PRINCIPLES OF MANAGEMENT OF ASCITES

Richard Warner

• Causes of Ascites

• Management of ‘Simple Ascites’

• Management of ‘Refractory Ascites’

Causes of Ascites- Normal Peritoneum

SAAG >11g/l• Cirrhosis

• 10th cause

of death in

USA

Causes of Ascites- Normal Peritoneum

SAAG >11g/l

• Cirrhosis• Portal Hypertension • Budd Chiari Syndrome• Fulminant Hepatic Failure• Massive Hepatic Metastases• Accounts for ~85% Ascites

Causes of Ascites- Normal Peritoneum

SAAG >11g/l

• Hepatic Congestion• Constrictive Pericarditis• Congestive Heart Failure• Tricuspid Insufficiency

Causes of Ascites-Normal Peritoneum

SAAG < 11g/lHypoalbuminaemia

• NEPHROTIC SYNDROME

• PROTEIN LOSING ENTEROPATHY

• SEVERE MALNUTRITION

Miscellaneous

• CHYLOUS ASCITES

• PANCREATITIS ASCITES

Causes of Ascites-Diseased Peritoneum

SAAG < 11g/l

• Bacterial, Fungal, TB, HIV Related Infections

Causes of Ascites-Diseased Peritoneum

SAAG < 11g/l

• Malignant – Peritoneal, Pseudomyxoma Peritonei, Primary Mesothelioma, Hepatocellular Carcinoma

• Rare – Familial Mediterranean Fever, Vasculitis , Eosinophilic Peritonitis, Granulomatous Peritonitis

•

Ascites is not just a Cosmetic Problem !

• Median Survival 2 years from onset

• Survival depends mainly on Liver Function

• SBP occurs ~25%• Low urinary Na+ &

SBP predict high mortality

Management of Ascites-Guidelines

• International Ascites Club (Hepatology 2003/2004) – supported by unconditional educational grant from Seale, Spain

• American Association for the Study of Liver Disease (AASLD) – Hepatology March 2004.

• 50 % of patients diagnosed with cirrhosis, develop ascites in 10 years.

Management

Treat the Underlying Cause

• Alcohol has best prognosis if abstain

• Childs C – 75% 3-year survival Vs. 0%

• Non-Alcoholic less reversible therefore consider referral for transplant earlier

Treatment Options

• Bed rest• Diet• Diuretics• Fluid Restriction• Paracentesis• TIPSS• Shunts• Transplant

Ascites- Grading

• Grade 1 – Ultrasound detected• Grade 2 moderate – symmetrical distension of

abdomen• Grade 3 – tense or gross ascites• (Refractory ascites (5 –10% of all ascites))

Management of ascites-Bed Rest

Bed rest : No clinical trials• Upright posture activates sodium retaining

mechanisms , impairs renal perfusion and sodium excretion.

Management of ascites-Sodium Restriction

Sodium restriction : Water will follow Sodium Educate the Patient Aim for 2000mg (88 mmol) per day Studies show severe restriction (22mmol/day) compared

with less restricted is associated with longer duration of evolution of ascites, but higher incidence of diuretic induced renal impairment and hyponatraemia (Gauthier 1986 , Reynolds 1978)

MANAGEMENT OF ASCITES- Salt restriction (cont)

• One controlled study, showed slightly reduced salt diet (120mmol/day) was equally effective when compared to a low salt diet ( 50mmol/day).

• No significant survival difference, although low salt diet (50mmol/day ) improved survival in those with previous GI bleed

MANAGEMENT OF ASCITES-

WATER RESTRICTION• Central hypovolaemia - > stimulates ADH receptors - > decreases free water clearance - > dilutional

hyponatraemia. • Therefore, treat by water restriction – no trials to assess

effect of water restriction in patients with cirrhosis and dilutional hyponatraemia. Restriction may worsen central hypovolaemia.

• Water restriction not first option, sodium restriction appropriate first line, water restrict if Na <125mmol/L

MANAGEMENT OF ASCITES-

DIURETICS

• Antimineralocorticoids –

Secondary hyperaldosteronism promotes sodium retention in distal tubules and collecting ducts

Controlled and uncontrolled trials - > Spironolactone effective antimineralocorticoid

• S.E gynaecomastia, renal impairment, hyperkalaemia

• Other K sparing diuretics: amiloride, triamterene

• Loop Diuretics : Frusemide – S.E : hyponatraemia, hypokalaemia, hypovolemia, renal impairment of prerenal origin

ASCITES-Assess response to diuretics :

• Weight loss of 0.5kg/day in absence of oedema and 1kg/day when oedema present

• Use Spironolactone & Frusemide 100mg/40mg ratio

• Medical treatment based on sodium restricted diet, diuretics – response in 90 % without renal failure in controlled trials (Bernadi 95, Gatta ’91)

Ascites-Paracentesis

• Repeated daily paracentesis ( 5L/day )

• Single total paracentesis- reduced hospital stay

Ascites-Paracentesis

• 5 randomised controlled trials comparing paracentesis to diuretics : more effective, shortened duration of hospitalisation, fewer complications

• Paracentesis should be followed by maintenance diuretics

• Ascites recurred in 4/52 postparacentesis in 18 % of patients receiving diuretics vs. 93 % receiving placebo (Fernandez –Gsparrach 1997)

Paracentesis-Systemic Effects

• Acute increase of cardiac output, lowering of systemic vascular resistance - > modest reduction of blood pressure.

• Pulmonary capillary pressure reduces 6 hours postparacentesis, right atrial pressure falls acutely sec to reduced intrathoracic pressure.

• Hypovolemia occurs – therefore volume expanders used• Gines et al –randomised controlled trial of repeat

paracentesis - patients received albumin or placebo• S.E in 30 % not receiving albumin vs. 16 % receiving

albumin• SE were renal impairment, hyponatraemia, elevation of

plasma renin and aldosterone levels

Paracentesis

• Volume expander : albumin vs. synthetic expanders.

• Albumin – expensive, risk of infection with non- eradicated viruses and prion related infections

• Practice guidelines committee of American association for study of liver disease have challenged use of albumin in view of this

Ascites-Refractory Ascites

• Unresponsive to Salt restriction & high dose diuretics (400mg Spironolactone & 160mg Frusemide)

• Recurs rapidly after Paracentesis (< 4/52)• Diuretic induced complication – encephalopathy,

renal impairment, hyponatraemia (<125mmol/L), hypo (3mmol/L) or hyperkalaemia (6mmol/L)

Refractory Ascites-Treatment Options

• Serial Paracentesis• Liver Transplantation• TIPSS• Peritoneovenous Shunts

Refractory Ascites-Treatment Options

Serial Paracentesis• Safe• Gives insight into patient salt compliance• Ascitic Na similar to serum• 6L Ascites(780mmol Na) = 10 days intake• Cost, Inconvenience & Infections are main

disadvantages

Refractory Ascites-Treatment Options

Liver Transplantation

• Once refractory 50% mortality @ 6/12 and 75% mortality @ 1 year

• Referral often delayed

• ? Suitability of patients?

Refractory Ascites-Treatment Options

Peritoneovenous Shunts• Popular in 1970s• LeVeen or Denver• Poor long term patency• No Survival advantage• Make Transplantation difficult• Use now limited to palliation

in rural areas

Refractory Ascites-Treatment Options

TIPSS

TIPSS

• Shunt between hepatic vein (low pressure) and portal vein (high pressure)

• Improvement of renal function and sodium excretion

• Resolution of ascites

• Effect on circulatory system : increase in cardiac output, right atrial pressure and pulmonary arterial pressure with secondary decrease of systemic vascular resistance. Increase in effective arterial blood volume

TIPS vs. ParacentesisStudy No.

PatientsControl of Ascites

Survival 1 Year

Encephalopathy

Rossle et al NEJM, 2000

60 61% vs.18% p=.006

69% vs. 52%

58% vs.48 %

Gines et al Gastroenterology, 2002

70 51% vs. 17% p=.003

41% vs. 35%

60% vs. 34%

Sanyal et al Gastroenterology 2003

109 58% vs. 16% p<.001

40% vs. 37%

38% vs. 12%

Salerno et al Hepatology 2002

57 74% vs.35% p=.008

71% vs. 35%

55% vs. 46%

TIPS- Complications

• Capsule rupture• Intra- abdominal bleeding• 70% shunt stenosis in 6 months- recurrence of ascites• Encephalopathy- risk increased in those with pre-TIPS

encephalopathy and age >60yrs• Risk of cardiac failure in those with underlying cardiac

disease due to sudden increase in cardiac preload• Liver function deteriorates significantly post TIPS –

secondary shunting of blood from liver

ASCITES MX

• GRADE 1: no specific treatment, adv re: reduced salt intake

• Grade 2 : dietary sodium restriction (2000mg /day/ 88mmol/day)

• Diuretics

• Grade 3 : Paracentesis 8g of albumin with 1L of ascitic fluid drained, maintenance diuretics

• Refractory : Repeat paracentesis, diuretics as tolerated – stop if complications or urine Na <30mmol/day. If >3 paracentesis/month, consider TIPS or liver transplant.

Any Questions?

TIPS VS PARACENTESIS

• 3) 49 % of patients with TIPS- recurrent ascites

83 % with paracentesis –recurrent ascites

Higher risk of encephalopathy and cost in TIPS

no survival rate difference

(Gines P 2002)

4) North American multicentre trial with 109 pts-

TIPS superior in control of ascites but mean survival equal in both patients

TIPS VS PARACENTEISIS

1) those with Child C, overall survival worse with TIPS. Therefore contraindicated (Lebreo D 1996)

2) 60 patients with refractory ascites – paracentesis without albumin vs. TIPS (Rossle M 2000)

TIPS – 15 deaths, 1 underwent liver transplantation

Paracentesis – 23 deaths, 2 underwent liver transplant

Probability of survival without transplant 69 % at 1year in TIPS, vs. 52 % in paracentesis. Frequency of encephalopathy similar