Management of ascites in cirrhosis

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Management of ascites in cirrhosis

• BSG 2006

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

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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

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• 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

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Grading of ascites

• Grade I Only detectable by US
• Grade II Moderate symmetrical distension of the
  abdomen
• Grade III Marked abdominal distension

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Pathogensis

• Portal hypertension
• Sodium and water retention

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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

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• 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

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• Increased splanchnic flow because of vasodilation
  due to release of NO

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• 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

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• 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

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• 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)

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1. Sinusoidal portal hypertension, in the presence
   of severe hepatic decompensation
2. Leads to splanchnic and systemic
   vasodilatation-role of NO
3. Decreased effective arterial blood volume
4. Activation of systemic vasoactive factors, such
   as the renin-angiotensin system, the sympathetic
   nervous system, and vasopressin aimed at
   restoring arterial filling pressure.
5. 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

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• Cirrhosis 75
• Malignancy 10
• Heart failure 3
• TB 2
• Pancreatitis 1

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• Blood tests- FBC/UE/LFT/INR
• Ultrasound- liver/spleen/portal vein/LN
• Ascitic fluid analysis

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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
  lt40
• Complication
• Haematomalt1
• Bowel perforation/haemoperitoneum lt0.1
• 10-20ml of fluid in a syringe with blue/green
  needle

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

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Ascitic fluid neutrophil count and culture

• SBP is present in 15 patients admitted to
  hospital
• Ascitic neutrophil count of gt250cells/mm3 is
  diagnostic of SBP in absence of perforated viscus
  or inflammation of intraabdominal organs
• RBC count is usually lt1000cells/mm3
• In 2 of cirrhotic bloody ascites gt50,000
• In bloody ascites 50 no cause and 30 HCC

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• 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.

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• Culture in sterile container will identify onlY
  40 of cases of SBP
• Whereas culture in blood culture bottle will
  identify 72-90
• Gram stain and AFFB stain inappropriate
• Fluid culture for mycobacteria 50 sensitivity

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• 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

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• Previously transudate if gt25g/L and exudate if
  gt25g/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

SAAGgt11g/L Cirrhosis Cardiac failure Nephrotic
syndrome
SAAGlt11g/L Malignancy Pancreatitis Tuberculosis
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• Amylase in pancreatic ascites
• Triglyceride in chylous ascites
• Bilirubin in post op ascites

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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

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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

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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.

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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

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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

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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

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Problem with hyponatraemia
Na 126-135 and normal creatinine Continue diuretic Do not water restrict
Na 121-125 and normal creatinine Continue/? discontinue
Na 121-125 and high Creatinine Stop diuretic and give volume expansion
Na lt120 Stop diuretic
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Controversy regarding normal saline

• Give only if renal function is worsening
  creatinine gt150 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

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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

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• International ascites club recommend if lt5L is
  removed synthetic plasma expander can be used and
  as good as albumin ( some hepatologist suggests
  no albumin/plasma expander if lt5L)
• 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 gt5L at dose of 8g/L of ascites drained ( 100ml
  of 20 albumin 20gm, so 3L of ascites fluid
  removal needs 3x824 gm of albumin replacement
  125ml but we tend to round it to 100ml)
• So if gt10L 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.

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• 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

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• 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

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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 gt60yrs
• May precipitate heart failure as increase cardiac
  preload
• TIPSS should be considered for patients who
  require frequent paracentesis ( gt3 a month)
• It also shown to resolve hepatic hydrothorax in
  60-70
• MELD was originally developed to predict survival
  after TIPSS insertion

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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