ASCITES Cengiz Pata Gastroenterology Department Yeditepe University Istanbul

. ASCITES Cengiz Pata Gastroenterology Department Yeditepe University, Istanbul

Cirrhosis is the late result of any disease that causes scarring of the liver. Patients with cirrhosis are susceptible to a variety of complications that include ascites, hepatic encephalopathy, and portal hypertension. Quality of life and survival are often improved by the prevention and treatment of these complications.

Ascites is defined as the accumulation of free fluid in the peritoneal cavity. It is a common clinical finding with a variety of both extraperitoneal and peritoneal etiologies. It is most often caused liver cirrhosis 75% malignancy (10%) heart failure (3%) pancreatitis (1%) TB (2%), or other rare causes.

Nonperitoneal Causes of Ascites Non-peritoneal causes Examples Intrahepatic portal hypertension Cirrhosis Fulminant hepatic failure Veno-occlusive disease Extrahepatic portal hypertension Hepatic vein obstruction (ie, Budd-Chiari syndrome) Congestive heart failure Hypoalbuminemia Nephrotic syndrome Protein-losing enteropathy Malnutrition Miscellaneous disorders Myxedema Ovarian tumors Pancreatic & Biliary ascites Chylous Secondary to malignancy, trauma

Peritoneal Causes of Ascites Peritoneal Causes Examples Malignant ascites Primary peritoneal mesothelioma Secondary peritoneal carcinomatosis Granulomatous peritonitis Tuberculous peritonitis Fungal and parasitic infections Sarcoidosis Foreign bodies (cotton , starch, barium) Vasculitis Systemic lupus erythematosus Henoch-Schönlein purpura Miscellaneous disorders Eosinophilic gastroenteritis Whipple disease Endometriosis

Prognosis The development of ascites is an indication of deterioration in clinical status and poor prognosis. Prognosis is worse for those with refractory ascites and SBP. Approximately 60% of patients with cirrhosis will develop ascites requiring therapy and/or liver transplantation in 10 years duration. Mortality in cirrhotic patients hospitalized with ascites is 40% at 2 years.

PATHOPHYSIOLOGY

The pathogenesis of ascites formation remains controversial. “Underfill" theory Ascites occurs as a primary event. Sequestration of fluid into the peritoneal cavity as a result of changes in Starling's forces leads to reduction of the circulatory volume and stimulation of the sympathetic nervous & RAAS that promote renal sodium & water retention.

“Overflow theory" Renal Na retention occurs as a primary event. It may be due to increased production of a sodium retaining factor or reduced synthesis of a natriuretic factor by the diseased liver. The circulatory volume is expanded & the retained fluid is preferentially localized to the peritoneal cavity as ascites.

The currently accepted theory of ascites formation which include features of both the underfill and overflow theories is the “Peripheral Arterial Vasodilation Hypothesis" According to this theory, Portal pressure >12 mm Hg is required for the development of PH which will lead to formation of ascites.

As PH develops, vasodilators are released affecting the splanchnic arteries resulting in decrease in effective arterial blood flow and arterial pressures. The precise agent (or agents) responsible for vasodilation is a subject of wide debate; however, most recent literature has focused on the role of: Nitric Oxide

Chronic endotoxemia associated with cirrhosis may stimulate the synthesis and release of a potent endothelin-derived relaxing factor, Nitric oxide. NO is the likely mediator in cirrhosis: (1) Increased activity of NO synthase. (2) High serum nitrite and nitrate levels (an index of NO synthesis). (3) Inhibition of NO leads to increased arterial pressures and systemic vascular resistance.

Portal hypertension Vasodilatation, Decrease Splanchnic Systemic vascular resistance Reduction in arterial blood volume Activation of neurohumoral pressor systems Renal sodium & water retention

When Na reabsorption cannot compensate for vasodilation, arterial underfilling leads to further activation of vasoconstrictor & antinatriuretic mechanisms which leads to increased Na retention & ultimately ascites is formed. In the late stages of cirrhosis, free water accumulation is more pronounced than the Na retention leading to dilutional hyponatremia.

DIAGNOSIS

I) History

II) Physical Examination

The older system 1+ is minimal and barely detectable. 2+ is moderate. 3+ is massive but not tense. 4+ is massive and tense. The International Ascites Club grading (2003) Grade 1: mild ascites detectable only by US. Grade 2: moderate ascites manifested by moderate symmetrical abdominal distension. Grade 3: large or gross ascites with marked abdominal distension.

III) Diagnostic Paracentesis Indications (1)Evaluation for a non-cirrhotic patient developing clinically apparent ascites of recent onset. (2)New development of ascites in a cirrhotic patient does not routinely require paracentesis only if : (a) General condition deteriorates. (b) In presence of unexplained fever, abdominal pain, encephalopathy. (c) Admission to hospital for any cause (SBP). (3)Laboratory investigations indicating infection: Leucocytosis Acidosis Worsening of renal functions

Site Midline was usually chosen. Abdominal wall in the left lower quadrant, 2 finger breadths cephalic & 2 finger breadths medial to ASIS, has been shown to be thinner with larger pool of fluid than midline. Complications (1% of patients) -Abdominal wall hematomas. -Hemoperitoneum or bowel entry. Contraindications Clinically evident fibrinolysis or DIC.

Gross Appearance of Ascitic Fluid Color Appearance Translucent or yellow Brown Cloudy or turbid Normal/sterile Hyperbilirubinemia GB or biliary perforation Infection Pink or blood tinged Mild Trauma Grossly bloody Malignancy Abdominal trauma Cirrhosis Thoracic duct injury Lymphoma Milky ("chylous")

Ascitic Fluid Testing Routine Sometimes useful Rarely helpful Cell count & differential Total protein p. H Albumin Culture LDH Glucose Lactate Gram stain Amylase Triglycerides Bilirubin Cytology TB smear and culture

Ascitic fluid analysis (Routine) I) Cell count with differential Abnormal results are an indication for further non routine tests. If the PMN count is >250 cells/mm 3, another specimen is injected into blood culture bottles at bedside. Bacterial growth occurs in about 80% of specimens with count of >250 cells/mm 3. The PMN count is calculated by multiplying the white cells/mm 3 by the percentage of neutrophils in the differential.

In a "bloody" sample that contains a high concentration of RBC, the PMN count must be corrected: one PMN is subtracted from the absolute PMN count for every 250 red cells/mm 3 in the sample. The results must be available within 1 hour, so that important diagnostic and therapeutic decisions can be made. A Gram stain is of particular low yield unless free gut perforation, is suspected.

II)Total protein , albumin & serum albumin. Serum-ascites albumin gradient (SAAG) = serum albumin - ascitic fluid albumin. If > 1. 1 g/d. L, the patient has PH-related ascites. If < 1. 1 g/d. L (about 97% accurate), the patient does not have PH-related ascites. The SAAG does not need to be repeated after the initial measurement.

III)Based on clinical judgment, additional testing can be performed : a) Cytology , smear & culture for mycobacteria b) Cytology : in peritoneal carcinomatosis (sensitivity increased by centrifuging large volume). c) Elevated bilirubin level suggest biliary or gut perforation. d) LDH >225 m. U/L, glucose <50 mg/d. L, total protein >1 g/d. L and multiple organisms on gram stain suggest secondary bacterial peritonitis. e) High level of TG's confirms chylous ascites. f) Elevated amylase level suggest pancreatitis or gut perforation.

AASLD Recommendations 1. Paracentesis should be performed , ascitic fluid should be obtained from inpatients & outpatients with clinically apparent new-onset ascites 2. Since bleeding is uncommon , prophylactic use of FFP or platelets is not recommended. 3. Initial evaluation of ascitic fluid should include cell count , differential, total protein & SAAG. 4. If infection is suspected, ascitic fluid should be cultured at the bedside in blood culture bottles. 5. Other studies can be ordered based on pretest probability of disease.

Cirrhotic Ascites n n n The management of all complications of uninfected cirrhotic ascites (pleural effusions, abdominal wall hernias, etc. ) begins with salt restriction (2 g. or less) and diuretics (generally a combination of spironolactone and furosemide) Fluid restriction is only indicated for marked hyponatremia Only 10% of cirrhotic patients have truly refractory ascites

treatment

Refractory Ascites n A definition: “failure to lose 200 g of weight in a patient despite severe Na restriction (50 meq/day) and maximal doses of loop diuretic (e. g. 160 mg/d Lasix) and distal tubule diuretic (e. g. 400 mg/d Aldactone)” Arroyo V et al, Hepatology 1996; 23: 164 -76 n 50% 6 -month mortality

Management: Refractory Ascites Repeat large-volume paracentesis (LVP), coupled with infusion of 6 -8 grams of IV albumin per liter of ascites removed, is first-line n TIPS: only in patients who require serial LVP, and have CTP score of <12 v

TIPS (Transjugular Intrahepatic Portosystemic Shunt)

TIPS for Refractory Ascites n n n Controversial, since TIPS may complicate subsequent transplantation In uncontrolled studies, 50 -90% of subjects were noted to become ascites-free after TIPS placement In controlled studies, TIPS controls ascites better than LVP except in Child’s C cirrhotics Rossle et al, NEJM 2000; 342: 1701 -07 n No mortality improvement for TIPS over LVP, and TIPS may increase mortality in Child’s C

Risk for Dying with TIPS 1) 2) 3) Serum bilirubin >3 mg/dl INR >2 Creatinine > 2 mg/dl Malinchoc et al Hepatology 2000; 31: 864 -71 n v Other relative TIPS contraindications: severe pre-TIPS encephalopathy, pulmonary hypertension or heart failure Paracentesis + albumin is first-line

Ascites infections Sbp n CNBA n NNBA n Secondary peritonites n

diagnosis

Spontaneous Bacterial Peritonitis (S. B. P. ) n n A diagnostic paracentesis should be performed in all cirrhotics with ascites who: 1)are admitted to the hospital, 2) have signs/symptoms, 3)worsened renal/liver function Dx: ascites PMN count >250/mm 3 Rimola A, et al. J Hepatol 2000; 32: 142 -153 v • Tx: Third generation cephalosporin, IV Augmentin for 5 -10 days (PMN <250/mm 3) Diuretics and large-volume paracentesis: hold until resolution of S. B. P.

Secondary S. B. P. Prophylaxis 1 -year recurrence of S. B. P. is 70% n Secondary prophylaxis with any ascites v Norfloxacin 400 mg qd (VA: Ciprofloxacin 250 mg po qd) is first-line prophylaxis against recurrence n Bactrim DS 5 days/wk, Ciprofloxacin 750 mg q week are second-line alternatives, but have not been as wellstudied n