Ascites

Modified 15:05, 27 Jan 2018 by apavel | Page History

1. Introduction
2. Undifferentiated Ascites
3. Treatment Principles
1. 3.1. Refractory Ascites
4. Spontaneous Bacterial Peritonitis
5. Cirrhosis and Ascites
1. 5.1. Pathophysiology
2. 5.2. Management:
  1. 5.2.1. Paracentesis:
  2. 5.2.2. Refractory Ascites
  3. 5.2.3. TIPS - Transjugular Intrahepatic Portosystemic Shunt
3. 5.3. Hepatorenal Syndrome

Table of Contents

1. Introduction
2. Undifferentiated Ascites
3. Treatment Principles
1. 3.1. Refractory Ascites
4. Spontaneous Bacterial Peritonitis
5. Cirrhosis and Ascites
1. 5.1. Pathophysiology
2. 5.2. Management:
  1. 5.2.1. Paracentesis:
  2. 5.2.2. Refractory Ascites
  3. 5.2.3. TIPS - Transjugular Intrahepatic Portosystemic Shunt
3. 5.3. Hepatorenal Syndrome

Introduction

Most frequent complication of portal HTN.
50% of pts with cirrhosis will get ascites in 10 years.
Diagnosis:
- Physcal exam
- Ultrasound for occult ascites
Diagnostic paracentesis is required:
- Cell count, differential, albumin, total protein.
- If infection suspected: culture! (AT BEDSIDE!!)
- Calculate SAAG - Serum Ascites

Undifferentiated Ascites

If diagnosis is unclear, perform a diagnostic paracentesis:

Workup of Ascites
Serum Ascites Albumin Gradient (SAAG) = Serum Albumin - Fluid Albumin If SAAG ≥ 1.1 g/dL (≥ 11 g/L) => portal hypertension (90-95% of cases) (Cirrhosis, Heart Failure, Budd-Chiari Syndrome, idiopathic portal fibrosis) High ascitic protein level ≥ 2.5 g/dL --> Cardiac etiology (includes Budd-Chiari, constrictive pericarditis, R-heart failure). Low Ascitic Protein Level < 2.5 g/dL --> Portal Hypertension If SAAG < 1.1 g/dL (< 11 g/L) => unlikely portal HTN (TB, pancreatitis, nephrotic syndrome, serositis, peritoneal carcinomatosis)

Workup of Ascites

Serum Ascites Albumin Gradient (SAAG) = Serum Albumin - Fluid Albumin

If SAAG ≥ 1.1 g/dL (≥ 11 g/L) => portal hypertension (90-95% of cases)
- (Cirrhosis, Heart Failure, Budd-Chiari Syndrome, idiopathic portal fibrosis)
  - High ascitic protein level ≥ 2.5 g/dL --> Cardiac etiology
    - (includes Budd-Chiari, constrictive pericarditis, R-heart failure).
  - Low Ascitic Protein Level < 2.5 g/dL --> Portal Hypertension
If SAAG < 1.1 g/dL (< 11 g/L) => unlikely portal HTN
- (TB, pancreatitis, nephrotic syndrome, serositis, peritoneal carcinomatosis)

Measuring hepatic venous pressure gradient
- Only helpful if uncertain after extensive investigations (echo, etc..)
- Measure hepatic vein pressure + wedge to get an estimate of portal vein pressure (seeing cross-liver gradient).
  - Helps understand if pre-hepatic, hepatic or post-hepatic cause of ascites.
Standard Workup of Ascitic Fluid:
- CBC, Differential, Albumin, Protein, (Gram stain + culture if suspect SBP), (cytology if suspect malignancy).

Treatment Principles

Sodium restriction < 2000 mg/day.
Oral diuretics
For moderate-to-severe ascites
- Large volume paracetesis
- Along with IV albumin 8g of Albumin per litre of fluid removed
  (5% albumin = 5g/100mL. Multiply grams by 20 to get volume of 5% albumin, and by 4 for 25% albumin)
  (i.e. 4L removed--> requires 32g of Albumin --> (640cc of 5% albumin or 128cc of 25% albumin)

Refractory Ascites

Definition of Refractory Ascites
Refractory Ascites = Resistance to sodium restriction and high dose diuretics (Upwards of 400mg spironolactone + 160 furosemide /day). Or if side effects prevent maximizing oral diuretics.

Definition of Refractory Ascites

Refractory Ascites = Resistance to sodium restriction and high dose diuretics
(Upwards of 400mg spironolactone + 160 furosemide /day).

Or if side effects prevent maximizing oral diuretics.

Treatment options:
- Serial theraputic paracentesis
- TIPS
- Liver transplantation

Spontaneous Bacterial Peritonitis

SBP - spotaneous infection of ascitic fluid w/o evidence of intraabdominal infection.
Pathobiology:
- Translocation of bacteria from intestinal lumen to lymph nodes --> bacteremia --> ascitic fluid.
- Most common organisms:
  - E.coli
  - Klebsiella pneumoniae
  - Pneumococcus
Prevalence remained stable, but mortality declined from 50% to 15%.
Diagnosis:
- Spontaneous Bacterial Peritonitis Definition:
  Ascitic fluid bacterial culture is POSITIVE
  AND
  
  Absolute fluid PMN Count ≥ 250 cells/mL
Complications:
- HRS (30%) --> high mortality!
- Recurrence (70%)
Treatment:
- 3rd generation cephalosporin(ceftriaxone, cefotaxime) until culture finalized.
- Give IV albumin (Dose: 1.5 g/kg of body weight at diagnosis + 1 g/kg 48hrs later [some say day 3)
  - Salerno et al (2013) Meta Analysis: IV albumin improves mortality by 20%
    - Various regimens in RCTs include dose at dx and 48hrs, and at dx and on day 3.
- - Give only if significant kidney and/or liver dysfunction (survival benefit vs. abx alone).
- Can repeat tap at 48hrs to document drop in PMNs (will rise if secondary peritonitis ie. bowel perf)
Secondary Prevention: (Post SBP episode)
- Norfloxacin 400mg PO OD --> reduces recurrence in studies
  - Quinolone resident SBP emerging.
- TMP-SMX is an alternative if allergic to quinolones or resistant (evidence is scarce)
  - (Double-Strength every other day or single strength daily, but VARIES!)
Primary Prevention:
- Indications for primary prevention of SBP
  ALL patients with low-protein ascitic fluid (<1 g/dL [10 g/L]) and severe liver dysfunction
  (especially when they are hospitalized)
- Primary prophylaxis against SBP with norfloxacin is warranted in patients with low-protein ascitic fluid (<1 g/dL [10 g/L]) and severe liver dysfunction, especially when they are hospitalized.

Spontaneous Bacterial Peritonitis Definition:
Ascitic fluid bacterial culture is POSITIVE AND Absolute fluid PMN Count ≥ 250 cells/mL

Indications for primary prevention of SBP
ALL patients with low-protein ascitic fluid (<1 g/dL [10 g/L]) and severe liver dysfunction (especially when they are hospitalized)

Cirrhosis and Ascites

Pathophysiology

Chief factor: splanchnic vasodilatation.
Increased hepatic resistance --> portal HTN --> production of vasodilators (nitric oxide etc) --> splanchnic arterial vasodilatation --> decreased effective arterial blood volume --> increases in plasma volume and cardiac output (initially adequate to maintain arterial pressure).
- If advanced --> worse splanchnic arterial vasodilatation --> activation of vasoconstrictor and antinatriuretic factors (to maintain BP) --> sodium + fluid retention.
  - Combination of: splanchnic arterial vasodilatation + portal HTN --> alters intestinal capillar pressure and permeability --> retained fluid in abdominal cavity.
    - In VERY advanced disease --> decrease in renal excretion of free H2O + renal vasoconstriction --> dilutional hyponatremia + hepatorenal syndrome (respectively).
    - (click to enlarge)

Management:

A. If sodium retention: Reduction of sodium intake (60-90mEq or 1.5-2g Na/day)
B. If dilutional hyponatremia: Fluid restriction to 1000mL/day) if Na < 130
if Moderate-Volume Ascites
- Have positive sodium balance. In most cases:
  - 1. Normal renal free water excretion (normal ADH and serum Na)
  - 2. Creatinine is normal.
- Negative sodium balance and loss of ascitic fluid achieve with diuretics:
  - C. Spironolactone (50-200mg/day) or amiloride (5-10mg/day)
  - D. Can add furosemide (20-40mg/day)
    - LOW DOSE in initial stages to increase naturesis (esp if edema). CAUTION: Can cause too much diuresis and worsening renal failure (pre-renal causes), window is small.
    - TWH internal medicine recommendation:
      spironolactone and furosemide (ratio: 100:40) to maintain normokalemia.
  - Target: loss 300-500g/day w/o peripheral edema and 800-1000 g/day with edema.
    - if no weight change, measure Urine Na.
      - Can tell you response to diuretics, and see if can increase diuretics dose.
If Large-Volume Ascites
- Severe sodium retention (U sodium < 10mmol/L)
  - Therefore ascitic fluid rapidly accummulates even if salt restricted.
  - Most have normal free water excretion (some have less excretion --> dilutional hyponatremia).
- Serum Creatinine (GFR) is often normal.
- Two strategies:
  - 1. Large-volume paracentesis
  - 2. Massive doses of Diuretics until ascites is lost.
    - (maximal doses 400mg spironolactone/day and 160mg furosemide/day)
- [Studies show: no difference in mortality between the two, but paracetesis is faster, more effective, associated with fewer adverse events]\
- Regardless of strategy: diuretics need to be given to prevent recurrence.
Paracentesis:
- Problem: derangement in circulatory function --> Decr BP --> activation of vasoconstrictor + antinatriuretic factors. --> complications; 20% develop:
  - Higher rate of recurrence
  - Risk of hepatorenal syndrome.
  - Dilutional hyponatremia
  - To offset this: MUST use plasma expanders: albumin, dextran 70, polygeline.
    - [Study: Albumin is superior to other two (above) in preventing circulatory dysfunction after paracentesis (if >5L removed). However, no difference in survival - prob b/c small sample sizes.]
    - Controversial: albumin is high cost, lack of survival benefit, but great circulatory protection!
  - Other complications:
    - Infection and GI perforation --> EXTERMELY rare - use appropriate technique and needle.
    - Bleeding at site / hemoperitoneum extremely low (trials excluded pts with PTT > 21s, INR > 1.6, and platelets < 50,000).
Refractory Ascites
- 5-10% incidence in those with ascites
- Defined as:
  - Lack of response to high doses of diuretics (400mg spironolactone + 160 furosemide /day).
  - Patients w/ hepatic encephalopathy, hyponatremia, hyperkalemia, azotemia at lower doses.
- Increased risk of recurrence of ascites + HRS.
- Treatments:
  - Repeated large-volume paracentesis + plasma expanders (q2-4 weeks).
  - trans-jugular IHPS (intra-hepatic portosystemic shunt).

TIPS - Transjugular Intrahepatic Portosystemic Shunt
- Stent placed btwn hepatic and portal veins by transjugular approach.
  - Advantages:
    - Effective to decrease recurrence in refractory ascites.
    - Decreases activity of Na-retaining mechanisms, increases response to diuretics.
  - Disadvantages:
    - Shunt stenosis (75% after 6-12mo).
      
      --> Recurrent ascites
    - High cost + lack of availability.
    - No survival benefit (initially showed survival benefit, but two recent randomized trials --> no survival benefit).
    - May make transplant difficult (but not a big problem)
  - Bottom line:
    - Only do if
      
      Severe liver failure or encephalopathy
      AND
      
      Loculated fluid cannot be accessed by paracentesis
      
      Unwilling to undergo paracentesis.

Hepatorenal Syndrome

Renal failure due to severe vasoconstriction of renal circulation (extreme arterial underfilling).
Incidence: 10% in cirrhosis/ascites:
Two patterns:
- Type 1 HRS - Precipitating event triggers renal impairment (commonly SBP)
- Type 2 HRS - Increase in creatinine is moderate and does not progress over time.
Must R/O non-functional causes (See table)
Poor prognosis (Esp Type 1 - less than a month w/o therapy)
Treatment Notes:
- Dopamine and prostaglandins are ineffective.
- Vasoconstrictor (vasopressins or a-adrenergic agents) + albumin effective in 2/3 of pts.
- Octreotide is ineffective alone, but effective with midodrine.
- Other notes:
  - Recurrence of HRS uncomming when discontinuing these.
  - Treatment of HRS improves survival to transplant and improve renal function before transplant.
  - TIPS: insufficient evidence (some evidence that helps HRS).
  - Hemodialysis: should not be used. Only in select cases to bridge to transplant.

Table of contents

Ascites

Table of contents

Introduction

Undifferentiated Ascites