fluid that is milky. Chylous ascites has a
triglyceride content greater than 200 mg/dL (2.26 mmol/L) and
usually greater than 1000 mg/dL (11.3 mmol/L)
• Bilirubin concentration – The bilirubin concentrate on should be
measured in patients with brown ascites. As mentioned above,
an ascitic fluid bilirubin value greater than the serum suggests
bowel or biliary perforation into ascites
• Serum pro-brain natriuretic peptide concentration –
Measurement of pro-brain natriuretic peptide in serum can help
distinguish ascitic fluid due to cirrhosis from ascitic fluid due to
heart failure
20. • Appropriate treatment of patients with ascites depends on the
cause of fluid retention.
• Patients with low SAAG (<1.1g/dl) ascites usually do not have
portal hypertension and, with the exception of nephrotic
syndrome, do not respond to salt restriction and diuretics.
• patients with a high SAAG (≥1.1 g/dL) have portal hypertension
and usually are responsive salt restriction and diuretics.
21. Malignant ascites
• Abnormal intra-peritoneal collection of fluid as a result of malignancy
• Indicates late disease state of malignant disease and indicates poor
prognosis
• Common with cancers such as: ovarian, pancreatic, colonic, breast,
gastric and endometrial
• Management is usually palliative aimed to improve quality of life
22. Epidemiology
• Accounts for about 10% of all ascites, and 15-50% of patients with
malignancy would develop ascites
• About 20% may have unknown primary
• Patients usually have < than 6 months to live except in some cases of
breast and ovarian malignancies
• Ovarian cancer had the highest proportion of patients who
developed ascites at 37.7%, followed by pancreaticobiliary cancers
(21%), gastric cancer (18.3%), esophageal cancer (4.0%), colorectal
cancer (3.7%), and breast cancer (3.0%).
24. Pathophysiology of malignant ascites generation
• Imbalance between normal
peritoneal fluid production and
absorption
• Lymphatic obstruction by
tumor cells
• excess vascular permeability
• Tumor-specific effects such as
excess metalloproteinase
production.
• Over-secretion/production
• By tumor
• Leaky capillaries (VEGF, VPF, 45-Kd
Glycoproteins) in ovarian, gastric,
colonic, pancreatic, hepatic and
omental mets
• Under-absorption
• Malignant lymphatic blockages
• Budd-chiari syndrome
• Combination of factors
25. Symptoms :
• Gastrointestinal symptoms include :
• Indistension
• Nausea
• Vomiting
• Patients experience dyspnea, as well as
weight gain and edema.
• Women with ovarian cancer describe
• Bloating
• Swelling
• Fatigue
• urinary frequency
• Constipation
• abdominal and pelvic pain, back pain,
• Anorexia
• and vaginal bleeding
• +/- gastrointestinal symptoms such as
indigestion, constipation, abdominal cramping,
diarrhea, gas, or movement in pelvis
Ascites can cause significant symptoms referable to the gastrointestinal and genitourinary tract.
26. Management: Diagnosis
History
• To suggest malignancy
• Intestinal or gynaecological
• Extraintestinal
• Metastasis
• Complications e.g coagulopathy
• To rule out differentials
• Previous treatment
Physical exam
• In keeping with malignancy
• Cachexia, Palor, jaundice,
Virchow’s node, edema
• Sister Mary-Josephs nodule,
Blummer’s shelf, adnexiae
• Abd distension, ecchymosis
29. Diagnosis:
Laboratory
Test Importance Diagnostic accuracy
Cytology (Gold standard) Malignant cells Usually around 50-60% (up to 89.5% when combined
with human gonadotropin B)
Telomerase activity Sensitivity of around 76% and specificity of about
95.7%
Ascitic Sialic acid Differentiate malignant
from non-malignant fluid
Diagnostic accuracy of about 82%. Cut off 300mg/l
Ascitic fibronectin Increased deection Diagnostic accuracy of 85% with No false positive. Cut
off ?7.5mg/dl
Tumor markers Guide to possible primary
tumor origin
Ascitic
immunohistochemistry
Tumor origin
Image guided Biopsies Tumor origin It provides a site-specific primary tumor diagnosis in
93% of cases
30. Diagnosis:
Laboratory
Non-specific
• SAAG <1.1 = exudation (97%
accuracy)
• Total protein level ≥ 2.5g/dl
• SBP = 250/mm3, m/c/s
• Ascitic fluid amylase = ↑in
perforation and IO
? usefulness
• Ascitic lactate
• Ascitic pH
• Ascitic cholesterol
Up to 25% of patient with Cirrhosis
Have protein rich ascites while up to 18% of
Patients with malignant ascites may have low
Ascitic protein level
31. Management options: No generally accepted
evidence-based guideline
• AIM: to reduce tension, improve comfort and quality of life
• MEDICAL, MINIMALLY INVASIVE & SURGICAL
A. Reduce immediate discomfort (‘external’ ascitic drainage)
B. Reduce ascites production (intra-cavitary or systemic)
C. Improve ascites reabsorption (shunting procedures)
D. Combination of above
32. Medical Management: role of
diuretics
Agent Dose Study
Spironolactone 150-450mg/day P.O Greenway et al 1982
Frusemide 100-200mg I.V Razis 1976
Bumetanide 3-5mg/day Razis 1976
Methylclothiazide + Spironolactone 5mg/day + 50-100mg/day Gough et al 1993
Spironolacone + Frusemide 100-200mg/day + frusemide 40-
80mg/day
Sharma 1995
When life expectancy is > 4 weeks
Commonly used by physicians as the first line of care but efficiency reported has been poor (<45%)
There are no randomized controlled trials assessing the efficacy of diuretic therapy in malignant ascites.
Poorer response in those with protein-rich peritoneal fluids than serous fluids of direct hepatic mets
33. Medical Management: Use of
octreotide
• Reduce intestinal secretion and increase rate of absorption
• May be useful in chylous ascites
• Dose 200-600mcg by subcute catheter over 24hr period
35. (A) “External” Large volume drainage
procedures: Abdominal Paracentesis
• Done within 48hrs of
presentation, Preferably
removed within 24hr of
insertion
• Endoscopic USS guided
Paracentesis (EUS-P)
• Issues with rate of flow
• Issues with volume per ‘tap’
• ? use of albumin except for
severe hypovolaemia
• Empty bladder
• Ensure analgesia
• Contraindicated in:
• DIC
• Severe bowel distension
• Multiple abdominal surgeries
• Multiple small loculations
37. Surgical
Management
• Diagnostics of underlying dx
• Treatment of ascites (shunting procedures)
• Cytoreductive surgeries
• Open or laparoscopic
38. Shunting
procedures
• Peritoneo-venous shunts
• More popular, 70% success rate
• Denver & Le Veen
• Contraindicated in hemorrhagic, loculated,
infected and chylous ascites, ascitic protein >
4.5g/L. Don’t use in CCF and RF.
• ? Benefit in Px with <1-3month life expectancy
Peritoneo-vesical shunts
• Less popular
• Contraindicated in haematuria,
UTI
Breast and ovarian cancer patients seem to
respond better (≥ 50%) than patients with
malignant ascites from GI origin (10-15%)
39. Denver Shunts
• Denver Biomedicals
•Originally a V-P shunt, currently marketed by
the CareFusion Corporation
•Kirsch et al modification of Denver V-P shunt,
1970
•Allows retrograde flow when the peritoneal
pressure is 1cm of H2O above intrathoracic
pressure
• Manual pumping best in supine position
40. • The most common cause of portal hypertension related ascites
is cirrhosis which usually caused by
Chronic hepatitis C
Alcohol abuse
Obesity/nonalcoholic steatohepatitis (NASH)
• Most important step in treating this form of ascites is to treat
the underlying cause of liver disease.
42. First-Line
• Cessation of alcohol use (when present)
• Sodium restricted diet and diet education
• Dual diuretics usually spironolactone and furosemide orally
with single daily dosing
• Discontinue non-steroidal anti-inflammatory drugs
• Evaluation for liver transplantation
43. Second-Line
• Discontinue beta blockers, angiotensin converting enzyme
inhibitors, and angiotensin receptor blockers
• Consider adding midodrine especially in the profoundly
hypotensive patient
• Serial therapeutic paracenteses
• Evaluation for liver transplantation
• Transjugular intrahepatic portasystemic stent-shunt (TIPS)
45. FIRST-LINE TREATMENT
• Most important step in treating ascites in cirrhosis due to ethanol is
by ceasing alcohol consumption.
• One study demonstrates that patients who have Child-Pugh C
cirrhosis due to alcohol and who stop drinking have an
approximately 75% 3-year survival, but all those who continue to
drink die in 3 years.
• Baclofen has been shown in a randomized trial to reduce alcohol
craving and reduce alcohol consumption.
46. • Liver diseases other than alcohol-related, hepatitis B and
autoimmune hepatitis are less reversible.
• By the time ascites is present, these patients may be best
served by referral for liver transplantation evaluation rather
than protracted medical therapy
47. DIET
• Education regarding dietary sodium restriction (2000 mg per
day [88 mmol per day])
• Fluid loss and weight change are directly related to sodium
balance in patients with portal hypertension-related ascites
• patient should be educated in a saltrestricted diet by a
dietician
48. URINE SODIUM MONITORING
• A random “spot” urine sodium concentration that is greater
than the potassium concentration correlates well with a 24-
hour sodium excretion.
• This urine sodium/ potassium ratio may replace the
cumbersome 24-hour collection.
• When this ratio is >1, the patient should be losing fluid weight.
The higher the ratio, the greater the urine sodium excretion.
49. DIURETICS
• Usual diuretic regimen consists of single morning doses of oral
spironolactone (100 mg) and furosemide (40 mg).
• Starting with both drugs appears to be the preferred approach
in achieving rapid natriuresis and maintaining normokalemia.
50. • Doses of both oral diuretics can be increased simultaneously
every 3 to 5 days (maintaining the 100 mg:40 mg ratio) if
weight loss and natriuresis are inadequate.
• This ratio maintains normokalemia.
• Usual maximum doses are 400 mg per day of spironolactone
and 160 mg per day of furosemide.
51. • All diuretics should be discontinued if there is severe
hyponatremia (serum sodium concentration <120mmol/L)
progressive renal failure, worsening hepatic encephalopathy,
or incapacitating muscle cramps
52. Hyponatremia
• Serum sodium <130 mEq/L
• Present in 22% of patients with ascites
• Risk factor for encephalopathy and the HRS syndrome
• Water restriction (1–1.5 L/day)
• No effective therapies, vaptans have a transient effect
• Poor prognostic marker
53. REFRACTORY ASCITES
• Defined as ascites that cannot be mobilized or prevented from
recurring by medical therapy.
• Diuretic resistant -ascites is not mobilized despite maximal
diuretic dosage
• Diuretic intractable-ascites development of diuretic‐induced
complications that preclude the use of an effective diuretic
dosage.
54. • Dietary history
• use of non-steroidal anti-inflammatory drugs, angiotensin-
converting enzyme inhibitors, angiotensin receptor blockers
• patient compliance with the treatment regimen
55. Treatment of refractory ascites
• First line: Serial therapeutic paracenteses
Relapse is the rule
• Second line: TIPS
When paracenteses >1–2/month
MELD <15
• Third line: Peritoneovenous shunt
Non‐LVP, non‐TIPS candidates
56. Criteria for TIPS
• Age <65 years
• Child–Pugh score ≤12 points
• MELD score <18
• No alcoholic hepatitis
• Cardiac ejection fraction ≥60%
• No severe spontaneous hepatic encephalopathy
57. • Beta blockers may shorten survival in refractory ascites.
• Oral midodrine 7.5 mg three times daily has been shown in a
randomized trial to increase urine volume, urine sodium, mean
arterial pressure, and survival.
61. Prognosis
• With SBP, 10–33% of patients will die during that hospital
admission.
• The 1‐year probability of SBP recurrence is 69% and median
survival of a patient who develops SBP is 9 months.
• Main predictors of mortality
Development of renal dysfunction
Lack of response to initial empirical antibiotic therapy
Nosocomial infection
62. Treatment
• Third generation cephalosporins usually cefotaxime
administered intravenously at a dose of 2 g every 12 h for 5–7
days.
• Amoxycillin‐clavulanic acid is as effective as cefotaxime.
• Repeat paracentesis after 48 h of start of treatment
• Lack of response (decrease in PMN <25% from baseline)
63. • Multidrug‐resistant bacteria are health‐care associated or
nosocomial
• Extended spectrum antibiotics (e.g. carbapenems,
imipenem/cilastatin, piperacillin/tazobactam) should be used as
initial empirical therapy
• Intravenous albumin- A dose of 1.5 g/kg body weight should be
given within 6–12 hours of diagnosis of SBP with a 1 g/kg dose at
72 hours.
64. PREVENTION
• A prospective study reported in 1988 documented a 69%
recurrence rate at 1 year.
• An ascitic fluid protein concentration of <1.0 g/dL was the best
predictor of recurrence.
• Antibiotic prophylaxis:
Prior SBP
Gut hemorrhage
Primary prevention of SBP
65.
66. Take home message
• Mainstay of therapy of patients with cirrhosis and ascites is dietary sodium restriction and
diuretics.
• Standard medical therapy is effective in >90% of patients.
• Therapeutic paracentesis should be performed to acutely treat tense ascites and as
second-line chronic treatment of a portion of the 10% of patients who are refractory to
medical therapy.
• Many patients who are refractory to medical therapy should be considered for TIPS.
• Patients who are liver transplant candidates and who develop refractory ascites should be
prioritized for transplantation.
67. Take home message
• Diagnosis requires a high degree of suspicion
• Clinical features may be absent and peripheral WBC normal
• Ascitic protein usually <1 g/dL
• Usually monomicrobial and Gram‐negative
• Start antibiotics if ascites >250 mm polymorphs
• Concomitant albumin use, particularly if renal dysfunction or
jaundice
• Antibiotic prophylaxis
• 20% die
• 69% recur in 1 year
