3. Dr Intekhab Alam MANAGEMENT OF ASCITES by Professor of Medicine
Department of Medicine
Postgraduate Medical Institute,
Lady Reading Hospital, Peshawar

4. Objectives
Understand the basic mechanisms of portal hypertension (PHT)
Study Ascites as a complication of PHT
Get an idea on the management of Ascites and its complications

5. What is Liver Cirrhosis?
Diffuse fibrosis of the liver with nodule formation
Abnormal response of the liver to any chronic injury

6. Causes of Cirrhosis Chronic viral hepatitis
Metabolic: hemochromatosis, Wilson dis, alfa-1-antitrypsin, NASH
Prolonged cholestasis (primary biliary cirrhosis, primary sclerosing cholangitis)
Autoimmune diseases (autoimmune hepatitis)
Drugs and toxins
Alcohol

7. Anatomy of the portal venous system

8. The Effect of The Liver Nodule

9. Mechanism of Portal HTN

10. Complications of Portal Hypertension in cirrhosis liver.
Development of Ascites.
Varices formation.
Hepatic encephalopathy.
Hepatorenal syndrome.

11. Ascites
Definition: presence of free fluid in the peritoneal cavity

12. Nonperitoneal Causes of Ascites
Examples
Intrahepatic portal hypertension
Cirrhosis Fulminant hepatic failure Veno-occlusive disease
Extrahepatic portal hypertension
Hepatic vein obstruction
(ie, Budd-Chiari syndrome) Congestive heart failure
Hypoalbuminemia
Nephrotic syndrome Protein-losing enteropathy Malnutrition
Miscellaneous disorders
Myxedema Ovarian tumors Pancreatic & Biliary ascites
Chylous
Secondary to malignancy, trauma

13. Peritoneal Causes of Ascites
Examples
Malignant ascites
Primary peritoneal mesothelioma Secondary peritoneal carcinomatosis
Granulomatous peritonitis
Tuberculous peritonitis Fungal and parasitic infections Sarcoidosis Foreign bodies (cotton ,starch, barium)
Vasculitis
Systemic lupus erythematosus Henoch-Schönlein purpura
Miscellaneous disorders
Eosinophilic gastroenteritis Whipple disease Endometriosis

14. Etiology Cirrhosis (75%) Malignancy (10%) Cardiac (3%) TB (2%)
Most common cause of ascites
Most common complication of cirrhosis
Other causes occur more frequently in cirrhotics
Malignancy (10%)
Cardiac (3%)
TB (2%)
Pancreatic Ascites(1%)
Various others
Hepatology 38:258-66

15. Pathophysiology of ascites in CLD:
Splanchnic HTN due to outflow obstruction
Increased vasodilatation (NO)
This sequesters volume in the abdomen
Decreases systemic filling
Decreases systemic BP
Activates antinatriuretic factors
Combination of increased splanchnic BP with vasodilatation leads to capillary leak
Lymph return can only keep up for sometime then ascites develops.

16. Physical Examination Bulging Flanks Flank Dullness Shifting Dullness
Fluid Wave
Puddle sign
Approximately 1.5 L must be present before flank dullness is detected. If no flank dullness is present, the patient has less than 10% chance of having ascites.
JAMA 1992; 267:

17. Bulging Flanks
Occur when weight of ascites is sufficient to push the flanks outwards
Difficult to distinguish from obesity
Sensitivity-72-93%
Pooled data 81%
Specificity-44-70%
Pooled data 59%
JAMA 1992; 267:

18. Flank Dullness Similar to bulging flanks, although uses percussion
Typically bowel will float to the top and ascitic fluid sinks to the bottom
Sensitivity-80-94%
Most sensitive test
Pooled data 84%
Specificity-29-69%
69% outlying value
Pooled data 59%
JAMA 1992; 267:

19. Shifting Dullness Find the point where flank dullness occurs Mark it
Roll the patient away from the examiner
Repeat percussion and ensure that the point moves to the dependent side
Sensitivity-60-83%
Pooled data 77%
Specificity-56-90%
Pooled data 72%
JAMA 1992; 267:

20. Fluid Wave (fluid thrill)
Medial edges of both hands down midline
Tap flank firmly and feel for an impulse on the other side
Sensitivity-50-80%
Pooled data 62%
Specificity-82-92%
Most specific test
Pooled data 90%
JAMA 1992; 267:

21. Puddle Sign Have patient prone 3-5 minutes then rise to crawling
Place the diaphragm of the stethoscope over the most dependent area of the abdomen
Flick a finger until sound detected
No longer recommended
Formerly used for high sensitivity
Sensitivity-43-55%
Pooled data 45%
Specificity-51-83%
Pooled data 73%
JAMA 1992; 267:

22. International Ascites Club Grading
Grade 1
Mild, only detectable by U/S
Grade 2
Moderate, symmetrical distension
Grade 3
Gross or large with marked distension
Large typically means painful/uncomfortable
Refractory Ascites (5-10%)
Can not be mobilized or early recurrence refractory to medical management
NEJM 350:
Hepatology 2003; 38:

23. Diagnosing Ascites
Ultrasound is the most sensitive test for ascites (100mL detection)
Have to use caution as small or even moderate ascites may be difficult to tap (even when marked)
Ensure mark is appropriate
Go with patient to U/S (ideal)
If not possible, in order specify location where you want to place your needle
Image from

24. Paracentesis: General Tips
Do NOT do paracentesis to see if ascites present, should know before
If unclear need U/S
Ensure patient has voided
FFP/Platelet transfusion if indicated
Ensure landmarks
Get Quick-Tap kit, plastic catheter does not work as well as the metal one.
Picture from

25. Paracentesis:
Site: 5cm cephalic & 5 cm medial to ASIS in the left lower quadrant of the abdomen has been shown to be the ideal site with larger pool of fluid.
Complications: (1% of patients) Abdominal wall hematomas. Hemoperitoneum or bowel entry.
Contraindications: Clinically evident fibrinolysis or DIC.

26. Gross Appearance of Ascitic Fluid
Color
Appearance
Translucent or yellow
Normal / sterile
Brown
Hyperbilirubinemia
GB or biliary perforation
Cloudy or turbid
Infection
Pink or blood tinged
Mild Trauma
Grossly bloody
Malignancy
Abdominal trauma
Milky ("chylous")
Cirrhosis
Thoracic duct injury
Lymphoma

27. Diagnostic Studies Recommended Studies If clinically appropriate
Albumin
Protein
Cell count
Looking for PMNs
Cultures
If clinically appropriate
Glucose
LDH
Amylase
RBC count
TB smear/culture
Cytology
Triglycerides
Polys > 250 infection

28. Diagnostic Studies SAAG > 1.1 SAAG < 1.1
1. Check serum
and fluid albumin
SAAG > 1.1
SAAG < 1.1
Hepatic Sinusoid source
Peritoneum source
2. Check Ascites
Protein
Ascites Protein <2.5
Ascites Protein >2.5
Ascites Protein >2.5
Capillarized sinusoid
Peritoneal lymph
Normal sinusoid
3. Differential
Diagnosis
Cirrhosis
Late Budd-Chiari
Cardiac ascites
Early Budd-Chiari
Veno-occlusive disease
Malignancy
Tuberculosis
The SAAG does not need to be repeated after the initial measurement.
Note: Exceptions exist: may have mixed features
Adapted from

29. Ascitic fluid analysis: If the PMN count is >250 cells/mm3, another specimen is injected into blood culture bottles at bedside. Bacterial growth occurs in about 80% of specimens with count of >250 cells/mm3. In a "bloody" sample that contains a high concentration of RBC, the PMN count must be corrected: One PMN is subtracted from the absolute PMN count for every 250 red cells/mm3 in the sample. The results must be available within 1 hour, so that important diagnostic and therapeutic decisions can be made. A Gram stain is of particular low yield unless free gut perforation, is suspected.

30. Based on clinical judgment, additional testing can be performed
Cytology ,smear & culture for mycobacteria.
Cytology : in peritoneal carcinomatosis (sensitivity increased by centrifuging large volume).
Elevated bilirubin level suggest biliary or gut perforation.
LDH >225mU/L, glucose <50mg/dL, total protein >1g/dL and multiple organisms on gram stain suggest secondary bacterial peritonitis.
High level of TG's confirms chylous ascites.
Elevated amylase level suggest pancreatitis or gut perforation.

31. Prognosis Poor outcomes Refractory ascites SBP HRS
MELD (Model for end-stage liver disease) is not specifically validated for patients with ascites
NEJM 350:

32. Prognosis
Any person with ascites due to cirrhosis needs transplant evaluation
If MELD is <15 can stop there
Average US wait time 500d
Average wait less in some other countries
120 days in UK
180 days in Spain
If admitted for ascites 40% chance of dying within 2 years
Improves to 70-80% 5 year survival after transplant
Cirrhosis is the 12th leading cause of death in the USA
Dig Dis 2005; 23:30-38
Hepatology 2003; 38:

33. Treatment Grade 1 No treatment necessary Modify risk factors
Start low sodium diet
Hepatology 2003; 38:

34. Treatment Grade 2 Bed rest Sodium and water restriction Diuretics
Diuretics work better supine
studied bemetanide
GFR lower standing as well
Sodium and water restriction
Diuretics
Br Med J. 1986;292:1351-3
Hepatology 2003; 38:

35. Treatment Grade 3 Paracentesis is the treatment of choice
Shown to have fewer complications than diuresis
Faster response
After this would do Grade 2 treatment options
Hepatology 2003; 38:

36. Treatment Refractory ascites Paracentesis with colloid infusion TIPS
Choice between these is controversial
If repeated paracentesis is contraindicated,TIPS not an option then consider porto-venous shunt
PVS shown inferior to repeat paracentesis in NEJM study
Hepatology 2003; 38:

37. Sodium Restriction
No survival benefit related to ascites shown, does have benefit in GIB mortality
50mm restriction is equivalent to 120mm (approx. 2g/day)
Tighter restriction had faster resolution
Higher incidence of renal dysfunction and hyponatremia
Hepatology 2003; 38:

38. Diuretics Spironolactone Can use potassium sparing diuretics
start per day
Titrate to max of 400 per day in severe hyper-aldo
Can use potassium sparing diuretics
Amiloride inferior to canrenoate (anti-mineralocorticoid)
No other comparison trials, but spironolactone accepted as first line
Use second line if spironolactone not possible 2/2 complications (ie gynecomastia)
Hepatology 2003; 38:

39. Diuretics Loop diuretics Lasix
Initial dose per day
Can adjust up to 160mg per day
Should be used only as an adjunct to spironolactone
Risks of K depletion, hyperchloremic alkalosis, hyponatremia and hypovolemia with subsequent renal dysfunction
Dig Dis 2005; 23:30-38
Hepatology 2003; 38:

40. Assessing Diuretic Response
Weight loss
Lose 0.5kg a day when no edema
Lose 1kg a day when edema is present
Avoid renal failure
Response rate in up to 90% patients who do NOT have renal dysfunction
Dig Dis 2005; 23:30-38
Hepatology 2003; 38:

41. Paracentesis

42. Paracentesis First used by the Ancient Greeks
Decreased in the 1950s when diuretics were discovered
Resurgence in 1980s after 1987 article found paracentesis with lower complications than diuretics
More effective than diuresis
Shorter hospital stay
Dig Dis 2005; 23:30-38

43. Paracentesis
Total volume paracentesis is as effective and as safe as sequential 3L paracentesis
Hemodynamics
RA pressure drops immediately
PCWP takes 6h to decrease
Hepatology 2003; 38:

44. Paracentesis Post paracentesis volume expansion
Side effects and albumin
without 30%
with 16%
Albumin prevents increased renin/aldo better than synthetic agents
HRS decreases
Less Hyponatremia
NEJM 350:
Hepatology 2003; 38:

45. Paracentesis-Complications
Bleeding - can be fatal
Ascitic fluid leak
Purse string suture
Lie with puncture site up
Bowel perforation
Renal impairment
Hypotension/Cardiovascular collapse

46. TIPS Transjugular Intrahepatic Portosystemic Shunt
Creates a conduit from the high pressure portal system to the lower pressure systemic circulation

47. TIPS Ascites can only form when portal pressure is >12
Response rates 51-79% in RCT
Dig Dis 2005; 23:30-38

48. TIPS - Benefits May improve nitrogen balance
Will decrease portal pressure reducing GIB risk
Improves hemodynamics
Increased CO, RA pressure, PCWP and decreased SVR with increased Na excretion
Improves response to diuresis
NEJM 350:
Hepatology 2003; 38:

49. TIPS - Risks Encephalopathy CHF - this is due to increased preload
30% those treated
Typically can improve with shunt revision or medical management
Increased risk if
Age >60
History of Encephalopathy
100% mortality if refractory to TIPS occlusion
CHF - this is due to increased preload
NEJM 350:
Am J Gastro 2003;98:

50. TIPS - Complications Capsule perforation Stenosis
75% in 6-12 months
Decreased risk with stents coated in polytetrafluoroethylene (PTFE)
Increased cost relative to paracentesis
NEJM 350:
Radiology 1999;231:

51. TIPS v. Paracentesis Several studies (2 examples) Lebrec 1996
No ascites recurrence benefit in CP class C patients with worsened survival
CP class B showed decreased recurrence
Small study (25 patients)
Salerno
Shown to have survival improvement with multivariate analysis (only trend to improved survival without this)
Non-blinded 3 center study
Had to have 4 taps in the last month
Decreased ascites recurrence HR 0.37 ( )
66 patients
J Hepatol 1996;25:135-44
Hepatology 2004;40:

52. Cochrane Database No difference in mortality
Decreased re-accumulation at 3 and 12 months
Increased PSE OR 2.11( )
Surprisingly no difference:
GIB, ARF, Infection or DIC
Some issues in differences between the studies, not all paracentesis had post-paracentesis albumin, differences in MELD/CP between studies
Hepatology 2003; 38:

53. Reasons for TIPS over Paracentesis
TIPS better if
Loculated ascites
Patient unwilling to have repeat taps
Frequent recurrences
Am J Gastro 2003;98:

54. Peritoneovenous Shunts

55. Peritoneovenous Shunts
Creates a communication between the peritoneal cavity and the systemic circulation by a vein
Used in only in limited cases currently
Used for palliation if TIPS and paracentesis are not available or contraindicated
Hepatology 2003; 38:

56. Spontaneous Bacterial Peritonitis
H/O Chronic Liver Disease.
Fever and abdominal pain (66%)
Signs of peritonitis uncommon (<50%)
Neutrocytic ascites on diagnostic paracentesis.
20-30% of pts with CLD develop SBP.
Almost always monomicrobial.
Anaerobes are not associated with SBP
20% are asymptomatic.
Typically due to translocation
This is why E. Coli is the most common

57. SBP: Diagnosis.
Diagnosed with >250 polys or > 50-70% of the total cell count.
Ascitic protein >1gm/dl against SBP.
10-30% are ascitic fluid culture negative.
3% have secondary Bacterial Peritonitis.
Ascitic fluid Glucose, LDH and total proteins may be helpful in DDx.
Erect Abd X-ray in suspicious cases.
NEJM 350:
Hepatology 2003; 38:

58. SBP: Treatment and Prophylaxis
Treat with 3rd generation Cephalosporins.
Repeat PMN count after 48 hrs.
40% develop HRS during the course of illness.
Human Albumin 1.5gm/Kg o day one and 1 gm/Kg on day three has shown improvement in both morbidity and mortality.
Prophylaxis:
70% recur within one year.
Norfloxacin 400mg qd
Ciprofloxacin 750mg q week
Tri-Sulpha: Has never been tested in a trial with mortality.
Ultimate treatment:
Liver transplant.

59. References
Moore K, Wong F, Gines P, Bernardi M et al. The Management of Ascites in Cirrhosis: Report on the Consensus Conference of the International Ascites Club. Hepatology 2003;38:
Gines P, Cardenas A, Arroyo V, Rodes J. Management of Cirrhosis and Asictes. NEJM. 2004;350:
Haskal Z. Improved Patency of TIPS in Humans: Creation and Revision with PTFE Stent-Grafts. Radiology. 1999; 213:
Cardenas A, Arroyo V. Refractory Ascites. Dig Dis. 2005; 23:30-38
Russo M, Sood A, Jacobson I, Brown R. TIPS for Refractory Ascites: An Analysis of the Literature on Efficacy, Morbidity and Mortality. Am J Gastroenterol. 2003; 98:
Heuman D, Abou-assi S, Habib A et al. Persistent Ascites and Low Serum Sodium Identify Patients with Cirrhosis and Low MELD Scores who are at High Risk for Early Death. Hepatology. 2004; 40:
Salerno F, Merli M, Riggio O, Cazzangia M, et al. Randomized Controlled Study of TIPS v. Paracentesis Plus Albumin in Cirrhosis with Severe Ascites. Hepatology 2004;40:
Ring-Larsen H, Henriksen J, Wilken C, Clausen J, et al. Diuretic treatment in decompensated cirrhosis and congestive heart failure: effect of posture. Br Med J 1986; 292:
Lebrec D, Giuily N, Hadengue A, Vilgrain V, et al. TIPS: comparison with paracentesis in patients with cirrhosis and refractory ascites: a randomized trial. French Group of Clinicians and a Group of Biologists.
Saabs, Nieto JM, Ly D, Runyon BA. TIPS versus paracentesis for cirrhotic patients with refractory ascites. The Cochrane database of Systematic Reviews 2004, Issue 3 Art. No.: CD004889
Cattau EL, Stanley BB, Knuff TE, et al. The Accuracy of the Physical Examination in the Diagnosis of Suspected Ascites. JAMA. 1982; 247:
Williams JW, Simel DL. Does This Patient Have Ascites?. JAMA. 1992; 267:
Mallory A, Schaefer JW. Complications of Diagnositc Paracentesis in Patients with Liver Disease. JAMA. 1978; 239:
Runyon BA. Paracentesis of Ascitic Fluid a Safe Procedure. Arch Intern Med. 1986; 146:
Simel DL, Halvorsen RA, Feussner JR. Quantitating bedside diagnosis: clinical evaluation of ascites. J Gen Intern Med. 1988; 3:
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60. Shukriya