Hepatic Coma

Hepatic coma is the loss of consciousness that results due to metabolic

alterations associated with liver failure. When the liver fails to function
normally, some byproducts of metabolism accumulate in the blood and may
reach levels toxic to the brain. Hepatic coma represents the final stage (stage
IV or grade IV) of a progressive brain dysfunction (encephalopathy)
secondary to the accumulation of substances toxic to the brain.

Liver failure may occur in severe inflammatory conditions of the liver

(hepatitis) caused by viruses, drugs, or toxins, but more commonly occurs
incirrhosis or other chronic disorders. In cirrhosis or other chronic liver
diseases, there is an associated rise in circulatory pressure (portal
hypertension) and altered circulation (portosystemic shunting). The altered
circulation, in turn, bypasses the liver and allows substances usually
detoxified by the liver to accumulate in the bloodstream and brain. As the
toxins accumulate, the brain function and level of consciousness deteriorates.
It remains unclear whether the cause of hepatic encephalopathy and
subsequent hepatic coma is solely due to the accumulation of these brain
toxins or if there is some alteration in the brain tissue itself that also
contributes to the problem.

Since the brain function seen in liver failure (hepatic encephalopathy)

progressively deteriorates as toxins accumulate, the syndrome of
encephalopathy is categorized into four stages or grades. Grade I and II
represent mild to moderate depression of brain function. In grade III, severe
depression of consciousness occurs with some abnormal body posturing that
signifies brain damage has occurred. The final stage of hepatic
encephalopathy is grade IV. At this stage, the entire brain is affected and the
individual becomes unconscious and unresponsive to painful stimuli (hepatic
coma).

Factors that precipitate or worsen encephalopathy include renal

failure, infection, gastrointestinal bleeding, constipation, drugs (barbiturates,
narcotics, sedatives) that act on the central nervous system, diuretic
medications, and dietary protein overload. These factors all increase the
production of the substances toxic to the brain.

The exact prevalence of hepatic coma is not documented. However,

approximately 70% of those with cirrhosis demonstrate at least subtle signs of
brain dysfunction (encephalopathy) and 30% of individuals dying from end-
stage liver failure have significant encephalopathy (grade III) or coma (grade
IV).

The leading cause of hepatic encephalopathy (fulminant hepatic failure) in the

US is viral hepatitis, and in the United Kingdom is acetaminophen toxicity,
where it is responsible for 50% to 70% of cases (Sass).

Individuals at increased risk for hepatic coma are those who have sustained
viral hepatitis, primary or secondary liver cancers, acetaminophen toxicity,
pre-eclampsia, and prescription medication toxicity.

Risk: Individuals who use illegal drugs such as cocaine or ecstasy, or who
use certain herbal medicines (ginseng, pennyroyal oil, and chaparral or
germander tea) also have increased risk (Jones).
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Incidence and Prevalence: Incidence of fulminant hepatic failure (FHF) is
2,300 to 2,800 cases per year in the US, which accounts for 6% of liver-
related deaths, and about 6% of liver transplants among adults (Sass).
Diagnosis

History: If coma is present, a history may only be gathered from significant

others or caregivers. They may report the individual has a history of liver
disease and describe a recent change in the individual's behavior and
alertness that led up to the loss of consciousness. This may include a change
in personality, memory lapses, and progressive drowsiness and confusion.
Individuals may have been incapable of writing simple words or even their
name. Other contributory factors in the individual's recent history include
vomiting blood (gastrointestinal hemorrhage), decreased urine output (renal
failure), or use of sedatives or diuretics prior to onset of coma.

Physical exam: The individual usually has signs of advanced liver disease
such as a swollen abdomen (ascites), yellow skin (jaundice), small broken
vessels on the face and chest (spider angiomata), and muscle wasting. The
individual is unconsciousness and may or may not respond to painful stimuli.
Individuals may display a flapping tremor of the hands (asterixis) when arms
are stretched out straight. The breath may be sweet and musty smelling due
to the exhalation of accumulated blood toxins (fetor hepaticus). Deep or rapid
respirations (hyperventilation) and decreased body temperature (hypothermia)
may be present. The individual's pupils are usual small (pinpoint) and reactive
to light. Abnormal body posture (decerebrate or decorticate) is often indicative
of brain dysfunction. Other precipitating factors may include bloody emesis
or diarrhea (gastrointestinal bleeding) or dehydration.

Tests: Blood tests show an increase in ammonia levels, which is an index of

the degree of accumulation of toxins. Measurement of brain activity (EEG)
shows abnormalities. Severe brain edema that can be visualized
by MRI commonly occurs. Other blood tests such as a complete blood count
(CBC), electrolytes, blood cultures, and renal function studies (BUN and
creatinine) may be done to determine if other contributory causes to the coma
are present.
Treatment
Treatment of hepatic coma and encephalopathy is aimed at elimination or
treatment of precipitating factors and lowering the blood ammonia levels by
decreasing the absorption of protein and nitrogenous products from the
intestine. Ammonia production and absorption is decreased with the
administration of antibiotic medications that decrease intestinal bacteria (a
source of ammonia) and certain osmotic laxatives that increase ammonia
excretion in the stool. Dietary protein (a source of ammonia) restriction may
be necessary. Nutritional formulas containing vegetable proteins or special
protein mixtures (branched chain amino acids) may help decrease the
ammonia production. If there is evidence of precipitating causes such as
gastrointestinal bleeding, infection, or dehydration, these conditions are
promptly treated and controlled. All medications known to be neurological
depressants (sedatives, narcotics etc.) are avoided. Deteriorating individuals

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with advanced liver failure may be promptly referred to a transplant center
since emergency liver transplantation can be lifesaving.

Prognosis
Coma associated with advanced liver inflammation (hepatitis) or chronic liver
failure is fatal in up to 80% of individuals despite intensive therapy. Liver
transplantation is the treatment for those with advanced hepatic
encephalopathy. In individuals who have received a liver transplantation, the
3-year survival rate is approximately 65%.

Individuals who survive hepatic coma are occasionally left with residual
neurologic abnormalities such as tremor of the head or arms, speech
disturbances, alterations in gait, or impairment of intellectual functioning.
These symptoms may worsen with repeated attacks of stupor and coma.

Complications
Hemorrhage, infection, dehydration, and kidney failure are commonly
associated with advanced chronic liver disease and may pose a complication
for individuals suffering from hepatic coma.

Return to Work (Restrictions / Accommodations)

In general, individuals with hepatic coma have functional and intellectual
impairments that preclude them from employment. Impairments may resolve
following liver transplantation, however, significant activity restrictions are often
associated with this procedure. The individual's physician should dictate
specific restrictions and accommodations in this case.

Failure to Recover
If an individual fails to recover within the expected maximum duration period,
the reader may wish to consider the following questions to better understand
the specifics of an individual's medical case.

Regarding diagnosis:

• Does individual have history of liver disease?

• Was a recent change in individual's behavior and alertness (i.e.,
change in personality, memory lapses, and progressive drowsiness and
confusion) noted that led up to the loss of consciousness? Did
individual have recent history of vomiting blood (gastrointestinal
hemorrhage), decreased urine output (renal failure), or use of sedatives
or diuretics prior to onset of coma?
• Does individual show signs of advanced liver disease such as a
swollen abdomen (ascites), yellow skin (jaundice), small broken blood

vessels on the face and chest (spider angiomata), and muscle wasting?

• When unconscious, does individual respond to painful stimuli?

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 • Does individual display a flapping tremor of the hands (asterixis)
when arms are stretched out straight? Does breath have a sweet and
musty smell? Are respirations deep or rapid (hyperventilation)? Is body
temperature decreased (hypothermia)? Are pupils small (pinpoint) and
reactive to light? Is body posture abnormal (decerebrate or
decorticate)?
• Were blood tests done? Did results show an increase in
ammonia levels? Did EEG show abnormalities? Did MRI visualize
severe brain edema?
• Was diagnosis of hepatic coma confirmed? If diagnosis is
uncertain, were conditions with similar symptoms ruled out?

Regarding treatment:

• Was treatment aimed at elimination or treatment of precipitating

factors such as gastrointestinal bleeding, infection, or dehydration?
• Were blood ammonia levels effectively lowered by decreasing
the absorption of protein and nitrogenous products from the intestine?
• Were medications known to be neurological depressants
(sedatives, narcotics etc.) eliminated?
• If individual with advanced liver failure is deteriorating, is he or
she a candidate for a liver transplant? Was individual referred to a
transplant center?

Regarding prognosis:

• Does individual have a coexisting condition such as malnutrition,

gastrointestinal bleeding, central nervous system disease, or kidney
failure that may complicate treatment or impact recovery?
• Did individual sustain residual neurologic abnormalities such as
tremor of the head or arms, speech disturbances, alterations in gait, or
impairment of intellectual functioning?
• Can therapy help individual compensate for impairment?
• Would work accommodations allow individual to continue in
present occupation?
• Have complications developed such as hemorrhage, infection,
dehydration, or kidney failure that may impact recovery and length of
disability?