Transcript Ascites - Intekhab Alam

MANAGEMENT OF ASCITES
by
Dr Intekhab Alam
Professor of Medicine
Department of Medicine
Postgraduate Medical Institute,
Lady Reading Hospital, Peshawar
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 Cirrhosis
1.
2.
3.
4.
5.
6.
Chronic viral hepatitis
Metabolic: hemochromatosis, Wilson dis,
alfa-1-antitrypsin, NASH
Prolonged cholestasis (primary biliary
cirrhosis, primary sclerosing cholangitis)
Autoimmune diseases (autoimmune
hepatitis)
Drugs and toxins
Alcohol
Anatomy of the portal venous system
The Effect of The Liver Nodule
Mechanism of Portal HTN
Cirrhosis
Resistance portal flow
Mechanical
Dynamic
Nodules
Nitric 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 Ascites
Non-peritoneal causes
Examples
Intrahepatic portal
hypertension
Cirrhosis
Fulminant hepatic failure
Veno-occlusive disease
Hepatic vein obstruction
(ie, Budd-Chiari syndrome)
Congestive heart failure
Nephrotic syndrome
Protein-losing enteropathy
Malnutrition
Extrahepatic portal
hypertension
Hypoalbuminemia
Miscellaneous disorders
Chylous
Myxedema
Ovarian tumors
Pancreatic & Biliary ascites
Secondary to malignancy, trauma
Peritoneal Causes of Ascites
Peritoneal Causes
Examples
Malignant ascites
Primary peritoneal mesothelioma
Secondary peritoneal carcinomatosis
Granulomatous peritonitis
Tuberculous peritonitis
Fungal and parasitic infections
Sarcoidosis
Foreign bodies (cotton ,starch, barium)
Vasculitis
Systemic lupus erythematosus
Henoch-Schönlein purpura
Miscellaneous disorders
Eosinophilic gastroenteritis
Whipple disease
Endometriosis
Etiology

Cirrhosis (75%)
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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:
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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



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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%
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
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%
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Most sensitive test
Pooled data 84%
Specificity-29-69%
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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)

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Medial edges of both
hands down midline
Tap flank firmly and feel
for an impulse on the
other side
Sensitivity-50-80%

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Pooled data 62%
Specificity-82-92%
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Most specific test
Pooled data 90%
JAMA 1992; 267:2645-48
Puddle Sign

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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


Grade 2

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Mild, only detectable by U/S
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
NEJM 350:1646-54
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.
Gross Appearance of Ascitic Fluid
Color
Appearance
Translucent or yellow
Normal / sterile
Brown
Cloudy or turbid
Hyperbilirubinemia
GB or biliary perforation
Infection
Pink or blood tinged
Mild Trauma
Grossly bloody
Malignancy
Abdominal trauma
Cirrhosis
Thoracic duct injury
Lymphoma
Milky ("chylous")
Diagnostic Studies

Recommended
Studies
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Albumin
Protein
Cell count
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Looking for PMNs
Cultures

If clinically
appropriate
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Glucose
LDH
Amylase
RBC count
TB smear/culture
Cytology
Triglycerides
www.gastro.org
Diagnostic Studies
1. Check serum
and fluid albumin
2. Check Ascites
Protein
3. Differential
Diagnosis
SAAG > 1.1
Hepatic Sinusoid source
Ascites Protein <2.5
Ascites Protein >2.5
Capillarized sinusoid
Peritoneal lymph
Cirrhosis
Late Budd-Chiari
SAAG < 1.1
Peritoneum source
Ascites Protein >2.5
Normal sinusoid
Cardiac ascites
Malignancy
Early Budd-Chiari
Tuberculosis
Veno-occlusive disease
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
NEJM 350:1646-54
Prognosis

Any person with ascites due to cirrhosis
needs transplant evaluation
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If MELD is <15 can stop there
Average US wait time 500d
Average wait less in some other countries

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120 days in UK
180 days in Spain

If admitted for ascites 40% chance of dying
within 2 years
 Improves to 70-80% 5 year survival after
transplant
Dig Dis 2005; 23:30-38
Hepatology 2003; 38: 258-266
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
Br Med J. 1986;292:1351-3
Hepatology 2003; 38: 258-266
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 shunt
 PVS
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
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start 100-200 per day
Titrate to max of 400 per day in severe hyper-aldo
Can use potassium sparing diuretics
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Amiloride inferior to canrenoate (antimineralocorticoid)
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 day
 Can 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
Dig Dis 2005; 23:30-38
Hepatology 2003; 38: 258-266
Assessing Diuretic Response

Weight loss
 Lose
0.5kg a day when no edema
 Lose 1kg a day when edema is present
Avoid renal failure
 Response rate in up to 90% patients
who do NOT have renal dysfunction

Dig Dis 2005; 23:30-38
Hepatology 2003; 38: 258-266
Paracentesis
Paracentesis
First used by the Ancient Greeks
 Decreased in the 1950s when diuretics
were discovered
 Resurgence 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
NEJM 350:1646-54
Hepatology 2003; 38: 258-266
Paracentesis-Complications

Bleeding - can be
fatal
 Ascitic fluid leak



Purse string suture
Lie with puncture site
up
Bowel perforation
 Renal impairment
 Hypotension/Cardio
vascular 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 balance
 Will decrease portal pressure reducing
GIB risk
 Improves hemodynamics

 Increased
CO, RA pressure, PCWP and
decreased SVR with increased Na
excretion

Improves response to diuresis
NEJM 350:1646-54
Hepatology 2003; 38: 258-266
TIPS - Risks

Encephalopathy
 30% those treated
 Typically can improve
with shunt revision
or medical management
 Increased risk if
 Age >60
 History of
Encephalopathy
 100%
mortality if refractory to TIPS
occlusion

CHF - this is due to increased preload
NEJM 350:1646-54
Am J Gastro 2003;98:2521-27
TIPS - Complications
Capsule perforation
 Stenosis

 75%
in 6-12 months
 Decreased risk with stents coated in
polytetrafluoroethylene (PTFE)

Increased cost relative to paracentesis
NEJM 350:1646-54
Radiology 1999;231:759-766
TIPS v. Paracentesis

Several studies (2 examples)

Lebrec 1996

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No ascites recurrence benefit in CP class C patients with
worsened survival
CP class B showed decreased recurrence
Small study (25 patients)
Salerno - 2004

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Shown to have survival improvement with multivariate
analysis (only trend to improved survival without this)
Non-blinded 3 center study
Had to have 4 taps in the last month
Decreased ascites recurrence HR 0.37 (0.18-0.76)
66 patients
J Hepatol 1996;25:135-44
Hepatology 2004;40:629-635
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 postparacentesis 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
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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.

NEJM 350:1646-54
Hepatology 2003; 38: 258-266
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.
References
Moore 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: 258-266
Gines P, Cardenas A, Arroyo V, Rodes J. Management of Cirrhosis and Asictes. NEJM. 2004;350:1646-1654
Haskal Z. Improved Patency of TIPS in Humans: Creation and Revision with PTFE Stent-Grafts. Radiology. 1999; 213: 759-766
Cardenas A, Arroyo V. Refractory Ascites. Dig Dis. 2005; 23:30-38
Russo 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; 98:2521-2527
Heuman 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: 802-810
Salerno 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: 1351-1353
Lebrec 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.: CD004889
Cattau EL, Stanley BB, Knuff TE, et al. The Accuracy of the Physical Examination in the Diagnosis of Suspected Ascites. JAMA. 1982; 247: 11641166.
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: 628-630
Runyon BA. Paracentesis of Ascitic Fluid a Safe Procedure. Arch Intern Med. 1986; 146: 2259-2261
Simel DL, Halvorsen RA, Feussner JR. Quantitating bedside diagnosis: clinical evaluation of ascites. J Gen Intern Med. 1988; 3:423-428.
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Shukriya
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