Ascites

Ascites is the pathological accumulation of fluid in the abdominal cavity, derived from the Greek word, askos, meaning bag or sac. A tiny amount of fluid is normal and helps to lubricate the surfaces of the peritoneum. For fluid to be detectable by clinical examination there has to be at least 1500 ml present, slightly less in a small, thin person, but significantly more in the obese, whilst ultrasound can detect much smaller volumes (≤ 500 ml).

Fluid retention (primarily ascites, but also peripheral oedema and pleural effusions) is the most frequent complication of end-stage liver disease. It significantly impairs the quality of life of patients with cirrhosis and is associated with poor prognosis, 1-year and 5-year survivals of 85% and 56%, respectively.¹

• Cirrhosis - approximately 75% of patients presenting with ascites have underlying cirrhosis, and about 50% of patients with cirrhosis will develop ascites over a 10 year period of follow up.²
• Malignancy accounts for around 15%. The usual causes are:
  • Malignancies of the GI tract (carcinoma of stomach, colon, pancreas, primary hepatocellular carcinoma and metastatic liver cancer)
  • Carcinoma of ovary (Note: Meigs' syndrome is a rare complication of ovarian cancer and produces ascites out of all proportion to the size of the tumour and pleural effusions, often unilateral.)
  • Hodgkin's lymphoma and non-Hodgkin's lymphoma
  • Metastatic carcinoma within the abdominal cavity
• Heart failure in 3%.
• Tuberculosis is responsible in 2% and is a disease that is easily overlooked.
• Pancreatitis is the cause in 1%.
• There are various other rare causes, including myxoedema.
• Ovarian hyperstimulation, as a consequence of IVF procedures, is an iatrogenic cause.

Portal hypertension

Portal hypertension encourages the transudation of fluid into the peritoneal cavity.

• In presinusoidal portal hypertension without cirrhosis, ascites is rare.²
• Ascites does not develop with isolated chronic extrahepatic portal venous occlusion or non-cirrhotic causes of portal hypertension such as congenital hepatic fibrosis, unless liver function is impaired as after gastrointestinal haemorrhage.
• Acute hepatic vein thrombosis, however, usually results in ascites (via postsinusoidal portal hypertension).

Portal hypertension with ascites requires a wedged hepatic venous portal gradient of >12 mm Hg.³ Conversely, insertion of a side to side portacaval shunt to decrease portal pressure often causes resolution of ascites.

Salt and water retention

Ascites represents a state of total-body sodium and water excess. The initial precipitating event is unclear:¹

• The peripheral arterial vasodilation hypothesis suggests that initially portal hypertension increases sinusoidal pressure and activates vasodilatory mechanisms via nitrous oxide overproduction. Fluid is sequestered in the splanchnic bed, reducing effective circulating blood volume.
• Compensatory mechanisms then adjust plasma volume and cardiac output: activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system (RAAS) lead to a compensatory sodium and water retention.
• Persistent renal sodium and water retention, increased splanchnic vascular permeability and lymph leakage into peritoneal cavity are thought to play the major role in a sustained ascites formation.

Hypoalbuminaemia

The old concept that ascites is due to decreased oncotic pressure is now known to be false - plasma albumin concentrations have little influence on the rate of formation of ascites, although hypoalbuminaemia is frequently present in cirrhotic patients.

History

• The patient usually acknowledges "getting fat", meaning an expanding waist line and tight clothes, but weight also rises with water retention.
• Discomfort - tense ascites is very uncomfortable but prior to this stage there is simply abdominal distension with only very mild discomfort. Malignancy related ascites is frequently painful.
• Nausea and appetite suppression - tense ascites presses on the stomach and GI tract.
• Increasing dyspnoea - due to limited venous return from the lower limbs (pressure on the inferior vena cava) and impaired expansion of the lungs (pressure on the diaphragm).
• There may be other symptoms related to the cause of the ascites.
• Consider risk factors for liver disease:
  • Alcohol consumption
  • History of jaundice
  • History of chronic Hepatitis B or Hepatitis C (or risk factors for these diseases)
  • Obesity (cause of nonalcoholic fatty liver changes, which can progress to cirrhosis)

Examination

• Look at the patient, both lying down and standing up. The shape of the abdomen often suggests fluid. On lying down, the flanks are full but on standing the fluid accumulates in the lower abdomen.
• The high intra-abdominal pressure may push out an umbilical hernia or even an inguinal hernia.
  
• There may be stigmata of other diseases. Look for signs of liver disease and cirrhosis including:
  • Jaundice
  • Muscle wasting
  • Gynaecomastia
  • Spider naevi
  • Palmar erythema
• Remember malignancy and the other causes too. Rarely, a firm nodule in the umbilicus, known as the Sister Mary Joseph nodule, is found and suggests peritoneal carcinomatosis originating from gastric, pancreatic, or hepatic primaries. Similarly a left-sided supraclavicular node or Virchow node suggests the presence of upper abdominal malignancy.
• Perform a full abdominal examination, as described in the article. Only the section specifically related to ascites will be elaborated here.

Examination for ascites

• Shifting dullness is used to detect ascites. One study found the absence of flank dullness to be the most accurate predictor against the presence of ascites - the probability of ascites without flank dullness was less than 10 percent.⁴
  • Percuss from the level of the umbilicus and repeat moving laterally towards one side.
  • When the sound becomes dull, keep your fingers there to mark the spot and ask the patient to move on to the opposite side.
  • Wait briefly for the fluid to sink and percuss again. If it is now resonant, that is a positive sign. Percuss down until dullness is reached again.
  • Repeat on the other side.
  • False positives do occur, probably from dilated coils of small intestine reacting to gravity.
  • At least 1500 ml of fluid must be present for a result. An ultrasound scan will detect much less fluid with greater certainty.
• A succussion splash is much more difficult to demonstrate. It needs a third hand in the examination and probably rather more fluid.

Monitoring

Simple assessment of the progress of ascites may be made by:

• Serial measurements of the abdominal girth - ensure the tape measure is placed in the same position each time.
• Serial measurement of weight - rapid changes indicate fluid gain or loss which are much faster than gain or loss of fat or lean body mass.

The differential diagnosis of ascites is with other causes of abdominal mass, especially large cysts, although sometimes plain obesity may seem like ascites. The essential feature is the fluidity and shifting with position.

The cause of the ascites is often apparent after an adequate history and examination. The patient with a high consumption of alcohol and ascites probably has cirrhosis but this must not be assumed and other possible causes should be sought. Beware the patient with a very long history of stable cirrhosis who then develops ascites - hepatocellular carcinoma must be excluded.

The aims of investigation for ascites are:

• Confirming the presence of ascites.
• Finding the cause for the ascites.
• Assessing any complication due to the ascites.

Blood tests

• FBC
• U&Es and creatinine
• LFTs including plasma proteins
• Clotting screen
• TFTs

If cirrhosis is confirmed, further tests will be required to elucidate the cause e.g. antibody tests for hepatitis B or C.

Imaging studies

• Abdominal ultrasound is a very sensitive way of assessing ascites and may also show the causative pathology such as carcinoma of ovary or metastatic liver disease.
• Chest x-ray may show pleural effusion, evidence of pulmonary metastases or heart failure.
• If ultrasound has failed to reveal a cause, then MRI scanning may be used.

Invasive procedures

• Ascites Tapping is discussed in its own article. A diagnostic paracentesis, when only about 20 ml is required, is standard in the investigation of ascites. The caveats and precautions are discussed in the article.
• Ascitic fluid should be sent for measurement of:²
  • Albumin or protein
  • Neutrophil count
  • Amylase
  • Culture and sensitivity
  • Cytology where malignancy is suspected
• If liver disease is suspected, especially cirrhosis, liver biopsy may be undertaken although this is not invariably required.

Ascites that is not infected and not associated with hepato-renal syndrome may be graded as follows:²

• Grade 1 is mild ascites and is only detectable by ultrasound examination.
• Grade 2 is moderate ascites causing moderate symmetrical distension of the abdomen.
• Grade 3 is large ascites causing marked abdominal distension.

Refractory ascites can be divided into two groups:

• Diuretic resistant ascites is refractory to dietary sodium restriction and intensive diuretic treatment for at least one week.
• Diuretic intractable ascites is refractory to therapy due to the development of diuretic induced complications that preclude the use of an effective dose of diuretic.

A working diagnosis of the underlying cause of the ascites is important to give a rationale for treatment. Management depends upon the aetiology.

Palliative care

In malignant ascites, paracentesis, diuretics and shunting are commonly used procedures but robust evidence supporting their use in this palliative setting is lacking. ⁶

• Paracentesis gives good, although temporary, symptom relief though there are unanswered questions as to the best rate of fluid withdrawal and the need for concurrent intravenous hydration.
• Shunts can control malignant ascites but there are potential risks entailed.
• The use of diuretics in the treatment of malignant ascites is controversial - they should be considered in all patients but need to be evaluated individually.

Non-drug management

• Avoiding alcohol is important in pancreatitis and cirrhosis of any aetiology, not just alcoholic.
• A no added salt diet restricted to <90 mmol/day (5.2 g of salt/day) is useful, especially in cirrhosis but is unlikely to be effective in other aetiologies such as malignancy.
• Bed rest is not recommended for uncomplicated ascites. Theoretically, the upright position in those with ascites will aggravate renin-angiotensin-aldosterone/sympathetic nervous system activation, reducing glomerular filtration rate and sodium excretion and response to diuretics,⁷ but there have been no clinical studies to demonstrate increased efficacy of diuresis with bed rest or decreased hospital stay. Bed rest leads to muscle atrophy and other complications and may have the paradoxical opposite effect, actually extending stays in hospital.

Drugs

The first line of management of ascites is medical treatment (sodium restriction and diuretic therapy) and is effective in the majority of cirrhotic patients with non-refractory ascites.

• Diuretics:
  • Spironolactone is the best initial choice in cirrhosis: it increases sodium excretion and potassium reabsorption in the distal tubules. 100 mg/day can gradually be increased to 400 mg as necessary. Serum potassium levels need monitoring as hyperkalaemia frequently limits spironolactone's use.
  • Loop diuretics may be used as an adjunct to spironolactone, generally only when maximum doses of the latter have been reached.² Start cautiously with e.g. furosemide 40 mg/day although up to 160 mg/day may be used. High doses cause severe electrolyte disturbance, particularly hyponatraemia.
• If the underlying problem is congestive heart failure then treatment needs to be energetic with diuretics, ACE inhibitors and other drugs.
• Malignancy may respond to appropriate chemotherapy, depending upon the type.
• Myxoedema will resolve with gradual introduction of thyroxine.

Therapeutic paracentesis

• Patients with large or refractory ascites generally benefit from therapeutic paracentesis.^2,8
• This needs to be a sterile procedure.
• Paracentesis of <5 litres of uncomplicated ascites should be followed by plasma expansion with synthetic plasma expander i.e. 150-200 ml of gelofusine or haemaccel®.²
• Larger volume paracenteses should be be followed by volume expansion, using 8 g albumin per litre of ascitic fluid removed.

Surgical

• Surgical treatment may be required for malignancy and some patients may be suitable for liver transplantation.
• Transjugular intrahepatic portosystemic shunt (TIPS) can be used in patients with refractory ascites needing frequent paracentesis (>3/month).
  • It is a local anaesthetic procedure (with sedation) and has generally replaced surgically created portocaval shunts.
  • Trial results are often conflicting as to whether such a procedure offers improved survival as compared with repeated therapeutic paracentesis. Shunts block in about a quarter of cases.⁹ The most recent Cochrane Review on this subject concluded that TIPS was more effective at removing ascites compared with paracentesis; there was no significant difference in mortality, gastrointestinal bleeding, infection, and acute renal failure but TIPS patients develop hepatic encephalopathy significantly more often.¹⁰ One meta-analysis of individual patient data does suggest an improved transplant-free survival time for those receiving TIPS¹¹ but this remains controversial.
  • The TIPS Risk score can be calculated¹² which is helpful in determining when the risk/benefit ratio for TIPS is favourable. The calculation involved is quite complex: an on-line calculator may assist,¹³ which can be used in conjunction with a creatinine units converter.¹⁴

Hyponatraemia on diuretics²

(See also hyponatraemia)

• Serum sodium 126-135 mmol/l with normal serum creatinine: continue diuretics but watch electrolytes regularly (do not fluid restrict).
• Serum sodium 121-125 mmol/l with normal serum creatinine: stop diuretics² or continue diuretics cautiously at lower dose and watch electrolytes frequently.
• Serum sodium 121-125 mmol/l with elevated serum creatinine (>150μmmol/l or >120 μmmol/l and rising): stop diuretics and give volume expansion.
• Serum sodium ≤120 mmol/l: Management is difficult. Guideline suggests stopping diuretics and giving volume expansion with colloid or saline but avoid increasing serum sodium by >12 mmol/24 hours.

Only fluid restrict patients who are not dehydrated, not receiving diuretics and in whom creatinine is normal.²

Spontaneous bacterial peritonitis (SBP)

• This occurs in 10-30% of patients with ascites and has mortality rate of 20%.
• It is frequently asymptomatic but most will have some symptom(s) such as fever, mild abdominal pain, vomiting, or confusion.
• Suspect SBP where patients present with hepatic encephalopathy, renal impairment or peripheral leucocytosis without any obvious precipitating factor.
• A diagnostic paracentesis is mandatory in all patients with cirrhosis requiring hospital admission to ensure that it is detected.
• Organisms are usually E. coli, streptococci and enterococci.
• Empirical antibiotics should be started if ascitic fluid contains >250 cells/mm³. There is no clear evidence favouring one particular antibiotic but in practice third generation cephalosporins have become the standard treatment for SBP.¹⁵
• Prophylactic antibiotics for SBP should be given in certain patient populations.
• All patients with SBP should be referred for consideration for liver transplantation.

Hepatorenal syndrome (HRS)¹⁶

• HRS is a severe complication, occurring in approximately 10% of patients with cirrhosis and ascites. It can be rapidly progressive, triggered by an event such as SBP, and requiring urgent intervention (typically treatment with a plasma expander, normally albumin, and a vasoconstrictor such as vasopressin) or occurs much more gradually, as a consequence of aggravation of end-stage
  liver disease, and requires no additional treatment.
• It is characterised by renal vasoconstriction leading to renal failure. The renal vasoconstriction is a compensatory effect of the renin-angiotensin-aldosterone system and antidiuretic hormone, triggered by an extreme underfilling in the arterial circulation.
• Liver transplant again should be considered in those developing HRS.

• Ascites is a major complication of cirrhosis, occurring in 50% of patients over 10 years of follow up.⁷ The development of ascites is an important landmark in the natural history of cirrhosis as it is associated with a 50% mortality over two years, and signifies the need to consider liver transplantation. Refractory ascites carries an even poorer prognosis, 50% patients dying within six months.
• Whilst they may improve quality of life, therapeutic paracentesis and TIPS are not thought to improve long term survival without transplantation significantly for most patients with cirrhosis.
• In malignancy ascites tends to suggest widespread disease and a poor prognosis.