MANAGEMENT OF ASCITES IN PATIENTS OF LIVER CIRRHOSIS
Deepak N Amarapurkar
Consultant Gastroenterologist,
Bombay Hospital and Medical Research Centre, Mumbai.
Ascites is a common complication in
patients of liver cirrhosis. Almost 50% of patients with cirrhosis will develop
ascites over a period of 10 years. Development of ascites also indicates
diminished survival. Fifty per cent of patients who develop ascites die over a
period of 2 years. [1]
In the last decade there has been tremendous improvement in understanding
pathogenesis, diagnosis and management of ascites. In this review I will
concentrate on current trends in management of cirrhotic ascites.
Pathogenesis :- Over the years pathogenesis of ascites in cirrhosis was discussed on the basis of underfilling therapy, overflow hypothesis and hypoalbuminaemia. But currently there is general agreement that initial event of renal dysfunction and ascites formation in cirrhosis is combination of increased sinusoidal pressure and hepatic insuffiency. This is based on observations showing higher sinusoidal pressure and more impaired liver function in cirrhotic patients with ascites compared with those patients of cirrhosis who never had ascites. [2] Presently ascites formation is explained on the basis of "peripheral arterial vasodilatation hypothesis", proposed in 1988. [3] According to this hypothesis splanchnic arteriolar vasodilatation secondary to portal hypertension is the initial event. This is followed by baro receptor mediated activation of renin angiotensin system, Sympathetic nervous system and ADH because of the underfilling of arterial vascular compartment not because the circulating blood volume is decreased but because arterial vascular compartment is disproportionally enlarged. Finally this leads to renal sodium and water retention. Splanchnic arterial vasodilation also play a role in increased microvascular hydrostatic pressure and therefore passage of fluid from intravascular compartment to interstitial space during portal hypertension leading to ascites formation. [4]
Diagnosis of ascites :-
Moderate to tense ascites can be diagnosed with reasonably high accuracy just by
clinical examination and demonstrating shifting dullness or fluid thrill. But in
minimal ascites accuracy of physical examination drops down to 50%.
Ultrasonography is 100% accurate in detecting free fluid as less as 50 to 100
ml. in peritoneal cavity.
[5] CT scan and peritoneoscopy
are also equally accurate but are rarely needed to detect ascites. Diagnostic
paracentesis is mandatory in diagnosis of ascites. Diagnostic paracentesis
especially with ultrasonography guidance is easy and safe. There is 1% risk of
abdominal wall haematoma. With USG guidance risk of perforation of viscera is
close to nil. Presence of coagulopathy, (abnormal prothrombin time) doesnot
preclude paracentesis. Prophylactic infusion of fresh frozen plasma or platelets
before paracentesis are not necessary and carry a finite risk of post
transfusion hepatitis.
[6] Ascitic fluid should be
subjected to estimation of cell count and cytology, albumin content, for culture
in blood culture bottles.
[7] Estimation of serum albumin
simultaneously should be carried out. When diagnosis of tuberculosis is
suspected estimation of ascitic fluid adenosine deaminase is required.
[8]
Ascitic fluid is classified as "transudate" or exudate depending upon specific
gravity, protein content and cell count. Fluid containing more than 3g% of
protein and 200 cells/mm3 and specific gravity 1015 were termed as
exudate and those with lower values were termed as transudates. This system of
classification has been shown to be faulty and unreliable.
There is significant overlap between transudates and exudates and almost 1/4
patients can not be categorized.
[9,10]
Hence serum-ascites albumin gradient is calculated by subtracting the albumin
concentration of ascitic fluid albumin from the albumin concentration of serum
obtained on the same day. The serum - ascites albumin gradient (SAAG) correlates
directly with portal hypertension. Patients with gradients of ô 1.1 g/dL have
portal hypertension and patient with gradients of 1.1 g/dL do not. The accuracy
of SAAG is 97%. Hence ascites should not be classified as exudate or transudate
but should be classified on SAAG more than 1.1 g/dL (portal hypertension
related) and less than 1.1 g/dL (nonportal hypertension related).
[9] Further characterizations
can be done on the basis of cell count, malignant cells, culture or ascitic
fluid ADA levels.
Spontaneous bacterial peritonitis (SBP) is a frequent complication in patients
of cirrhotic ascites and is seen in 1/3 of patients at admission.
[10,11] Some of these patients
do not have signs and symptoms of peritonitis. Hence bedside inoculation of
ascitic fluid in blood culture bottles is essential in every case of cirrhotic
ascites. In patients of SBP bacterial load the fluid being very low sending the
fluid to laboratory and culturing it after few hours invariably gives poor
results. [10,11]
Ascitic fluid adenosine adeaminase estimation has been shown to be highly
accurate in diagnosis of tuberculous peritonitis hence should be ordered when
tuberculosis is suspected.
[8] Minority of patients with
cirrhotic ascites have superadded tuberculous peritonitis.
[10]
Ultrasonography and CT scanning are useful in detecting intra abdominal masses
and other associated findings. But in case of difficult situation when all these
modalities fail to give appropriate diagnosis, peritoneoscopy is investigation
of choice which is safe and accurate investigations giving histological
diagnosis. [10]
Treatment of ascites :- Patients with mild to moderate ascites with corrected
diagnosis based on the ascitic fluid analysis can be treated on out patient
basis. Hospitalization is required in patients with tense ascites, presence of
other complications, careful monitoring of renal function and when accurate
diagnosis is not established.
[1]
Patients with mild to moderate ascites are treated with Sodium restriction of 88
meq/day and fluid restriction 1.2 to 1.5 litres/day depending on serum Na+
levels. Sr. Na+ < 120 meq/litres warrants fluid restriction. Patient should be
weighed daily and strict intake and output chart should be maintained. Though
formerly it was advised to observe the patients only on fluid and water
restriction and expect natriuresis to occur, it has been seen that natriuresis
is very rarely seen on expectant treatment hence diuretic therapy should be
started immediately.
[13] Ideally using aldesteron
antagonist first and then introducing frusemide if required was the policy, it
is more practical and economical to use combination of aldesteron antagonist and
frusemide since beginning. In patients with odema of feet associated with
ascites daily wt loss upto 1 kg is acceptable while in patients without
peripheral oedema, a loss of 500 gm/day should be achieved.
Diuretic dosages can be adjusted accordingly. A typical starting daily dose of
100 mg spironolactone and 40 mg of frusemide given once in the morning is used.
[14,15]
Though 400 mg of spironolactone and 160 mg of frusemide have been shown to be
safe upper limit; It is wise to increase diuretic dosage stepwise with strict
check on renal function. Any rise in serum creatinine or blood urea nitrogen
should warrant reduction in dosage of diuretics or stoppage of diuretics.
Therapeutic paracentesis is treatment of choice for diuretic resistant ascites,
but can be offered as primary therapy in patients with tense ascites. In
patients of ascites with peripheral oedema tapping 8 to 10 litres of ascitic
fluid is safe while in patients without oedema 5 to 6 litres of fluid can be
removed safely. [16]
In patients with peripheral oedema. I.V. replacement of albumin may not be
required.
Generally 75% of fluid protein is replaced by intravenous albumin infusion.
Albumin being very expensive, replacement with cheaper agents like dextran and
haemaccele have been shown to be safe and effective. Patients treated with
paracentesis need to observe salt and water restriction and use diuretic to
avoid recurrence of ascites. Therapeutic paracentensis is safe, effective and
reduces hospital stay. When treated with volume replacement has significantly
less complication rates as compared to diuretic therapy.
[17]
Patients treated with potassium sparing diurectics take spironolactone or
ameloride should be instructed to avoid potassium supplements and potassium rich
foods like coconut water, banana and fruitjuices. Use of intravenous frusemide
which leads to sudden fall in GFR should be avoided in patients of ascites and
prostaglandin inhibitors like Nonsteroidal anti inflammatory drugs should be
avoided as they can induce azotaemia.
Medical management including therapeutic paracentesis is effective in almost 95%
patients of cirrhotic ascites. Refractory ascites is defined as ascites that can
not be mobilized or the early recurrence after paracentesis cannot be
satisfactorily prevented by medical therapy.
[18] Treatment options for
refractory ascites includes peritoneovenous shunt, transjugular intra hepatic
portosystemic shunts, extra corporeal ultrafiltration of ascitic fluid with
reinfusion and liver transplantation. Novel pharmacological approaches under
investigations include use of angiotensin converting enzyme inhibitors,
prostaglandins, ornipressin.
Early detection of SBP and its appropriate treatment with antibiotics is also
integral part of management of ascites. Use of antibiotics like norfloxacin or
Sulphamethoxazole trimethoprim combination for prophylaxis against SBP have been
shown to effective may be considered as a part of treatment of ascites.
[19]
REFERENCES