38

R.W. has some degree of renal impairment (SCr, 1.4 mg/dL) and is receiving

spironolactone and furosemide. Therefore, his electrolytes and renal function tests

should be monitored daily while hospitalized. After hospital discharge, monitoring

will be dictated by the stability of the patient and need for diuretic dosage

adjustments. For example, outpatients may need electrolytes and renal function

monitoring once or twice weekly early after hospital discharge to as infrequently as

every 3 months for very stable patients.

38

Pre-renal Azotemia

Pre-renal azotemia usually results from over diuresis with subsequent compromise of

intravascular volume and decreased renal perfusion. In addition to looking for

clinical signs of hypovolemia, such as dizziness, orthostatic hypotension, and

increased heart rate, frequent measurements of BUN and serum creatinine

concentrations provide a relatively simple means of assessing the intravascular

volume. A gradual rise in serum creatinine, BUN, as well as the BUN:serum

creatinine ratio can serve as a warning to slow the rate of diuresis.

69

In a small

study,

64 serial measurements of plasma volume and ascites volume were made during

treatment with diuretics in patients with cirrhosis. Patients with ascites and no edema

were able to mobilize more than 1 L/day during rapid diuresis, but at the expense of

plasma volume contraction and renal insufficiency. Patients with peripheral edema

appear to be somewhat protected from these effects and may safely undergo diuresis

at a more rapid rate (>2 kg/day) until edema resolves.

64 Others suggest, however, that

the maximal daily fluid loss should not exceed more than 0.5 L/day (>0.5 kg/day) for

patients with ascites alone or 1 L/day (>1 kg/day) for those with both ascites and

edema to prevent plasma volume depletion and decreased renal perfusion. If faster

removal of ascites is required because of respiratory distress, large-volume

paracentesis may be more effective than rapid diuresis (see Case 25-1, Question

9).

38,45,70,71

In cirrhotic patients, azotemia may also occur because of nonsteroidal

anti-inflammatory drugs (NSAIDs). All NSAIDs should be discontinued, except low

dose aspirin in patients at high risk for a cardiac or neurological event.

38

Because R.W. presented with both edema and ascites, an initial weight loss of up

to 1 kg/day would be reasonable with slowing to 0.5 kg/day when the edema

resolves. Gradual diuresis avoids diuretic-induced depletion of intravascular fluid

volume by permitting ascitic fluid to equilibrate with intravascular fluid. Long-term

management of ascites is done in the outpatient setting. Severe cases with respiratory

distress or impaired ambulation as well as patients with spontaneous bacterial

peritonitis (see Chapter 70, Intra-Abdominal Infections) require hospitalization. If

outpatient therapy is an option, a weekly evaluation initially would be prudent to

prevent over diuresis and electrolyte disturbances.

38

Refractory Ascites

CASE 25-1, QUESTION 9: Over the next several days, R.W.’s spironolactone dosage was increased to 400

mg/day. Furosemide was simultaneously increased to 80 mg BID without major improvement in diuresis.

Laboratory data revealed that R.W.’s SCr had increased to 3.2 mg/dL (estimated creatinine clearance: 26

mL/minute) and his BUN had increased to 45 mg/dL. Serum electrolytes were as follows:

K, 3.1 mEq/L

Na, 130 mEq/L

Cl, 88 mEq/L

Bicarbonate, 32 mEq/L

R.W. became progressively short of breath because of restricted diaphragmatic movement secondary to his

significantly enlarged abdomen. What therapeutic measures are appropriate for R.W.’s refractory (diureticresistant) ascites?

The AASLD guidelines mention a few treatment options for refractory ascites.

Midodrine 7.5 mg given 3 times daily to increase blood pressure in hypotensive

patients could possibly convert diuretic-resistant patients to diuretic-sensitive. In

addition, discontinuation of β-blockers is recommended since these drugs are

associated with increased mortality in patients with refractory ascites. The guidelines

also mention avoiding angiotensin converting enzyme inhibitors (ACEIs) and

angiotensin receptor blockers (ARBs) because of the risk of hypotension.

38

Because of the increase in SCr and respiratory distress, R.W.’s ascites treatment

needs modification. Patients with cirrhosis experiencing respiratory distress despite

diuretic therapy, sodium restriction, and appropriate management of hypotension

(discontinuation of β-blockers and adding midodrine) may warrant more aggressive

second-line treatment, including large-volume paracentesis, shunting procedures, or

both.

38 Paracentesis involves the removal of ascitic fluid from the abdominal cavity

with a needle or a catheter. Although paracentesis can remove large amounts of

ascitic fluid (e.g., 10 L), removal of as little as 1 L of fluid may provide considerable

relief from the painful stretching of skin and the respiratory distress that occurs with

massive ascites. The ascitic fluid often re-accumulates rapidly after paracentesis.

The major complications of overly aggressive, large-volume paracentesis include

hypotension, shock, oliguria, encephalopathy, and renal insufficiency. Other potential

complications of paracentesis are hemorrhage, perforation of the abdominal viscera,

infection, and protein depletion.

38

ALBUMIN

CASE 25-1, QUESTION 10: R.W. continues to re-accumulate ascitic fluid and is exhibiting signs of declining

renal function. A 6-L paracentesis coupled with a 50-g albumin infusion is ordered. Why are albumin infusions

used in conjunction with paracentesis?

p. 544

p. 545

Large-volume (>4 L) paracentesis should be performed for patients with tense

ascites, resulting in respiratory distress or impaired ambulation. However, largevolume paracentesis is associated with paracentesis-induced circulatory dysfunction

(PICD), which manifests clinically as worsening renal function 24 to 48 hours postprocedure.

72,73

Intravenous (IV) albumin infusions are commonly administered to

prevent PICD after large-volume paracentesis.

38 Use of albumin in combination with

large-volume paracentesis produces an expansion of circulating blood volume,

increases cardiac output, and suppresses release of renin and norepinephrine.

73

Although albumin is costly and sometimes in short supply, for some patients it is

appropriate with paracentesis.

74

In one study, patients requiring large-volume

paracentesis (≥6 L/day) received either concomitant IV albumin (40 g) or saline. The

incidence of PICD was significantly higher in the saline than the albumin group

(33.3% vs. 11.4%, respectively). The prevalence of PICD after paracentesis depends

on the volume of ascites removed such that albumin infusion may not be necessary for

a single paracentesis <4 to 5 L.

38,74 For large-volume paracentesis greater than or

equal to 6 L, 6 to 8 g of albumin is typically administered for each liter of ascites

removed.

38

Wilkes et al.

75 conducted a meta-analysis of 55 randomized, controlled trials

evaluating the effects of albumin administration for a variety of indications on patient

mortality. They found no improvement in mortality with albumin administration.

75

However, albumin administered to patients with spontaneous bacterial peritonitis

lowered the incidence of renal impairment (10% vs. 33%; p = 0.002), overall

mortality at 3 months (22% vs. 41%; p = 0.03), and hospital mortality (10% vs. 29%;

p = 0.01) than the group that did not receive albumin.