Evaluation and diagnosis of ascites
In Western Europe or the United States, approximately 75% of patients with ascites have cirrhotic ascites, and the remainder may be due to other diseases such as malignancy, heart failure, tuberculosis, or pancreatic disease.
The initial assessment of ascites should include history, physical examination, abdominal ultrasound, liver and renal function, blood and urine electrolytes, and ascites analysis.
The International Club of Ascites recommends that treatment of uncomplicated ascites should be based on quantitative criteria (see Table 1), and this guideline agrees with that recommendation, whereas the 2009 US Guidelines for the Management of Cirrhotic Ascites do not describe the grading of ascites.
Diagnostic laparotomy is essential to identify the cause of ascites and to help rule out spontaneous bacterial peritonitis (SBP) in cirrhosis. A serum- ascites albumin gradient (SAAG) ≥11 g/L helps to diagnose portal hypertensive ascites with 97% accuracy. Total ascitic fluid protein concentration <15 g/L has an increased risk of SBP, so total ascitic fluid protein concentration can be used to assess the risk of SBP. An ascitic fluid neutrophil count is useful to rule out SBP. all patients with ascites should have bedside inoculation of ascites (10 mL) into blood culture bottles.
Recommendations
(i) Diagnostic laparotomy should be performed in all hospitalized patients with new grade 2 or 3 ascites, worsening ascites, or combined cirrhotic complications.
②Neutrophil count and ascites culture (bedside inoculation into a blood culture bottle) should be used to rule out bacterial peritonitis.
③The determination of total ascites protein concentration is important, and patients with ascites with concentrations <15 g/L are at increased risk of SBP, which can be avoided by prophylactic antibiotics in such patients.
④ When the diagnosis of cirrhotic ascites is not based on sufficient evidence, or when it is uncertain whether cirrhosis is the cause of ascites, a serum- ascites albumin gradient can help to identify it (LevelA2).
Prognosis of ascites
The formation of ascites in cirrhosis suggests a poor prognosis. Other indicators of poor prognosis include low blood sodium, low blood pressure, elevated blood creatinine, and low urine sodium.
Recommendations
As the presence of grade 2 or 3 ascites in patients with cirrhosis suggests a poor prognosis, liver transplantation should be considered as a backup treatment option (LevelB1).
Management of uncomplicated ascites
Patients with cirrhotic ascites are often complicated by intractable ascites, SBP, hyponatremia, or hepatorenal syndrome (HRS). Ascites without these ascites complications is called uncomplicated ascites.
Grade 1 or small amounts of ascites
There are no data on the natural course of grade 1 ascites, nor is it known how long it takes to progress to grade 2 or 3 ascites.
Grade 2 or moderate ascites
Patients with moderate ascites generally do not require hospitalization unless they have other co-morbidities. Treatment is directed at antagonizing renal sodium retention to achieve negative sodium balance, which can be achieved by reducing sodium uptake and increasing renal sodium excretion with diuretics. Upright position activates the sodium retention system and reduces renal perfusion, but absolute bed rest is not recommended because there is insufficient clinical evidence that it improves ascites.
Sodium restriction is achieved by reducing sodium intake in approximately 10% to 20% of patients with cirrhotic ascites, especially in the first episode. Although there are no controlled clinical studies on sodium restriction versus non-sodium restriction, the general opinion is that sodium restriction should be appropriate (about 80-120 mmol/d). Excessively strict sodium restriction is not recommended because it may compromise nutritional status. Fluid intake should be restricted in patients with dilutional hyponatremia.
Recommendations
① Moderate restriction of sodium intake is an important component of ascites treatment (sodium intake of 80 to 120 mmol/d, equivalent to 4.6 to 6.9 g/d of sodium) (Level B1). This intake is equivalent to not adding additional sodium to the diet.
(ii) There is insufficient evidence for bed rest as part of the treatment of ascites. There are no data to support the need for fluid intake restriction in ascites patients with normal blood sodium (LevelB1).
Diuretic evidence suggests that renal sodium retention in patients with cirrhotic ascites is primarily due to increased proximal and distal tubular sodium reabsorption, rather than decreased filtration. Increased distal tubular sodium reabsorption is mainly associated with increased aldosterone, therefore aldosterone antagonists are more effective than tab diuretics in the treatment of ascites and should be preferred. Aldosterone has a slow onset of action, and the dose of aldosterone antagonists is recommended to be increased every 7 days. Amiloride, a diuretic that acts on the collecting duct, is less effective than aldosterone antagonists and should only be used in patients with ascites who cannot tolerate aldosterone antagonist therapy.
The use of aldosterone antagonists alone or in combination with tab diuretics (e.g., furosemide) has long been debated in the treatment of ascites. The lack of consistent results between the two studies may be related to differences in the patient populations in each study, especially the proportion of patients with ascites that included a first episode may have led to different results. What is certain is that: aldosterone antagonist and furosemide combination therapy is more appropriate for patients with recurrent ascites.
Complications of diuretic therapy The use of diuretics may cause some complications such as renal failure, hepatic encephalopathy, electrolyte disturbances, gynecomastia and muscle cramps. Renal failure due to hypovolemia is the most common and is usually the result of excessive diuresis. Diuresis is often thought to be a trigger for hepatic encephalopathy, but the exact mechanism of action is unknown. The use of tab diuretics alone can induce hypokalemia, and aldosterone antagonists or other potassium-preserving diuretics can lead to hyperkalemia, especially in patients with renal impairment.
Hyponatremia is another common complication of diuretic therapy. It is controversial at what level of sodium should diuretics be discontinued, however, most experts believe that diuretics should be temporarily discontinued when serum sodium is as low as 120 to 125 mmol/L. The use of aldosterone antagonists is often associated with gynecomastia, but discontinuation is usually not necessary. Diuretics can also cause muscle spasms and should be reduced or discontinued in severe cases, and albumin infusion may relieve symptoms.
Complications tend to appear during the first week of diuretic therapy. Therefore, blood creatinine, sodium and potassium concentrations should be monitored during this period, but urinary sodium is not routinely tested. Only those who do not respond to diuretic therapy need to monitor urinary sodium to assess the effect of diuretic therapy.
Recommendations
①Patients with initial grade 2 (moderate) ascites should receive simple aldosterone antagonist therapy, such as spironolactone, at a starting dose of 100 mg/d; if there is no response, the dose should be increased every 7 days (100 mg each time) until the maximum dose.
②Treatment with aldosterone antagonists without response (weight loss <2kg per week) and those who develop hyperkalemia after treatment should be combined with furosemide.
(③Biochemical parameters should be tested frequently in diuretic-treated patients, especially in the first month of treatment.
④ Patients with recurrent ascites should receive a combination of an aldosterone antagonist and furosemide, with a gradual increase in dose based on response to treatment, as previously described.
⑤ The recommended maximum daily weight loss after diuretic therapy is ≤0.5 kg in patients without edema and no more than 1 kg in patients with edema.
⑥The long-term goal of diuretic therapy is to maintain an ascites-free state at the lowest dose.
(7) Patients with ascites who present with renal impairment, hyponatremia, or abnormal serum potassium concentrations should start diuretic therapy with caution and closely monitor biochemical parameters. There are insufficient data to indicate the severity of renal impairment and hyponatremia that should prohibit diuretic therapy. Serum potassium levels should be corrected before starting diuretic therapy. Diuretic therapy is usually contraindicated in patients with overt hepatic encephalopathy (LevelB1).
(8) The presence of severe hyponatremia (serum sodium <120 mmol/L), progressive renal failure, exacerbation of hepatic encephalopathy, or severe muscle spasms.
⑨ Furosemide should be discontinued for severe hypokalemia (<3mmol/L); aldosterone antagonist (LevelB1) should be discontinued for severe hyperkalemia (>6mmol/L).
Grade 3 or massive ascites
Laparotomy for massive fluid release (LVP) is the preferred treatment for patients with grade 3 ascites. LVP combined with albumin infusion is more effective and safer than diuretics, but there is no difference between the two treatments in terms of readmission or survival.
The massive release of ascites can cause a reduction in effective blood volume, called post-peritoneal cavernosal circulation disorder (PPCD), which is detrimental to the maintenance of circulatory homeostasis and can lead to rapid reaccumulation of ascites, with hepatorenal syndrome (HRS) and/or dilutional hyponatremia occurring in 20% of patients, and an increase in portal pressure due to the constrictive system of the hepatic vascular bed, which may also lead to a shortened survival rate. The most effective way to prevent circulatory disturbances is concomitant albumin infusion. Compared to other plasma expanders (dextran-70, polymelanin), albumin is more effective in preventing PPCD, especially when peritoneal puncture releases ascites >5L. A recent health economic analysis also suggests that albumin infusion after LVP has a better cost-benefit ratio. However, despite this, randomized trials did not find a difference in their survival rates.
It is generally accepted that LVP is not contraindicated, except for encapsulated ascites, but should be performed under strict aseptic conditions. bleeding complications of LVP are uncommon, and no data support the transfusion of fresh frozen plasma or platelets prior to LVP. Nevertheless, caution should be exercised in patients with severe coagulation disorders, and LVP should be avoided in the presence of disseminated intravascular coagulation.
Recommendations
①Large volume peritoneal puncture (LVP) is the first-line treatment option for patients with massive ascites (grade 3 ascites). lvp should be done in a single session.
②LVP should be combined with albumin infusion (1L ascites: 8g albumin) to prevent circulatory disturbance after LVP.
③Patients with LVP>5L, plasma bulking agents other than albumin are not recommended because they are not effective in preventing circulatory disturbances after laparotomy.
④Patients with LVP <5L are at a lower risk of circulatory disturbance after laparotomy; however, it is generally accepted that these patients should still be transfused with albumin, considering the issue of plasma volume expanders substitution.
⑤ After LVP, patients should receive a minimum dose of diuretics to prevent recurrence of ascites.
Contraindications to medications in patients with ascites
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with cirrhotic ascites carries the risk of acute renal failure, hyponatremia, and diuretic resistance. Inhibition of renal prostaglandin synthesis, resulting in decreased renal perfusion and impaired glomerular filtration rate, is the main cause. Therefore, NSAIDs are not recommended for patients with cirrhotic ascites.
Angiotensin-converting enzyme inhibitors (ACEI) can induce arterial hypotension and renal failure, α1-adrenergic receptor blockers aggravate ascites and/or edema, pansentin can induce renal impairment, and aminoglycoside antibiotics have a high incidence of nephrotoxicity; all such drugs should be avoided. Contrast-induced nephrotoxicity is also a common cause of renal failure in hospitalized patients, but the use of contrast agents does not increase the risk of renal damage in cases of cirrhotic ascites with approximately normal renal function.
Recommendations
(i) NSAIDs are contraindicated in patients with ascites because of the increased risk of sodium retention, hyponatremia, and renal failure.
② Drugs that reduce arterial pressure or renal blood flow, such as ACEIs, angiotensin 2 receptor antagonists, or α1-adrenergic receptor blockers are usually not recommended for patients with ascites because of the increased risk of renal damage.
(iii) The use of aminoglycoside antibiotics increases the risk of renal failure and therefore should only be used in patients with infections that have failed to respond to other antibiotic therapy.
④The use of contrast agents does not increase the risk of renal damage in patients with ascites without renal failure.
⑤ There is insufficient information on the use of contrast agents in patients with renal failure. Nevertheless, contrast agents need to be used with caution and are recommended for routine prevention of renal damage.
Intractable ascites
Evaluation of patients with intractable ascites
According to the criteria of the International Club of Ascites, intractable ascites is defined as “ascites that does not subside after treatment or recurs early after treatment (e.g., after LVP) and cannot be effectively prevented by pharmacologic therapy”. The diagnostic criteria for intractable ascites are shown in Table 2.
The median survival of patients with refractory ascites is approximately 6 months. The Model for End-Stage Liver Disease (MELD) scoring system predicts survival in patients with cirrhosis, and patients with refractory ascites may have a poor prognosis despite a relatively low MELD score (e.g., <18) and should be considered for liver transplantation as a priority.
Recommendations
(i) Assess response to diuretic and salt restriction therapy only in patients with stable ascites without associated complications such as bleeding or infection (LevelB1).
②Patients with intractable ascites have a poor prognosis and therefore should be considered for liver transplantation (LevelB1).