Cirrhotic Ascites Review

Topic Review

Brian Lee, MD Internal Medicine Resident, Siriraj HospitalAdvisor: 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 & discharge2. Start oral diuretics, restrict water 2L/d & discharge3. 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 unit2. FFP 500 ml 3. platelet conc & FFP4. 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

CirrhosisAlcoholic hepatitisCardiac ascites“mixed ascites”Massive liver metastasis Fulminant hepatic failureBudd-Chiari syndromePortal or splenic vein thrombosisSinusoidal obstruction syndromeMyxedema Fatty liver of pregnancy

Peritoneal carcinomatosisTB peritonitisPancreatic ascitesBowel obst/infarctBiliary ascitesNephrotic syndromePostoperative lymphatic leakSerositis 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/dlSerum 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;146:2259-22612. 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 consumptionTreat 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 mgSingle 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 an

d 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 thera py

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 use2. 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 therapy

Options for patients refractory to medical therapy (1) Serial therapeutic paracenteses(2) Transjugular intrahepatic portasystemic stent-sh

unt (TIPS)(3) Peritoneovenous shunt(4) Liver transplantation HEPATOLOGY, Vol. 49, No. 6, 2009

S erial large volume paracent esis (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 par

acentesis 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.


P - ost 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 impairment.

Severity correlates inversely with patient survival.


P - ost paracentesis circulatory dysfunction (PCD)

Severity correlates with the amount of fluid removed in paracentesis being most significant when it exceeds 5L

Albumin infusion reduces the incidence to 15%-20%.

An albumin infusion of 8-10 g per liter of fluid removed.


T ransjugular intrahepatic por -tasystemic stent shunt(TIPS)

TIPS reduce the portal venous pressure.

It causes a decrease in the renin-angiotensin-aldosterone system and improves renal sodium excretion.


TIPS Improvement in renal function increased urine vol

ume, increased sodium excretion and a reduction in serum creatinine.

Improvement in the nutritional status and improvements in quality of life.

N Engl J Med 1995; 332:1

192-1197 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 normal.

10th ed. Philadelphia: Lippincott Williams & Wilkins, 2007 Gut 2000; 46: 578-581


TIPS1. Patients who require paracentesis > 3 times/month2. Bilirubin < 3 mg/dL3. Serum sodium level >130 mEq/L4. Child-Pugh score < 125. Model for endstage liver disease (MELD) score < 18 6. Aged < 70 years7. Without hepatic encephalopathy, central hepatocellular

carcinoma, or cardiopulmonary disease


Peritoneovenous shunt A inserted shunt that drains ascitic fluid from the p

eritoneal 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 abdominal 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 highe

r.

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 Heart + Lung : WNL Abdomen : Distend, generalized tender, no guarding,

shifting dullness+, Liver not palpable span 9 cm, increase splenic dullness

PR : yellow feces, no mucosal mass

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 SBP3. Abdominal paracentesis, send ascitic profile and

septic W/U, then start Cefotaxime 2 gm iv4. 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


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. Gastroenterology 1996;111:1011-1017

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

HEPATOLOGY 2004;39:841-856

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Cirrhotic Ascites Review