Management of Fulminant Liver Failure
General Supportive Measures.
Patients with ALF are
prone to rapid deterioration and should be closely monitored,
usually in an intensive care setting. The cause of
the ALF should be identified, and
suitable candidates for
orthotopic liver transplantation should be moved early
to a transplantation center. Early tracheal intubation may
be necessary if neurologic status deteriorates and leads to
airway compromise. Volume expansion with crystalloids
and colloids is usually required to help maintain blood
pressure. Correction of acid-base disturbances, treatment
of hyperthermia, and close glucose monitoring are
important to prevent cerebral edema. Renal failure from
hepatorenal syndrome may develop and is reversible with
the return of hepatic function. Continuous renal replacement
therapy (CRRT) is often required in patients with
advanced ALF to treat renal insufficiency, volume status,
and cerebral edema. Early antibiotics and source control
are important because the incidence of bacteremia and
sepsis is higher in these patients than in the general population.
138 Although abnormalities exist in both the coagulation
and fibrinolytic pathways, the defects appear to
be balanced, and there is a relative preservation of hemostasis
unless the platelet count is very low.139 If a cause
is identified, then initiation of antidotes is needed (e.g.,
N-acetylcysteine for acetaminophen poisoning, penicillin
G for mushroom poisoning, early delivery for pregnancyrelated
ALF).134
Management of Increased Intracranial Pressure.
The
development of cerebral edema and intracranial hypertension
is the most devastating complication associated
with ALF (see also Chapter 70). Osmotically active compounds,
normally cleared by the liver, accumulate in
blood and diffuse into the brain parenchyma. Movement
of water into neurons and glia results in swelling and can
cause herniation. The exact compounds responsible for
cerebral edema are unknown, but ammonia is probably a
major contributor.
Diagnosis of cerebral edema can be difficult. Serial
neurologic examination is essential, and frequent computed
tomography of the head can identify early signs
of edema. Many centers implement early invasive monitoring
of intracranial pressure, although this practice has
not been shown to improve outcome.140 Monitoring can
be achieved with either cranial or lumbar epidural monitors
because traditional intraventricular monitors carry
an unacceptable risk of bleeding.
Techniques to reduce intracranial pressure include
the removal of ammonia with CRRT, hypothermia, barbiturate
coma, and the administration of mannitol and
hypertonic saline.141 Although most available laboratory
evidence suggests that hypothermia should be helpful in
controlling the cerebral complications of ALF, randomized
clinical trials in patients to demonstrate its safety or
efficacy are currently lacking.142
Liver Support Devices
Bioartificial Livers. Bioartificial livers use hepatocytes to
mimic the synthetic, detoxifying, and excretory function
of the dying liver. Porcine hepatocytes are preferentially
used because human hepatocytes are difficult to grow
in culture.143 The device works by passing the patient’s
plasma through hollow-fiber capillaries while the hepatocytes
are placed in the extracapillary space. Molecules
are exchanged between hepatocytes and plasma across
a membrane that prevents passage of immunoglobulin,
complement, and cells. A prospective, multicenter, randomized
controlled trial using the HepatAssist liver support
system was published in 2004.144 The results did not
show any improvement in survival in the treated group.
Only during subgroup analysis were patients with fulminant
or subfulminant liver failure found to have improved
survival, but the results were marginal.
Artificial Extracorporeal Devices. Artificial extracorporeal
devices have received renewed interest because of
technology allowing the production of membranes that
can increase selectivity through small pores. The system
can be tailored for albumin-bound substances, which
include most of the toxins that accumulate with FHF.
Larger molecules such as immunoglobulins cannot cross.
This system is associated with significant biochemical
improvements,145 but these studies are small and uncontrolled,
and whether this will translate into improved
clinical outcomes still remains a matter of debate (see also
Chapter 107).
Overall, the liver support devices appear to be safe, but
adverse events can include bleeding, systemic infection,
disseminated intravascular coagulation, and anaphylaxis.
A meta-analysis of the use of artificial and bioartificial life
support systems in 8 randomized controlled trials involving
only 139 patients concluded that the evaluated support
systems have no significant effect on the mortality
in patients with ALF.146 Randomized clinical trials are
limited, considering the patient’s severity of illness. More
controlled trials addressing survival are warranted before
this therapy can be strongly recommended.
General Supportive Measures.
Patients with ALF are
prone to rapid deterioration and should be closely monitored,
usually in an intensive care setting. The cause of
the ALF should be identified, and
suitable candidates for
orthotopic liver transplantation should be moved early
to a transplantation center. Early tracheal intubation may
be necessary if neurologic status deteriorates and leads to
airway compromise. Volume expansion with crystalloids
and colloids is usually required to help maintain blood
pressure. Correction of acid-base disturbances, treatment
of hyperthermia, and close glucose monitoring are
important to prevent cerebral edema. Renal failure from
hepatorenal syndrome may develop and is reversible with
the return of hepatic function. Continuous renal replacement
therapy (CRRT) is often required in patients with
advanced ALF to treat renal insufficiency, volume status,
and cerebral edema. Early antibiotics and source control
are important because the incidence of bacteremia and
sepsis is higher in these patients than in the general population.
138 Although abnormalities exist in both the coagulation
and fibrinolytic pathways, the defects appear to
be balanced, and there is a relative preservation of hemostasis
unless the platelet count is very low.139 If a cause
is identified, then initiation of antidotes is needed (e.g.,
N-acetylcysteine for acetaminophen poisoning, penicillin
G for mushroom poisoning, early delivery for pregnancyrelated
ALF).134
Management of Increased Intracranial Pressure.
The
development of cerebral edema and intracranial hypertension
is the most devastating complication associated
with ALF (see also Chapter 70). Osmotically active compounds,
normally cleared by the liver, accumulate in
blood and diffuse into the brain parenchyma. Movement
of water into neurons and glia results in swelling and can
cause herniation. The exact compounds responsible for
cerebral edema are unknown, but ammonia is probably a
major contributor.
Diagnosis of cerebral edema can be difficult. Serial
neurologic examination is essential, and frequent computed
tomography of the head can identify early signs
of edema. Many centers implement early invasive monitoring
of intracranial pressure, although this practice has
not been shown to improve outcome.140 Monitoring can
be achieved with either cranial or lumbar epidural monitors
because traditional intraventricular monitors carry
an unacceptable risk of bleeding.
Techniques to reduce intracranial pressure include
the removal of ammonia with CRRT, hypothermia, barbiturate
coma, and the administration of mannitol and
hypertonic saline.141 Although most available laboratory
evidence suggests that hypothermia should be helpful in
controlling the cerebral complications of ALF, randomized
clinical trials in patients to demonstrate its safety or
efficacy are currently lacking.142
Liver Support Devices
Bioartificial Livers. Bioartificial livers use hepatocytes to
mimic the synthetic, detoxifying, and excretory function
of the dying liver. Porcine hepatocytes are preferentially
used because human hepatocytes are difficult to grow
in culture.143 The device works by passing the patient’s
plasma through hollow-fiber capillaries while the hepatocytes
are placed in the extracapillary space. Molecules
are exchanged between hepatocytes and plasma across
a membrane that prevents passage of immunoglobulin,
complement, and cells. A prospective, multicenter, randomized
controlled trial using the HepatAssist liver support
system was published in 2004.144 The results did not
show any improvement in survival in the treated group.
Only during subgroup analysis were patients with fulminant
or subfulminant liver failure found to have improved
survival, but the results were marginal.
Artificial Extracorporeal Devices. Artificial extracorporeal
devices have received renewed interest because of
technology allowing the production of membranes that
can increase selectivity through small pores. The system
can be tailored for albumin-bound substances, which
include most of the toxins that accumulate with FHF.
Larger molecules such as immunoglobulins cannot cross.
This system is associated with significant biochemical
improvements,145 but these studies are small and uncontrolled,
and whether this will translate into improved
clinical outcomes still remains a matter of debate (see also
Chapter 107).
Overall, the liver support devices appear to be safe, but
adverse events can include bleeding, systemic infection,
disseminated intravascular coagulation, and anaphylaxis.
A meta-analysis of the use of artificial and bioartificial life
support systems in 8 randomized controlled trials involving
only 139 patients concluded that the evaluated support
systems have no significant effect on the mortality
in patients with ALF.146 Randomized clinical trials are
limited, considering the patient’s severity of illness. More
controlled trials addressing survival are warranted before
this therapy can be strongly recommended.
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