chronic liver disease is present. Altered mental status accompanied by jaundice and elevated serum

transaminases and prothrombin time is the hallmark of presentation. Rapid loss of liver mass can lead to

multisystem organ failure and death.64 Encephalopathy may be accompanied by myopathy and

neuropathy, loss of vascular tone with hypotension, cardiac dysfunction, acute lung injury,

gastrointestinal bleeding, pancreatitis, acute renal failure, and/or disseminated intravascular

coagulopathy. Intracranial hypertension is recognized in 50% or greater of patients with stage IV coma.

Therefore, neurocritical care with ability to respond to hemodynamic fluctuations becomes an important

component of management. Other precepts are maintenance of normoxia, euglycemia, control of

seizure, therapeutic hypothermia, osmotic therapy, and judicious hyperventilation.69

Initial management includes identification and treatment of infection, titration of intravascular

volume expansion, and selection of fluids to minimize cerebral edema. Hypertonic saline may be

considered to maintain serum sodium in the mildly hypernatremic range. Norepinephrine is the

vasopressor of choice and early initiation of renal replacement therapy is important for tight control of

intravascular volume. Mild reduction in blood CO2

tension can also restore cerebral vasoreactivity and

autoregulation.69

Advanced cerebral edema is associated with hyperventilation, hypertension, papillary abnormalities,

decerebrate posturing, and ultimately uncal herniation and death. Arterial ammonia levels greater than

200 μg/dL may be correlated with herniation.64 Although powered controlled trials are still needed to

determine the role of intracranial pressure monitoring,70 management should aim to keep the cerebral

perfusion pressure (mean arterial pressure–intracranial pressure) over 50 mm Hg and the intracranial

pressure below 25 mm Hg. Sustained pressures greater than these values for longer than 2 hours usually

signifies irreversible brain damage.64 Mannitol intravenous bolus doses of 0.5 to 1 g/kg are effective in

decreasing cerebral edema by maintaining osmotic diuresis and can be repeated provided serum

osmolarity does not exceed 320 mOsm/L.62 Profound coagulopathy (INR >7) and/or planned invasive

procedures warrant correction of coagulopathy with fresh frozen plasma (FFP) in combination with

recombinant activate factor VII (rFVIIa).62

Liver Transplantation

Establishing the cause of ALF is an important determination of outcomes following liver transplantation,

with the best results achieved with Wilson disease and the worst seen with idiosyncratic drug reactions.

Overall survival rates following liver transplantation at 1 year are 20% below those seen for elective

transplants performed for chronic disease but are similar to those achieved in patients with chronic

disease who go to transplant from the ICU.71

5 Patients who are at high risk of progression to death should be identified and listed for

transplantation in a timely fashion. Likewise, it is also crucial to identify patients who have become too

sick to benefit from liver transplant. Relative contraindications to liver transplant include: sustained

cerebral hypoperfusion (CPP <40 mm Hg) for longer than 2 hours, high doses of vasopressor, acute

respiratory distress syndrome (ARDS) requiring high inspired FiO2 and elevated PEEP.69

Life Support Systems

Various biologic and charcoal-based sorbent systems have been tested to date with no demonstrable

clinical impact. Total plasma exchange has been studied retrospectively when used to stabilize patients

until a transplant can be obtained or self-regeneration occurs.63 Sorbent systems have shown transient

detoxification with no long-term benefits at the expense of worsening coagulopathy. Porcine cell-based

and hepatoblastoma-derived extracorporeal systems, the molecular adsorbents recirculating system

(MARS),72 and the Prometheus system73 are available only for clinical trials and their future in the

management of ALF remains uncertain.62

STAGING

Table 58-2 King’s College Criteria of Poor Prognostic Indicators

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Prognosis

Accurate prognosis in ALF is important to avoid unnecessary liver transplantation, and the traditionally

accepted King’s College Criteria are most commonly used for this purpose (Table 58-3). Of note is that

the Model for End-Stage Liver Disease (MELD) system cannot be applied in ALF.62

ALF due to acetaminophen overdose, hepatitis A, shock liver, or pregnancy-related disease show a

50% or more transplant-free survival, while most other etiologies show only a 25% transplant free

survival.62 Other proposed but not widely accepted poor prognostic criteria include alpha fetoprotein

levels, ratio of factor VIII and V levels, liver histology, and serum phosphate levels.

Recipients who underwent liver transplant for drug induced ALF in the United States from 1987 to

2006 were retrospectively studied and the most common drug groups were identified as acetaminophen,

antituberculosis medicines, antiepileptics, and other antibiotics. Patients aged 7 years or younger with

antiepileptic toxicity had the highest risk of death following liver transplantation compared to all other

groups. Mechanical ventilation and elevated serum creatinine were identified as other predictors of poor

survival after transplant.74

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