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CHAPTER 107: Management of the Patient With Cirrhosis 1027

on chronic liver failure require a systematic multiorgan system approach TABLE 107-1 Grading of Hepatic Encephalopathy Based on West Haven Criteria
to management in order to address hepatic and extrahepatic organ dys-
function. An optimization of hepatic and extrahepatic derangements, Clinical Manifestations
including cardiopulmonary, neurologic and renal dysfunction, is essential Grade I Decreased attention span/concentration; abnormal sleep pattern; mildly
for the successful management of the critically ill cirrhotic patient. slowed mentation; mild confusion; minimal changes in memory
■ ACUTE ON CHRONIC LIVER FAILURE Grade II Lethargy; inappropriate behavior; slurred speech; personality changes

The pathophysiology and sequelae of chronic liver disease warrant a Grade III Somnolence; disorientation; marked confusion; incomprehensible speech
unique approach to ICU management and treatment of disease. Namely, Grade IV Unresponsive to verbal or noxious stimuli; coma
portal hypertension marks the transition from compensated to decom-
pensated cirrhosis, resulting in life-threatening conditions including
gastrointestinal variceal bleeding, hepatorenal syndrome, pulmonary the ICU setting, given that patients with cirrhosis are sensitive to sedat-
complications, and hepatic encephalopathy. 1 ing agents, a shorter acting agent such as propofol is preferred. Imaging
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Portal hypertension in cirrhosis is a result of the combined effect of the brain should also be considered to rule out other etiologies of
of intrahepatic resistance to portal flow and increased portal inflow. altered mental status including CVA, intracranial bleed, or masses. The
The resistance to portal flow consists of both fixed and functional precipitating factor(s) of hepatic encephalopathy must be identified and
components. The fixed component occurs from sinusoidal fibrosis and treated. These include gastrointestinal bleeding, infection, alkalosis or
compression by regenerative nodules. The functional component is sec- acidosis, electrolyte disturbances, overdiuresis, dehydration, placement
ondary to vasoconstriction, resulting from both decreased intrahepatic of recent TIPS, constipation, medication or dietary noncompliance,
nitric oxide and enhanced intrahepatic vasoconstrictor activity. The sedatives, tranquilizers, narcotics, or progressive hepatic dysfunc-
paradoxical decreased intrahepatic nitric oxide and overproduction of tion. Supportive care with IV fluid hydration, correction of electrolyte
extrahepatic nitric oxide produces splanchnic vasodilation and increased disturbances, and aspiration and fall precautions should be instituted.
portal inflow. Combined, the effects of the intrahepatic resistance to flow Nonabsorbable disaccharides such as lactulose are the main phar-
and increased portal inflow result in a portal hypertensive state. In addi- macological agent to aid in the clearance of ammonia in treatment of
2
tion, the pathologic splanchnic vasodilation results in a shunting of the hepatic encephalopathy. These drugs work by decreasing ammonia
cardiac output to the splanchnic circulation, and an associated decrease production in the gastrointestinal tract and increasing fecal nitrogen
in effective systemic arterial blood volume perfusing other organ systems. excretion. Specifically, when oral lactulose reaches the cecum, it is
These hemodynamic derangements in the splanchnic and systemic metabolized by enteric bacteria, causing a drop in the pH. This leads
circulation form the basis for current management strategies in decom- to a shift in bacteria favoring uptake of ammonia, leaving less for
pensated cirrhosis. An organ-system-based review of the management of mucosal absorption. If the patient is unable to take oral lactulose,
1
specific disease manifestations in acute on chronic liver failure follows. then an NG tube must be placed for luminal administration, or lactu-
lose enemas should be administered. The dosage should be titrated to
HEPATIC ENCEPHALOPATHY approximately three bowel movements per day. Antibiotics including
flagyl, rifaximin, and vancomycin have also been studied and shown
Hepatic encephalopathy is a serious complication of portal hypertension to be effective in the treatment of hepatic encephalopathy. These
occurring both in the acute and acute on chronic liver failure setting. Its work primarily by eliminating urease-producing bacteria flora. While
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neuropsychiatric clinical presentation ranges widely from mild cogni- these agents can reduce blood ammonia levels and improve menta-
tive impairment to frank coma. The pathophysiology is accepted to be a tion, the degree of encephalopathy has not been shown to correlate
result of a failed hepatic clearance of toxic products from the gastroin- with specific ammonia levels. Other treatment methods including zinc
testinal tract in the setting of impaired liver function. 3 administration and protein restriction are also used but lack strong
While the debate continues over which toxins mediate the develop- clinical supporting evidence. The phenomenon of cerebral edema
1
ment of hepatic encephalopathy, elevated ammonia levels have long and intracranial hypertension noted in acute liver failure (ALF) due
been implicated in its pathogenesis. Specifically, ammonia’s effect on to hyperammonemia-induced astrocyte swelling does not occur in
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brain astrocytes is suspected in the development of hepatic encepha- chronic liver disease, and is therefore not a concern in the management
lopathy. The astrocytes in chronic liver disease take on an Alzheimer- of hepatic encephalopathy in the cirrhotic patient.
type morphology known as Alzheimer type II astrocytosis. In chronic
liver disease, excess serum ammonia levels alter neuronal proteins on HEMODYNAMIC DERANGEMENTS
the surface of astrocytes leading to abnormal glutamate trafficking. This
alteration in glutamate is thought to be partially responsible for abnor- The hemodynamic state associated with cirrhosis is distinctive with a
mal neurotransmission seen in hepatic encephalopathy. Other studies low systemic vascular resistance, an increased cardiac output, and a low
4
have suggested the involvement of serotonergic and GABA receptors, mean arterial pressure, thereby mimicking septic physiology. During
manganese, as well as catecholamine pathways in the pathogenesis of decompensation or sepsis, hemodynamic abnormalities worsen with
hepatic encephalopathy. 1 increased portal pressures and further exacerbation of systemic hypo-
The diagnosis of hepatic encephalopathy requires a high level of tension. Vasopressor support is often needed in these patients to main-
suspicion in patients with chronic liver disease and careful attention tain adequate end-organ perfusion. Despite this hyperdynamic state,
to neuropsychiatric abnormalities. Patients may present with symp- patients with decompensated cirrhosis may also show signs of primary
toms ranging from subtle changes in sleep-wake cycle, to lethargy, to cardiac depression with reduced ejection fraction under conditions of
worsened levels of consciousness including somnolence and coma. The stress and a decreased response to inotropic support, suggesting the
West Haven criteria grade hepatic encephalopathy from grade I to grade possibility of a cirrhotic cardiomyopathy. Based on current evidence,
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IV based on varying levels of consciousness, intellectual function, and the initial vasoactive agent of choice for distributive shock is norepi-
behavior (Table 107-1) and are used widely. Neurologic abnormalities nephrine. Its α- and β-adrenergic properties increase systemic vascular
5
on physical exam may be seen in more advanced presentations and tone while preserving cardiac output. Low-dose vasopressin may be
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include asterixis, hyperactive deep tendon reflexes, and hemiplegia. 6 used as a second-line agent but can increase afterload. Dopamine should
Initial management of hepatic encephalopathy involves determining be used with caution as it may cause vasodilation in the splanchnic cir-
the grade of encephalopathy with prompt ICU transfer and elective intu- culation, thereby worsening portal hypertension. Fluid resuscitation
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bation for airway protection in grades III and IV. If sedation is needed in should be guided by dynamic fluid-responsiveness predictors so as to

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