Management of ascites

University of ilorin teaching hospital presentation.

1. Management of Ascites. Presenter: Dr. Owolabi A.A

2. Outline. Pre-test Introduction Epidemiology causes Pathophysiology Physical examination Investigation Summary Post test Conclusion

3. Pre-test Ascitic fluid with total protein>1 g/ dL is a high risk for developing SBP T/F Serum Ascites Albumin Gradient(SAAG) of >1.1 is likely of portal hypertension aetiology T/F SBP is usually polymicrobial T/F Bacterascites is the presence of PMN <250cells/mm3 + + ve culture of a single organism T/F Runyon criteria is used to differentiate Chylous Ascites from SBP T/F

4. Introduction Ascites is derived from the greek word “ASKOS” means bag or sac. Acites means pathologic fluid collection within the abdominal cavity. Normal: Females(</=20mls). The development of ascites is associated with a poor prognosis and impaired quality of life in patients with cirrhosis

5. Epidemiology Healthy men have little or no intraperitoneal fluid but women normally have as much as 20ml . About 50% of patients with cirrhosis develop ascites over 10years. The prognosis is dependent on the underlying disorder and the response to treatment.

6. Causes Cirrhosis:Chronic hepatitis , NASH Nephrotic syndrome Hypoalbuminemia Peritonitis( tuberculous , Bacterial, fungal) Tumors:(Ovary, pancreas, colon, mesothelioma , psudomyxoma peritonei )

7. Ascites in heart failure can mimic ascites in cirrhosis, and the distinction between the two entities can be challenging.

8. Pathophysiology : Based on three theories: Underfilling Overflow Peripheral Arterial vasodilation Portal hypertension occurs as a consequence of structural changes which involve progressive collagen deposition within the liver in cirrhosis and this alters vascular architecture.( pre,sinusoidal,post )

9. Underfilling theory: that the primary abnormality is the pooling of fluid within the splanchnic vascular bed of the liver due to portal hypertension Pooling of blood in liver  ineffective circulatory systemic blood volume  activation of RAAS  sodium and water retention.

10. Peripheral arterial vasodilation : portal hypertension, causes a compensatory response of vasodilatation, which causes decreased effective arterial blood volume. Portal hypertension  NO 2  Vasodilation  effective areterial blood volume . The nitric oxide mediates splanchnic and peripheral vasodilation .

11. Overflow: innapropriate retention of sodium and water by the kidneys in the absence of fluid depletion.

12. Other factors: Other factors that contribute to the accumulation of fluid in the peritoneal cavity: Elevated epinephrine and norepinephrine Hypoalbuminemia

13. Grading\classification Uncomplicated Grade 1-Mild(only detectable by USS) Grade 2-Moderate(moderate symmetrical abdominal distension) Grade 3-Large/tense(Marked abdominal distension)

14. Clinical Presentation History: Abdominal distension: painless or with abdominal discomfort, course(acute/chronic) Aetiology Alcohol Jaundice MSP Hepatitis status Blood transfusion Tattoos/scars/scarification marks Long history of Stable cirrhosis Gastric malignancy Hx of chronic medical illness.

15. Physical findings Abdominal distention. Peripheral stigmata of CLD Obesity/Metabolic syndrome Elevated JVP SMJ nodule Virchows node Puddle sign Shifting dullness/ fluid wave ~120mls >1500mls

16. Diagnostic paracentesis Indications of Diagnostic tap: New onset ascites or at time of hospitalization To detect presence of cancerous cells When there is evidence of clinical decompensation , such as ?secondary bacterial peritonitis(SBP) , hepatic encephalopathy, gastrointestinal hemorrhage, or deterioration of renal function. Site: Left lower abdominal quadrat

17. Contraindications Absolute : Acute abdomen that requires surgery Relative: Severe thrombocytopenia (platelet count < 20 x 10 3 cells/mm 3 , Pregnancy, Distended Urinary bladder, Abdominal wall cellulitis

18. Ascitic fluid analysis Inspection: Clear, turbid, bloody, green, white Albumin concentration: allows calculation of the serum- ascites albumin gradient (SAAG) to classify specimens into high- or low-gradient categories. Amylase, LDH and glucose Assay Cell count and MCS:Lymphocytes predominate in tuberculous pertitonitis and carcinomatosis . CEA >5ng/ml ALP >240u/l

19. Cytology is 60-90% accurate in malignant ascites if several hundred ml of fluid is sent and concentration technique is used but it is not investigation of choice in HCC. Amylase in pancreatic ascites Triglyceride in chylous ascites >1000mg/dl Bilirubin in post op ascites

20. SAAG The SAAG is the best single test for classifying ascites into portal hypertensive and non- portal hypertensive causes. The accuracy of the SAAG is approximately 97% in classifying ascites SAAG= serum albumin – ascitic albumin Previously transudate if >25g/L and exudate if >25g/L of protein up to 30% of cirrhosis will be exudate if we use protein to categorize.

21. SAAG

22. Chylous Ascites Chylous ascites : Turbid, milky or creamy peritoneal fluid due to the presence of thoracic or interstitial lymph, shows fat globules when stained with sudan black Has a triglyceride concentration of >1000mg/dl Mostly the result of lymphatic obstruction from:trauma , tumor, tuberculosis, filariasis , congenital abnormalities

23. Treatment goals: Provide comfort to patient Minimize ascitic volume and peripheral edema Avoid intravascular volume depletion Avoid SBP Improve nutrition

24. TREATMENT Treatment of the Underlying Disorder Cessation of alcohol use is vital to the management of ascites due to alcoholic liver disease. In one study of hospitalized patients with Child- Turcotte -Pugh class C cirrhosis due to severe alcoholic liver disease, 75% of those who remained abstinent were still alive at 3 years whereas most who continued to drink alcohol were not. Treatment of autoimmune hepatitis and chronic hepatitis B can also lead to significant clinical improvement and resolution of ascites in some cases. Treatment of ascites in non-hepatic cases should focus on treatment of the underlying disorder (e.g. treatment of tuberculosis, treatment of secondary bacterial peritonitis, or surgical resection of benign ovarian tumor).

25. Treatment-bed rest No clinical data to back up the finding that upright position is asscociated with reduced GFR and reduced Na excretion and reduced diuretic efficacy Bed rest promote muscle atrophy and other complications and extends hospital stay So bed rest not recommended

26. Treatment Sodium restriction and diuretics are the mainstays of treatment for patients with ascites due to portal hypertension, but patients with low SAAG (less than 1.1 g/ dL ) ascites do not respond well to these measures, with the exception of those with nephrotic syndrome

27. Treatment- salt restriction Diet: moderate restriction of salt intake is an important component in the management of ascites (4.6-6.9g/day 80-120mmol/day), and there has been no data to support salt restriction in patients who have never had ascites . ?water: its been found not to be necessary unless serum sodium is less than 120-125mmol/l. Lowers diuretic requirement, faster resolution of ascites and shorter hospital stay

28. Treatment- water restriction No role in uncomplicated ascites The downside is water restriction causes increase in the central effective hypovolaemia - more ADH- more water retention and further dilutional hyponatraemia . So hepatologist including the authors of the BSG guidelines suggest further plasma expansion to inhibit ADH secretion Data emerging supporting use of specific vasopressin 2 receptor antagonists.

29. Treatment- diuretic Patients with grade 2 ascites should receive an aldosterone antagonist (the diuretics of choice in management of ascites ); spironolactone starting at 100mg/day and increasing stepwise to a maximum of 400mg/day

30. Treatment- diuretic Aldosterone antagonist acting in distal tubule to increase natriuresis and conserve potassium Initial dose 100mg and increasing up to 400mg Lag of 3-5days Better natriuresis and diuresis than a loop diuretic Antiandrogenic effect- gynaecomastia - tamoxifen 20mg bd Hyperkalaemia frequently limits the use

31. Diuretics

32. Treatment- diuretic Frusemide can be added if response is not adequate, or Hyperkalemia . Starting from a dose of 40mg/day to a maximum of 160mg/day. In patients with recurrent ascites a combination of Spironolactone and loop diuretics. Frusemide has low efficacy in cirrhosis Use only if 400mg of spironolactone fails to achieve weight loss Start at 40mg a day and increasing by 40mg every 3 rd day to max of 160mg Watch out for metabolic alkalosis and electrolyte disturbance

33. Treatment- diuretic If oedema is present daily weight loss should be 1.5kg per day and 1g if edema is absent. Over diuresis is associated with intravascular volume depletion, leading to renal impairment, hepatic encephalopathy and hyponatraemia

34. Refractory Ascites : Refractory Ascites:Refractory ascites is an inadequate response to sodium-restricted diet and high-dose diuretic treatment (400 mg/day spironolactone and 160 mg/day furosemide

35. Refractory Ascites There are two different subtypes: Diuretic-resistant ascites (lack of response to dietary sodium restriction and intensive diuretic treatment) Diuretic-intractable ascites (diuretic-induced complications such as hepatic encephalopathy, renal insufficiency, hyponatremia , or hyperkalemia that prevent optimization of diuretic dosing). Early ascites recurrence (within 4 weeks after initial mobilization) is also considered refractory ascites . Excessive sodium intake, bacterial infection, occult gastrointestinal hemorrhage, and intake nonsteroidal antiinflammatory drugs should be excluded before labeling patients as refractory.

36. Controversy regarding normal saline Give only if renal function is worsening – creatinine >150 or 120 and rising Gelofusion/Haemaccel/ 4.5% albumin –all have 153mmol of Na per L This will worsen salt retention but better to have ascites than to develop HRS

37. Tx : Therapeutic paracentesis Paracentesis is a procedure in which a needle or catheter is inserted into the peritoneal cavity to drain ascitic fluid. Once a patient is deemed diuretic resistant, diuretics should be discontinued, and management may rely upon serial large volume therapeutic paracenteses alone. Typically, a large volume paracentesis (up to 5 L removed) performed every 2 weeks should control ascites in a patient who is compliant with dietary sodium restriction.

38. Therapeutic paracentesis Need for more frequent paracenteses suggests dietary noncompliance. Paracentesis is associated with significant haemodynamic changes Paracentesis -induced circulatory dysfunction, defined as an increase in plasma renin activity of more than 50% of the preparacentesis value to a level of more than 4 ng / mL /h

39. How is paracentesis done? Use Z technique- puncture site on the skin does not overlie the puncture site on peritoneum Left flank is preferrable to right flank After drain is out patient lie on opposite site Colostomy bag if continuous leakage ( some use purse string suture) As rapidly as possible- should not be left overnight No upper limit of 8 litres or maximum time of 6 hours has been mentioned in the guidelines

40. TIPSS Highly effective treatment Complete resolution in 75% of cases No effect on survival in one study and reduced on others- compared with therapeutic paracentesis HE occurs in 25% of patients , more if >60yrs May precipitate heart failure as increase cardiac preload TIPSS should be considered for patients who require frequent paracentesis ( >3 a month) It also shown to resolve hepatic hydrothorax in 60-70% MELD was originally developed to predict survival after TIPSS insertion

41. Peritoneovenous Shunts (PVS) The use of peritoneovenous shunts for management of ascites has fallen out of favor due to limited long-term patency (less than 20% at 2 years), risk of complications, and no improvement in survival compared to medical therapy. It is reserved as palliative treatment in select patients who are not candidates for transplantation, TIPS, or serial therapeutic paracenteses .

42. Contraindications: The absolute contraindications to placement of TIPS include congestive heart failure (particularly right-sided heart failure), severe tricuspid regurgitation, severe pulmonary hypertension (mean pulmonary pressure greater than 45 mmHg), extensive polycystic liver disease, and uncontrolled infection or biliary obstruction

43. Cirrhosis liver transplant Intrahepatic resistance Portal hypertension  TIPS Splanchnic /systemic vasodilation Effective arterial blood volume Albumin Activation of neurohumoral systems  Sodium retention  spironolactone / fruse Ascites  paracentesis -LVP/ PVS

44. Complications The absence of the following qualifies ascites as uncomplicated. SBP(fever): HRS:The hepatorenal syndrome occurs in patients with advanced liver failure and portal hypertension. It is a functional renal failure caused by intrarenal vasoconstriction resulting from arterial vasodilatation in the splanchnic circulation and severe reflex activation of the endogenous vasoconstrictive systems. Hepatorenal syndrome can be divided into two types: Type I HRS Type 2 HRS Clinical presentation is acute renal failure.

45. Other terms Hepatic hydrothorax(- cardiac,pulmonary and pleural cause) SBP: PMN >250cells/mm3 + + ve culture Culture negative neutrocytic ascites : PMN >250cells/mm3 + - ve culture Bacterascites : PMN <250cells/mm3 + + ve culture. Polymicrobial Bacterascites : PMN <250cells/mm3 + + ve polymicrobial culture

46. Risk factors for SBP

47. Secondary bacterial peritonitis should be suspected when ascitic fluid analysis shows two or three of the following criteria (Runyon criteria): Total protein more than 1 g/ dL Glucose less than 50 mg/ dL LDH more than 225 mU / mL (or more than the upper limit of normal for serum). These criteria were recently validated and shown to have a sensitivity of 66.6% and specificity of 89.7%. When combined with the presence of a polymicrobial ascitic fluid culture, specificity improved to 95.6%. Most of the ascitic fluid cultures in patients with secondary bacterial peritonitis are polymicrobial , whereas in patients with SBP the infection is usually monomicrobial

48. Which subgroups of patients with liver disease should receive prophylaxis against bacterial infection? Gastrointestinal hemorrhage ( ceftriaxone 1 g/day or norfloxacin 400 mg twice daily or ceftri ) or Prior episodes of SBP ( norfloxacin 400 mg/day) Low ascitic fluid protein ( norfloxacin 400 mg/day) and Fulminant hepatic failure ( norfloxacin 400 mg/day)

49. Prognosis The prognosis for patients with ascites depends on the underlying disease, the degree of reversibility of the disease and response to treatment. Ambulatory patients with an episode of cirrhotic ascites have a 3 year survival rate of 50%. Development of refractory ascites has a poor prognosis with a 1 year survival rate of <50% Time for referral to transplant centre as paracentesis and TIPSS does not improve long term survival except improving quality of life

50. Pre-test Ascitic fluid with total protein>1 g/ dL is a high risk for developing SBP T/F Serum Ascites Albumin Gradient(SAAG) of >1.1 is likely of portal hypertension aetiology T/F SBP is usually polymicrobial T/F Bacterascites is the presence of PMN <250cells/mm3 + + ve culture of a single organism T/F Runyon criteria is used to differentiate Chylous Ascites from SBP T/F

51. Conclusion Ascites is the most common decompensating event in cirrhosis

52. References Kumar and clark’s clinical medicine, 8 th ed. Harrison’s principle of internal medicine, 19 th ed. 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;59:98-104. Ginès P, Arroyo V, Quintero E, et al. Comparison of paracentesis and diuretics in the treatment of cirrhotics with tense ascites . Results of a randomized study. Gastroenterology 1987;93:234-41. Heuman DM, Abou-Assi SG, Habib A, et al. Persistent ascites and low serum sodium to identify patients with cirrhosis and low MELD scores who are high risk for early death.Hepatology . 2004;40