Fulminant hepatic failure is a syndrome defined by the abrupt loss of liver function, associated with hepatic encephalopathy (HE) and coagulopathy. Early and appropriate therapy is critical. In chronic or end-stage liver disease and in acute liver disease with no apparent underlying cause, treatment provides supportive care to allow time for hepatic regeneration and compensation.
Specific treatment should be administered if an underlying cause is identified. Decontamination of oral, dermal, and enteric surfaces is mandatory if toxin exposure has occurred within 36 hr. If an adverse drug reaction is implicated, administration of the drug in question must be stopped and antidotes investigated. Life-threatening infection, cerebral edema, and coagulopathies are major complications.
Attention to fluid, electrolyte, and acid-base balance, glycemic status, and nutritional support optimizes chance of survival. Lactated Ringer's solution should be avoided because hepatic failure may thwart lactose metabolism and cause lactic acidosis. Chronic vomiting and diarrhea can lead to dehydration, hypokalemia, hypochloremia, and metabolic alkalosis. Alkalosis and hypokalemia can increase renal ammonia production, escalating HE. Neuroglycopenia can induce neurologic effects that contribute to HE. Administration of 0.9% NaCl with supplemental vitamins and glucose is usually a safe first option. Dextrose (2.5%) and potassium (sliding scale) should be judiciously added to IV fluids and water-soluble vitamins supplemented (fortified B-soluble vitamins at 2 ml/L of fluid).
In cats, a B12 injection (250–1,000 μg total dose, IM or SC) should be considered if severe gut disease, pancreatic disease, or starvation are suspected. Thiamine deficiency can produce neurobehavioral signs similar to those of HE. While hyperglycemia must be avoided because it can worsen cerebral edema, euglycemia must be established before thiamine administration; otherwise, neuroglycopenia may aggravate neurologic signs and cause more extensive neurologic injury. Thiamine can be supplemented PO or slowly with IV fluids (fortified B-soluble vitamin solution), in cats a rate of 25–100 mg/day is recommended.
Broad-spectrum antibiotics should be given empirically if HE, renal failure, or components of the systemic inflammatory response syndrome (SIRS) are identified.
In most cases, N-acetylcysteine is administered for the first 2 days to provide cysteine for glutathione synthesis, to improve microcirculatory perfusion, and to protect against development of SIRS. A loading dose (140 mg/kg) is initially administered through a 0.25 μM filter and given over 20 min; prolonged infusion can precipitate hyperammonemia. Thereafter, 70 mg/kg is given IV at intervals of 6–8 hr for 2 days. Rarely, an adverse reaction develops in dogs, manifesting as urticaria, pruritic rash, vomiting, and most severely as angioneurotic edema.
When oral medications can be tolerated, biologically available S-adenosylmethionine (SAMe) is recommended at 20–40 mg/kg/day, PO, given on an empty stomach to sustain hepatic glutathione adequacy.
Vitamin K1 (0.5–1.5 mg/kg, IM or SC) is given in 3 doses at 12-hr intervals. Inhibition of gastric acid secretion with a histamine-2 receptor antagonist (eg, famotidine) or HCl pump inhibitor (eg omeprazole) is also advised. If overt hemorrhagic tendencies are observed, fresh frozen plasma or cryoprecipitate (for vWF and fibrinogen) may be needed. Desmopressin acetate (DDAVP, 0.3 μg/kg, IV diluted to 10% in saline) can sometimes arrest serious hemorrhage by improving primary hemostasis.
Development of cerebral edema is mul-tifactorial, complex, and incompletely understood. The head and neck should be maintained in a neutral position, avoiding compression of jugular blood flow. Elevation of the head and neck can reduce intracranial pressure and decrease CSF hydrostatic pressure. Central venous lines increase risk of serious iatrogenic hemorrhage, which may require use of compression bandaging. Spontaneous hyperventilation sustains a mild respiratory alkalosis that promotes cerebral arterial vasoconstriction; this tends to reduce intracerebral pressure. Hypoxia must be avoided because of its associated cerebral vasodilatory effect. Mannitol (0.25–0.5 g/kg, given as an IV bolus), can help reduce cerebral edema; boluses can be repeated if serum osmolality is not increased. Furosemide (0.5–1 mg/kg, every 6–8 hr) has been used to increase renal elimination of sodium and water. Use of hypothermia, barbiturate coma, hypertonic saline, or flumazenil infusion are not recommended.
Last full review/revision March 2012 by Sharon A. Center, DVM, DACVIM