Download Ascites

Attending Version
Ascites Module; created by Dr. Yvonne Dalton-Etheridge
Objectives:
1) Discuss briefly the causes and pathophysiology of ascites.
2) Summarize the treatment options for and management of a patient with ascites.
3) Recognize when to perform peritoneal fluid analysis and be able to calculate the
SAAG.
4) Recognize a patient who has developed complications associated with their
ascites.
References:
Sandhu, B and Arun Sanyal Management of Ascites in Cirrhosis. Clin Liver Dis 9
(2005) 715– 732.
Gilbert, David The Sanford Guide to Antimicrobial Therapy 2006 35.
Zimmerman, Michael, Andrew Cameron and R. Ghobrial. Budd-Chiari Syndrome. Clin
Liver Dis 10 (2006) 259-273.
Ascites
I.
Causes – liver cirrhosis (85%), malignancy, cardiac failure, pancreatitis,
tuberculosis, Budd -Chiari syndrome, etc.
II.
Pathophysiology
Figure taken from Sandhu, B and Arun Sanyal Management of Ascites in Cirrhosis. Clin Liver Dis 9 (2005) 715– 732.
III.
Treatment
A.
Diuretics
1.
Aldosterone antagonists
a. Mechanism: elevated aldosterone levels cause sodium
retention and ascites, so therefore drugs that block
aldosterone can help.
b. Spironolactone can be started at 100 mg/day and can be
titrated up to 400 mg/day. Effect can be seen in 2 to 7
days. Adjustments should be made on a weekly basis.
Adverse effects include gynecomastia and hyperkalemia.
2.
Loop diuretics
a. Mechanism: inhibit active chloride reabsorption in the
ascending limb of the loop of Henle, which increases the
amount of Na, Cl, and water delivered to the distal tubule.
An aldosterone antagonist should be given simultaneously
so that reabsorption of this Na load to the distal tubule is
blocked, which produces a marked natriuresis.
b. Furosemide is started at 40 mg/day and can be titrated up to
160 mg/day. Effect can be seen from 30 minutes to 4
hours. Adverse effects include hyponatremia,
hypokalemia, intravascular volume contraction, azotemia,
B.
C.
D.
and hepatic encephalopathy (furosemide increases renal
ammonia production).
Large volume paracentesis (drainage of > 5 L ascitic fluid)
1.
Postparacentesis circulatory dysfunction (occurs in 20%)
a. worsened hyponatremia and increased catecholamine levels
and renin activity; worsened effective hypovolemia
b. peaks at 24 to 48 hours post procedure
c. associated with increased renal failure and mortality (30
day)
d. Albumin can be administered to increase the effective
circulating volume (6 – 8 g for each liter of ascites
removed). Not required if < 4 -5 L of fluid is removed.
2.
Indications: tense ascites, respiratory distress, impending
umbilical hernia rupture, poor response to medical therapy
and to allow adequate US imaging of liver.
3.
Ascites recurs in 93% patients after 4 weeks if diuretics are
not initiated.
4.
Complications (rare) : local infection, intestinal perforation,
bleeding.
5.
No data to support the correction of mild-to-moderate
coagulopathy with blood products before paracentesis.
TIPS
1.
shunt between the hepatic vein and an intrahepatic portal vein
branch
2.
increases venous return to the heart from the splanchnic bed
3.
Mechanism: improves renal perfusion and decreases Na
reabsorption in the proximal tubules. This causes a
natriuresis, helps get rid of retained Na and causes
mobilization of ascites.
4.
effects can take several weeks to occur
5.
associated with hepatic encephalopathy (30%)
6.
stenosis rate of 75%
7.
studies show no improvement in survival or quality of life
Liver transplantation: After development of ascites, only 50% of
patients will survive for 2 to 5 years. Therefore, patients who develop
ascites should always have their cases reviewed to see if they meet
criteria for liver transplantation. Prognosis is usually evaluated by
MELD score.
IV.
Initial evaluation
Box taken from Sandhu, B and Arun Sanyal Management of Ascites in Cirrhosis. Clin Liver Dis 9 (2005) 715– 732.
V.
Grading
A. Grade I: mild and detectable only on imaging studies
B. Grade II: moderate, manifested by symmetrical distension of abdomen
C. Grade III: large or gross with massive abdominal distension
VI.
Fluid analysis
A. Indications: new-onset ascites, worsening ascites, cirrhotic patients with
ascites and unexplained renal failure, GI bleeding, hepatic
encephalopathy, sepsis/shock and suspicion of SBP.
B. Serum albumin ascites gradient (SAAG)
1. Serum albumin – ascitic fluid albumin
2. Value > 1.1 g/dL suggests of portal hypertension, usually caused by
liver disease (accuracy of 97%)
3. Value < 1.1 g/dL suggests other causes of ascites, such as peritoneal
carcinomatosis, infections by mycobacteria, syphilis or fungi, pancreatic
ascites, bile leak, nephrotic syndrome, serositis, etc.
VII.
Management
A. Uncomplicated Ascites
1.
Na restriction (1.5 – 2 g Na per day)
2.
Fluid restriction (1000 mL per day) in those patients with
dilutional hyponatremia
3.
Diuretics
a) Spironolactone 100mg – 200mg per day
b) Furosemide 20mg – 40mg per day to improve
natriuresis
c) Recent study found that in nonazotemic subjects
with moderate ascites, spironolactone alone was as
effective as combination therapy
d) Measuring urinary sodium excretion can help
determine if the diuretic dose should be increased: if
the urine Na is very low in a patient with Na restriction
but has worsening ascites, you should increase the
diuretic dose to induce a natriuresis, unless renal failure
already has set in.
4.
Large volume paracentesis with albumin infusion
B.
Complicated Ascites
1.
Refractory Ascites (5 – 10%) is either diuretic resistant or
diuretic intractable (unable to reach maximal dose of diuretics because of adverse effects)
a) Continue diuretics as tolerated
b) Repeated large volume paracentesis
c) TIPS should be used in patients who fail repeated LVP
and have somewhat preserved liver functions.
d) Liver transplantation is the only therapy that is
associated with improved survival and quality of life.
2. Dilutional hyponatremia
a) Volume restriction
b) Vasopressin receptor 2 antagonists improve free
water clearance and serum sodium levels (not yet approved
for routine clinical use)
c) Central opioid k receptor agonists (niravoline) have
been used to decrease the hypothalamic release of vasopressin
which will improve water excretion.
3. Hepatorenal syndrome
a) Mechanism: renal circulation profound vasoconstriction
secondary to endogenous vasoactive substances
b) Diagnostic criteria
Box taken from Sandhu, B and Arun Sanyal Management of Ascites in Cirrhosis. Clin Liver Dis 9 (2005) 715– 732.
4. Spontaneous Bacterial Peritonitis
a) Mechanism: transient bacteremia (usually of enteric
origin) causes seeding of the ascitic fluid
b) Diagnosis: >250 PMNs in ascites
c) Treatment: 3rd generation cephalosporin
d) Associated with high mortality rate and development of
HRS in 30%
e) 70% have SBP recurrence in one year
f) Prophylaxis with quinolone or trimethoprimsulfamethoxazole to prevent recurrence
Board Review Questions
1) 65 yo female with previous ETOH abuse (stopped drinking 2 years ago) and ESRD on
chronic peritoneal dialysis is seen who has been having altered mental status and fevers
for the past five days. The patient’s vital signs show a fever of 102, pulse 102 and BP
90/62. On exam, the patient is somnolent, but arousable, a protuberant abdomen with
detectable ascites and diffuse abdominal tenderness without guarding or rebound
tenderness. Exam is negative for nuchal rigidity. The patient has a history of being
anuric. On labs, you note an elevation of WBC at 15 and an INR of 2. Peritoneal fluid
analysis shows WBCs of 200 with 60% PMNs. What is the NEXT appropriate step in
the management of this patient?
(a) Initiation of broad spectrum antibiotics since the patient is hemodynamically
unstable and infectious source has not yet been determined
(b) Performing lumbar puncture to evaluate for meningitis
(c) Antibiotics for treatment of peritonitis
(d) Haloperidol for seizure prophylaxis in alcohol withdrawal
(e) Further infectious work-up to include bladder catherization and CXR
The correct answer is (c), starting antibiotics for peritonitis. This patient has
peritonitis associated with chronic ambulatory peritoneal dialysis based on the
patient’s clinical presentation and lab data (confusion, fever, abdominal
tenderness, leukocytosis, peritoneal fluid with >100 WBCs, >50% PMNs). In this
patient population, staph aureus is the most common infectious organism. In
order to make this diagnosis in PD patients, you should remove approximately
300 mL of dialysis fluid and concentrate it by centrifuge. You can perform cell
count analysis, Gram stain and inject blood culture bottles with the concentrate.
If patient’s peritonitis is only of moderate severity, you can treat by adding
antibiotics to the dialysis fluid. If the patient is severely ill such as our patient
(hemodynamic instability, altered mental status suggesting systemic infection),
you treat with IV antibiotics (adjusted for renal failure) in addition to antibiotics
in the PD fluid. Suggested empiric therapy is vancomycin and ceftazidime or
vancomycin and APAG. (a) is partially a correct answer, however a substantiated
diagnosis has been determined. (b) is incorrect because the patient’s altered
mental status can be explained by infection and peritonitis. There is no mention
of nuchal rigidity or meningeal signs which would make you want to pursue an
LP. Furthermore, if you did want to pursue LP, you would probably need to
correct the patient’s coagulopathy by administering vitamin K and FFP prior to
performing an LP. (d) is incorrect the patient has not abused ETOH in two years,
and the patient’s clinical presentation can be explained by infection and
peritonitis. (e) is incorrect because an infectious source has been determined.
Bladder catherization, even in an anuric patient, may be necessary to exclude such
diagnosis as pyocystitis if the infectious source is still undetermined. Although
the patient probably had a CXR in the ER, performing one in this patient is not
necessary (you have determined the infectious source, and there is no mention of
signs or symptoms concerning for pneumonia or other pulmonary process).
Reference: Gilbert, David The Sanford Guide to Antimicrobial Therapy 2006 35.
2) 72 yo male with past medical history of ETOH abuse, HTN and DM presents
with right upper quadrant pain and increase in abdominal girth. The patient’s
vital signs are all within normal limits. On exam, the patient is alert and oriented.
Liver span is percussed to be 18 cm and there is detectable ascites on exam. The
patient has tenderness to palpation in the right upper quadrant, without guarding
or rebound tenderness. Lab values are as follows:
WBC 6, HCT 42, PLT 1, 000, 000
Chem 7 WNL
INR 1.0 PT 13 S (nml 11.6 - 15.4 S)
Albumin 3.6 g/dL
Other liver function tests WNL
AFP WNL
A paracentesis is performed which reveals a leukocyte count of 149 (80%
polymorphonuclear leukocytes) and an albumin level of 1.1 g/dL. Cytology is
negative for any malignant cells.
What is the next appropriate step in the evaluation/management of this patient?
(a) Diuretic therapy with furosemide
(b) Steroids
(c) Antibiotics
(d) Doppler ultrasound
(e) Abdominal CT
The correct answer is (d), performing Doppler ultrasound. The patient’s clinical
presentation should raise suspicion for Budd-Chiari syndrome (hepatomegaly, right upper
quadrant pain and abdominal ascites in the setting of thrombocytosis which can be a
prothrombotic state). Doppler US is still the initial study of choice for evaluating for
hepatic outflow obstruction. (a) is incorrect because although studies show that
aldosterone antagonists can be used alone in the treatment of ascites, loop diuretics
cannot be used alone since all the sodium delivered to the distal tubule will be reabsorbed
due to the unopposed action of aldosterone. An aldosterone antagonist should be given
simultaneously so that reabsorption of this Na load to the distal tubule is blocked, which
produces a marked natriuresis. In addition, even though starting diuretics to start to
mobilize the ascites is a good idea, further investigation needs to be done to determine the
etiology of the patient’s ascites. One cannot assume that the patient simply has ETOH
abuse  cirrhosis  ascites because the patient has relatively normal lab values
(bilirubin, albumin, INR). (b) is incorrect because although the patient has a history of
ETOH abuse and the presentation for ETOH hepatitis can include hepatomegaly, right
upper quadrant pain and ascites, the patient’s laboratory values (nml WBC, LFTs,
bilirubin, INR) do not support this diagnosis and steroids would not be indicated. (c) is
incorrect because with the given information, the patient does not meet criteria for SBP
(PMNs 119) and there is no other mention of any other infectious etiology. In addition,
SAAG is > 1.1. SAAG is usually < 1.1 in peritonitis in the absence of cirrhosis. (e) is
incorrect because Doppler US is still the initial study of choice for evaluating for hepatic
outflow obstruction. The accuracy of this study is about 70%. There appears to be no
other indication for CT scan, such as to evaluate for massive liver metastasis or HCC
since LFTs and AFP WNL, so therefore Doppler US should be sufficient.
Clinical Case
62 yo male brought in by his family for “slurring his speech, falling asleep and belly
increasing in size”. These symptoms have been getting worse for the past few weeks.
You are told by the ED physician that family stated that patient “drinks a lot of alcohol”
and has been admitted several times to a local hospital for alcohol withdrawal. There had
been no report of anything that sounded like hematemesis or melena by the family. After
you make your way to the emergency room, the family has left and you are unable to get
further history from them. You scan the patient’s vitals which show that the patient has a
P 72, BP 110/65, RR 16 and O2 sat 93% on RA. The patient is afebrile. The patient is
lying in a stretcher, asleep. You carefully shake the patient and he opens his eyes. The
patient is able to tell you his name, but stares blankly when you ask him where he is and
tells you it is 1972. The patient answers “no” to all of your questions and keeps falling
asleep in between your questions.
Physical Exam:
General – patient is lying in stretcher, NAD
Head – no obvious trauma
Eyes – no scleral icterus
Ear exam – tympanic membranes pearly gray, no erythema, bulging or blood
Neck – no stiffness, no LAD, no JVD, no carotid bruits
Cardiac – RRR, no murmurs
Pulm – CTA B, no wheezing, no rales
Abd - Protuberant abdomen with fluid wave present. In the RUQ, the liver is
percussed to 8 cm. No abdominal tenderness.
Skin - +multiple telangectasias present on chest
No tremor; +asterixis present
Rectal exam: prostate not enlarged, brown stool present which was guaiac
negative
Labs:
WBC 6, HCT 38, PLT 81
Chem 7 WNL
INR 1.5 PT 20 S (nml 11.6 – 15.4 S)
Albumin 2.4 g/dL
Bilirubin 4.5 mg/dL
AST 40 U/L
ALT 31 U/L
Alkaline phosphatase 136 U/L
AFP WNL
UA LCE, nitrite negative, WBC 1, no bacteria noted
Radiologic studies:
KUB: nl bowel gas pattern; no free air present
CXR: negative for acute cardiopulmonary disease
Noncontrasted head CT: mild volume loss for age, otherwise nl head CT
Abdominal US is performed and shows evidence of a nodular liver and a large
amount of ascites. Doppler shows no evidence of hepatic outflow obstruction.
A paracentesis is performed which reveals a leukocyte count of 190 (80%
polymorphonuclear leukocytes) and an albumin level of 1.1 g/dL.
Case Questions:
1) Does the patient have spontaneous bacterial peritonitis? The patient’s
PMN count in his ascitic fluid is 152, so he does not meet criteria for SBP at this
time.
2) What is the patient’s SAAG? What is the most likely etiology of this
patient’s ascites? The patient’s SAAG is 1.3 which predicts portal hypertension.
Causes under this category could include cirrhosis, “cardiac ascites” (CHF,
tricuspid regurgitation, constrictive pericarditis, tamponade), massive liver
metastasis or HCC, portal vein thrombosis, Budd-Chiari syndrome, hepatic
failure, acute hepatitis (viral or ETOH). Given the patient’s symptoms, signs, labs
and radiologic work-up, the most likely etiology is cirrhosis from his ETOH
abuse.
3) What is the likely explanation for the patient’s altered mental status?
Most likely this patient has hepatic encephalopathy, however while treating the
patient with lactulose and checking an ammonia level to help support your
diagnosis, you should make sure that all other etiologies of altered mental status
are excluded. This patient does not appear to have an active infection (no stiff
neck or mention of meningeal signs to suggest meningitis; UA does not suggest
UTI; lung exam and CXR is negative so pneumonia not likely; as stated above,
patient currently does not appear to have SBP). Even though the patient is a
known ETOH abuser, he does not appear to be in alcohol withdrawal (no
physiologic signs of WD such as fever, tachycardia, elevated BP or tremor);
checking for other toxin or drug ingestion (obtaining a UTOX) would probably be
worthwhile. Head CT was negative for intracranial hemorrhage. Basically you
need to treat hepatic encephalopathy as almost a “diagnosis of exclusion” so that
you don’t miss any other causes of altered mental status which could be life
threatening.
4) Besides starting treatment with lactulose for hepatic encephalopathy,
what other therapies should you consider? Patient and family should meet
with dietician and be educated on a low Na (2g/day) diet. Since the patient’s
renal function appears intact, patient could be started on diuretics (spironolactone
100mg and furosemide 40mg) to help mobilize the ascites. Large volume
paracentesis with albumin infusion could be considered if the patient had a lot of
discomfort from his ascites. The case however, does not suggest definite
indications for LVP (tense ascites, respiratory distress, impending umbilical
hernia rupture, poor response to medical therapy and to allow adequate US
imaging of liver). Finally, there is still debate about whether there is benefit of
primary prophylaxis for SBP. Current recommendations are to limit SBP
prophylaxis to those patients who have had one or more episodes of SBP.
Therefore, since the patient in the above case has never had SBP before, he will
not yet be on a quinolone or trimethoprim-sulfamethoxazole.