The Patient with Liver Failure

Fluid management of the patient with liver failure (see Chapter 55 and Chapter 56 ) is complicated by several interacting problems. These patients appear to be simultaneously hypervolemic and hypovolemic. Most infused fluid is retained, but renal function deteriorates, along with avid sodium retention and arterial underfilling. Neither explains all the clinical findings or leads to consistently successful therapy.

According to the arterial underfilling (primary vasodilation) hypothesis,^[130] some factor produced by or not catabolized by the failing liver causes inappropriate arterial dilation. The relative hypotension leads to activation of the systematic nervous system, the RAS, and vasopressin release. These lead to subsequent sodium and water retention, resulting in ascites and tissue edema.

Cirrhotic patients have a low systemic vascular resistance, high cardiac output, and relative hypotension. Persistent endotoxemia (shunting through portosystemic anastomoses and enhanced endotoxin absorption from the intestine due to bile salt deficiency) may contribute to the vasodilation by activation of a cascade of secondary mediators, beginning with tumor necrosis factor and interleukins. Other vasodilator neurotransmitters may be produced or may not be cleared by the damaged liver.

The primary sodium retention hypothesis explains the avid sodium retention on the basis of hormonal (aldosterone) hyperactivity because of failure of the liver to metabolize aldosterone. Given the ECF volume expansion, the distribution into ascites and tissue edema is explained by the abnormally high portal venous pressures and hypoalbuminemia. Abnormalities of atrial natriuretic peptide (ANP) have been investigated. ANP levels are normal or low in cirrhotic patients; this contrasts with the increase usually found in volume-expanded patients.^[131] ANP increased with water immersion or fluid administration, but natriuresis was not closely correlated with ANP levels. Water immersion of the lower body compresses the venous capacitance system, resulting in centralization of blood volume. This simulates a volume infusion without adding any sodium or water to the body and should cause ANP release. Water immersion did not increase ANP levels in patients with ascites, who therefore have blunted responses. Impaired ANP release failed to explain sodium retention.^[131] Patients with tense ascites had increased ANP, renin, and aldosterone concentrations. After paracentesis, ANP increased, but renin and aldosterone levels decreased.^[132] The reasons for these findings were not clarified, but a reduction in intra-abdominal pressure could have decreased inferior caval pressure, facilitated venous return, and increased ANP levels. Decreased intra-abdominal pressures would also improve renal perfusion pressure, causing a reduction in renin release and subsequent aldosterone generation.

The role of increased intra-abdominal pressure may be important in sustaining sodium retention after ascites develops. Increased intra-abdominal pressure raises caval pressure. This decreases renal blood flow and glomerular filtration rate because the renal perfusion pressure gradient (i.e., mean arterial pressure minus renal venous pressure) is decreased by systemic hypotension and increased caval pressure. The hypotension and reduction in renal blood flow can lead to renin activation, with aldosterone production. Hypotension, increased aldosterone, and a decreased glomerular filtration rate lead to enhanced sodium reabsorption and low fractional excretion of sodium.

Hypoalbuminemia results from impaired synthesis by the liver, transudation into ascitic fluid due to portal hypertension, and malnutrition. Low COP favors loss of fluid from the vascular space into the interstitial space, producing intravascular hypovolemia. Ascites results from high portal venous pressure and hypoalbuminemia, markedly increasing the volume of transcellular fluid, which is functionally excluded from rapid exchange in the ECF volume.

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Splanchnic blood pooling resulting from increased portal venous resistance plus lower body pooling resulting from elevated caval pressures from ascites tend to decrease net systemic venous return. Patients are functionally hypovolemic despite normal or elevated total blood volume. Heart failure from alcoholic cardiomyopathy may further complicate the clinical picture.

The goals in these patients are to avoid increasing interstitial fluid overload, maintain normal potassium concentration, and maintain intravascular volume. If cardiac failure is present, treatment must include administration of inotropic drugs and diuretics when filling pressures are increased. Intravascular COP should be restored by infusion of 25% albumin when possible. If the patient is acutely hypovolemic, 5% albumin solutions should be preferred to crystalloid, which tend to further expand the already overexpanded ECF volume (i.e., produce more edema and ascites). Intra-abdominal pressure should be estimated from urinary bladder pressure and paracentesis performed whenever it increases above 20 to 25 mm Hg. Trials of dopamine, norepinephrine, phenylephrine, or vasopressin may be performed in hypotensive patients with low vascular resistance and hypotension to increase renal perfusion pressure and renal blood flow.