Jan 052014
Acute Liver Failure: Treatment (Part 2 of 2)

See also: Acute Liver Failure: Causes & Initial Management

Management of acute liver failure is largely supportive critical care for the multiorgan failure that frequently results. Severe acute liver failure results in rapidly progressive hepatic encephalopathy and lethal cerebral edema; this complication requires special vigilance and expert management. Hypoglycemia, hyponatremia, and metabolic disturbances from renal failure may also require continual attention. Whenever possible, transfer to a liver transplant center should be considered for any patient with severe acute liver failure. If this is not possible, local or remote consultation of a liver transplant physician (hepatologist and/or transplant surgeon) should be sought, as well as a neurologist.

Neurologic Care in Acute Liver Failure

Rising ammonia concentration in blood, resulting from impaired detoxification to urea by the liver, is the major contributor to cerebral edema in acute liver failure. Ammonia is a neurotoxin and an osmotic agent; sustained ammonia levels of 150 to 200 µmol/L (255 to 340 µg/L) greatly increase intraneuronal osmolarity (through its metabolism to glutamine) and the risk for intracranial hypertension and encephalopathy. Unfortunately, ammonia-reducing agents are of limited value. Lactulose (the usual agent to reduce ammonia in chronic liver failure) may be harmful, and other agents (neomycin, nonresorbable antibiotics like rifaxamin et al) are not proven effective in acute liver failure. The ammonia-detoxifying L-ornithine L-aspartate (LOLA) did not help either, in a large randomized trial.

Instead, neurologic care for encephalopathy in acute liver failure focuses on preventing and controlling intracranial hypertension. Sedation to lower cerebral metabolism and hyperosmotic agents to directly reduce cerebral edema are the cornerstones of therapy.

white-pearl-iconPearl: Hypertonic saline bolus dosing: King's College physicians treat sustained elevations in intracranial pressure during acute liver failure with boluses of intravenous hypertonic saline (20 ml of 30% NaCl, or 200 ml of 3% NaCl), maintaining sodium level of < 150 mmol/L. Mannitol (2 mL of 20% solution / kg body weight) to maintain serum osmolality < 320 mOsm/L is an alternative. In one randomized trial, prophylactic hypertonic saline delayed intracranial hypertension onset in patients with high-grade encephalopathy.

white-pearl-iconTargeted temperature management to maintain core body temperature at 35 to 36° C is advised, to prevent brain-damaging fevers. Although hypothermia to 34° C was not shown to help in a randomized trial, King's College physicians support reducing core temperature to 32 to 34° in resistant intracranial hypertension, based on their experience. A bolus of 0.5 mg/kg I.V. indomethacin may be used in those with cerebral hyperemia.

white-pearl-iconInvasive intracranial pressure monitoring is performed routinely by some centers to optimize management, but others tend to avoid its low but real risk for intracranial hemorrhage and infections, reserving its use for patients with clinical signs of worsening intracranial hypertension. Sustained arterial ammonia concentrations of >150 μmol/L or a single level of 200+ μmol/L during treatment, multiorgan (renal) failure, or age < 35 increase risk for severe intracranial hypertension. Invasive ICP monitoring has not been clearly shown to improve outcomes.

Managing Other Organ Failure in Acute Liver Failure

Cardiovascular: Acute liver failure commonly results in hypotension and shock (circulatory failure), often with vasodilatory and hypovolemic physiology. After intitial volume resuscitation, norepinephrine is a recommended vasopressor for those in persistent hypotension. Vasopressin or its analogs can be added. Echocardiogram should be obtained to assess myocardial function.

Respiratory: Most people with acute liver failure do not initially have lung injury; endotracheal intubation is usually required for encephalopathy, but not respiratory failure. For patients with cerebral edema, short-term hyperventilation by mechanical ventilation is appropriate to induce hypocapnia in an emergency situation; normal ventilation should be reinstated once hyperosmotic agents (the preferred method) are available to reduce cerebral pressure. Sedation should be used to prevent spontaneous hyperventilation.

Renal: More than half of people with acute liver failure suffer acute renal failure. Continuous renal replacement therapy can help mitigate acid-base and metabolic derangements and control hyperammonemia. CRRT is preferred to the metabolic and hemodynamic fluctuations induced by intermittent hemodialysis.

Endocrine: Patients with acute liver failure are at high risk for hypoglycemia, which can be prevented with continuous glucose (dextrose) infusions.

Nutrition: To maintain muscle mass and immune function, King's College administers 1.0 to 1.5 g/kg/day of protein as part of enteral feedings for acute liver failure patients, while closely monitoring ammonia levels. Protein dose may be lowered in patients with high risk for intracranial hypertension or with very high ammonia levels.

Prognosis and Transplantation

The King's College, Clichy, and Japanese prognostic criteria compete for prominence, each with its advantages and drawbacks in identifying the best candidates for liver transplantation in acute liver failure.

Although liver transplantation and postoperative management in critically ill patients with acute liver failure is challenging, outcomes have steadily improved over the years. Recent registry data show a 79% 1 year survival and 72% 5 year survival after liver transplantation for acute liver failure.

See also: Acute Liver Failure: Causes & Initial Management

William Bernal and Julia Wendon. Acute Liver Failure. N Engl J Med 2013; 369: 2525-34

DOI: 10.1056/NEJMra1208937

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Acute Liver Failure: Treatment (Part 2 of 2)