Ascites 소화기내과 F1 김경엽

 Ascites: pathologic accumulation of fluid in the peritoneal cavity Causes of ascitesPercentage Cirrhosis81 % Cancer10 % Heart failure3 % Tuberculosis2 % Dialysis1 % Pancreatic disease1 % Other2 % Ann Intern Med 1992;117:215

Diagnosis  Physical examination + imaging test (usually ulatrasonography)  Imaging test  To confirm or refute the presence of ascites, cirrhosis, or malignancy  Grade 1: mild ascites detectable only by ultrasound examination  Grade 2: moderate ascites manifested by moderate symmetrical distension of the abdomen  Grade 3: large or gross ascites with marked abdominal distension

Abdominal paracentesis  Abdominal paracentesis with appropriate ascitic fluid analysis is the most efficient way  Confirm the presence of ascites  Diagnose the cause of ascites  Determine if the fluid is infected

 Serum-ascites albumin gradient (SAAG) ≥ 1.1 g/dL  Portal hypertension (97% accuracy)

Portal hypertension  The 1 st step toward fluid retention in the setting of cirrhosis  A portal pressure > 12 mmHg appears to be required for fluid retention  Ascites will usually disappear if portal pressure is reduced below 12 mmHg  After a surgical or radiologic portosystemic shunt  Portal hypertension leads to profound changes in the splanchnic circulation

 Patients with cirrhosis and ascites  Systemic vascular resistance ↓  Mean arterial pressure ↓  Cardiac output ↑  These abnormalities result in a hyperdynamic circulation

 Mechanisms of vasodilation  Nitric oxide (NO): primary mediator of vasodilation in cirrhosis  Cirrhotic rats with ascites: ↑ activity of endothelial NO synthase in the arterial vessels  Serum levels of nitrite and nitrate (index of in vivo NO synthesis): higher in patients with cirrhosis than in controls  Nitric oxide production may be simulated by endotoxin or other bacterial products, such as bacterial DNA from the gastrointestinal tract  Oral administration of the antibiotic colistin to patients with cirrhosis significantly reduces plasma endotoxin levels and the serum concentration of nitrite and nitrate

 Consequences of vasodilation  Activation of endogenous vasoconstrictors  Sodium and water retention  Increase of renal vasoconstriction

 Activation of endogenous vasoconstrictor agents  Reduction in pressure (or stretch) at the carotid and renal baroreceptors → activation of the sodium-retaining neurohumoral mechanisms  Renin-angiotensin-aldosterone system  Sympathetic nervous system  Antidiuretic hormone (vasopressin)

Cirrhosis Portal hypertension Splanchnic and systemic vasodilation ↓ Effective arterial blood volume ↑ Activation of neurohumoral systems Sodium and water retention Plasma volume expansion Hyperdynamic circulation

Treatment of in patients with cirrhosis and ascites  Stop alcohol consumption  First-line treatment  Sodium restriction (88 mmol/day [2000 mg/day])  Diuretics (oral spironolactone with or without oral furosemide)  Fluid restriction is not necessary unless serum sodium is less than mmol/L  Patients with tense ascites  Initial therapeutic abdominal paracentesis  Sodium restriction  Oral diuretic  Liver transplantation should be considered

 Random spot urine [Na]/[K] ratio > 1  Correlate with a 24-hour sodium excretion greater than 78 mmol/day (90% accuracy)  Serum sodium < mmol/L: reasonable threshold  Usual diuretic regimen  Single morning doses  Start: spironolactone 100 mg + furosemide 40 mg  Single-agent furosemide  Less efficacious than spironolactone (randomized controlled trial)  The doses of both oral diuretics can be increased simultaneously every 3-5 days if weight loss and natriuresis are inadequate (max: spironolactone 400 mg, furosemide 160 mg)

 There is no limit to the daily weight loss of patients who have massive edema  Once the edema has resolved, 0.5 kg is probably a reasonable daily maximum  Cessation of diuretics  Uncontrolled or recurrent encephalopathy  Serum sodium < 120 mmol/L despite fluid restriction  Serum creatinine > 2.0 mg/dL

Refractory ascites  Refractory ascites if defined as fluid overload  Unresponsive to sodium-rescticted diet and high-dose diuretic treatment (400 mg/day spironolactone and 160 mg/day furosemide)  Recur rapidly after therapeutic paracentesis  Failure of diuretic therapy  Minimal to no weight loss together with inadequate (<78 mmol/day) urinary sodium excretion despite diuretics  Development of clinically significant complications of diuretics  Encephalopathy  Cr > 2.0 mg/dL, serum Na 6.0 mmol/L

 Options for patients refractory to routine medical therapy  Serial therapeutic paracenteses  Liver transplantation  Transjugular intrahepatic portasystemic stent-shunt (TIPS)  Peritoneovenous shunt  Experimental medical therapy

 Serial therapeutic paracenteses: a treatment option for patients with refractory ascites  Postparacentesis albumin infusion may not be necessary for a single paracentesis of less than 4-5L  Large-volume paracenteses  Albumin infusion of 6-8 g/L of fluid removed  Referral for liver transplantation  Once patients become refractory to routine medical therapy, 21% die within 6 months  TIPS  Peritoneovenous shunt: no candidate for paracentesis, transplant, or TIPS

Spontaneous bacterial peritonitis  Diagnosis  Positive ascitic fluid bacterial culture  Elevated ascitic fluid absolute PMN count (i.e., ≥ 250 cells/mm 3 )  No evidence of intra-abdominal, surgically treatable source of infection  Elevated ascitic fluid PMN count  Evidence of failure of the first line of defense, the peritoneal macrophages, to kill invading bacteria  Three most common pathogens  E. coli, K. pneumoniae, and pneumococci

 One controlled trial randomized patients with SBP (cefotaxime alone vs. cefotaxime plus 1.5 g albumin/kg body weight within 6 hours of enrollment and 1.0 g/kg on day 3)  Decrease in mortality from 29% to 10 %  Albumin should be given  Serum creatinine > 1 mg/dL  Blood urea nitrogen > 30 mg/dL  Total bilirubin > 4 mg/dL  Albumin has been shown to be superior to hydroxyethylstarch in treatment of SBP

 Culture-negative neutrocytic ascites  Negative ascitic fluid bacterial culture  Elevated ascitic fluid absolute PMN count (i.e., ≥ 250 cells/mm 3 )  No evidence of intra-abdominal, surgically treatable source of infection  Patients with culture-negative neutrocytic ascites  Similar signs, symptoms, and mortality as patients with SBP  Warrant empiric antibiotic treatment

 Monomicrobial non-neutrocytic bacterascites  Bacterascites stage before there is a neutrophil response (PMN < 250 cells/mm 3 )  Most patients-62% in one study-resolve the colonization without antibiotics and without a neutrophil response  Patients with bacterascites who do not resolve the colonization and who progress to SBP  Have signs or symptoms of infection (fever, abdominal pain, or unexplained encephalopathy) at the time of the paracentesis that documents bacterascites

 Secondary bacterial peritonitis (free perforation)  PMN count ≥ 250 cells/mm 3 (usually many thousands)  Multiple organisms (frequently including fungi and enterococcus) on Gram stain and culture  At least two of the following criteria  Total protein > 1 g/dL  LDH greater than the upper limit of normal for serum  Glucose < 50 mg/dL  Anaerobic coverage + 3 rd generation cephalosporin + laparotomy

 Risk factors for development of SBP  Ascitic fluid protein concentration < 1.0 g/dL  Variceal hemorrhage  Prior episode of SBP

 Prevention of SBP  To prevent bacterial infection in patients with cirrhosis and gastrointestinal hemorrhage  IV ceftriaxone for 7 days or twice-daily norfloxacin for 7 dyas  Patients who have survied an episode of SBP  Long-term prophylaxis with daily norfloxacin  Cirrhosis and ascites + no GI bleeding: long-term use of norfloxacin  Ascitic fluid protein < 1.5 g/dL  At least one of the following  Cr ≥ 1.2 mg/dL  BUN ≥ 25 mg/dL  Na ≥ 130 mmol/L  CTP ≥ 9 points with bilirubin ≥ 3 mg/dL