Interpretation of 2010 EASL cirrhosis ascites treatment guidelines-----Interpretationof2010EASLTreatmentGuidelinesforPatientswithCirrhosisFu
Interpretation of 2010 EASL cirrhosis ascites treatment guidelines
Further reading: "hepatology digest" in August 2009 seventh (total phase twenty-sixth) "in the United States in 2009 to guide the diagnosis and treatment of liver cirrhosis ascites
Evaluation and diagnosis of ascites
In Western Europe or the United States, about 75% of ascites patients with cirrhosis ascites, the rest can be caused by cancer, heart failure, tuberculosis, pancreatic diseases and other diseases.
Preliminary evaluation of ascites should include medical history, physical examination, abdominal ultrasound, liver and kidney function, blood and urine electrolytes and ascites analysis.
The international ascites Club recommendations: treatment of uncomplicated ascites should be established in quantitative standards (see Table 1), this guide agrees with the proposal, and the "2009 American guidelines for the diagnosis and treatment of ascites due to cirrhosis without ascites" about classification description.
Diagnostic abdominal paracentesis is essential for the identification of the cause of ascites and is helpful in the prevention of spontaneous bacterial peritonitis (SBP). Serum ascites albumin gradient (SAAG = 11g/L) is helpful to the diagnosis of portal hypertension ascites, accuracy of 97%. Ascites total protein concentration of 15g/L increases the risk of SBP, and therefore the ascitic fluid total protein concentration can be used to assess the risk of SBP. Ascites neutrophil count helps to exclude SBP. All patients with ascites should be inoculated with ascites (10mL) to the blood culture bottle.
All patients with newly developed grade 2 or grade 3 ascites, ascites, or cirrhosis complicated with liver cirrhosis were treated with diagnostic abdominal paracentesis (LevelA1).
The bacterial peritonitis (LevelA1) should be excluded by neutrophil count and ascites culture (inoculated into blood culture bottle).
It is important to measure the total protein concentration of ascites, and the risk of SBP is increased (LevelA1) in patients with ascites concentration of 15g/L (LevelA1), which can prevent the occurrence of SBP by prophylactic use of antibiotics.
When the diagnosis of liver cirrhosis ascites or lack of evidence, can not determine whether the cause of liver cirrhosis ascites, serum ascites albumin gradient contributes to differential (LevelA2).
Ascites formation in cirrhotic patients is associated with poor prognosis. Other indicators of poor prognosis included low sodium, low blood pressure, elevated serum creatinine and low urinary sodium.
Liver cirrhosis should be considered as an alternative treatment option (LevelB1) because of a grade 2 or grade ascites in patients with liver cirrhosis with poor prognosis.
Treatment of uncomplicated ascites
Cirrhotic patients with ascites often complicated with intractable ascites, SBP, hyponatremia or hepatorenal syndrome (HRS). Ascites that does not appear to be associated with these complications is called uncomplicated ascites.
1 or a few ascites
There is no data on the development of the natural course of the 1 stages of ascites, but also do not know how long it progresses to grade 2 or grade 3 ascites.
2 or moderate ascites
Patients with moderate ascites do not require hospitalization unless combined with other complications. The treatment is mainly aimed at the inhibition of renal sodium retention in order to achieve a negative sodium balance, which can be achieved by reducing sodium intake and the use of diuretics to increase the excretion of sodium. Upright posture can activate sodium retention system, reduce renal perfusion, but because there is not enough clinical evidence that absolute bed rest can improve ascites, so it is recommended not to bed.
Sodium restricted 10%〜 20% patients with liver cirrhosis ascites can be negative sodium balance by reducing sodium intake, especially in patients with primary. Although there are currently no clinical studies on the treatment of sodium and sodium, it is generally accepted that sodium should be appropriately Limited (80〜 120mmol/d). Excessive sodium restriction is not recommended because it may impair nutritional status. Fluid restriction should be restricted in patients with diluted hyponatremia.
Appropriate amount of sodium intake is an important component of ascites treatment (sodium intake of 80〜 120mmol/d, equivalent to sodium 4.6〜 6.9g/d) (LevelB1). The intake is equivalent to the addition of additional sodium in the diet.
There is not enough evidence to treat bed rest as part of the treatment of ascites. There is no data to support the need for fluid restriction (LevelB1) in patients with normal ascites.
Diuretic evidence suggests that renal sodium retention in cirrhotic patients with ascites is primarily due to an increase in proximal and distal tubular reabsorption of sodium, rather than a decrease in filtration. The distal renal tubular sodium reabsorption and aldosterone increased, therefore in the treatment of ascites of aldosterone antagonist than loop diuretics are more effective, should be the first choice. Aldosterone was slow, and the dose recommended for aldosterone antagonists increased 1 times every 7 days. In the collection of the efficacy of diuretic amiloride with aldosterone antagonists, only for ascites patients intolerant of aldosterone antagonist therapy.
Use of aldosterone antagonists should be treated separately or combined with loop diuretics (such as furosemide) therapy in the treatment of ascites in the long-standing debate. The results of the two studies did not agree with each other, which may be related to the difference in the number of patients in each study, especially the proportion of patients with ascites, including the first episode may lead to different results. It is certain that aldosterone antagonists and furosemide combined treatment is more suitable for the patients with recurrence of ascites. The primary treatment of ascites in patients with the initial list of suggestions with aldosterone antagonists (spironolactone 100mg/d), treatment of non responders every 7 days plus the amount of time, until the dose reached 400mg/d. All patients received diuretic therapy, dosage should be adjusted according to the weight change: no edema in patients with daily weight lower than 0.5kg/d; edema patients daily weight loss less than 1kg to prevent renal failure induced by diuretics and / or hyponatremia. After reduction of ascites, the dosage of diuretics should be reduced to the minimum amount of maintenance to avoid the occurrence of complications. Abstinence is the key to the treatment of ascites in patients with alcoholic cirrhosis.
The use of diuretics may cause complications such as renal failure, hepatic encephalopathy, electrolyte disturbances, male breast development, and muscle spasms. Insufficiency of blood volume is the most common cause of renal failure, usually the result of excessive diuresis. Diuretics are often thought to be the cause of hepatic encephalopathy, but the mechanism is not clear. The use of loop diuretics alone can induce hypokalemia, aldosterone antagonists or other potassium sparing diuretics can cause hyperkalemia, especially in patients with renal damage. Hyponatremia is another common complication of diuretic therapy, low blood sodium to which level should stop the diuretic is still controversial, however, most experts believe that low serum sodium to 120〜 125mmol/L, diuretics should be suspended. The use of aldosterone antagonists is often associated with gynecomastia, but usually does not require discontinuation. Diuretics can also cause muscle cramps, severe should be reduced or stopped diuretic, infusion of albumin can relieve symptoms.
Complications occurred more than first weeks of diuretic therapy. Therefore, the level of serum creatinine, serum sodium and potassium should be monitored during this period, but the urine sodium should not be routinely detected. Only those who do not respond to diuretic therapy should be monitored.
The primary grade 2 (in volume) ascites patients should receive aldosterone antagonist therapy, such as pure spironolactone, initial dose of 100mg/d; if there is no response, every 7 days plus the amount of time (100mg each time) until the maximum dose of 400mg/d (LevelA1).
The use of aldosterone antagonists in the treatment of non responders (weekly weight loss less than 2kg) and after the treatment of hyperkalemia in patients should be combined with furosemide treatment, the initial dose of 40mg/d, gradually increased to the maximum dose of 160mg/d (every 40mg) (LevelA1).
The biochemical parameters of diuretics should be routinely detected in patients, especially at first months of treatment (LevelA1).
The recurrence of ascites in patients with aldosterone antagonists and furosemide should receive combination treatment, according to the response of treatment gradually increase the dose, dose as mentioned earlier (LevelA1).
The recommended maximum daily weight less than 0.5kg decreased after treatment in patients with diuretic without edema, edema in patients less than 1kg (LevelA1).
The long-term goal is to the lowest dose of diuretics in the treatment of ascites state maintenance. Therefore, once the ascites subsided, the dosage should be reduced as much as possible and eventually deactivated (LevelB1).
Renal damage, and hyponatremia or abnormal serum potassium concentration in ascitic patients, should be careful to diuretic treatment and close monitoring of biochemical indexes. There is not enough data to show the extent to which renal damage and hyponatremia should be treated with diuretics. Serum potassium levels should be corrected prior to initiation of diuretic therapy. Patients with overt hepatic encephalopathy are usually treated with diuretics (LevelB1).
The emergence of severe hyponatremia (serum sodium < 120mmol/L), renal failure, hepatic encephalopathy or exacerbation of severe muscle cramps, diuretic should be discontinued (LevelB1).
9 severe hypokalemia (< 3mmol/L) should be discontinued furosemide; severe hyperkalemia (> 6mmol/L) should be discontinued aldosterone antagonist (LevelB1).
Grade 3 or massive ascites
Patients with grade 3 ascites were treated with large volume paracentesis (LVP). Compared with diuretics, LVP combined with albumin infusion was more effective and safe than diuretics, but there was no difference between the two treatments in terms of readmission or survival.
A large number of ascites can lead to a reduction in the effective blood volume, known as post abdominal surgery circulatory disorder (PPCD). PPCD is unfavorable to maintain circulation steady, can lead to rapid re accumulation of ascites, of which 20% patients had hepatorenal syndrome (HRS) and / or dilutional hyponatremia, and because the vasoconstrictor system of hepatic vascular bed resulting in portal pressure increased, while the survival rate may be shortened. The most effective way to prevent circulatory disorders is to simultaneously albumin. With other plasma expanders (dextran -70 and polygeline) compared to albumin can more effectively prevent PPCD, especially on > ascites in the abdominal puncture; 5L, albumin compared with other plasma expander is more effective. A recent health economic analysis also suggested that LVP infusion of albumin has a better cost-effectiveness ratio. However, randomized trials did not find a difference in survival rates.
It is generally believed that, in addition to encapsulated ascites, LVP has no contraindications, but should be performed under strict aseptic conditions. LVP bleeding complications are rare, with no data available for transfusion of fresh frozen plasma or platelets prior to LVP. Nevertheless, patients with severe coagulopathy should remain cautious and avoid LVP when disseminated intravascular coagulation is present.
Massive abdominal paracentesis (LVP) is a first-line treatment for patients with massive ascites (grade 3 ascites) (LevelA1). LVP should be done once (LevelA1).
LVP should be combined with albumin (1L ascites: albumin 8G) in order to prevent LVP posterior circulation disorder (LevelA1).
Patients with LVP> 5L, do not recommend the use of other plasma expanders other than albumin, since they are not effective in preventing postoperative circulatory dysfunction (LevelA1).
The LVP< 5L patients with abdominal puncture of posterior circulation disorders of lower risk, however, generally, taking into account the plasma expander substitute, these patients should be infusion of albumin (LevelB1).
The LVP, in order to prevent the recurrence of ascites, patients should receive the lowest dose of diuretic therapy (LevelA1).
Drug contraindication of ascites patients
The use of nonsteroidal anti-inflammatory drugs (NSAID) in patients with cirrhosis of the liver is associated with the risk of acute renal failure, hyponatremia, and diuretic resistance. Renal prostaglandin synthesis was inhibited, leading to decreased renal perfusion, glomerular filtration rate is the main cause of damage. Therefore, patients with liver cirrhosis ascites is not recommended to use NSAID.
Angiotensin converting enzyme inhibitor (ACEI) can induce arterial hypotension and renal failure, alpha 1 adrenergic receptor blockers increase the ascites and / or edema, Pan Shengding induced renal damage, aminoglycoside nephrotoxicity high incidence of 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 patients with ascites and normal renal function.
Ascites patients with NSAID, because of increased risk of sodium retention, hyponatremia and renal failure (LevelA1).
The reduction of drug arterial pressure or renal blood flow, such as ACEI, angiotensin 2 receptor antagonist or alpha 1 adrenergic receptor blockers are usually not recommended for patients with ascites, because of increased risk of renal damage (LevelA1).
The use of aminoglycoside antibiotics increases the risk of renal failure and is therefore only used in patients who are not treated with other antibiotics (LevelA1).
The non renal failure patients with ascites, the use of contrast agents did not increase the risk of kidney damage (LevelB1).
5 on renal failure in patients with contrast agent does not provide enough data. Nevertheless, the contrast agent should be used with caution and recommend routine prevention of renal damage (LevelC1).
Evaluation of patients with refractory ascites
According to the criteria of the international ascites club, refractory ascites is defined as "the treatment of ascites can not subside after treatment or after treatment (such as LVP) early recurrence and can not be effectively prevented by drug therapy". The diagnostic criteria of refractory ascites are shown in table 2.
The median survival time of patients with refractory ascites was about 6 months. End stage liver disease model (MELD) scoring system can predict survival in patients with cirrhosis, although MELD score is relatively low (< 18) in patients with refractory ascites, the prognosis may be poor.
Evaluation of diuretic and limited salt response (LevelB1) in patients with stable ascites without related complications such as bleeding or infection.
The prognosis of patients with refractory ascites is poor, so liver transplantation (LevelB1) should be considered.
Treatment of refractory ascites
A large number of data show that repeated LVP is a safe and effective method for the treatment of intractable ascites.
Diuretic therapy in patients with refractory ascites
Patients with diuretic induced complications (hepatic encephalopathy, renal damage, or electrolyte disorders) should be discontinued. The rest of the patients were able to continue to use diuretics only when they were treated with sodium > or 30mmol/d
Transjugular intrahepatic portosystemic shunt (TIPS)
LVP can effectively reduce the recurrence of ascites by placing a stent between the portal region of high pressure and the low pressure area of the hepatic vein, which can effectively improve the survival rate of TIPS compared with that of the control group. Although TIPS may contribute to improved quality of life, randomized studies have shown that the improvement is similar to that of patients treated with LVP plus albumin. The main complications after TIPS were hepatic encephalopathy, 30%〜, 50%, and other complications, including shunt thrombosis and stenosis. Because of insufficient data on efficacy and safety, TIPS is not recommended for patients with very advanced liver disease or with severe extrahepatic disease. TIPS may be helpful in symptomatic recurrence of hepatic hydrothorax, but the results are closely related to liver function and age.
Abdominal vein bypass
Because of the high incidence of complications, this method is rarely used in the treatment of refractory ascites.
Vasoconstrictor drugs (such as alpha 1 adrenoceptor agonists midodrine or terlipressin) may improve circulation and renal function in patients with refractory ascites with or without, but the lack of large sample randomized controlled study. Selective vasopressin V2 receptor antagonist (Vaptans) combined with a fixed dose of diuretics, showing a serum sodium level and weight loss related to improve, and has been reported to contribute to the recurrence of ascites subsided after LVP, but the data suggest possible treatment-related morbidity and mortality related to growth.
Repeated LVP+ albumin (1L ascites: 8g albumin) is a first-line treatment for refractory ascites (LevelA1).
After diuretic treatment, patients with intractable ascites due to 30mmol/d of urinary sodium should not be treated with diuretics. TIPS is effective in the treatment of refractory ascites, but the risk of hepatic encephalopathy is high, compared with LVP, can not effectively improve the survival rate (LevelA1).
TIPS should be considered for patients with recurrent LVP and abdominal paracentesis (such as encapsulated ascites) (LevelB1).
The ascites faded slowly after TIPS, most patients need to continue using diuretics and sodium restriction (LevelB1).
The TIPS is not recommended for severe liver failure (serum bilirubin > 50mg/L, INR> 2 or Child-Pugh score > 11, grade 2 or above grade of hepatic encephalopathy in patients with chronic hepatic encephalopathy), active infection, renal failure or severe pulmonary heart disease (LevelB1).
In certain patients, TIPS may help to symptomatic recurrence of hepatic hydrothorax (LevelB2).