Cirrhotic Ascites: Customizing Therapy

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Cirrhotic Ascites Customizing Therapy

• Mohamed El-Bokl
• Prof. of Hepatology Gastroenterology
• Ain Shams University

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Objectives

• Causes of Ascites
• Treatment of uncomplicated cirrhotic ascites.
• Hyponatremia during therapy
• Treatment options of refractory ascites

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Ascites

• Is the most common of the three
• major complications of cirrhosis

• Ascites
• Encephalopathy
• Variceal Hge

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Ascites is an Important Landmark in the Natural
History

• Poor Prognosis
• 50 of Pts 2 years survival
• With refractory ascites 506month
  survival.

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• Mechanism of Ascites Formation

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Portal hypertension
Splanchnic VD
Increased Capillary permeability
Arterial under filling
Stimulation of RAS, SNS, ADH
Ascites
Sod water retention
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Ascites
Uncomplicated
Complicated
No SBP No HRS
SBP or HRS
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Grading International Ascites Club
Mild Ascites detectable only by ultrasound
exam.
Large or gross ascites with marked abdominal
distension.
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1
Moderate Ascites manifested by moderate
symmetrical distension of the abdomen
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Grade 1
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Diagnosis

• The initial Lab investigation of ascitic fluid
  should include
• Cell count, Cytology
• Total protein
• SAAG serum albumin ascitic gradient
• If infection is suspected culture at the bedside
  in blood culture bottles

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Diagnosis

• Abdominal ultrasound scan
• Blood tests should be taken for measurement of
  urea and electrolytes, liver function tests,
  prothrombin time, and full blood count.

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Indications for abdominal paracentesis in a
patient with ascites

• Mental status change
• Hypotension
• Peripheral leukocytosis
• Acidosis
• Worsening of renal function
• Gastrointestinal bleeding (a high risk for
  infection)

• New onset ascites
• At the time of each admission to the hospital
• Clinical deterioration, either inpatient or
  outpatient
• Fever
• Abdominal pain
• Abdominal tenderness

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SAAG
Serum Albumin Ascitic Albumin
lt1.1 g/dL
gt 1.1 g/dL

• Tuberculous peritonitis
• Malignant conditions
• Chylous ascites
• Pancreatic ascites
• Bacterial peritonitis
• Nephrotic syndrome

• Portal Hypertension (97 accuracy)
• Liver cirrhosis
• Hepatic congestion
• CHF
• Const pericarditis
• Budd-Chiari

Respond to Diuretics
Does NOT Respond to Diuretics Except NS
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Treatment of Ascites

• First line consists of
• Sodium restriction (2gm 88mmol/d)
• Diuretics
• Spironolactone
• Furosemide po
• Fluid restriction is not necessary unless serum
  sodiumlt120-125 mmol/L.
• An initial therapeutic paracentesis should be
  performed in tense ascites

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Diuretics

• A major goal of treatment is to induce Negative
  Sod balance.
• By increasing urinary sodium excretion to gt78
  mmol/day, i.e. greater than intake of 88 mmol/day
  (non-urinary losses 10 mmol/day).

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Diuretics

• Single morning doses (better compliance) of oral
  spironolactone plus frusemide.
• Start with 100mg Spiro and 40 mg
  Furosemide.
• The doses of both drugs can be increased
  simultaneously every 3-5 days if weight loss and
  natriuresis are inadequate.
• Maintain the ratio of 100mg40mg to maintain
  normokalemia

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Diuretics Monotherapy

• Single agent furosemide is Less effective than
  Spironolactone.
• Spironolactone may be used as single agent only
  in Pts with minimal fluid overload (But
  Risk of hyperkalemia)

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Diuretics in Healthy Subjects
Furosemide gt Spironolactone
The amount of sod Reabsorption in the Distal
nephron is low (5 of filtered sod) So
Spironolacton is Weak diuretics
NA
X

• Furosemide prevent sod Reabsorption in the thick
  ascending Loop of Henle. 50 of the filtered sod
  is reabsorped at this site. So frusemide is a
  powerful Diuretic.

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Diuretics in Cirrhotic Patients
Spironolactone gt Furosemide
Marked Hyperaldosteronism
SNS Angioten II
Most of Na not Reabsorp. in loop of Henle is
reabsorp by the Effect of aldosterone
NA
Increased Sod reabsorption
X
XXX
Spironolactone is the basic diuretics In
cirrhotics
Low Sod delivery to the ascending loop of Henle
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Diuretics in Cirrhotic Patients
Furosemide is less Effective
Impaired due to toxic Or competitive inhibition
Loop D are Prot-bound
XX No glom filtration
Enter the proximal T By Secretion
Limited Diuretic entry Limited effect
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Diuretics Furosemide iv ??

• Oral route is favored
• Good oral bioavailability of frusemide in
  cirrhotic patients.
• Acute reduction of GFR with iv route.

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Diuretics The Limit of Weight Loss

• No limit to daily weight loss of Pts. Who have
  massive pedal edema (1 kg/d).
• Once edema has resolved, 0.5 kg is a reasonable
  daily maximum to avoid intravascular volume
  depletion.

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Diuretics The Limit of Weight Loss
Intravascular space
Ascites Rate of flow is limited 500mL/d
Edema No limit to the rate of flow
Diuretics
Kidney
Wt. loss 0.5 kg/d
No limit To Wt loss
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Diuretics When to Stop?

• Encephalopathy
• Serum Sodium lt120 mmol/L despite fluid
  restriction.
• Serum Creatinine gt 1.7-2.0 mg/dL.

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• Management of Hyponatremia in Patients on
  Diuretic Therapy

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Hyponatremia
Continue diuretic

• Stop Diuretic
• Volume expansion with colloid or saline if
  Cr.gt1.7

Cr normal
S. Na 126135
Serum Na lt120
Serum Na 121125
normal S Cr.
ElevatedS Cr.

• International opinion is to continue diuretic
  therapy,
• European guidelines is to stop diuretic therapy
  or adopt a more cautious approach.

Stop diuretics and give volume expansion.
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Management of Tense Ascites

• An initial large-volume paracentesis rapidly
  relieves tense ascites.
• Sodium restricted diet and diuretics should then
  be initiated
• Titrate the doses upward every 3-5 days

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• The Patient is Not Responding
• !!

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The Patient is Not Responding

• Lack of response mean Wt. loss lt0.8 kg over 4
  days.
• Treatment Duration At least one week on maximum
  doses of diuretics
• 400 mg spironolactone plus 160 mg furosemide.

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The Patient is Not Responding
Refractory Ascites
Diuretic Resistant
Not strict to low Sodium 88mmol/d
24 h urinary sodium
If lt78 mmol/d
If gt78 mmol/d
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Refractory Ascites
10
Randomized trials have shown that lt10 of
cirrhotic ascites are refractory to Standard
medical therapy
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Treatment Options

• ? Liver Transplantation
• ? Serial Paracentesis
• ? TIPS
• ? Peritoneovenous Shunts

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? Serial Therapeutic Paracentesis

• Performed approximately every 3 wks.
• Frequency of paracentesis provide insight into
  the patients degree of compliance with the diet.
• Pts. Requiring paracentesis of approx. 10 L more
  frequently than every 2 wk are clearly Not
  complying with the diet.

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Diuretics after paracentesis

• Pts. May continue diuretics as tolerated, to
  reduce the frequency of paracentesis.

IAC
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Post-paracentesis Colloid Infusion
Recommendations

• Single 5-L paracentesis can be performed safely
  without post-paracentesis colloid infusion.
• For Large volume paracentesis, an albumin
  infusion of 8 gm/L of fluid removed can be
  considered.

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Low vs. standard albumin dosages

• 25 patients undergoing large-volume paracentesis
  
• low-dosage infusion of albumin (4g/L of ascitic
  fluid removed)
• were Compared with the standard dose of 8g/L.

Alessandria et al, J Hepatol. 2005
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• Results
• Similar incidence of paracentesis-induced
  circulatory dysfunction
• Conclusion
• Low doses of albumin are as effective as standard
  doses in the prevention of this complication.
• A finding that may lead to significant Cost
  Reduction.

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!!?Contraindications of Paracentesis

• Renal Failure
• Severe Hepatic Encephalopathy.
• Thrombocytopenia.
• Low Blood Pressure.
• Severe Jaundice.

• There is No evidence that these should be
  considered as Contraindications for paracentesis
• IAC

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TIPS Transjugular Intrahepatic
Portosystemic Shunt
?

• Is a side to side portacaval shunt placed through
  the IJV by interventional radiologist.
• The goal is to divert portal blood flow into the
  hepatic vein to reduce the portal pressure.
• TIPS usually converts diuretic-resistant ascites
  into diuretic sensitive ascites.

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Rt HV
PV
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TIPS Recommendations

• It is an effective treatment for Refractory
  Ascites.
• It should be considered when
• The frequency of paracentesis is greater than 3
  times/month.
• Paracentesis is contraindicated.
• Recurrent massive hepatic hydrothorax.

IAC
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TIPS Contraindications

• Pre-existing hepatic encephalopathy.
• Pre-existing cardiac dysfunction.
• Ejection Fraction should be gt55
• Child-pugh score gt 12
• Age greater than 70 years.

IAC
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? Peritoneovenous Shunts

• LeVeen shunt, Denever shunt
• Drain into the IJV.
• This procedure has been virtually abandoned due
  to high rate of complications.

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Complications

• Poor long-term patency.
• DIC
• Infection of the shunt
• Bacteremia
• Variceal bleeding (volume expansion).
• Small bowel obstruction.

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Peritoneovenous Shunts

• The only indication is the rare patient who is
  Not candidate for repeated large volume
  paracentesis, TIPS, or liver transplantation.

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Thank You