Approach — Management of ascites in cirrhotic patients

Approach - Management of ascites in cirrhotic patients Dr. Khaled sheha

Causes of ascites Causative disorders Percentage Cirrhosis 85% PHT-related disorder 8% Cardiac disease 3% Peritoneal carcinomatosis 2% Miscellaneous non-PHT disorders 2%

Diagnosis of ascites * • Ascites can be graded as Grade 1 (mild) Detectable only by US Grade 2 (moderate) Moderate abdominal distension Grade 3 (large) Marked abdominal distension * Moore KP et al. Hepatology 2003 ; 38 : 258 – 66.

Ascites grade 1 Detectable only by US

Pathogenesis of ascites in cirrhosis PHT Nitric oxide Vasodilatation Renal Na retention Overfill of intravascular volume Sympathetic activity RAA system Ascites formation

Indications for diagnostic paracentesis • Patients with new-onset ascites • Cirrhotic patients with ascites at admission • Cirrhotic patients with ascites & symptoms or signs of infection: fever, leukocytosis, abdominal pain • Cirrhotic patients with ascites & clinical condition deteriorating during hospitalization: renal function impairment, hepatic encephalopathy, GI bleeding

Needle-entry sites Superior & inferior epigastric arteries run just lateral to the umbilicus towards mid-inguinal point & should be avoided.

The Z-tract technique Green (21 G) or blue (23 G) needle Diagnostic purpose: 10 - 20 ml of fluid ascites Cytologic study: 50 ml of fluid ascites Thomsen TW et al. N Engl J Med 2006 ; 355 : e 21.

The angular insertion technique Green (21 G) or blue (23 G) needle Diagnostic purpose: 10 - 20 ml of fluid ascites Cytologic study: 50 ml of fluid ascites.

What are the contraindications & complications of paracentesis? MA

Complications of paracentesis • Abdominal hematomas Up to 1 % of patients Rarely serious or life threatening • Hemoperitoneum or bowel perforation Rare (< 1/1000 procedures) Serious complications Guidelines on management of ascites in cirrhosis. Gut 2006 ; 55 ; 1 – 12.

Contraindications to paracentesis • Clinically evident fibrinolysis or DIC Preclude paracentesis • Abnormal coagulation profile Paracentesis not contraindicated Majority of pts have prolonged PT & thrombocytopenia No data to support the use of FFP before paracentesis AASLD practice guidelines Runyon BA. Hepatology 2004; 39: 841 – 856.

Ascitic Fluid Laboratory Data Routine Optional Unusual Unhelpful Cell count * Culture TB smear & culture p. H Albumin Glucose Cytology Lactate Total protein LDH TG Cholesterol Amylase Bilirubin Fibronectin Gram’s stain * Automated counting can replace manual cell count.

Serum Ascites Albumin Gradient (SAAG) Albumin Serum – Albumin Ascites (g/d. L) in the same day

Differential diagnosis according to SAAG High Gradient ≥ 1. 1 g/d. L Low Gradient < 1. 1 g/d. L

Differential diagnosis of ascites according to SAAG High Gradient ≥ 1. 1 g/d. L (11 g/L) Low Gradient <1. 1 g/d. L (11 g/L) Cirrhosis Peritoneal carcinomatosis Liver metastases Tuberculous peritonitis Cardiac ascites Pancreatic ascites Portal-vein thrombosis Biliary ascites Budd–Chiari syndrome Nephrotic syndrome Hypothyroid Serositis.

What is the treatment?

Tapping ascitic fluid (1672) German National Museum, Nürnberg, Germany

What do you prescribe to this patient? What are the side effects of these drugs? How do you follow-up the patient? ND

Recommendation Low sodium diet Dietary salt should be restricted to a no-added salt diet of 90 mmol salt/day (5. 2 g salt/day) by adopting a no-added salt diet & avoidance of pre-prepared foodstuffs ND

Diuretics treatment in cirrhotic ascites Oral route – Single morning dose Progressive Schedule Combined Schedule SP * 100 200 300 400 mg/d SP 100 mg/d + FUR 40 mg/d Progressive increase every 3 -5 days SP 400 mg/d + FUR** 40 80 120 160 mg/d *SP **FUR SP 200 300 400 mg/d + FUR 80 120 160 mg/d Spironolactone Furosemide

Follow-up of patients on diuretics – 1 • Weight loss Massive edema Resolved edema No limit to daily weight loss 0. 5 kg / day • Weight loss less than desired 24 -hour urine sodium > 78 mmol/24 h & no weight loss: patient not compliant < 78 mmol/24 h & no weight loss: increased diuretics “spot” urine NA/K>1= 24 -hour urine Na>78 mmol/24 h

Follow-up of patients on diuretics – 2 • Body weight • Blood pressure • Pulse • Electrolytes • Urea • Creatinine Every 2 – 4 weeks Every few months thereafter

Side effects of diuretics • Spironolactone Men libido, impotence, gynecomastia Women Menstrual irregularity • Hydro-electrolytes disturbances Hypovolemia: hypotension – renal insufficiency Hyponatremia Hypo or hyperkalemia Hepatic encephalopathy

Water restriction • Not necessary in most cirrhotic patients with ascites • Cirrhotic patients have symptoms from hyponatremia if Na < 110 mmol/L or if very rapid decline in Na • Water restriction indicated in patients who are clinically euvolaemic withs severe hyponatraemia & not taking diuretics with normal creatinine • Avoid increasing serum sodium > 12 mmol/l per day ND

Bed rest in cirrhotic ascites • Upright posture associated with activation of RAA system, reduction in GFR & sodium excretion, & decreased response to diuretics • Bed rest muscle atrophy & other complications • No clinical studies to demonstrate efficacy of bed rest

Recommendation Bed rest is NOT necessary for the treatment of cirrhotic ascites

How do you treat the tense ascites in this patient? OH

Is this a refractory ascites? How do you treat refractory ascites? RA

Refractory ascites ( 10 %) • Diuretic resistant ascites Unresponsive to LSD (< 88 mmol/day) & High-dose diuretics SP 400 mg & FUR 160 mg/d for at least 1 week • Diuretic intractable ascites Diuretic induced complications Encephalopathy Creatinine > 2. 0 g/d. L Na < 125 mmol/L K > 6 or < 3 mmol/L International ascites club Arroyo V et al. Hepatology 1996 ; 23 : 164 – 76.

Recommendations Treatment of refractory ascites • Therapeutic paracentesis is the first line treatment: < 5 L: Colloid - No need for albumin > 5 L: Albumin after paracentesis (8 g/l) • TIPS should be considered in refractory ascites • LT referral should be considered in refractory ascites • Peritoneovenous shunt should be considered in patients who are not candidates for paracentesis, TIPS, or LT ND

Refractory Ascites LT evaluation LVP + Albumin 1 st Step Na restricted diet (90 m. Eq/d) Fluid restriction if Na < 130 m. Eq/L Repeated LVP + albumin Maintenance Treatment Preserved liver function? Loculated ascites? Paracentesis more frequent than 2 -3 /month? No Yes Continue LVP + Albumin Consider TIPS Clin Gastroenterol Hepatol 2005 ; 3 : 1187 – 1191.

Treatment of refractory ascites • Serial therapeutic paracentesis • TIPS • Liver transplantation • Peritoneovenous shunt: Le. Veen – Denver

TIPS for refractory ascites I s practice guidelines Runyon BA. Hepatology 2004; 39: 841 – 856.

Albumin in cirrhotic ascites • Large paracentesis > 5 L 8 g albumin/liter of ascites removed (100 ml of 20% albumin / 3 L ascites) • SBP with renal impairement First six hours 1. 5 g albumin / kg bw Day 3 1 g albumin / kg bw • HRS-I First day 1 g / kg bw (maximum 100 g) Following days 20 – 40 g / day

Prognosis of ascites in cirrhotic patients • Ascites 50 % survival at 2 years • Refractory ascites 50% survival at 6 months 25% survival at 1 year • SBP 30 - 50% survival at 1 year • HRS-2 40% survival at 6 months • HRS-1 < 5% survival at 6 months Referral to liver transplantation unit