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

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

3. 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.

4. Ascites grade 1 Detectable only by US

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

6. 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

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

8. The Z-tract technique Thomsen TW et al. N Engl J Med 2006 ; 355 : e21. Green (21 G) or blue (23 G) needle Diagnostic purpose: 10- 20 ml of fluid ascites Cytologic study: 50 ml of fluid ascites

9. 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

10. What are the contraindications & complications of paracentesis? MA

11. 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.

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.

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

14. Serum Ascites Albumin Gradient (SAAG)  Albumin  Serum –  Albumin  Ascites (g/dL) (g/dL) in the same day  Albumin  Serum –  Albumin  Ascites (g/dL) (g/dL) in the same day

15. Differential diagnosis according to SAAG High Gradient ≥ 1.1 g/dL Low Gradient < 1.1 g/dL.

16. Differential diagnosis of ascites according to SAAG High Gradient ≥1.1 g/dL (11g/L) Low Gradient <1.1 g/dL (11g/L) CirrhosisPeritoneal carcinomatosis Liver metastasesTuberculous peritonitis Cardiac ascitesPancreatic ascites Portal-vein thrombosisBiliary ascites Budd–Chiari syndromeNephrotic syndrome HypothyroidSerositis.

17. What is the treatment?

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

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

20. 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 Recommendation Low sodium diet ND

21. Diuretics treatment in cirrhotic ascites Oral route – Single morning dose Progressive ScheduleCombined Schedule SP * 100  200  300  400 mg/d SP 400 mg/d + FUR** 40  80  120  160 mg/d SP 100 mg/d + FUR 40 mg/d SP 200  300  400 mg/d + FUR 80  120  160 mg/d Progressive increase every 3-5 days *SPSpironolactone **FURFurosemide

22. Follow-up of patients on diuretics – 1 Weight loss Massive edemaNo limit to daily weight loss Resolved edema  0.5 kg / day Weight loss less than desired 24-hour urine sodium > 78 mmol/24h & no weight loss: patient not compliant < 78 mmol/24h & no weight loss: increased diuretics “spot” urine NA/K>1= 24-hour urine Na>78 mmol/24h

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

24. 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

25. 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

26. 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

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

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

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

30. Refractory ascites (  10 %) Diuretic resistant ascites Unresponsive to LSD (< 88 mmol/day) & High-dose diuretics SP 400 mg & FUR 160 mg/d Diuretic intractable ascites D iuretic induced complications Encephalopathy Creatinine > 2.0 g/dL Na < 125 mmol/L K > 6 or < 3 mmol/L International ascites club Arroyo V et al. Hepatology 1996 ; 23 : 164 – 76. for at least 1 week

31. Recommendations Treatment of refractory ascites Therapeutic paracentesis is the first line treatment: < 5 L: Colloid - No need for albumin > 5 L: Albumin after paracentesis (8g/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

32. Refractory Ascites LT evaluation LVP + Albumin Na restricted diet (90 mEq/d) Fluid restriction if Na < 130 mEq/L Repeated LVP + albumin Preserved liver function? Loculated ascites? Paracentesis more frequent than 2-3 /month? Continue LVP + Albumin Consider TIPS 1 st Step Maintenance Treatment YesNo Clin Gastroenterol Hepatol 2005 ; 3 : 1187 – 1191.

33. Treatment of refractory ascites Serial therapeutic paracentesis TIPS Liver transplantation Peritoneovenous shunt: LeVeen – Denver

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

35. 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 hours1.5 g albumin / kg bw Day 31g albumin / kg bw HRS-I First day1 g / kg bw (maximum 100 g) Following days20 – 40 g / day

36. Ascites50 % survival at 2 years Refractory ascites50% survival at 6 months 25% survival at 1 year SBP30 - 50% survival at 1 year HRS-2 40% survival at 6 months HRS-1 < 5% survival at 6 months Prognosis of ascites in cirrhotic patients Referral to liver transplantation unit