Management of Ascites

by

Dr Intekhab AlamProfessor of Medicine

Department of MedicinePostgraduate Medical Institute,

Lady Reading Hospital, Peshawar

MANAGEMENT OF ASCITES

Objectives

1. Understand the basic mechanisms of portal hypertension (PHT)

2. Study Ascites as a complication of PHT

3. Get an idea on the management of Ascites and its complications

What is Liver Cirrhosis?

Diffuse fibrosis of the liver with nodule formation

Abnormal response of the liver to any chronic injury

Causes of Cirrhosis1. Chronic viral hepatitis2. Metabolic: hemochromatosis, Wilson dis,

alfa-1-antitrypsin, NASH3. Prolonged cholestasis (primary biliary

cirrhosis, primary sclerosing cholangitis)4. Autoimmune diseases (autoimmune

hepatitis)5. Drugs and toxins6. Alcohol

Anatomy of the portal venous system

The Effect of The Liver Nodule

Mechanism of Portal HTN

Cirrhosis

Resistance portal flow

MechanicalNodules

DynamicNitric oxide

Complications of Portal Hypertension in cirrhosis liver.

Development of Ascites.

Varices formation.

Hepatic encephalopathy.

Hepatorenal syndrome.

Ascites

Definition: presence of free fluid in the peritoneal cavity

Nonperitoneal Causes of AscitesNon-peritoneal causes Examples Intrahepatic portal hypertension Cirrhosis

Fulminant hepatic failureVeno-occlusive disease

Extrahepatic portal hypertension

Hepatic vein obstruction (ie, Budd-Chiari syndrome)Congestive heart failure

Hypoalbuminemia Nephrotic syndromeProtein-losing enteropathy Malnutrition

Miscellaneous disorders MyxedemaOvarian tumorsPancreatic & Biliary ascites

Chylous Secondary to malignancy, trauma

Peritoneal Causes of Ascites

Peritoneal Causes Examples

Malignant ascites Primary peritoneal mesotheliomaSecondary peritoneal carcinomatosis

Granulomatous peritonitis Tuberculous peritonitisFungal and parasitic infections SarcoidosisForeign bodies (cotton ,starch, barium)

Vasculitis Systemic lupus erythematosusHenoch-Schönlein purpura

Miscellaneous disorders Eosinophilic gastroenteritisWhipple diseaseEndometriosis

EtiologyCirrhosis (75%)

Most common cause of ascites Most common complication of cirrhosis Other causes occur more frequently in cirrhotics

Malignancy (10%) Cardiac (3%) TB (2%) Pancreatic Ascites(1%) Various others

Hepatology 38:258-66

Pathophysiology of ascites in CLD:

Splanchnic HTN due to outflow obstruction Increased vasodilatation (NO) This sequesters volume in the abdomen Decreases systemic filling Decreases systemic BP Activates antinatriuretic factors Combination of increased splanchnic BP with

vasodilatation leads to capillary leak Lymph return can only keep up for sometime

then ascites develops.

Physical Examination

Bulging Flanks Flank Dullness Shifting Dullness Fluid Wave Puddle sign Approximately 1.5 L must

be present before flank dullness is detected. If no flank dullness is present, the patient has less than 10% chance of having ascites.

JAMA 1992; 267:2645-48

Bulging Flanks Occur when weight of

ascites is sufficient to push the flanks outwards

Difficult to distinguish from obesity

Sensitivity-72-93% Pooled data 81%

Specificity-44-70% Pooled data 59%

JAMA 1992; 267:2645-48

Flank Dullness Similar to bulging

flanks, although uses percussion

Typically bowel will float to the top and ascitic fluid sinks to the bottom

Sensitivity-80-94% Most sensitive test Pooled data 84%

Specificity-29-69% 69% outlying value Pooled data 59%

JAMA 1992; 267:2645-48

Shifting Dullness Find the point where

flank dullness occurs Mark it Roll the patient away

from the examiner Repeat percussion and

ensure that the point moves to the dependent side

Sensitivity-60-83% Pooled data 77%

Specificity-56-90% Pooled data 72%

JAMA 1992; 267:2645-48

Fluid Wave (fluid thrill) Medial edges of both

hands down midline Tap flank firmly and feel

for an impulse on the other side

Sensitivity-50-80% Pooled data 62%

Specificity-82-92% Most specific test Pooled data 90%

JAMA 1992; 267:2645-48

Puddle Sign Have patient prone 3-5

minutes then rise to crawling Place the diaphragm of the

stethoscope over the most dependent area of the abdomen

Flick a finger until sound detected

No longer recommended Formerly used for high

sensitivity Sensitivity-43-55%

Pooled data 45% Specificity-51-83%

Pooled data 73%

JAMA 1992; 267:2645-48

International Ascites Club Grading

Grade 1 Mild, only detectable by U/S

Grade 2 Moderate, symmetrical distension

Grade 3 Gross or large with marked distension

Large typically means painful/uncomfortable Refractory Ascites (5-10%)

Can not be mobilized or early recurrence refractory to medical management

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Hepatology 2003; 38: 258-266

Diagnosing Ascites Ultrasound is the most

sensitive test for ascites (100mL detection) Have to use caution as

small or even moderate ascites may be difficult to tap (even when marked)

Ensure mark is appropriate

Go with patient to U/S (ideal)

If not possible, in order specify location where you want to place your needle

Image from www.gastro.org

Paracentesis: General Tips

Do NOT do paracentesis to see if ascites present, should know before

If unclear need U/S

Ensure patient has voided

FFP/Platelet transfusion if indicated

Ensure landmarks

Get Quick-Tap kit, plastic catheter does not work as well as the metal one.

Picture from www.kchealthcare.com

Paracentesis:

Site: 5cm cephalic & 5 cm medial to ASIS in the left lower quadrant of the abdomen has been shown to be the ideal site with larger pool of fluid.

Complications: (1% of patients) Abdominal wall hematomas. Hemoperitoneum or bowel entry.

Contraindications:Clinically evident fibrinolysis or DIC.

Color Appearance

Translucent or yellow Normal / sterile

Brown HyperbilirubinemiaGB or biliary perforation

Cloudy or turbid Infection

Pink or blood tinged Mild Trauma

Grossly bloody MalignancyAbdominal trauma

Milky ("chylous") CirrhosisThoracic duct injuryLymphoma

Gross Appearance of Ascitic Fluid

Diagnostic Studies

Recommended Studies

Albumin Protein Cell count

Looking for PMNs Cultures

If clinically appropriate

Glucose LDH Amylase RBC count TB smear/culture Cytology Triglycerides

www.gastro.org

Diagnostic StudiesSAAG > 1.1 SAAG < 1.1

Ascites Protein <2.5 Ascites Protein >2.5

1. Check serumand fluid albumin

Ascites Protein >2.52. Check AscitesProtein

Hepatic Sinusoid source Peritoneum source

Capillarized sinusoid Normal sinusoidPeritoneal lymph

CirrhosisLate Budd-Chiari

3. DifferentialDiagnosis

Cardiac ascitesEarly Budd-ChiariVeno-occlusive disease

Malignancy Tuberculosis

The SAAG does not need to be repeated after the initial measurement.Note: Exceptions exist: may have mixed features

Adapted from www.gastro.org

Ascitic fluid analysis: If the PMN count is >250 cells/mm3, another specimen is injected into blood culture bottles at bedside.

Bacterial growth occurs in about 80% of specimens with count of >250 cells/mm3.

In a "bloody" sample that contains a high concentration of RBC, the PMN count must be corrected: One PMN is subtracted from the absolute PMN count for every 250 red cells/mm3 in the sample.

The results must be available within 1 hour, so that important diagnostic and therapeutic decisions can be made.

A Gram stain is of particular low yield unless free gut perforation, is suspected.

Based on clinical judgment, additional testing can be performed

a) Cytology ,smear & culture for mycobacteria.

b) Cytology : in peritoneal carcinomatosis (sensitivity increased by centrifuging large volume).

c) Elevated bilirubin level suggest biliary or gut perforation.

d) LDH >225mU/L, glucose <50mg/dL, total protein >1g/dL and multiple organisms on gram stain suggest secondary bacterial peritonitis.

e) High level of TG's confirms chylous ascites.

f) Elevated amylase level suggest pancreatitis or gut perforation.

Prognosis

Poor outcomes Refractory ascites SBP HRS MELD (Model for end-stage liver disease)

is not specifically validated for patients with ascites

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Prognosis Any person with ascites due to cirrhosis

needs transplant evaluation If MELD is <15 can stop there Average US wait time 500d Average wait less in some other countries

120 days in UK180 days in Spain

If admitted for ascites 40% chance of dying within 2 years

Improves to 70-80% 5 year survival after transplant

Hepatology 2003; 38: 258-266

Dig Dis 2005; 23:30-38

Treatment

Grade 1 No treatment necessary Modify risk factors Start low sodium diet

Hepatology 2003; 38: 258-266

Treatment

Grade 2 Bed rest

Diuretics work better supine studied bemetanide GFR lower standing as well

Sodium and water restriction Diuretics

Hepatology 2003; 38: 258-266

Br Med J. 1986;292:1351-3

Treatment

Grade 3 Paracentesis is the treatment of choice

Shown to have fewer complications than diuresis

Faster response After this would do Grade 2 treatment

options

Hepatology 2003; 38: 258-266

Treatment

Refractory ascites Paracentesis with colloid infusion TIPS

Choice between these is controversial If repeated paracentesis is

contraindicated,TIPS not an option then consider porto-venous shuntPVS shown inferior to repeat paracentesis in

NEJM study

Hepatology 2003; 38: 258-266

Sodium Restriction

No survival benefit related to ascites shown, does have benefit in GIB mortality

50mm restriction is equivalent to 120mm (approx. 2g/day) Tighter restriction had faster resolution Higher incidence of renal dysfunction and

hyponatremia

Hepatology 2003; 38: 258-266

Diuretics Spironolactone

start 100-200 per day Titrate to max of 400 per day in severe hyper-aldo

Can use potassium sparing diuretics Amiloride inferior to canrenoate (anti-

mineralocorticoid) No other comparison trials, but spironolactone

accepted as first line Use second line if spironolactone not possible 2/2

complications (ie gynecomastia)

Hepatology 2003; 38: 258-266

Diuretics

Loop diuretics Lasix

Initial dose 20-40 per dayCan adjust up to 160mg per day

Should be used only as an adjunct to spironolactone

Risks of K depletion, hyperchloremic alkalosis, hyponatremia and hypovolemia with subsequent renal dysfunction

Hepatology 2003; 38: 258-266

Dig Dis 2005; 23:30-38

Assessing Diuretic Response

Weight loss Lose 0.5kg a day when no edema Lose 1kg a day when edema is present

Avoid renal failureResponse rate in up to 90% patients

who do NOT have renal dysfunction

Hepatology 2003; 38: 258-266

Dig Dis 2005; 23:30-38

Paracentesis

ParacentesisFirst used by the Ancient Greeks Decreased in the 1950s when diuretics

were discoveredResurgence in 1980s after 1987 article

found paracentesis with lower complications than diuretics

More effective than diuresis Shorter hospital stay

Dig Dis 2005; 23:30-38

Paracentesis

Total volume paracentesis is as effective and as safe as sequential 3L paracentesis

Hemodynamics RA pressure drops immediately PCWP takes 6h to decrease

Hepatology 2003; 38: 258-266

Paracentesis

Post paracentesis volume expansion Side effects and albumin

without 30%with 16%

Albumin prevents increased renin/aldo better than synthetic agents

HRS decreases Less Hyponatremia

Hepatology 2003; 38: 258-266

NEJM 350:1646-54

Paracentesis-Complications Bleeding - can be fatal Ascitic fluid leak

Purse string suture Lie with puncture site

up Bowel perforation Renal impairment Hypotension/

Cardiovascular collapse

TIPS

Transjugular Intrahepatic Portosystemic Shunt

Creates a conduit from the high pressure portal system to the lower pressure systemic circulation

TIPS

Ascites can only form when portal pressure is >12

Response rates 51-79% in RCT

Dig Dis 2005; 23:30-38

TIPS - Benefits

May improve nitrogen balanceWill decrease portal pressure reducing

GIB riskImproves hemodynamics

Increased CO, RA pressure, PCWP and decreased SVR with increased Na excretion

Improves response to diuresis

Hepatology 2003; 38: 258-266

NEJM 350:1646-54

TIPS - RisksEncephalopathy

30% those treated Typically can improve with shunt revision

or medical management Increased risk if

Age >60History of Encephalopathy

100% mortality if refractory to TIPS occlusion

CHF - this is due to increased preload

Am J Gastro 2003;98:2521-27

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TIPS - Complications

Capsule perforationStenosis

75% in 6-12 months Decreased risk with stents coated in

polytetrafluoroethylene (PTFE)Increased cost relative to paracentesis

Radiology 1999;231:759-766

NEJM 350:1646-54

TIPS v. Paracentesis Several studies (2 examples)

Lebrec 1996 No ascites recurrence benefit in CP class C patients with

worsened survivalCP class B showed decreased recurrenceSmall study (25 patients)

Salerno - 2004Shown to have survival improvement with multivariate

analysis (only trend to improved survival without this) Non-blinded 3 center studyHad to have 4 taps in the last monthDecreased ascites recurrence HR 0.37 (0.18-0.76)66 patients

Hepatology 2004;40:629-635

J Hepatol 1996;25:135-44

Cochrane Database

No difference in mortality Decreased re-accumulation at 3 and 12

months Increased PSE OR 2.11(1.22-3.66) Surprisingly no difference:

GIB, ARF, Infection or DIC Some issues in differences between the

studies, not all paracentesis had post-paracentesis albumin, differences in MELD/CP between studies

Hepatology 2003; 38: 258-266

Reasons for TIPS over Paracentesis

TIPS better if Loculated ascites Patient unwilling to have repeat taps Frequent recurrences

Am J Gastro 2003;98:2521-27

Peritoneovenous Shunts

Peritoneovenous Shunts

Creates a communication between the peritoneal cavity and the systemic circulation by a vein

Used in only in limited cases currently Used for palliation if TIPS and paracentesis

are not available or contraindicated

Hepatology 2003; 38: 258-266

Spontaneous Bacterial Peritonitis H/O Chronic Liver Disease. Fever and abdominal pain (66%) Signs of peritonitis uncommon (<50%) Neutrocytic ascites on diagnostic

paracentesis. 20-30% of pts with CLD develop SBP. Almost always monomicrobial. Anaerobes are not associated with SBP 20% are asymptomatic. Typically due to translocation

This is why E. Coli is the most common

SBP: Diagnosis.

Diagnosed with >250 polys or > 50-70% of the total cell count.

Ascitic protein >1gm/dl against SBP.10-30% are ascitic fluid culture negative.3% have secondary Bacterial Peritonitis.Ascitic fluid Glucose, LDH and total

proteins may be helpful in DDx.Erect Abd X-ray in suspicious cases.

Hepatology 2003; 38: 258-266

NEJM 350:1646-54

SBP: Treatment and Prophylaxis

Treat with 3rd generation Cephalosporins. Repeat PMN count after 48 hrs. 40% develop HRS during the course of illness. Human Albumin 1.5gm/Kg o day one and 1 gm/Kg on day three

has shown improvement in both morbidity and mortality.

Prophylaxis: 70% recur within one year.

Norfloxacin 400mg qd Ciprofloxacin 750mg q week Tri-Sulpha: Has never been tested in a trial with mortality.

Ultimate treatment:Liver transplant.

ReferencesMoore K, Wong F, Gines P, Bernardi M et al. The Management of Ascites in Cirrhosis: Report on the Consensus Conference of the International

Ascites Club. Hepatology 2003;38: 258-266Gines P, Cardenas A, Arroyo V, Rodes J. Management of Cirrhosis and Asictes. NEJM. 2004;350:1646-1654Haskal Z. Improved Patency of TIPS in Humans: Creation and Revision with PTFE Stent-Grafts. Radiology. 1999; 213: 759-766Cardenas A, Arroyo V. Refractory Ascites. Dig Dis. 2005; 23:30-38Russo M, Sood A, Jacobson I, Brown R. TIPS for Refractory Ascites: An Analysis of the Literature on Efficacy, Morbidity and Mortality. Am J

Gastroenterol. 2003; 98:2521-2527Heuman D, Abou-assi S, Habib A et al. Persistent Ascites and Low Serum Sodium Identify Patients with Cirrhosis and Low MELD Scores who are at

High Risk for Early Death. Hepatology. 2004; 40: 802-810Salerno F, Merli M, Riggio O, Cazzangia M, et al. Randomized Controlled Study of TIPS v. Paracentesis Plus Albumin in Cirrhosis with Severe

Ascites. Hepatology 2004;40: 629-635.Ring-Larsen H, Henriksen J, Wilken C, Clausen J, et al. Diuretic treatment in decompensated cirrhosis and congestive heart failure: effect of posture.

Br Med J 1986; 292: 1351-1353Lebrec D, Giuily N, Hadengue A, Vilgrain V, et al. TIPS: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized

trial. French Group of Clinicians and a Group of Biologists.Saabs, Nieto JM, Ly D, Runyon BA. TIPS versus paracentesis for cirrhotic patients with refractory ascites. The Cochrane database of Systematic

Reviews 2004, Issue 3 Art. No.: CD004889Cattau EL, Stanley BB, Knuff TE, et al. The Accuracy of the Physical Examination in the Diagnosis of Suspected Ascites. JAMA. 1982; 247: 1164-

1166.Williams JW, Simel DL. Does This Patient Have Ascites?. JAMA. 1992; 267: 2645-2648.Mallory A, Schaefer JW. Complications of Diagnositc Paracentesis in Patients with Liver Disease. JAMA. 1978; 239: 628-630Runyon BA. Paracentesis of Ascitic Fluid a Safe Procedure. Arch Intern Med. 1986; 146: 2259-2261Simel DL, Halvorsen RA, Feussner JR. Quantitating bedside diagnosis: clinical evaluation of ascites. J Gen Intern Med. 1988; 3:423-428.www.uptodate.com

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