Ascites-Park022310.pdf

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AscitesFred Park

David Kravetz

February 23, 2010

Causes of ascites Cirrhosis 81% Cancer 10% Mixed ascites more than one cause (e.g., cirrhosis

plus another cause) 5% Heart failure 3% Tuberculous peritonitis 2% Pancreatitis 1% Nephrotic syndrome 1% Alcoholic hepatitis Acute liver failure Budd-Chiari syndrome There are many other rare causes of ascites

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+ AscitesPathologic accumulationof fluid in the peritoneal

cavity


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Initial approach to a patient with

ascites

Historyo Determine rapidity of onset. Abdominal obesity can masquerade as

ascites, but generally develops over months to years, while ascites

accumulates more rapidly, often causing shortness of breath.

o Assess risk factors for liver disease. Alcohol use. Volume and duration. Development of cirrhosis

requires, on average, 1L wine, 8 beers, or half pint of hard liquor

daily for 10-20 years.

Hepatitis C IV drugs, snorting cocaine, transfusion before 1990,tattoos, acupuncture, emigration from Japan or SE Asia.

Hepatitis B transfusion before 1971, IVDU, dialysis, HIV, MSM,close contact with infected person, birth in hyperendemic areas

(Africa, SE Asia, China, Korea, Middle East, Caribbean, SW Pacific

islands, Amazon river basin).

Family history of liver disease. NASH risk factors obesity, DM, hyperlipidemia. Ask lifetime max

body weight. Calculate # of years BMI has been >30.o History of cancer, heart failure, renal disease/hemodialysis,

pancreatitis, tuberculosis .

Physical Examo Almost all patients with cirrhosis severe enough to cause ascites will

have stigmata of cirrhosis spider angiomata, palmar erythema, caput

medusiae.

o Flank dullness to percussion that shifts when patient is rotated (shiftingdullness) is the best PE exam finding for ascites, with sensitivity of 83%and specificity of 53%, but ~1500 mL is needed to detect this and it is

harder to detect in obese patients.

o Elevated JVP should raise suspicion of heart failure or constrictivepericarditis as a cause, although cirrhosis with tense ascites or

pulmonary HTN may cause this.

o Order a BNP level to distinguish ascites due to heart failure from ascitesdue to cirrhosis.

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Initial approach to a patient with

ascites (continued)o Sister Mary Joseph nodule with ascites may be caused by gastric or

colon CA, HCC, or lymphoma. If found, FNA can provide a rapid tissue

diagnosis.

Imagingo To confirm/refute presence of ascites, cirrhosis, splenomegaly, biliary

obstruction, vessel patency, signs of portal hypertension, and cancer.

Rarely, giant cysts or pseudocysts can mimic ascites.o Abdominal ultrasound is most cost-effective and avoids radiation and IV

contrast.

o CT/MR has obvious advantages for workup of cancers, including HCC,pancreatic disease, etc.

Abdominal paracentesiso The etiology of ascites formation can usually be diagnosed with just

history, physical exam, and ascitic fluid analysis.

oIt is a safe procedure. Serious complication rate is ~1%. In a study of1100 LVPs, there were no bleeding complications despite INRs up to

8.7 and platelets as low as 19K. In a larger study of 4729 paracenteses, 8

of 9 bleeding complications were seen in patients with renal failure.

o When to perform? New onset ascites, upon admission, clinicaldeterioration (fever, abdominal pain, mental status change, etc.), labs

indicating infection (leukocytosis, acidosis, worsening renal function),

GI bleed (high risk for infection).

Ascitic fluid analysiso Appearance

Turbid/cloudy 98% sensitive but only 23% specific for SBP. Milky chylous ascites, TG level usually greater than serum TG

level and >200.

Bloody/pink usually a traumatic tap, but seen in 50% of patientswith HCC and 22% with malignancy overall.

Dark brown if bili level is higher than in serum, worry aboutruptured gallbladder or perforated duodenal ulcer.

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o Lab tests In general, start with cell count and differential, TP, and albumin

when uncomplicated ascites due to cirrhosis is suspected.

Culture is also usually sent.

In patients with PMN >250, only 50% of cultures grow bacteria ifsent down to lab in a syringe or plain tube. 80% grow bacteria if

inoculated into blood culture vials at bedside (prior to

antibiotics).

Glucose < 50, LDH > upper limit of normal for serum, TP >1, andculture results can help differentiate secondary from

spontaneous peritonitis.

SAAG > or = 1.1 has ~97% accuracy for portal hypertension. TP > or = 2.5 can help differentiate cardiac from cirrhosis

ascites.

When PMN > or = 250, but less than 50% of WBC, considerperitoneal carcinomatosis and tuberculous ascites.

Cytology has 96.7% sensitivity for peritoneal carcinomatosis if 3samples are sent promptly. Sensitivity of one sample is only82.8%.

Sensitivity of smear for mycobacteria is ~0%, culture sensitivityis ~50%.

Peritoneoscopy with culture of peritoneal biopsy has ~100%sensitivity for tuberculous peritonitis.


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Ascites due to Cirrhosis

Ascites is the most common complication of cirrhosis that leads to hospitaladmission.

Within 10 years of diagnosis of compensated cirrhosis, ~50% will developascites.

After ascites develops, 15% of patients die within 1 year, 44% die within 5years.

Pathophysiology

The Peripheral Arterial Vasodilation Hypothesis

The most widely accepted explanation for ascites development and renaldysfunction in cirrhosis.

Fits hemodynamic data better than the prior Underfill or Backward Theoryand Overflow Theory.

As portal hypertension increases due to cirrhosis, splanchnic arteries becomevasodilated.

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The mechanism behind splanchnic arterial vasodilation is not completelyclear at this time, but there is evidence that:

o Opening of porto-systemic collaterals/shunts contributes.o Decreased clearance of endotoxins and other bacterial products occurs

likely due to porto-systemic shunting and decreased reticuloendothelial

cell activity.

o Endotoxemia causes increased synthesis of vasodilators. Mostimportant is nitric oxide and prostaglandins.

Arterial vasodilation decreases SVR, but prior to the development of ascites,circulatory homeostasis is maintained by a hyperdynamic circulation with

increased cardiac index and circulating plasma volume.

However, as the disease progresses and portal pressures rise above 12mmHg, splanchnic arterial vasodilation overcomes compensation by

hyperdynamic circulation.

Central arterial blood volume declines and mean arterial pressures fall,leading to activation of the vasoactive systems with stimulation of low

pressure baroreceptors, increase in sympathetic activity, renin-angiotensinsystem activity, and ADH.

Cirrhotics with ascites thus display urinary sodium retention with increasedtotal body sodium but hyponatremia due to water retention.

The increase in ADH secretion is roughly proportional to the severity ofcirrhosis; the severity of hyponatremia correlates with worsening survival.

Ascites forms as leakage of fluid from splanchnic vessels overcomesreabsorption by lymphatics due to worsening splanchnic capillary

permeability, declining oncotic pressure and increasing hydraulic pressure

gradients across the splanchnic circulation.

Hepatorenal syndrome develops when renal perfusion declines as renalvasoconstriction in response to increasing splanchnic vasodilation overcomes

local vasodilatory mechanisms mediated by prostaglandins and NO.

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Management

Successful treatment is defined as minimization of ascitic fluid volume andperipheral edema without intravascular volume depletion.

AASLD recommendations:o Cessation of alcoholic consumptionin those with alcohol-induced liver

disease. Child C cirrhotics who stop drinking have a 75% 3-year

survival, but none survive 3 years if they continue to drink.

o Cirrhosis due to AIH and Hepatitis B also may reverse with treatment,but in general, evaluation for liver transplant is appropriate for patients

with cirrhosis and ascites.

o First line treatment includes 2 gram per day sodium restricted diet andoral diuretics (spironolactone +/- lasix).

o The usual diuretic regimen is single morning doses of 100mgspironolactone and 40mg lasix.

o Single agent spironolactone can be used in patients with minimal fluidoverload (generally outpatients), but hyperkalemia and slow diuresis

limits its usefulness for moderate-severe ascites.

oDiuretic dose can be increased every 3-5 days to achieve adequatenatriuresis and weight loss. The 100:40 ratio generally maintains

normokalemia. Usual max dose is 400mg and 160mg per day.

o Na restricted diet and dual diuretic regimen was shown to achievereduction in ascites to acceptable levels in > 90% of patients.

o A negative sodium balance is needed to reduce ascites. 24-hour urinecollection, if done properly, can determine if urinary Na excretion is

adequate. A simpler method, spot urine Na/K ratio >1 correlates with

negative sodium balance on a 2 gram (88 mmol) Na diet with 90%

accuracy. (Thus, if a patient is not losing weight and spot Na/K is >1,

they are probably not adherent to the 2g Na diet.)o Fluid restriction to improve hyponatremia is not necessary. May

consider if serum Na < 120-125. Patients usually remain asymptomatic

until Na < 110.

o Traditionally, bed rest to prevent rise in plasma renin caused by uprightposture has been recommended, but there is currently no data to

support this practice.

o Initial therapeutic paracentesis should be performed for patients withtense ascites.

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Refractory ascites

o Defined as fluid overload that is unresponsive to Na-restricted diet andmax dose diuretic treatment or recurs rapidly after therapeutic

paracentesis.

o NSAIDs and other prostaglandin inhibitors can reduce Na excretion andconvert diuretic-sensitive ascites to refractory.

o Also, HCC and/or portal vein thrombosis can precipitate diureticresistance.

o Options for treatment include: Serial therapeutic paracenteses Liver transplant TIPS Peritoneovenous shunt

o Serial paracenteses are effective. Even in patients with no urine sodiumexcretion, paracenteses every 2 weeks has been shown to control

ascites.

o How often a patient needs serial paracentesis gives an indication ofhis/her compliance with Na-restricted diet.

A 10-L paracentesis removes ~17 days worth of retained sodium ona 2 gram per day diet in a patient with no urinary sodium

excretion.

With some urinary sodium excretion, paracentesis is needed evenless frequently. Thus, a patient requiring removal of 10-L more

often than every 2 weeks is clearly not compliant with 2 gram Na

diet.

o For large volume paracenteses (> 5L), consider IV albumin 6-8 g perliter of fluid removed, although no reduction of morbidity or mortality

has been demonstrated.o Liver transplantation evaluation should be expedited because once

patients develop refractory ascites, 21% die within 6 months.

o TIPS Five randomized controlled trials have shown improved control of

ascites with TIPS compared to serial LVPs in patients with

refractory ascites (62% vs. 24%).

However, there was also more encephalopathy with TIPS (39% vs23%). The incidence of new or worsening HE was 20-31%.

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Patients with MELD > 15-18 or serum bilirubin >4.0 should have

TIPS only if there is no other options. Given uncertainty of the effect of TIPS on survival and increased

risk of HE, TIPS should be used in those who are intolerant of LVP.

The degree of reduction of HVPG to control ascites is unclear, but< or = 12 mmHg is considered a reasonable goal.

o Peritoneovenous shunt have high complication rates and so are onlyused on rare occasion now in patients who are not candidates for

paracentesis, transplant or TIPS.

Hepatorenal Syndrome

Diagnostic criteria:o Cirrhosis with asciteso Serum Cr > 1.5o Serum Cr remains > 1.5 after at least 2 days with diuretic withdrawal and

volume expansion with albumin

o Absence of shocko No current or recent treatment with nephrotoxic drugso Absence of parenchymal renal disease (proteinuria > 500mg/day,

microhematuria with >50 RBCs per HPF, or abnormal renal u/s)

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Type 1 HRS is defined as doubling of initial serum Cr or 50% reduction ofinitial 24-hour Cr clearance to a level < 20 mL/min in less than 2 weeks.

Type 2 HRS is not as rapidly progressive but is a common cause of death incirrhotics.

Without transplantation, prognosis is very poor when HRS develops. In onestudy, only 8 of 30 patients survived 30 days with the use of HD or CVVHD.

Treatment:o Midodrine/octreotide/albumin has shown reduced mortality comparedto albumin alone (43% vs. 71%)o Octreotide alone shows no benefit, midodrine appears to be required in

addition.

Spontaneous Bacterial Peritonitis

AASLD recommendations:o Ascitic fluid infection was present in 12% of patients with cirrhosis at

time of admission in a recent series. Thus, all patients with ascitesadmitted to the hospital should have a paracentesis.

o Paracentesis should be repeated in patients who develop signs,symptoms, or lab abnormalities suggestive of infection.

o Patients with PMN count > or = 250 should receive empiric antibiotics,preferably an IV 3rdgen cephalosporin.

o Oral ofloxacin can be used in inpatients without prior exposure toquinolones, vomiting, shock, grade II or higher HE, or serum Cr > 3.

o Patients with PMN count < 250 but signs or symptoms of infection (e.g.,fever or abdominal pain) should also get empiric antibiotics pending

culture results.o When there is a high suspicion for secondary peritonitis, ascites should

be tested for total protein, LDH, glucose, gram stain, CEA, and alk phos.

(CEA > 5 or alk phos > 240 has sensitivity of 92% and specificity of 88%

for gut perforation).

o Patients with PMN count > or = 250 who also have serum Cr > 1, BUN >30, or total bilirubin > 4 should receive 1.5 g albumin per kg of body

weight within 6 hours of detection and 1.0 g/kg on day 3. A decrease inmortality from 29% to 10% has been reported with this.

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o Prevention of SBP IV ceftriaxone or BID norfloxacin for 7 days should be given to

cirrhotics with GI hemorrhage. (Although ceftriaxone is superior to

PO norfloxacin.)

Patients who have survived and episode of SBP should receive longterm prophylaxis with daily norfloxacin or septra.

Cirrhotics with ascites but no GI bleeding should receive long-termprophylaxis if:

Ascites total protein is < 1.5 And at least one of the following:

o Serum Cr > or = 1.2o BUN > or = 25o Serum Na < or = 130o Child-Pugh 9 or above with bilirubin > or = 3

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Selected References

1. Sleisinger & Fordrans Gastrointestinal and Liver Disease:Pathophysiology/Diagnosis/Management, 7thedition, Volume 2 (2002).

2. UpToDate articles: Diagnosis and evaluation of patients with ascites by RunyonBA, Pathogenesis of ascites in patients with cirrhosis by Such J and Runyon BA.

3. Runyon BA. AASLD Practice Guidelines, Management of adult patients with ascitesdue to cirrhosis: an -update. Hepatology (2009) 49: 2087-2107.

4. Runyon BA, Montano AA, Akriviadis EA, et al.The serum-ascites albumin gradient issuperior to the exudates-transudate concept in the differential diagnosis of ascites.

Ann Int Med (1992) 117: 215.

5. Grabau CM, Crago SF, Hoff LK, et al. Performance standards for therapeuticabdominal paracentesis. Hepatology (2004) 44: 1039-1046.

6. Pache I, Bilodeau M. Severe haemorrhage following abdominal paracentesis forascites for ascites in patients with liver failure. Aliment Pharmacol Ther (2005) 21:

525-529.

7. Runyon BA, et al. Optimization of ascitic fluid culture technique. Gastroenterology(1988) 95: 1351-5.

8.Arroyo V, Colmenero J. Ascites and hepatorenal syndrome in cirrhosis:pathophysiological basis of therapy and current management. J Hepatology (2003)

38: S69-S89.

9. Heuman DM, Abou-assi SG, Habib A, at al. Persistent ascites and low serum sodiumidentify patients with cirrhosis and low MELD scores who are at high risk of early

death. Hepatology (2004) 40: 802.

10.Stanley MM, Ochi S, Lee KK, et al. Peritoneovenous shunting as compared withmedical treatment in patients with alcoholic cirrhosis and massive ascites. N Engl J

Med (1989) 321: 1632-1638.

11.Boyer TD and Haskal ZJ. AASLD Practice Guidelines: The role of transjugularintrahepatic portosystemic shunt (TIPS) in the management of portal hypertension.

Hepatology (2010) 51: 1-16.

12.Angeli P, Volpin R, Gerunda G, et al. Reversal of type 1 hepatorenal syndrome withthe administration of midodrine and octreotide. Hepatology (1999) 29: 1690-1697.

13.Sort P, Navasa M, Arroyo V, et al. Effect of intravenous albumin on renal impairmentand mortality in patients with cirrhosis and spontaneous bacterial peritonitis. N Engl

J Med (1999) 341: 403-409.

14.Fernandez J, Ruiz del Arbol L, Gomez C, et al. Norfloxacin vs ceftriaxone in theprophylaxis of infections in patients with advanced cirrhosis and hemorrhage.

Gastroenterology (2006) 131: 1049-1056.

15.Rolachon A, Cordier L, Bacq Y, et al. Ciprofloxacin and long-term prevention ofspontaneous bacterial peritonitis: results of a prospective controlled trial.

Hepatology (1995) 22: 1171-1174.

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