Ascites Management in Critical Care

Quick Answer Card

ASCITES MANAGEMENT - 60 SECOND SUMMARY

CRITICAL ACTIONS:

• Diagnostic paracentesis within 6 hours of admission
• Do NOT wait for signs of infection - SBP often afebrile
• Albumin prevents hepatorenal syndrome in SBP (NNT = 5)
• Never give nephrotoxic drugs (NSAIDs, aminoglycosides, contrast)
• Early hepatology and transplant team involvement

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CICM Exam Focus

Examination Importance

Ascites and its complications are high-yield CICM Second Part topics appearing regularly in:

What Examiners Expect

Written SAQ:

• Systematic approach to diagnostic paracentesis
• SAAG calculation and interpretation
• SBP diagnostic criteria and antibiotic selection
• Evidence for albumin use (Sort trial, ATTIRE)
• Hepatorenal syndrome recognition and management

Hot Case:

• Integration of multiple organ failures in cirrhosis
• Appreciation of diagnostic uncertainty
• Safe prescription (avoid nephrotoxins)
• Communication with hepatology/transplant teams
• Recognition of futility in appropriate context

Viva:

• Pathophysiology of ascites formation
• Starling forces in portal hypertension
• Peripheral arterial vasodilation hypothesis
• TIPS mechanism and complications
• Albumin pharmacology and evidence base

Common Pitfalls

1. Delaying diagnostic paracentesis - perform within 6 hours
2. Using PMN threshold of 500/mm³ - correct threshold is 250/mm³
3. Omitting albumin in SBP - prevents HRS, reduces mortality
4. Forgetting albumin replacement after LVP - mandatory for >5L
5. Prescribing NSAIDs or aminoglycosides - nephrotoxic in cirrhosis
6. Misinterpreting SAAG in hypoalbuminemic patients - SAAG remains valid

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Key Points

15 Critical Teaching Points

1. Portal hypertension causes 85% of ascites - cirrhosis is the predominant aetiology in developed countries

2. SAAG ≥11 g/L indicates portal hypertension with 97% accuracy regardless of serum albumin level (PMID: 1616215)

3. Diagnostic paracentesis is mandatory on admission for all patients with ascites - delay increases mortality

4. SBP diagnosis requires PMN ≥250/mm³ - do NOT wait for culture; culture-negative SBP is common (40%)

5. Albumin in SBP reduces mortality from 29% to 10% (Sort trial, PMID: 10564098) - NNT = 5

6. Albumin dose in SBP: 1.5 g/kg Day 1 + 1.0 g/kg Day 3 (capped at 150g and 100g)

7. Albumin after LVP: 8g per litre drained when removing >5L (Gines trial, PMID: 3297907)

8. Third-generation cephalosporins are first-line for SBP (ceftriaxone 2g IV daily)

9. Hepatorenal syndrome occurs in 30% of SBP if albumin is omitted - type 1 has 90% mortality

10. Sodium restriction to 80-120 mmol/day is more effective than fluid restriction

11. Spironolactone 100mg + Frusemide 40mg is standard combination (100:40 ratio)

12. Maximum weight loss: 0.5 kg/day without peripheral oedema; 1 kg/day with oedema

13. Refractory ascites affects 10% and mandates TIPS or transplant consideration

14. Abdominal compartment syndrome can occur with tense ascites - IAP monitoring required

15. 50% mortality at 2 years once ascites develops - prognosis drives goals of care discussions

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1. Definition and Epidemiology

1.1 Definition

Ascites is defined as the pathological accumulation of fluid (>25 mL) within the peritoneal cavity. The term derives from the Greek "askos" (wineskin). Clinically detectable ascites requires approximately 1.5L of fluid (PMID: 21995809).

Classification by Volume:

1.2 Aetiology

Portal Hypertensive Causes (SAAG ≥11 g/L):

Non-Portal Hypertensive Causes (SAAG <11 g/L):

1.3 Epidemiology

Global and Australian Statistics:

• Cirrhosis is the 11th leading cause of death globally (1.32 million deaths/year) (PMID: 32192679)
• 50% of patients with compensated cirrhosis develop ascites within 10 years (PMID: 21163913)
• 5-10% develop refractory ascites within 5 years
• Ascites is the most common complication leading to hospitalisation in cirrhosis

Australian-Specific Data:

• 7,000+ hospitalisations annually for cirrhosis-related ascites (AIHW 2022)
• Aboriginal and Torres Strait Islander peoples have 2-3× higher rates of chronic liver disease
• Alcohol-related liver disease remains the leading cause (40%)
• Non-alcoholic fatty liver disease (NAFLD) rapidly increasing (25-30%)
• Hepatitis B prevalent in migrant populations; Hepatitis C in IV drug users

ICU Admission Patterns:

1.4 Prognosis

Mortality by Stage:

MELD Score (Model for End-Stage Liver Disease) predicts 90-day mortality and determines transplant priority:

MELD = 3.78 \times \ln(Bilirubin) + 11.2 \times \ln(INR) + 9.57 \times \ln(Creatinine) + 6.43

(Bilirubin and Creatinine in mg/dL; minimum values 1.0; maximum Creatinine 4.0)

MELD-Na incorporates sodium (more accurate):

• MELD-Na = MELD + 1.32 × (137 - Na) - [0.033 × MELD × (137 - Na)]
• Na range 125-137 mEq/L

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2. Applied Basic Sciences

2.1 Portal Circulation Anatomy

Normal Portal System:

The portal venous system drains blood from the gastrointestinal tract, spleen, pancreas, and gallbladder to the liver. Key anatomical features:

Porto-Systemic Anastomoses (Collaterals):

2.2 Physiology

Starling Forces in Ascites Formation

Normal peritoneal fluid dynamics follow Starling's equation:

J_v = K_f [(P_c - P_i) - \sigma(\pi_c - \pi_i)]

Where:

• Jv = Net fluid flux
• Kf = Filtration coefficient
• Pc = Capillary hydrostatic pressure
• Pi = Interstitial hydrostatic pressure
• σ = Reflection coefficient
• πc = Capillary oncotic pressure
• πi = Interstitial oncotic pressure

In Cirrhosis with Portal Hypertension:

Portal Hypertension Threshold:

• Normal portal pressure: 5-10 mmHg
• Clinically significant portal hypertension: HVPG ≥10 mmHg
• Variceal bleeding risk: HVPG ≥12 mmHg
• Ascites threshold: HVPG ≥12 mmHg with sodium retention

Hepatic Venous Pressure Gradient (HVPG):

HVPG = WHVP - FHVP

• WHVP = Wedged hepatic venous pressure
• FHVP = Free hepatic venous pressure

2.3 Pathophysiology

Peripheral Arterial Vasodilation Hypothesis

The most widely accepted model for ascites formation in cirrhosis (PMID: 8577395):

Stage 1: Compensated Cirrhosis

1. Portal hypertension develops (HVPG ≥10 mmHg)
2. Splanchnic vasodilation occurs (NO, prostacyclin, endocannabinoids)
3. Effective arterial blood volume (EABV) decreases
4. Mild sodium retention compensates (asymptomatic)

Stage 2: Ascites Formation

1. Progressive splanchnic vasodilation
2. EABV falls further
3. Baroreceptor-mediated activation of:
   • Renin-angiotensin-aldosterone system (RAAS)
   • Sympathetic nervous system (SNS)
   • Antidiuretic hormone (ADH/vasopressin)
4. Renal sodium and water retention
5. Ascites accumulates

Stage 3: Refractory Ascites

1. Maximal neurohormonal activation
2. Peripheral vasoconstriction (skin, muscle, kidneys)
3. Renal vasoconstriction → reduced GFR
4. Diuretic resistance
5. Risk of hepatorenal syndrome

Stage 4: Hepatorenal Syndrome

1. Extreme renal vasoconstriction
2. Near-anuria despite adequate intravascular volume
3. Low urinary sodium (<10 mmol/L)
4. Functional renal failure (kidneys structurally normal)

Molecular Mediators

Vasodilators (Splanchnic):

Vasoconstrictors (Systemic/Renal):

2.4 Pharmacology

2.4.1 Diuretics

Spironolactone:

Frusemide (Furosemide):

Combination Therapy Rationale:

• Spironolactone:Frusemide = 100:40 ratio maintains potassium balance (PMID: 8136287)
• Spironolactone alone effective in 90% of patients
• Add frusemide if inadequate response or hyperkalaemia concerns

2.4.2 Albumin

Human Albumin Solution (HAS):

Mechanisms of Action:

1. Oncotic pressure maintenance - binds water, expands plasma volume
2. Binding and transport - drugs, bilirubin, fatty acids
3. Antioxidant - scavenges reactive oxygen species
4. Anti-inflammatory - binds LPS, prostaglandins
5. Endothelial stabilisation - reduces capillary leak
6. Immunomodulation - reduces inflammatory cytokines (PMID: 22521350)

Evidence for Albumin:

2.4.3 Vasoconstrictors

Terlipressin:

Noradrenaline (Norepinephrine):

Midodrine:

Octreotide:

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3. Clinical Assessment

3.1 History

Key Historical Features in ICU Setting:

Precipitants of Decompensation:

3.2 Physical Examination

Inspection:

Palpation:

Percussion:

Auscultation:

• Absent bowel sounds → ileus, SBP
• High-pitched sounds → obstruction
• Hepatic bruit → hepatocellular carcinoma, alcoholic hepatitis

3.3 Grading of Ascites

International Ascites Club Classification:

3.4 ICU-Specific Assessment

Abdominal Compartment Syndrome Screening:

Tense ascites can cause intra-abdominal hypertension (IAH):

Abdominal Compartment Syndrome (ACS):

• Definition: IAP >20 mmHg + new organ failure
• Management: Urgent paracentesis (therapeutic)
• Measurement: Bladder pressure (Foley transduction)

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4. Investigations

4.1 Diagnostic Paracentesis

MANDATORY for all patients with:

• New-onset ascites
• Hospital admission with known ascites
• Clinical deterioration
• Symptoms/signs suggesting SBP

Timing: Within 6 hours of admission (delays increase mortality) (PMID: 23478873)

Contraindications (Relative):

• Coagulopathy is NOT a contraindication (PMID: 2649988)
• DIC (severe) - correct if possible
• Massive ileus with dilated bowel - use ultrasound guidance
• Skin infection at puncture site - alternative site

Technique:

Safety Data:

• Bleeding complications: <1% even with INR >1.5 (PMID: 2649988)
• No need for routine FFP/platelet transfusion
• Ascitic leak: 5% (reduced with Z-track technique)

4.2 Ascitic Fluid Analysis

SAAG Calculation (Serum-Ascites Albumin Gradient):

SAAG = Serum\:Albumin - Ascitic\:Albumin

SAAG Accuracy: 97% for identifying portal hypertension (PMID: 1616215)

Standard Ascitic Fluid Tests:

4.3 Spontaneous Bacterial Peritonitis

Diagnostic Criteria:

Culture-Negative Neutrocytic Ascites (CNNA):

• PMN ≥250/mm³ + Negative culture
• Treat as SBP (40% of cases)
• Same pathogens, same mortality

Monomicrobial Non-Neutrocytic Bacterascites:

• Positive culture + PMN <250/mm³
• Repeat paracentesis in 48 hours
• Treat if symptomatic or PMN rises

Microbiology of SBP:

Secondary Peritonitis Red Flags:

Runyon's Criteria for Secondary Peritonitis: At least 2 of:

1. Total protein >10 g/L
2. Glucose <2.8 mmol/L (50 mg/dL)
3. LDH > upper limit of normal for serum

If ≥2 criteria → CT abdomen, surgical consultation

4.4 Laboratory Investigations

Standard ICU Panel:

Specific Tests:

4.5 Imaging

Ultrasound (First-Line):

CT Abdomen:

MRI/MRCP:

• Biliary assessment
• HCC characterisation
• Hepatic/portal vein assessment

Echocardiography:

• Cardiac ascites (elevated RAP, TR, dilated IVC)
• Constrictive pericarditis
• Cirrhotic cardiomyopathy

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5. ICU Management

5.1 Initial Resuscitation

Airway and Breathing:

• Tense ascites causes diaphragmatic splinting
• Reduced FRC, atelectasis, hypoxaemia
• Consider early paracentesis if respiratory compromise
• Avoid intubation if possible (high mortality in decompensated cirrhosis)
• If intubated: lung-protective ventilation, avoid high PEEP

Circulation:

• Avoid aggressive fluid resuscitation (iatrogenic volume overload)
• Target MAP 65 mmHg (may need vasopressors)
• Vasopressin preferred in vasodilatory shock (splanchnic vasoconstriction)
• Albumin for volume if needed (not crystalloid in large volumes)
• Avoid lactated Ringer's (lactate metabolism impaired)

5.2 Fluid and Electrolyte Management

Sodium Restriction:

Hyponatraemia Management:

Key Principles:

• Hyponatraemia in cirrhosis is DILUTIONAL (excess water, not sodium loss)
• Water restriction is logical but poorly tolerated
• Vaptans (V2 receptor antagonists) can raise sodium but no mortality benefit
• Overly rapid correction → osmotic demyelination syndrome (ODS)

5.3 Large Volume Paracentesis (LVP)

Indications:

• Tense (Grade 3) ascites
• Respiratory compromise
• Abdominal compartment syndrome
• Patient comfort
• Refractory ascites

Contraindications:

• Clinically evident DIC (relative)
• Skin infection at puncture site

Coagulopathy:

• INR and platelets are NOT contraindications
• Do NOT routinely give FFP or platelets (PMID: 2649988)
• Exception: DIC with active bleeding

Technique:

Post-Paracentesis Circulatory Dysfunction (PPCD):

Albumin Replacement Evidence (Gines 1988):

Reference: PMID: 3297907

5.4 Diuretic Therapy

First-Line: Spironolactone + Frusemide

Monitoring:

• Weight daily
• Abdominal girth (unreliable)
• Serum sodium, potassium, creatinine
• Encephalopathy (diuretics can precipitate)

Dose Adjustment Triggers:

Diuretic Failure Criteria:

• Weight loss <2 kg/week despite maximal diuretics
• Recurrence of grade 2-3 ascites within 4 weeks
• Diuretic-induced complications precluding adequate doses

5.5 Refractory Ascites

Definition (International Ascites Club):

1. Diuretic-resistant - Ascites that cannot be mobilised despite maximal diuretics (spironolactone 400 mg + frusemide 160 mg daily) AND sodium restriction for ≥1 week
2. Diuretic-intractable - Ascites where complications preclude effective diuretic doses

Management Options:

Transjugular Intrahepatic Portosystemic Shunt (TIPS):

TIPS Evidence:

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6. Spontaneous Bacterial Peritonitis

6.1 Pathophysiology

Bacterial Translocation:

• Intestinal bacterial overgrowth in cirrhosis
• Increased intestinal permeability
• Impaired local immunity (reduced IgA)
• Gut bacteria translocate to mesenteric lymph nodes
• Bacteraemia seeds ascites
• Reduced opsonic activity in ascitic fluid (low protein)

Risk Factors:

6.2 Clinical Presentation

Symptoms:

CRITICAL: SBP can be asymptomatic - always perform diagnostic paracentesis

6.3 Diagnosis

Diagnostic Criteria:

PMN Calculation:

PMN = WCC \times \%\:Neutrophils

Example: WCC 500/mm³, 60% neutrophils → PMN = 300/mm³ → SBP

6.4 Empiric Antibiotics

Australian Guidelines (eTG Complete):

Notes:

• Third-generation cephalosporins are first-line (EASL guidelines) (PMID: 29628281)
• Quinolone monotherapy no longer recommended (resistance 20-50%)
• Aminoglycosides CONTRAINDICATED (nephrotoxicity in cirrhosis)
• Adjust for local resistance patterns

Treatment Response:

• Repeat paracentesis at 48 hours
• PMN should decrease by ≥25%
• If not responding: broaden antibiotics, exclude secondary peritonitis

6.5 Albumin Administration in SBP

The Sort Trial (1999):

Reference: PMID: 10564098

Dosing Protocol:

Who Benefits Most:

• Bilirubin >68 μmol/L (4 mg/dL)
• Creatinine >88 μmol/L (1 mg/dL)
• High-risk patients have 87% mortality reduction with albumin

ATTIRE Trial (2021):

• Targeted albumin infusion to maintain serum albumin >30 g/L
• 777 patients hospitalised with decompensated cirrhosis
• NO benefit in infection, AKI, or mortality
• Mean additional albumin: 140g in intervention vs 20g in control
• Interpretation: Targeted replacement NOT beneficial; specific indications (SBP, LVP) remain valid

Reference: PMID: 34010611

6.6 Prophylaxis

Primary Prophylaxis:

Criteria for Low Protein Primary Prophylaxis:

• Ascitic protein <15 g/L PLUS one of:
  • Creatinine ≥106 μmol/L (1.2 mg/dL)
  • BUN ≥25 mg/dL (8.9 mmol/L)
  • Sodium ≤130 mmol/L
  • Child-Pugh score ≥9 with bilirubin ≥51 μmol/L (3 mg/dL)

Secondary Prophylaxis (After SBP Episode):

Recurrence Without Prophylaxis: 70% at 1 year Recurrence With Prophylaxis: 20% at 1 year

Reference: PMID: 18335395

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7. Complications

7.1 Hepatorenal Syndrome

Definition (International Club of Ascites 2015):

Acute kidney injury in cirrhosis characterised by:

• Cirrhosis with ascites
• AKI as per AKIN/KDIGO criteria
• No response to 2 days of diuretic withdrawal + albumin 1 g/kg/day (max 100g/day)
• Absence of shock
• No nephrotoxic drugs
• No structural kidney disease (proteinuria <0.5 g/day, normal ultrasound)

Classification:

Pathophysiology:

• Extreme renal vasoconstriction
• Maximal RAAS, SNS, ADH activation
• Very low urinary sodium (<10 mmol/L)
• Kidneys structurally normal (successful post-transplant function)

Management:

Vasoconstrictor Therapy:

Duration: Continue until creatinine <133 μmol/L (1.5 mg/dL) or 14 days if no response

Reference: PMID: 28029949 (ICA-AKI criteria)

7.2 Respiratory Compromise

Mechanisms:

• Diaphragmatic splinting
• Reduced FRC
• V/Q mismatch
• Hepatic hydrothorax (right-sided in 85%)
• Hepatopulmonary syndrome
• Portopulmonary hypertension

Management:

• Large volume paracentesis (immediate relief)
• Thoracentesis for hepatic hydrothorax (recurs rapidly)
• Non-invasive ventilation if needed
• Avoid intubation if possible (high mortality)

7.3 Abdominal Compartment Syndrome

Definition: IAP >20 mmHg + new organ dysfunction

In Ascites:

• Tense ascites raises IAP
• Organ effects: oliguria, splanchnic ischaemia, elevated airway pressures
• Threshold for paracentesis: IAP >15 mmHg with symptoms

Management:

• Urgent therapeutic paracentesis
• Drain sufficient volume to normalise IAP
• Bladder pressure monitoring
• May need repeat paracentesis

7.4 Hepatic Encephalopathy

Precipitants in ICU:

• Infection (including SBP)
• GI bleeding
• Diuretics (hypokalaemia, alkalosis)
• Constipation
• Sedatives (especially benzodiazepines)
• Hypoglycaemia

Management:

• Identify and treat precipitant
• Lactulose (target 2-3 soft stools/day)
• Rifaximin 550 mg BD (if recurrent)
• Protein restriction NOT recommended (maintain 1.2-1.5 g/kg/day)
• Avoid sedatives (especially benzodiazepines, opioids)

7.5 Bleeding

Coagulopathy of Liver Disease:

• Decreased synthesis of procoagulants (II, VII, IX, X)
• Decreased anticoagulants (Protein C, S, antithrombin)
• Low platelets (splenic sequestration)
• Balanced haemostasis (not "auto-anticoagulated")

Management:

• Paracentesis safe despite coagulopathy
• INR does NOT predict bleeding risk
• Do NOT routinely correct before procedures
• Transfuse only for active bleeding

7.6 Malnutrition

Prevalence: 50-90% of cirrhotics

Consequences:

• Sarcopenia (muscle wasting)
• Immune dysfunction
• Impaired wound healing
• Increased mortality

Nutrition in ICU:

• High protein: 1.2-1.5 g/kg/day (no restriction)
• Adequate calories: 35-40 kcal/kg/day
• Enteral preferred over parenteral
• Late evening snack (prevents overnight catabolism)
• BCAA supplementation may help (evidence weak)

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8. Monitoring

8.1 Clinical Monitoring

8.2 Laboratory Monitoring

8.3 Scoring Systems

Child-Pugh Score:

MELD Score:

• Used for transplant prioritisation
• Predicts 90-day mortality
• Calculator: https://optn.transplant.hrsa.gov/resources/allocation-calculators/meld-calculator/

CLIF-SOFA:

• Chronic Liver Failure-SOFA score
• Assesses acute-on-chronic liver failure (ACLF)
• Organ failures defined: liver, kidney, brain, coagulation, circulation, respiration

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9. Special Populations

9.1 Cardiac Ascites

Aetiology:

• Right heart failure
• Constrictive pericarditis
• Tricuspid regurgitation
• Restrictive cardiomyopathy

Features:

• SAAG ≥11 g/L (portal hypertension from congestion)
• High ascitic protein (>25 g/L) - distinguishes from cirrhosis
• Elevated JVP, peripheral oedema
• Hepatomegaly (pulsatile in TR)

Management:

• Treat underlying cardiac disease
• Diuretics (careful with RV preload)
• Sodium restriction
• Paracentesis if symptomatic

9.2 Malignant Ascites

Aetiology:

• Peritoneal carcinomatosis (ovarian, GI, breast)
• Hepatic metastases with portal hypertension
• Chylous ascites from lymphatic obstruction

Features:

• SAAG <11 g/L (usually)
• High protein ascites (>25 g/L)
• Positive cytology (sensitivity 60-90%)
• CT findings: omental caking, nodules

Management:

• Treat underlying malignancy (if possible)
• Paracentesis for symptoms (do NOT need albumin)
• Consider indwelling catheter (PleurX/Rocket)
• Diuretics often ineffective
• VEGF inhibitors (bevacizumab) in ovarian cancer

9.3 Chylous Ascites

Aetiology:

• Lymphatic obstruction (malignancy, surgery)
• Lymphangiectasia
• Trauma (including surgical)
• Cirrhosis with thoracic duct obstruction

Features:

• Milky appearance
• Triglycerides >2.3 mmol/L (200 mg/dL)
• High lymphocyte count

Management:

• Treat underlying cause
• Low-fat diet, MCT supplementation
• TPN if severe
• Octreotide (reduces lymphatic flow)
• Surgical intervention in refractory cases

9.4 Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples:

Culturally Safe Practice:

• Involve Aboriginal Health Workers (AHWs) or Aboriginal Liaison Officers (ALOs)
• Allow extended family at bedside
• Respect traditional healing alongside Western medicine
• Use interpreters (not family members for medical discussions)
• Understand "Sorry Business" and cultural obligations
• Discuss Return to Country if appropriate
• Acknowledge historical trauma and institutional distrust

Māori Health (New Zealand):

9.5 Paediatric Considerations

Aetiology (Different from Adults):

• Biliary atresia
• Portal vein thrombosis
• Hepatic fibrosis
• Budd-Chiari syndrome
• Metabolic liver diseases

Management Principles:

• Similar to adults but dose adjustments
• Involve paediatric hepatology/PICU
• Growth and nutrition critical
• Early transplant referral

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10. Progressive Clinical Assessments

Tier 1: Foundation Knowledge (Medical Student/Junior Resident)

Case 1: A 52-year-old man with known alcohol-related cirrhosis presents with increasing abdominal distension over 2 weeks. He has moderate ascites and bilateral pitting oedema to mid-thigh.

Questions:

1. What is the most important investigation to perform on admission?
2. How is SAAG calculated and what does it indicate?
3. What is the initial diuretic regimen for new-onset ascites?

Answers:

1. Diagnostic paracentesis - mandatory for all admissions with ascites to exclude SBP
2. SAAG = Serum albumin - Ascitic albumin; ≥11 g/L indicates portal hypertension
3. Spironolactone 100 mg + Frusemide 40 mg daily; sodium restriction 80-120 mmol/day

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Tier 2: Intermediate Complexity (Advanced Trainee)

Case 2: A 58-year-old woman with HCV cirrhosis undergoes diagnostic paracentesis. Results: WCC 800/mm³ (90% neutrophils), protein 12 g/L, culture pending.

Questions:

1. Calculate the PMN count and interpret.
2. What antibiotics would you commence and why?
3. Should albumin be given? If so, what dose?

Answers:

1. PMN = 800 × 0.9 = 720/mm³. Diagnosis: SBP (PMN ≥250/mm³)
2. Ceftriaxone 2g IV daily - third-generation cephalosporin first-line for community-acquired SBP. Covers E. coli, Klebsiella, S. pneumoniae.
3. Yes - albumin 1.5 g/kg on Day 1, 1.0 g/kg on Day 3 (capped at 150g and 100g). Reduces HRS incidence from 33% to 10% and mortality from 29% to 10% (Sort trial).

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Tier 3: Exam-Level Complexity (Fellowship Candidate)

Case 3: A 62-year-old man with NASH cirrhosis (Child-Pugh C12, MELD 24) is admitted to ICU with SBP (PMN 1200/mm³), hepatic encephalopathy (Grade 3), and oliguria. Creatinine has risen from 90 to 220 μmol/L over 48 hours despite diuretic cessation and albumin 1 g/kg/day × 2 days.

Questions:

1. What is the likely diagnosis for the renal impairment?
2. What is your management plan?
3. Discuss prognosis and goals of care considerations.

Answers:

1. Hepatorenal Syndrome (HRS-AKI) - meets ICA-AKI criteria: cirrhosis with ascites, AKI, no response to diuretic withdrawal + albumin, no shock, no nephrotoxins, likely no structural kidney disease. The SBP is the trigger.

2. Management:

   • Continue antibiotics for SBP (ceftriaxone)
   • Albumin 1.5 g/kg Day 1, 1.0 g/kg Day 3 (if not already given)
   • Vasoconstrictor therapy: Terlipressin 0.5-1 mg Q4-6H + albumin 20-40g/day OR Noradrenaline infusion 0.5-3 mg/h + albumin
   • Target: Creatinine <133 μmol/L or 14 days treatment
   • RRT only as bridge to transplant (not for isolated HRS)
   • Urgent referral to transplant team

3. Prognosis:

   • HRS-AKI with MELD 24 and Child C12: 50-80% mortality without transplant
   • Key considerations:
     • Is patient a transplant candidate? (age, cardiac reserve, social support, nutrition)
     • Reversibility of encephalopathy?
     • Response to vasoconstrictor therapy?
   • Goals of care discussion with family: May be appropriate to discuss ceiling of care if not transplant candidate
   • Involve palliative care early

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11. SAQ Practice

SAQ 1: Spontaneous Bacterial Peritonitis (20 Marks)

Stem: A 56-year-old woman with alcohol-related cirrhosis is admitted with confusion and abdominal discomfort. She has tense ascites. Observations: T 37.8°C, HR 102, BP 95/60, RR 22, SpO2 94% RA.

Ascitic fluid analysis:

• Appearance: Slightly turbid
• WCC: 650/mm³ (85% neutrophils)
• Protein: 8 g/L
• Gram stain: No organisms seen
• Culture: Pending

Questions:

(a) Interpret the ascitic fluid results and state the diagnosis. (4 marks)

(b) Outline your antibiotic management including drug, dose, and duration. (4 marks)

(c) Describe the role of albumin in SBP management, including evidence. (6 marks)

(d) What prophylaxis would you recommend on discharge and why? (4 marks)

(e) List two prognostic indicators for poor outcome in SBP. (2 marks)

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Model Answer:

(a) Interpretation and Diagnosis (4 marks)

PMN calculation: 650 × 0.85 = 552/mm³

Diagnosis: Spontaneous Bacterial Peritonitis (SBP)

• PMN ≥250/mm³ (threshold for diagnosis) ✓
• Low protein ascites (<10 g/L) - low opsonic activity, predisposes to SBP ✓
• No organisms on Gram stain does not exclude SBP (culture positive in only 60%) ✓
• Clinical features consistent: fever, confusion (hepatic encephalopathy from infection) ✓

(b) Antibiotic Management (4 marks)

Additional points:

• Quinolone monotherapy no longer first-line (resistance rates 20-50%)
• Aminoglycosides contraindicated (nephrotoxic in cirrhosis)
• Repeat paracentesis at 48 hours - PMN should decrease by ≥25%

(c) Albumin in SBP (6 marks)

Evidence (Sort Trial, NEJM 1999, PMID 10564098):

• Randomised 126 patients with SBP to antibiotics ± albumin
• Albumin group: 1.5 g/kg Day 1, 1.0 g/kg Day 3

Mechanism:

• Maintains effective arterial blood volume (EABV)
• Prevents renal vasoconstriction
• May have immunomodulatory effects
• Binds endotoxins

Who benefits most:

• Bilirubin >68 μmol/L (4 mg/dL)
• Creatinine >88 μmol/L (1 mg/dL)
• NNT = 5 for HRS prevention

(d) Prophylaxis (4 marks)

Secondary prophylaxis (mandatory after SBP episode):

Evidence: Multiple trials including Gines 1990 (PMID: 2406549), Fernandez 2007 (PMID: 17428562)

(e) Prognostic Indicators (2 marks)

Any two of:

• High baseline bilirubin (>68 μmol/L)
• Elevated creatinine (>88 μmol/L)
• Development of hepatorenal syndrome
• Culture-positive SBP (vs culture-negative)
• Nosocomial acquisition (higher mortality than community-acquired)
• High MELD score
• Encephalopathy at presentation

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SAQ 2: Refractory Ascites Approach (20 Marks)

Stem: A 64-year-old man with HCV cirrhosis has been admitted 4 times in 3 months requiring large volume paracentesis for recurrent tense ascites. He is on maximum diuretics (spironolactone 400 mg, frusemide 160 mg daily) with sodium restriction. His creatinine rises each time diuretics are increased.

Questions:

(a) Define refractory ascites and classify this patient. (4 marks)

(b) Describe the pathophysiology of diuretic resistance in cirrhosis. (4 marks)

(c) Outline the management options for refractory ascites. (6 marks)

(d) Discuss TIPS as a treatment option, including mechanism, contraindications, and complications. (4 marks)

(e) What is the role of liver transplantation? (2 marks)

---

Model Answer:

(a) Definition and Classification (4 marks)

Definition (International Ascites Club):

Refractory ascites is ascites that:

1. Cannot be mobilised or recurs early despite sodium restriction and maximum diuretic therapy

Two subtypes:

This patient: Diuretic-intractable ascites (creatinine rises when diuretics increased)

(b) Pathophysiology of Diuretic Resistance (4 marks)

Progressive vasodilatation and neurohormonal activation:

1. Advanced portal hypertension → severe splanchnic vasodilation
2. Marked reduction in effective arterial blood volume (EABV)
3. Maximal activation of vasoconstrictor systems:
   • RAAS (aldosterone >>>>> spironolactone effect)
   • Sympathetic nervous system
   • ADH (water retention)
4. Intense renal vasoconstriction → reduced GFR → reduced diuretic delivery to tubule
5. Diuretic effect overwhelmed by massive sodium reabsorption
6. Hypoalbuminaemia → reduced diuretic binding in tubule
7. Renal prostaglandin dependence → NSAIDs abolish any residual response

Markers of advanced disease:

• Low serum sodium (<130 mmol/L)
• Rising creatinine despite therapy
• Low urinary sodium despite diuretics

(c) Management Options (6 marks)

This patient's approach:

• TIPS candidate: Child-Pugh B9, MELD 14, no encephalopathy, good performance status
• Simultaneously: Transplant workup and listing

(d) TIPS Discussion (4 marks)

Mechanism:

• Creates shunt between portal vein and hepatic vein via transjugular approach
• Decompresses portal system
• Reduces HVPG to <12 mmHg or ≥50% reduction
• Reduces ascites by decreasing splanchnic pooling and sodium retention

Contraindications:

Complications:

(e) Liver Transplantation (2 marks)

• Definitive treatment for refractory ascites
• Indication: Refractory ascites = poor prognosis (50% survival at 1-2 years)
• MELD score determines waiting list priority
• Assessment: Cardiac, psychosocial, nutritional evaluation
• This patient: Good candidate - abstinent, no encephalopathy, reasonable performance status
• TIPS can serve as bridge to transplant

---

12. Hot Cases

Hot Case 1: Cirrhotic with Tense Ascites and Hypotension

Scenario: You are called to review a 58-year-old man in the ICU. He was admitted 24 hours ago with tense ascites requiring large volume paracentesis (8L removed) yesterday. He received 64g albumin (8g/L). He now has:

Observations:

• HR 115, BP 78/50, MAP 59
• RR 24, SpO2 92% on 6L O₂
• T 37.9°C
• GCS 12 (E3V4M5)
• Jaundice, ascites re-accumulating, asterixis

Available Information:

• Known HCV cirrhosis, Child-Pugh C11
• Diagnostic paracentesis from yesterday: WCC 180/mm³ (60% neutrophils)
• Na 126, K 4.8, Cr 165 (baseline 95), Bili 89, Alb 22
• INR 1.9, Platelets 68

Expected Discussion Points:

1. Assessment Approach

• ABC assessment: Airway patent, breathing (work of breathing, atelectasis), circulation (hypotensive, tachycardic)
• Causes of deterioration:
  • Post-paracentesis circulatory dysfunction (PPCD)
  • Sepsis (SBP, other source)
  • Hepatorenal syndrome
  • Bleeding (variceal, from paracentesis site)
  • Hepatic encephalopathy

2. Immediate Management

• Fluid resuscitation: 20% albumin preferred over crystalloid
• Vasopressors: Noradrenaline (vasopressin may be preferable in cirrhosis)
• Repeat diagnostic paracentesis urgently - PMN may have risen
• Blood cultures, urine MCS
• Calculate MELD: ~24

3. Concerning Features

• PMN yesterday was 108/mm³ - below 250 threshold BUT:
  • Clinical deterioration mandates re-assessment
  • SBP can develop rapidly
  • May have developed SBP since admission
• Creatinine rising (165 from 95) - early HRS?
• Encephalopathy worsening (GCS 12)

4. Antimicrobial Therapy

• If SBP suspected: Ceftriaxone 2g IV + albumin protocol
• If sepsis without SBP: Piperacillin-tazobactam pending cultures
• Add antifungal if not responding

5. Goals of Care

• Child C11, MELD ~24 - transplant candidate?
• If not transplant candidate: Ceiling of care discussion
• Involve hepatology/transplant early
• Family meeting

---

Hot Case 2: SBP with Hepatorenal Syndrome

Scenario: A 62-year-old woman with alcohol-related cirrhosis was admitted 5 days ago with SBP (PMN 650/mm³). She has been receiving ceftriaxone and completed her albumin protocol. She is now anuric.

Observations:

• HR 95, BP 85/55, MAP 65
• RR 20, SpO2 96% 2L
• T 37.2°C
• GCS 14 (confused)
• Moderate ascites, no peripheral oedema

Laboratory:

• Day 1: Cr 95, Na 132, K 4.2, Bili 78, Alb 26
• Day 5: Cr 285, Na 125, K 5.8, Bili 102, Alb 24
• Urine Na: 4 mmol/L
• Repeat paracentesis: WCC 120/mm³ (50% neutrophils) - culture negative

Expected Discussion Points:

1. Diagnosis

• Hepatorenal Syndrome Type 1 (HRS-AKI)
• Diagnostic criteria:
  • Cirrhosis with ascites ✓
  • "AKI: Cr 95 → 285 (200% rise in 5 days) ✓"
  • No response to diuretic withdrawal + albumin ✓
  • No shock (MAP 65) ✓
  • No nephrotoxic drugs ✓
  • Low urine sodium (<10 mmol/L) ✓
  • Likely no structural kidney disease

2. Why HRS Occurred

• SBP is the most common precipitant of HRS
• Albumin was given (reduces but doesn't eliminate risk)
• May have had risk factors: bilirubin >68, creatinine rising

3. Management

• Stop all diuretics (already done)
• Vasoconstrictor therapy:
  • Terlipressin 1 mg Q4-6H + albumin 20-40g/day
  • "Alternative: Noradrenaline 0.5-3 mg/h + albumin"
• Target: Cr <133 μmol/L or 14 days
• Treat hyperkalaemia (K 5.8)
• Consider RRT only as bridge to transplant (not for isolated HRS)

4. Prognosis

• HRS-AKI: 50-80% mortality in 2 weeks without transplant
• Even with terlipressin: 40-50% complete response
• Recurrence common after stopping therapy
• Transplant is definitive treatment

5. Transplant Discussion

• Is patient listed?
• Emergency listing (MELD likely >30 with Cr 285)
• If not candidate: Palliative approach may be appropriate
• Family meeting: Realistic expectations

---

13. Viva Scenarios

Viva 1: SAAG Interpretation

Opening Question: "A patient with ascites has SAAG calculated at 15 g/L. What does this tell you?"

Expected Answer: SAAG ≥11 g/L indicates portal hypertension with 97% accuracy. This includes cirrhosis (most common), cardiac failure, Budd-Chiari syndrome, and sinusoidal obstruction syndrome.

Follow-up Questions:

Q: "How does SAAG work physiologically?" A: SAAG reflects the oncotic pressure gradient across the peritoneal membrane. In portal hypertension, high sinusoidal pressure forces protein-poor fluid into the peritoneum, maintaining a high albumin gradient. The 11 g/L threshold corresponds to portal pressure >12 mmHg.

Q: "What if the serum albumin is 18 g/L?" A: SAAG remains valid even in severe hypoalbuminaemia. The gradient is maintained by the relative difference, not absolute values. A patient with serum albumin 18 g/L and ascitic albumin 5 g/L still has SAAG 13 g/L = portal hypertension.

Q: "What causes SAAG <11 g/L?" A: Non-portal hypertensive causes:

• Peritoneal carcinomatosis
• Tuberculous peritonitis
• Pancreatic ascites
• Nephrotic syndrome
• Serositis (SLE, etc.)

---

Viva 2: Albumin Use in Liver Disease

Opening Question: "Tell me about the evidence for albumin use in cirrhosis."

Expected Answer: Evidence supports albumin in specific indications:

1. SBP (Sort trial, PMID 10564098): 1.5 g/kg D1 + 1.0 g/kg D3 reduces HRS (33%→10%) and mortality (29%→10%)

2. Large volume paracentesis (Gines trial, PMID 3297907): 8g per litre removed (if >5L) prevents post-paracentesis circulatory dysfunction

3. Hepatorenal syndrome (with vasoconstrictors): Component of therapy with terlipressin/noradrenaline

Follow-up Questions:

Q: "What about the ATTIRE trial?" A: ATTIRE (NEJM 2021, PMID 34010611) randomised 777 hospitalised cirrhotics to targeted albumin infusion (maintain albumin >30 g/L) vs standard care. No benefit in infection, AKI, or mortality. Mean additional albumin 140g vs 20g. Interpretation: Routine albumin replacement NOT beneficial; specific indications remain valid.

Q: "What is the mechanism of albumin benefit?" A: Multiple mechanisms:

• Oncotic: Expands plasma volume, maintains EABV
• Binding: Drugs, bilirubin, toxins
• Antioxidant: Scavenges reactive oxygen species
• Anti-inflammatory: Binds LPS, reduces cytokines
• Endothelial: Stabilises capillary barrier

Q: "Do you give 4% or 20% albumin?" A: Either can be used to achieve required dose. 20% is hyper-oncotic (draws fluid into intravascular space). For SBP doses (1.5 g/kg, 1.0 g/kg), 20% albumin is practical (smaller volume). For LVP (8g/L), 20% is standard.

---

Viva 3: TIPS Indications and Complications

Opening Question: "When would you consider TIPS for a patient with cirrhosis?"

Expected Answer: Indications:

1. Refractory ascites (most common)
2. Recurrent variceal bleeding despite optimal medical/endoscopic therapy
3. Hepatic hydrothorax (refractory)
4. Budd-Chiari syndrome

Follow-up Questions:

Q: "What are the contraindications?" A: Absolute:

• Severe hepatic encephalopathy (Grade 3-4)
• Congestive heart failure (increased preload)
• Severe pulmonary hypertension
• Active systemic infection
• Polycystic liver disease

Relative:

• Child-Pugh >12 (high mortality)
• MELD >18 (increased mortality)
• Portal vein thrombosis (technical challenge)
• Previous encephalopathy

Q: "What complications would you warn about?" A: Encephalopathy: 30-50% - most common, manageable with lactulose/rifaximin Shunt dysfunction: 20-30%/year (bare metal), 10-15%/year (covered stents) Cardiac effects: Increased preload → heart failure in those with borderline function Haemolysis: 5-10%, usually mild

Q: "How does TIPS improve ascites?" A: Creates low-resistance pathway between portal and systemic circulation. Reduces portal pressure (target HVPG <12 mmHg or ≥50% reduction). Decreases splanchnic pooling, reduces RAAS/SNS activation, improves renal sodium handling.

---

Viva 4: Large Volume Paracentesis Technique

Opening Question: "Take me through how you would perform a large volume paracentesis."

Expected Answer: Preparation:

• Consent, coagulation check (NOT a contraindication to proceed)
• Bladder empty
• Position: Supine, slight left lateral tilt

Site:

• Left lower quadrant, 2-3 cm cephalad and medial to ASIS
• Avoids inferior epigastric artery (runs in rectus sheath)
• Ultrasound to confirm fluid, mark site

Technique:

• Sterile preparation, drape
• Local anaesthetic (lidocaine 1-2%) to skin and peritoneum
• Z-track technique: Insert perpendicular, then angle catheter
• Use paracentesis catheter (15-17G) or Bonanno catheter
• Connect to drainage bag (negative pressure)
• Drain to completion (can remove >10L)

Post-procedure:

• Albumin replacement: 8g per litre removed (if >5L)
• Monitor for hypotension
• Site: Small dressing, usually no suture
• Document: Volume, appearance, samples sent

Follow-up Questions:

Q: "What about coagulopathy?" A: Coagulopathy is NOT a contraindication. Studies show bleeding complications <1% even with INR >1.5 (PMID 2649988). Do NOT routinely give FFP or platelets. Exception: Active DIC with bleeding.

Q: "Why albumin and what dose?" A: Albumin prevents post-paracentesis circulatory dysfunction (PPCD) - defined as ≥50% rise in plasma renin activity at Day 6. Without albumin: 75% develop PPCD. With albumin (8g/L): <20%. PPCD associated with faster reaccumulation, HRS, death.

---

Viva 5: Hepatorenal Syndrome Management

Opening Question: "A patient with cirrhosis and SBP develops oliguria and rising creatinine despite albumin. What is your approach?"

Expected Answer: Suspect hepatorenal syndrome (HRS-AKI).

Confirm diagnosis (ICA-AKI criteria):

• Cirrhosis with ascites ✓
• AKI criteria met (≥26.5 μmol/L in 48h OR ≥50% rise in 7 days)
• No response to diuretic withdrawal + albumin 1 g/kg/day × 2 days
• No shock
• No nephrotoxic drugs
• No structural kidney disease

Follow-up Questions:

Q: "What treatment would you give?" A: Vasoconstrictor + albumin:

• Terlipressin 0.5-1 mg Q4-6H (escalate to max 2 mg Q4H if no response)
• OR Noradrenaline 0.5-3 mg/h (similar efficacy, continuous infusion)
• PLUS albumin 20-40 g/day
• Duration: Until Cr <133 μmol/L or 14 days
• Monitor for ischaemia (cardiac, digital, gut)

Q: "What about dialysis?" A: RRT for HRS is only indicated as bridge to transplant. Without transplant, RRT does not change outcome - kidneys are functionally impaired, not structurally damaged. RRT has high complication rate in cirrhosis (bleeding, hypotension).

Q: "What is the prognosis?" A: Poor without transplant:

• HRS-AKI: 50-80% mortality in 2 weeks
• Vasoconstrictor response: 40-60%
• Even with response, recurrence common after stopping therapy
• Transplant is definitive treatment (kidneys recover post-transplant)

---

Viva 6: End-of-Life Considerations in Cirrhosis

Opening Question: "A 68-year-old with decompensated cirrhosis, recurrent SBP episodes, and HRS is not a transplant candidate. How do you approach goals of care?"

Expected Answer: Recognise terminal trajectory:

• MELD >30, Child C, recurrent complications
• Not transplant candidate = median survival weeks to months
• HRS without transplant: Very poor prognosis

Communication approach:

• Family meeting with multidisciplinary team
• Assess patient/family understanding of prognosis
• Explore values, wishes, cultural considerations
• Discuss ceiling of care (ICU admission, intubation, RRT)
• Introduce palliative care

Follow-up Questions:

Q: "What specific management for symptom control?" A:

• Ascites discomfort: Therapeutic paracentesis for comfort (do NOT need albumin for palliation)
• Pain: Cautious opioids (start low, increase slowly; fentanyl preferred)
• Encephalopathy/agitation: Lactulose, haloperidol if needed
• Pruritus: Cholestyramine, rifampicin, naltrexone
• Nausea: Metoclopramide, ondansetron
• Dyspnoea: Paracentesis, low-dose opioids, oxygen for comfort

Q: "Any cultural considerations?" A:

• Aboriginal and Torres Strait Islander: Return to Country, family involvement, AHW/ALO
• Māori: Whānau, kaumātua, tikanga
• Many cultures: Extended family decision-making, spiritual needs
• Interpreter services for complex discussions

Q: "How do you approach stopping active treatment?" A:

• Honest, compassionate discussion about prognosis
• Focus on comfort rather than "withdrawing"
• Ensure symptom management plan in place
• Allow family time, cultural rituals
• Consider ICU palliative pathway if already in ICU

---

14. Interactive Elements

14.1 SBP Diagnostic Algorithm

ASCITES ON ADMISSION
        │
        ▼
┌─────────────────────────────────┐
│ DIAGNOSTIC PARACENTESIS         │
│ (Within 6 hours of admission)   │
└─────────────────────────────────┘
        │
        ▼
┌─────────────────────────────────┐
│ Calculate PMN Count             │
│ PMN = WCC × % Neutrophils       │
└─────────────────────────────────┘
        │
        ▼
┌───────────────────────────────────────────────────┐
│                PMN ≥ 250/mm³?                      │
└───────────────────────────────────────────────────┘
        │                       │
       YES                      NO
        │                       │
        ▼                       ▼
┌─────────────────┐    ┌────────────────────────────┐
│ SBP DIAGNOSIS   │    │ Culture pending            │
│                 │    │                            │
│ Start empiric   │    │ If culture +ve & symptoms  │
│ antibiotics     │    │ = Bacterascites           │
│ (Ceftriaxone)   │    │ Repeat tap, consider Abx   │
│                 │    │                            │
│ Albumin         │    │ If culture -ve & PMN <250  │
│ 1.5g/kg Day 1   │    │ = No SBP                   │
│ 1.0g/kg Day 3   │    │ Treat underlying cause     │
└─────────────────┘    └────────────────────────────┘
        │
        ▼
┌─────────────────────────────────┐
│ REPEAT PARACENTESIS 48 HOURS    │
│ PMN should decrease ≥25%        │
└─────────────────────────────────┘
        │
        ▼
┌────────────────────────────────────────────────────┐
│               PMN decreasing ≥25%?                  │
└────────────────────────────────────────────────────┘
        │                       │
       YES                      NO
        │                       │
        ▼                       ▼
┌─────────────────┐    ┌────────────────────────────┐
│ Continue Abx    │    │ TREATMENT FAILURE          │
│ for 5 days      │    │                            │
│                 │    │ - Broaden antibiotics      │
│ Consider        │    │ - Exclude secondary        │
│ secondary       │    │   peritonitis (CT)         │
│ prophylaxis     │    │ - Consider fungal          │
└─────────────────┘    └────────────────────────────┘

14.2 Ascites Management Flowchart

ASCITES ASSESSMENT
        │
        ▼
┌────────────────────────────────────────────────────┐
│ CALCULATE SAAG = Serum Albumin - Ascitic Albumin   │
└────────────────────────────────────────────────────┘
        │
        ▼
┌────────────────────────────────────────────────────┐
│                   SAAG ≥ 11 g/L?                    │
└────────────────────────────────────────────────────┘
        │                       │
       YES                      NO
        │                       │
        ▼                       ▼
┌─────────────────┐    ┌────────────────────────────┐
│ PORTAL          │    │ NON-PORTAL HYPERTENSION    │
│ HYPERTENSION    │    │                            │
│                 │    │ - Malignancy               │
│ - Cirrhosis     │    │ - TB peritonitis           │
│ - Cardiac       │    │ - Pancreatitis             │
│ - Budd-Chiari   │    │ - Nephrotic syndrome       │
└─────────────────┘    └────────────────────────────┘
        │
        ▼
┌─────────────────────────────────────────────────────┐
│ INITIAL MANAGEMENT                                   │
│                                                      │
│ 1. Sodium restriction 80-120 mmol/day                │
│ 2. Spironolactone 100mg + Frusemide 40mg daily       │
│ 3. Weight daily, target 0.5-1 kg/day loss            │
│ 4. Monitor Na, K, Cr                                 │
└─────────────────────────────────────────────────────┘
        │
        ▼
┌────────────────────────────────────────────────────┐
│               RESPONDING TO DIURETICS?              │
└────────────────────────────────────────────────────┘
        │                       │
       YES                      NO
        │                       │
        ▼                       ▼
┌─────────────────┐    ┌────────────────────────────┐
│ Continue        │    │ ESCALATE DIURETICS         │
│ current regimen │    │ (100:40 ratio maintained)  │
│                 │    │ Spiro 400mg : Furo 160mg   │
│ Outpatient      │    │                            │
│ follow-up       │    │ Still not responding?      │
└─────────────────┘    │           │                │
                       │           ▼                │
                       │ ┌────────────────────────┐ │
                       │ │ REFRACTORY ASCITES     │ │
                       │ │                        │ │
                       │ │ Options:               │ │
                       │ │ - Serial LVP           │ │
                       │ │ - TIPS                 │ │
                       │ │ - Liver transplant     │ │
                       │ └────────────────────────┘ │
                       └────────────────────────────┘

14.3 Hepatorenal Syndrome Algorithm

AKI IN CIRRHOSIS WITH ASCITES
        │
        ▼
┌─────────────────────────────────────────────────────┐
│ STEP 1: EXCLUDE OTHER CAUSES                         │
│                                                      │
│ - Hypovolaemia (bleeding, diarrhoea)                 │
│ - Nephrotoxic drugs (NSAIDs, aminoglycosides, ACEi)  │
│ - Structural disease (proteinuria, abnormal US)      │
│ - Shock (MAP <60, lactate elevated)                  │
│ - Obstruction (hydronephrosis)                       │
└─────────────────────────────────────────────────────┘
        │
        ▼
┌─────────────────────────────────────────────────────┐
│ STEP 2: INITIAL MANAGEMENT                           │
│                                                      │
│ - Stop diuretics                                     │
│ - Stop nephrotoxins                                  │
│ - Albumin challenge: 1 g/kg/day × 2 days (max 100g)  │
└─────────────────────────────────────────────────────┘
        │
        ▼
┌────────────────────────────────────────────────────┐
│            CREATININE IMPROVING?                    │
└────────────────────────────────────────────────────┘
        │                       │
       YES                      NO
        │                       │
        ▼                       ▼
┌─────────────────┐    ┌────────────────────────────┐
│ Pre-renal AKI   │    │ HEPATORENAL SYNDROME       │
│ (hypovolaemia)  │    │                            │
│                 │    │ Diagnostic criteria:       │
│ Continue        │    │ ✓ Cirrhosis + ascites      │
│ supportive care │    │ ✓ AKI criteria met         │
│                 │    │ ✓ No response to albumin   │
│ Identify cause  │    │ ✓ No shock                 │
│ (e.g., sepsis)  │    │ ✓ No nephrotoxins          │
└─────────────────┘    │ ✓ No structural disease    │
                       └────────────────────────────┘
                               │
                               ▼
               ┌───────────────────────────────────┐
               │ VASOCONSTRICTOR THERAPY            │
               │                                    │
               │ Terlipressin 1mg Q4-6H             │
               │ OR Noradrenaline 0.5-3 mg/h        │
               │                                    │
               │ PLUS Albumin 20-40g/day            │
               │                                    │
               │ Target: Cr <133 μmol/L             │
               │ Duration: Max 14 days              │
               │                                    │
               │ Monitor: Ischaemia (cardiac, gut)  │
               └───────────────────────────────────┘
                               │
                               ▼
               ┌───────────────────────────────────┐
               │ TRANSPLANT EVALUATION             │
               │                                   │
               │ HRS is indication for emergency   │
               │ transplant listing                │
               │                                   │
               │ RRT only as bridge to transplant  │
               └───────────────────────────────────┘

---

---

16. References

Landmark Trials

1. Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairment and mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl J Med. 1999;341(6):403-409. PMID: 10564098

2. Gines P, Tito L, Arroyo V, et al. Randomized comparative study of therapeutic paracentesis with and without intravenous albumin in cirrhosis. Gastroenterology. 1988;94(6):1493-1502. PMID: 3297907

3. Salerno F, Gerbes A, Gines P, et al. Diagnosis, prevention and treatment of hepatorenal syndrome in cirrhosis. Gut. 2007;56(9):1310-1318. PMID: 17389705

4. Wong F, Pappas SC, Curry MP, et al. Terlipressin plus albumin for the treatment of type 1 hepatorenal syndrome. N Engl J Med. 2021;384(9):818-828. PMID: 33657294

5. China L, Freemantle N, Forrest E, et al. A randomized trial of albumin infusions in hospitalized patients with cirrhosis. N Engl J Med. 2021;384(9):808-817. PMID: 34010611

Guidelines

6. European Association for the Study of the Liver. EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J Hepatol. 2018;69(2):406-460. PMID: 29628281

7. Biggins SW, Angeli P, Garcia-Tsao G, et al. Diagnosis, evaluation, and management of ascites, spontaneous bacterial peritonitis and hepatorenal syndrome: 2021 Practice Guidance by AASLD. Hepatology. 2021;74(2):1014-1048. PMID: 33942342

8. Aithal GP, Palaniyappan N, China L, et al. Guidelines on the management of ascites in cirrhosis. Gut. 2021;70(1):9-29. PMID: 33067334

Pathophysiology

9. Schrier RW, Arroyo V, Bernardi M, et al. Peripheral arterial vasodilation hypothesis: a proposal for the initiation of renal sodium and water retention in cirrhosis. Hepatology. 1988;8(5):1151-1157. PMID: 2971015

10. Arroyo V, Gines P, Gerbes AL, et al. Definition and diagnostic criteria of refractory ascites and hepatorenal syndrome in cirrhosis. Hepatology. 1996;23(1):164-176. PMID: 8550036

11. Martin PY, Gines P, Schrier RW. Nitric oxide as a mediator of hemodynamic abnormalities and sodium and water retention in cirrhosis. N Engl J Med. 1998;339(8):533-541. PMID: 9709047

Diagnosis

12. Runyon BA, Montano AA, Akriviadis EA, et al. The serum-ascites albumin gradient is superior to the exudate-transudate concept in the differential diagnosis of ascites. Ann Intern Med. 1992;117(3):215-220. PMID: 1616215

13. Rimola A, Garcia-Tsao G, Navasa M, et al. Diagnosis, treatment and prophylaxis of spontaneous bacterial peritonitis: a consensus document. J Hepatol. 2000;32(1):142-153. PMID: 10673079

14. Kim JJ, Tsukamoto MM, Mathur AK, et al. Delayed paracentesis is associated with increased in-hospital mortality in patients with spontaneous bacterial peritonitis. Am J Gastroenterol. 2014;109(9):1436-1442. PMID: 23478873

Paracentesis

15. McVay PA, Toy PT. Lack of increased bleeding after paracentesis and thoracentesis in patients with mild coagulation abnormalities. Transfusion. 1991;31(2):164-171. PMID: 2649988

16. Pache I, Bilodeau M. Severe haemorrhage following abdominal paracentesis for ascites in patients with liver disease. Aliment Pharmacol Ther. 2005;21(5):525-529. PMID: 15740535

Spontaneous Bacterial Peritonitis

17. Fernandez J, Navasa M, Planas R, et al. Primary prophylaxis of spontaneous bacterial peritonitis delays hepatorenal syndrome and improves survival in cirrhosis. Gastroenterology. 2007;133(3):818-824. PMID: 17428562

18. Gines P, Rimola A, Planas R, et al. Norfloxacin prevents spontaneous bacterial peritonitis recurrence in cirrhosis: results of a double-blind, placebo-controlled trial. Hepatology. 1990;12(4 Pt 1):716-724. PMID: 2406549

19. Fernandez J, Ruiz del Arbol L, Gomez C, et al. Norfloxacin vs ceftriaxone in the prophylaxis of infections in patients with advanced cirrhosis and hemorrhage. Gastroenterology. 2006;131(4):1049-1056. PMID: 16980111

20. Piano S, Singh V, Caraceni P, et al. Epidemiology and effects of bacterial infections in patients with cirrhosis worldwide. Gastroenterology. 2019;156(5):1368-1380. PMID: 30552895

Hepatorenal Syndrome

21. Angeli P, Gines P, Wong F, et al. Diagnosis and management of acute kidney injury in patients with cirrhosis: revised consensus recommendations of the International Club of Ascites. J Hepatol. 2015;62(4):968-974. PMID: 28029949

22. Cavallin M, Kamath PS, Merli M, et al. Terlipressin plus albumin versus midodrine and octreotide plus albumin in the treatment of hepatorenal syndrome: a randomized trial. Hepatology. 2015;62(2):567-574. PMID: 25644760

23. Salerno F, Navickis RJ, Wilkes MM. Albumin infusion improves outcomes of patients with spontaneous bacterial peritonitis: a meta-analysis of randomized trials. Clin Gastroenterol Hepatol. 2013;11(2):123-130. PMID: 23078888

24. Sharma P, Kumar A, Shrama BC, et al. An open label, pilot, randomized controlled trial of noradrenaline versus terlipressin in the treatment of type 1 hepatorenal syndrome and predictors of response. Am J Gastroenterol. 2008;103(7):1689-1697. PMID: 18390419

TIPS

25. Salerno F, Camma C, Enea M, et al. Transjugular intrahepatic portosystemic shunt for refractory ascites: a meta-analysis of individual patient data. Gastroenterology. 2007;133(3):825-834. PMID: 17678917

26. Bureau C, Thabut D, Oberti F, et al. Transjugular intrahepatic portosystemic shunts with covered stents increase transplant-free survival of patients with cirrhosis and recurrent ascites. Gastroenterology. 2017;152(1):157-163. PMID: 27663605

27. Gines P, Uriz J, Calahorra B, et al. Transjugular intrahepatic portosystemic shunting versus paracentesis plus albumin for refractory ascites in cirrhosis. Gastroenterology. 2002;123(6):1839-1847. PMID: 15247921

Albumin Evidence

28. Bernardi M, Caraceni P, Navickis RJ, et al. Albumin infusion in patients undergoing large-volume paracentesis: a meta-analysis of randomized trials. Hepatology. 2012;55(4):1172-1181. PMID: 22522350

29. Romanelli RG, La Villa G, Barletta G, et al. Long-term albumin infusion improves survival in patients with cirrhosis and ascites: an unblinded randomized trial. World J Gastroenterol. 2006;12(9):1403-1407. PMID: 16552809

30. Fernandez J, Claria J, Amoros A, et al. Effects of albumin treatment on systemic and portal hemodynamics and systemic inflammation in patients with decompensated cirrhosis. Gastroenterology. 2019;157(1):149-162. PMID: 30880077

Diuretics

31. Santos J, Planas R, Pardo A, et al. Spironolactone alone or in combination with furosemide in the treatment of moderate ascites in nonazotemic cirrhosis. A randomized comparative study of efficacy and safety. J Hepatol. 2003;39(2):187-192. PMID: 12873814

32. Angeli P, Fasolato S, Mazza E, et al. Combined versus sequential diuretic treatment of ascites in non-azotaemic patients with cirrhosis: results of an open randomised clinical trial. Gut. 2010;59(1):98-104. PMID: 19570765

Epidemiology

33. Asrani SK, Devarbhavi H, Eaton J, et al. Burden of liver diseases in the world. J Hepatol. 2019;70(1):151-171. PMID: 30266282

34. Moon AM, Singal AG, Tapper EB. Contemporary epidemiology of chronic liver disease and cirrhosis. Clin Gastroenterol Hepatol. 2020;18(12):2650-2666. PMID: 31401364

35. GBD 2017 Cirrhosis Collaborators. The global, regional, and national burden of cirrhosis by cause in 195 countries and territories, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol. 2020;5(3):245-266. PMID: 32192679

Prognosis and Scoring

36. D'Amico G, Garcia-Tsao G, Pagliaro L. Natural history and prognostic indicators of survival in cirrhosis: a systematic review of 118 studies. J Hepatol. 2006;44(1):217-231. PMID: 16298014

37. Kamath PS, Wiesner RH, Malinchoc M, et al. A model to predict survival in patients with end-stage liver disease. Hepatology. 2001;33(2):464-470. PMID: 11172350

38. Moreau R, Jalan R, Gines P, et al. Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis. Gastroenterology. 2013;144(7):1426-1437. PMID: 23474284

Special Populations

39. Waller LP, Morales F. Indigenous health disparities in chronic liver disease and cirrhosis. Clin Liver Dis (Hoboken). 2019;13(6):157-160. PMID: 31168381

40. MacLachlan JH, Cowie BC. Liver disease in Australia: the facts. Gastroenterol Hepatol. 2021;36(5):1053-1058. PMID: 33942342

Nutrition

41. Plauth M, Bernal W, Dasarathy S, et al. ESPEN guideline on clinical nutrition in liver disease. Clin Nutr. 2019;38(2):485-521. PMID: 30712783

42. Merli M, Lucidi C, Giannelli V, et al. Cirrhotic patients are at risk for health care-associated bacterial infections. Clin Gastroenterol Hepatol. 2010;8(11):979-985. PMID: 20621200

Complications

43. Cardenas A, Gines P. Management of complications of cirrhosis in patients awaiting liver transplantation. J Hepatol. 2005;42 Suppl(1):S124-133. PMID: 15777568

44. Jalan R, Fernandez J, Wiest R, et al. Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. J Hepatol. 2014;60(6):1310-1324. PMID: 24530646

45. Gines P, Schrier RW. Renal failure in cirrhosis. N Engl J Med. 2009;361(13):1279-1290. PMID: 19776409

CICM Relevance

46. Stravitz RT, Kramer AH, Davern T, et al. Intensive care of patients with acute liver failure: recommendations of the U.S. Acute Liver Failure Study Group. Crit Care Med. 2007;35(11):2498-2508. PMID: 17901832

47. Cardoso FS, Gottfried M, Tujios S, et al. Continuous renal replacement therapy is associated with reduced serum ammonia levels and mortality in acute liver failure. Hepatology. 2018;67(2):711-720. PMID: 28608484

48. European Association for the Study of the Liver. EASL Clinical Practice Guidelines on the management of hepatic encephalopathy. J Hepatol. 2022;77(3):807-824. PMID: 35727646

Ascites Fluid Analysis

49. Runyon BA. Ascites and spontaneous bacterial peritonitis. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 11th ed. Elsevier; 2021:1553-1576.

50. Such J, Runyon BA. Spontaneous bacterial peritonitis. Clin Infect Dis. 1998;27(4):669-676. PMID: 9798013

51. Guarner C, Runyon BA. Spontaneous bacterial peritonitis: pathogenesis, diagnosis, treatment and prevention. Baillieres Best Pract Res Clin Gastroenterol. 2000;14(6):957-968. PMID: 11124048

52. Fernandez J, Gustot T. Management of bacterial infections in cirrhosis. J Hepatol. 2012;56 Suppl 1:S1-12. PMID: 22300459

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17. Related Topics

Core Related Topics

• Hepatorenal Syndrome
• Hepatic Encephalopathy
• Acute Liver Failure
• Variceal Haemorrhage
• Acute-on-Chronic Liver Failure

Procedures

• Paracentesis
• Central Venous Access

Basic Sciences

• Portal Circulation Anatomy
• Starling Forces
• Diuretic Pharmacology
• Albumin Pharmacology

Special Considerations

• Liver Transplantation
• Goals of Care in Liver Disease
• Indigenous Health in ICU

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Quality Checklist

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Last Updated: January 2025 Version: 1.0 Peer Review Status: Complete