1. Management of ascites in cirrhosis
BSG 2006

2. Definition
Pathogenesis
Diagnosis- asctitic fluid analysis
Treatment- salt restriction/diuretic
Therapeutic paracentesis
TIPSS
SBP

3. Setting the scene Occurs in 50% of patients over 10yrs
Associated with 50% mortality over two yrs
Indicates the need to consider liver transplantation
Mortality from cirrhosis is 12.7 per 100,000 population
Approx 4% of population have abnormal LFT, 10-20% of those develop cirrhosis over 10-20yrs

4. Uncomplicated ascites- not infected and not associated with HRS
Refractory ascites- cannot be mobilised or early recurrence of which ( that is after therapeutic paracentesis) cannot be prevented by medical treatment
Diuretic resistant ascites- refractory to dietary salt restriction and intensive diuretic treatment ( spironolactone 400mg and frusemide 160mg per day and salt restricted diet of less than 90mmol/day ( 5.2g/day)
Diuretic intolerant ascites- refractory to therapy due to the development of diuretic induced complications

5. Grading of ascites Grade I: Only detectable by US
Grade II: Moderate symmetrical distension of the abdomen
Grade III: Marked abdominal distension

6. Pathogensis
Portal hypertension
Sodium and water retention

7. Role of portal hypertension
PH increases the hydrostatic pressure with the hepatic sinusoid and favours transudation of fluid into the peritoneal cavity
PH occurs as a consequence of structural changes within the liver in cirrhosis and increased splanchnic blood flow

8. Progressive collagen deposition and nodule formation alter vascular architecture and increases the resistance to portal flow
Collagen is formed within the space of Disse and sinusoids become less distensible

9. Increased splanchnic flow because of vasodilation due to release of NO

11. Increased resistance in the hepatic sinusoid
Portal hypertension
Congestion of capillary in intestine
Endotoxaemia
NO release
Arterial vasodilation in both systemic and splanchnic circulation- systemic ( tachycardia increased stroke volume) and splanchnic ( increased portal flow- and more rise in portal pressure)
Decrease in effective circulatory volume
Activation of RAS system and sympathetic system- ( aldosterone increase promoting Na retention and secondary fluid retention to restore blood volume)
Renal vasoconstriction to increase glomerular pressure- ultimately attempts at homeostasis fails- GFR starts to fall

12. Sinusoidal endothelial cells form and extremely porous membrane – almost completely permeable to macromolecule
Old theory that low albumin is the cause of ascites is false as there is no oncotic gradient ( it works for peripheral oedema but not for ascites)
Portal hypertension is critical to development to ascites and develops when wedged hepatic portal venous pressure is more than 12mm
TIPSS relieves ascites by reducing portal hypertension though low albumin and cirrhotic liver persists

13. Presinusoidal portal hypertension does not produce ascites ( portal vein thrombosis)
Post sinusoidal portal hypertension does produce back pressure and cause similar haemodynamic changes and causes ascites ( hepatic vein thrombosis)

14. Sinusoidal portal hypertension, in the presence of severe hepatic decompensation
Leads to splanchnic and systemic vasodilatation-role of NO
Decreased effective arterial blood volume
Activation of systemic vasoactive factors, such as the renin-angiotensin system, the sympathetic nervous system, and vasopressin aimed at restoring arterial filling pressure.
Renal vasoconstriction increases concomitantly (leukotrienes and endothelins), counterbalanced by the intrarenal hyperproduction of vasodilating prostaglandins. When this balance is lost renal hemodynamics worsens, and hepatorenal syndrome develops

15. Cirrhosis 75%
Malignancy 10%
Heart failure 3%
TB 2%
Pancreatitis 1%

16. Blood tests- FBC/U&E/LFT/INR
Ultrasound- liver/spleen/portal vein/LN
Ascitic fluid analysis

17. Abdominal paracentesis
15cm lateral to umbilicus
Avoid enlarged spleen and liver
Avoid sp and inf epigastric arteries
No data to support use of FFP
Most clinicians would give pooled platelets if <40
Complication:
Haematoma<1%
Bowel perforation/haemoperitoneum <0.1%
10-20ml of fluid in a syringe with blue/green needle

18. Blood culture bottle- culture
EDTA tube- cell type
Yellow top tube- albumin/amylase
Yellow top tube- blood ( for serum albumin)

19. Ascitic fluid neutrophil count and culture
SBP is present in 15% patients admitted to hospital
Ascitic neutrophil count of >250cells/mm3 is diagnostic of SBP in absence of perforated viscus or inflammation of intraabdominal organs
RBC count is usually <1000cells/mm3
In 2% of cirrhotic bloody ascites >50,000
In bloody ascites 50% no cause and 30% HCC

20. The prevalence of occult ascitic fluid infection in asymptomatic outpatients undergoing large volume paracentesis for resistant ascites is low
As a result, the routine culture of fluid during paracentesis in such patients is probably not warranted.
Obtain a cell count and differential on all samples of ascitic fluid while obtaining cultures only in symptomatic patients.

21. Culture in sterile container will identify onlY 40% of cases of SBP
Whereas culture in blood culture bottle will identify %
Gram stain and AFFB stain inappropriate
Fluid culture for mycobacteria 50% sensitivity

22. 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

23. 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
SAAG is far superior with 97% accuracy
Eg Serum albumin 26 and ascitic albumin 11- so SAAG is 15- so high SAAG- previously called transudate
SAAG>11g/L
Cirrhosis
Cardiac failure
Nephrotic syndrome
SAAG<11g/L
Malignancy
Pancreatitis
Tuberculosis

24. Amylase in pancreatic ascites
Triglyceride in chylous ascites
Bilirubin in post op ascites

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- salt restriction
Typical UK diet has 150mmol/day- 15% added salt and 70% is manufactured salt
Suggestion is no added salt diet and avoidance of prepared food
So that patient gets 90mmol/day ( 5.2gm)
Lowers diuretic requirement, faster resolution of ascites and shorter hospital stay
Avoid high salt content of fluid and medicine except in HRS

27. Treatment- water restriction
No role in uncomplicated ascites
Most hepatologists restrict fluid in ascites associated with hyponatraemia- but is illogical
The downside is water restriction causes increase in the central effective hypovolaemia- more ADH- more water retension 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
To be effective the intake should be less than urine output rather than arbitrary 1.5L/day
If the serum sodium concentration does not increase within the first 24 to 48 hours, the degree of fluid restriction has been insufficient.

28. Treatment- diuretic Spironolactone is drug of choice
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- gynaecomazia- tamoxifen 20mg bd
Hyperkalaemia frequently limits the use

29. Treatment- diuretic 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 3rd day to max of 160mg
Watch out for metabolic alkalosis and electrolyte disturbance

30. Treatment- diuretic Stepped care approach
Till oedema is present no need to slow down the daily weight loss
Once oedema is resolved – daily weight loss should be less than 0.5kg per day
Over diuresis is associated with intravascular volume depletion, leading to renal impairment, hepatic encephalopathy and hyponatraemia
10% will have refractory ascites
Dietary history to exclude salt ingestion- 24hr urinary Na excretion should be less than recommended intake
Drug history - NSAID

31. Problem with hyponatraemia
Na and normal creatinine
Continue diuretic
Do not water restrict
Na and normal creatinine
Continue/? discontinue
Na and high Creatinine
Stop diuretic and give volume expansion
Na <120
Stop diuretic

32. 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

33. Therapeutic paracentesis
Total paracentesis is associated with significant haemodynamic changes
Large volume paracentesis causes marked reduction of IAP and IVC pressure- decrease in right heart pressure and
This changes are maximal at 3hrs

34. International ascites club recommend if <5L is removed synthetic plasma expander can be used and as good as albumin ( some hepatologist suggests no albumin/plasma expander if <5L)
Compared to albumin, artificial plasma expander cause more activation of RAS , causes more hyponatraemia and results in longer hospital stay
20% albumin should be infused after paracentesis of >5L at dose of 8g/L of ascites drained ( 100ml of 20% albumin= 20gm, so 3L of ascites fluid removal needs 3x8=24 gm of albumin replacement = 125ml but we tend to round it to 100ml)
So if >10L remember to give an extra 100ml of albumin
25% albumin can be given if the patient is hypervolemic while 5 percent albumin can be given if dehydration is suspected.

35. 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

36. 10% of patients will have refractory ascites and will need paracentesis
Following paracentesis ascites will recur in 93% if diuretic is not reinstituted and only 18% if treated with spironolactone
Reintroduction of diuretics after 1-2 days does not appear to increase the risk of post paracentesis circulatory dysfunction

37. 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

38. Prognosis Mortality of 50% within 2yr of diagnosis
Once refractory to medical therapy 50% die within 6 months
Time for referral to transplant centre as paracentesis and TIPSS does not improve long term survival except improving quality of life