Cirrhotic Ascites Review

Topic Review
Brian Lee, MD
Internal Medicine Resident, Siriraj Hospital
Advisor: Assist. Prof. Siwaporn Chainuvati, MD
30.11.2009

Case scenario
 A 50 year-old man with history 30 yr alcoholic drinking.
Present with abdominal discomfort for 1 week.
He denies history of fever, jaundice, nausea and vomiting
 PE : T 36.8 c P 80/min R16/min BP 120/80 mmHg
GA : good consciousness, not pale, no jaundice, no edema
spider nevi +, palmar erythema +, parotid gland enlargement
CVS &RS : WNL
Abd : soft, distension, liver & spleen not palpable
liver span 8 cm, fluid thrill & shifting dullness +
NS : grossly intact

 Hb 10g/dl Hct 30% wbc 6700 N 70% L 29% plt 60,000
Na 132 K 3.6 Cl 102 HCO3 23 BUN 10 Cr 0.9
TB/DB 1.2/.5 AST/ALT 35/20 ALP 48 A/G 3/4.5
PT 16 sec APTT 30 sec
 How to manage?
1. Start oral diuretics & discharge
2. Start oral diuretics, restrict water 2L/d & discharge
3. Abdominal paracentesis
4. Septic work up & empiric antibiotic
5. Consult 1653

Hepatology .vol 49,No.6,2009
1. Abdominal paracentesis should be performed
and ascitic fluid should be obtained from inpatients
and outpatients with clinically apparent new-onset
ascites. (Class 1, Level C)

Indication for paracentesis
 New-onset ascites
 Tense ascites: large volume paracentesis
 Symptoms, signs, or lab abnormalities suggestive
of infection develop
 abdominal pain or tenderness,
 fever,
 encephalopathy,
 renal failure,
 acidosis,
 peripheral leukocytosis
Sleisenger and Fordtran’s Gastrointestinal and Liver Disease.
8th ed. Philadelphia, PA: Saunders; 2006:1935-1964

Is blood component necessary
before paracentesis?
1. platelet conc 6 unit
2. FFP 500 ml
3. platelet conc & FFP
4. No need blood component
2. Because bleeding is sufficiently uncommon,
the routine prophylactic use of FFP or platelets
before paracentesis is not recommend. (class 3,
level C)
Hepatology .vol 49,No.6,2009,2087-2107

Contraindication for paracentesis
 Coagulopathy is a potential C/I if severe
 No data: cut off for coagulopathy
 Fibrinolysis or DIC
Caution in pregnancy, organomegaly,
bowel obstruction, intra-abdominal
adhesions, or a distended urinary bladder

U/S
guide
is
option
Z tract
Caution !!!!!!!
cutaneous infection,
visibly engorged
cutaneous vessels,
surgical scars, or
abdominal-wall
hematomas.
Inf epigastric a.

Bruce A. Runyon.Hepatology .vol 49,No.6,2009,2087-2107
3. The initial laboratory investigation of ascitic fluid
should include an ascitic fluid cell count and differential,
ascitic fluid protein, and SAAG. (class 1, level B)
4. If ascitic fluid infection is suspected, ascitic fluid
should be cultured at the bedside in blood culture bottles
prior to initiation of antibiotics. (class 1, level C)

Case scenario
 Ascites fluid profile
protein 2 g/dl, albumin 0.6 g/dl
cell count 200 cell/mm3
( PMN 30% )
 SAAG 3 - 0.6 = 2.4
PMN < 250  no SBP

Classification of Ascites by SAAG
High gradient
SAAG > 1.1
Low gradient
SAAG < 1.1
Cirrhosis
Alcoholic hepatitis
Cardiac ascites
“mixed ascites”
Massive liver metastasis
Fulminant hepatic failure
Budd-Chiari syndrome
Portal or splenic vein thrombosis
Sinusoidal obstruction syndrome
Myxedema
Fatty liver of pregnancy
Peritoneal carcinomatosis
TB peritonitis
Pancreatic ascites
Bowel obst/infarct
Biliary ascites
Nephrotic syndrome
Postoperative lymphatic leak
Serositis in CNT
Portal HT
related

Sensitivity- SAAG
 If SAAG is 1.1 g/dl or more, considered to have
portal HT (accuracy 97%)
 Serum albumin and ascitic albumin obtained
nearly simultaneously (same hour)
 Borderline SAAG (1-1.1 g/dl): repeat paracentesis
 Ascites fluid total protein ( SAAG > 1.1 )
AFTP < 2.5  cirrhosis
AFTP > 2.5  cardiac ascites

Diuretics effect
 Wbc count can concentrate to > 1000 cells/mm3
(lymphocyte predominate, absent clinical suspected of infection)
 Absolute PMN count: 250 cell/mm3
(short survival of PMNs)
 Ascitic fluid total protein: doubling (10 Kg diuresis)
 Cardiac ascites: SAAG narrow with diuretic
 Cirrhotic ascites: SAAG not change

Pitfall SAAG
 Falsely low
Arterial hypotension ( decrease portal P)
If Serum albumin less than 1.1 g/dl
Serum hyperglobulinemia (> 5g/dl)
Corrected SAAG = uncorrected SAAG x 0.16 x
(serum globulin (g/dl) + 2.5)
 Falsely high
Lipid, chylous ascites

Complications
 Only about 1% of patients (abdominal wall
hematomas), despite the fact that 71% of the
patients had an abnormal PT.1
 Iatrogenic gut perforation
 Traumatic ascites 2
Corrected PMN = absolute PMN – RBC count/ 250
1. Runyon BA. Arch Intern Med 1986;146:2259-2261
2. Hoefs JC: Hepatology 1;249,1981

NO
Hypoalbuminemia
plasma oncotic p.
RAAS
ECF
hyperaldosteronism

What is the best treatment of
cirrhotic ascites?
 A. Fluid restriction
 B. Dietary Na restriction
 C. Bed rest
 D. Oral diuretics
 E. B and D

Treatment of Ascites (High SAAG)
 Treat underlying disorder
Stop alcohol consumption
Treat hepatitis B infection
 Improved response to medical treatment

What’s the 1st
line treatment?
< 2 g (88mmol)/ day
N Eng J Med 1994;330:337-342

What are the goals of treatment?
Hepatology 2009;6:2087-2107
Hepatology 2002;36:222A

When to restrict fluids?
 Fluid restriction is not necessary
unless serum Na < 120-125 mmol/L.
 Chronic hyponatremia usually seen in
pts with cirrhosis and ascites is seldom
morbid.
Hepatology 2009;6:2087-2107

How to start diuretics?
Ratio 100 mg : 40 mg
Single morning dose for both
N Eng J Med 1994;330:337-342

When to use single-agent
(spironolactone)?
 Minimal ascites in OPD setting
 Slower diuresis and need less dose
adjustment
 Less preferred due to hyperkalemia,
long half-life
Gastroenterology 1992;102:1680-1685

How to adjust dosage of
diuretics?
 Increase both simultaneously every 3-5
days (maintain 100mg : 40mg ratio)
 Maximum 400 mg/d spironolactone, 160
mg/d furosemide
 No limit to daily weight loss if massive
edema
 Once edema resolved: maximum 0.5
kg/day
N Eng J Med 1994;330:337-342

When to hold diuretics?
 Uncontrolled, recurrent encephalopathy
 Serum Na < 120 mmol/L despite fluid
restriction
 Serum Cr > 2.0 mg/dL
Hepatology 2009;6:2087-2107

Case scenario
 Single large volume paracentesis was
done.
 Dietary salt restriction is advised.
 Started on spironolactone 25 mg/d and
furosemide 20 mg/d.
 F/U q 1-2 weeks for dose adjustments.

Case scenario
 2 mo later, pt comes back to hospital
due to increased abdominal swelling.
 Increased weight 5 kgs / 2 wks.
 Denied fever, abdominal pain, black
stool, confusion.
 Stopped alcohol, took only prescribed
meds.
 He had restricted his Na intake and did
not miss any medications.

Case scenario
 PE: T 37 C, PR 80/m, RR 22/m, BP
100/60 mmHg
 GA: Alert, oriented, not pale, mild
jaundice, no flapping tremor
 Abd: normal bowel sounds, tense and
marked distension; no tenderness,
guarding, or rigidity
 Ext: pitting edema 2+ equally

What is “tense” ascites?
 Severe enough to compress the IVC
and collaterals, as determined by
 Failure to increase diuresis in the supine
position
TENSE ASCITES IN CIRRHOTICS: A NEW DEFINITION?
Am J Gastroenterol;90:513-514

What’s the best treatment for
tense ascites?
 A. Large-volume paracentesis, then Na
restriction and diuretics
 B. Albumin infusion after paracentesis
 C. Increase diurectics and F/U
 D. 24-hour urine Na
 E. Liver transplant

Ascites grading
 1+ minimal and barely detectable
 2+ moderate
 3+ massive, but not tense
 4+ massive and tense
VA Cooperative Study on Treatment of Alcoholic Cirrhosis with Ascites
N Eng J Med 1989 Dec 14;321(24):1632-8

Ascites grading
 Grade 1 – mild; detectable only by U/S
 Grade 2 – moderate; moderate
symmetrical distension of abdomen
 Grade 3 – large or gross ascites;
marked abdominal distension
International Ascites Club
Hepatology2003 Jul;38(1):238-66

How to manage tense ascites?
 Initial single large-volume paracentesis
 Then dietary Na restriction and diuretics
Am J Gastroenterol 1997;92:394-399

Is albumin infusion after
paracentesis necessary?
 If > 5 liters removed, give albumin 6-8
g/L of fluid
Am J Gastroenterol 1997;92:394-399

Albumin and postparacentesis
circulatory dysfunction
GASTROENTEROLOGY 1996;111:1002–1010

OPD management of tense
ascites
 Monitor BW, orthostatic hypotension
 Serum electrolytes, BUN, Cr
 Check urinary Na excretion
Hepatology 2009;6:2087-2107

Inadequate weight loss
 Inadequate urinary excretion: Na
restriction before going to 2nd
line
treatment
 Adequate urinary excretion: increase
dose of diuretics
Hepatology 2009;6:2087-2107

Case scenario
 The patient’s ascites could not be
controlled.
 Increased spironolactone 200mg/d,
furosemide 80 mg/d.
 Developed renal dysfunction, Cr 2.5.
Refractory ascites

Refractory Ascites:
 Unresponsive to sodium-restricted diet and
high-dose diuretic treatment
(400 mg/day spironolactone and 160 mg/
day furosemide)
 Recurs rapidly after therapeutic
paracentesis.
HEPATOLOGY, Vol. 49, No. 6, 2009

Failure of diuretic therapy
 Minimal to no weight loss with inadequate
(<78 mmol/day) urinary sodium excretion
despite diuretics
 Development of clinically complications of
diuretics
 Encephalopathy
 Serum creatinine>2.0 mg/dL,
 Serum sodium<120 mmol/L,
 Serum potassium >6.0 mmol/L.

EVALUATION OF
REFRACTORY ASCITES
 Exclude other causes that are not responsive to diuretic
therapy
1. NSAIDS use
2. Non compliance with medications and low sodium diet
3. Other causes  malignant ascites, nephrogenic
ascites, portal vein thrombosis, infection
World J Gastroenterol 2009 January 7; 15(1): 67-80

 Fewer than 10% of patients with cirrhosis and
ascites are refractory to standard medical therap
y
 Options for patients refractory to medical therapy
(1) Serial therapeutic paracenteses
(2) Transjugular intrahepatic portasystemic stent-
shunt (TIPS)
(3) Peritoneovenous shunt
(4) Liver transplantation

Serial large volume paracentesis
(LVP)
 LVP with intravenous albumin represents the
standard therapy for refractory ascites.
 Therapeutic paracentesis does not modify the
mechanisms that lead to ascites formation.
 Ascites will always recur in patients with refractory
ascites unless there is an improvement in liver
disease

Frequency of LVP
 Two weeks are considered a interval between
paracentesis in patients with refractory ascites.
 Less frequent sessions  patient with some
sodium excretion
 More frequent sessions  patients who are not
compliant with dietary sodium restriction.

Post-paracentesis circulatory
dysfunction (PCD)
 Defined as a 50% increase in plasma renin activity
over baseline on the sixth day after treatment, up
to a value greater than 4 ng/mL per hour
 PCD affects the clinical course of the disease with
higher incidences of hyponatremia, and renal impa
irment.
 Severity correlates inversely with patient survival.

Post-paracentesis circulatory
dysfunction (PCD)
 Severity correlates with the amount of fluid removed
in paracentesis being most significant when it exceed
s 5L
 Albumin infusion reduces the incidence to 15%-20%.
 An albumin infusion of 8-10 g per liter of fluid
removed.

Transjugular intrahepatic
portasystemic stent-shunt(TIPS)

 TIPS reduce the portal venous pressure.
 It causes a decrease in the renin-
angiotensin-aldosterone system and impro
ves renal sodium excretion.

TIPS
 Improvement in renal function  increased urine
volume, increased sodium excretion and a reducti
on in serum creatinine.
 Improvement in the nutritional status and
improvements in quality of life.
N Engl J Med 1995;
332:1192-1197
AJR Am J Roentgenol 1996; 167: 963-969
Am J Gastroenterol 2001; 96: 2442-24479

TIPS
 Ascites was controlled in 27-92%.
 It takes about 1 -3 mo for ascites to resolve after TIPS
procedure.
 Diuretic therapy will still be required in 95% of patients.
 Portal pressure and renin and aldosterone levels
markedly reduced after TIPS, they are not back to norm
al.
10th ed. Philadelphia: Lippincott Williams & Wilkins, 2007
Gut 2000; 46: 578-581

TIPS
1. Patients who require paracentesis > 3 times/month
2. Bilirubin < 3 mg/dL
3. Serum sodium level >130 mEq/L
4. Child-Pugh score < 12
5. Model for endstage liver disease (MELD) score < 18
6. Aged < 70 years
7. Without hepatic encephalopathy, central hepatocellular
carcinoma, or cardiopulmonary disease

Peritoneovenous shunt
 A inserted shunt that drains ascitic fluid from the
peritoneal cavity into the internal jugular vein.
 No survival advantage & frequent complications
including bacteremia, small bowel obstruction and
volume overload.
 Indication  Refractory ascites & not candidate
for TIPS or liver transplantation, and has a lot of a
bdominal scars that makes frequent paracentesis
unsafe.

Probability of survival in patients with cirrhosis
and refractory ascites according to the age

LIVER TRANSPLANTATION
 The survival rate for liver transplantation is much
higher.
 Patients who develop refractory ascites ideally should
be on the transplantation list.
 After liver transplantation, portal hypertension reversed
immediately and completely.
 However, ascites disappearance may take 3 to 6
month.

Patient with cirrhotic ascites who became non responsive to diuretics
Exclude NSAIDS use, diet non compliance, other causes
Think about refractory ascites
Evaluation for liver transplantation
Search for reversible liver pathology
Keep on paracentesis plus albumin, low sodium diet
Prevention for other complications
Patient require paracentesis > 3 taps/month
Consider TIPS
Not candidate and frequent paracentesis is not possible
Peritoneovenous shunt

 3 days PTA, he developed fever,
abdominal pain and swelling.
He took paracetamol and
antibiotics without improvement.
 PE : T 38.0˚c, BP 96/62 mmHg, P
98/min , RR 20/min
GA : Alert, well cooperated, not
pale, no jaundice, pitting edema 2+,
sign CLD+
Pharynx: not injected , LN :
notpalpable

 What is the provisional diagnosis ?
 What should be done next ?
1. Abdominal paracentesis and wait for the C/S result
for proper antibiotic
2. Empiric ATB first, as the provisional Dx is SBP
3. Abdominal paracentesis, send ascitic profile and
septic W/U, then start Cefotaxime 2 gm iv
4. After abdominal tapping and septic W/U
start IV or Oral Antibiotics, depend on Pt condition

Spontaneous Bacterial
Peritonitis
 Definition
- Spontaneous infection of ascites w/o
intraabdominal source
 It occurs almost exclusively in cirrhotic ascites
 Risk factor
- Severity of underlying liver disease : most
Child-pugh B or C
- Large volume ascites
- Low protein ascites
- GI bleeding
- Prior SBP

Diagnosis of SBP
All criteria required
 Positive ascites fluid bacterial culture
 Absolute PMN count ≥ 250 cell/mm³
 Without an evident intra-abdominal,
surgically source of infection
“ No clinical diagnosis - without a
paracentesis”

Empiric Treatment
 Cefotaxime : treatment of choice for
suspected SBP
 covers 95% of the flora including the
three most common isolates
- Escherichia coli
- Klebsiella pneumoniae
- pneumococci
 Cefotaxime 2 g IV every 8 hr x 5 days

 Ofloxacin 400 mg PO bid x 8 days
effective as parenteral cefotaxime in Pts
without
- vomiting
- shock, grade II (or higher)
- hepatic encephalopathy
- serum creatinine > 3 mg/dL
Empiric Treatment : Oral
form
Randomized, comparative study of oral ofloxacin versus
intravenous cefotaxime in spontaneous bacterial peritonitis.

Empiric Treatment
 Pts with ascitic fluid PMN ≥ 250 cells/mm3
in a clinical setting compatible with ascitic fluid
infection should receive empiric antibiotic Rx
 Most of ascitic fluid culture will positive if
- the fluid is cultured in blood culture bottle
- no prior antibiotic treatment
- no other explanation for an elevated PMN count

Classification of Ascitic Fluid
Infection
Categories
Ascitic fluid
culture
Absolute
PMN/ mm3
Spontaneous bacterial
peritonitis
Positive ≥ 250
Culture-negative neutrocytic
ascites
No growth ≥ 250
Monomicrobial non-
neutrocytic bacterascites
Positive < 250
Polymicrobial bacterascites Positive < 250

Natural history of ascitic fluid
infection
Gastrointestinal and Hepatic Infections
Philadelphia, 1994, p. 455.

IV Albumin Infusion in Addition
to Cefotaxime
Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis
and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403-409

IV Albumin Infusion in Addition to
Cefotaxime
 One RCT‫٭‬ has been used
Albumin1.5 gm/kg BW within 6 hours of
enrollment and 1.0 gm/kg on day 3
● Decrease in mortality from 29% to 10%
 Recent study‫٭٭‬ : albumin should be given when
- Serum creatinine is > 1 mg/dL
- Blood urea nitrogen > 30 mg/dL
- Total bilirubin > 4mg/dL
‫٭‬Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis
and spontaneous bacterial peritonitis. N Engl J Med 1999;341:403-409
‫٭٭‬Restricted use of albumin for spontaneous bacterial peritonitis. Gut 2007;56:597-599.

Ascites characteristic in 2˚
peritonitis

Follow-Up Paracentesis
 Repeat paracentesis can be performed to
document the treatment response
:but not necessary
 If the setting, symptoms, analysis, organism(s),
or response are atypical
:repeat paracentesis can be helpful
The value of an algorithm in differentiating
spontaneous from secondary bacterial peritonitis.
Gastroenterology1990;98:127-133

Prevention of SBP
 Prophylactic antibiotics
in Pts at risk
- ascitic fluid protein concentration 1.0 g/dL
- prior episode of SBP
- variceal hemorrhage
 Norfloxacin PO 400 mg/day is successful
preventing SBP in at risk Pts
 Norfloxacin 400 mg BID for 7 days helps
prevent infection in patients with variceal
hemorrhage

Cirrhotic Ascites Review

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