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Professional Version

Fulminant Hepatic Failure in Small Animals


Sharon A. Center

, DVM, DACVIM, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University

Reviewed/Revised May 2015 | Modified Oct 2022

Fulminant hepatic failure is a syndrome defined by the abrupt loss of liver function, associated with hepatic encephalopathy (HE) and coagulopathy. Early, appropriate therapy is critical. In chronic or end-stage liver disease with an acute or chronic insult and in acute liver injury 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 determined. Decontamination of oral, dermal, and enteric surfaces is mandatory if toxin exposure has occurred within 36 hr. If an adverse drug reaction is implicated, the drug in question must be discontinued 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. Restoration of intravascular volume and systemic perfusion may prevent or mitigate the severity of organ failure that often accompanies fulminant hepatic failure (eg, renal, cardiac, adrenal, pancreatic dysfunction). Lactated Ringer’s solution should be avoided in animals with compromised lactate metabolism, leading to lactic acidosis. Chronic vomiting and diarrhea often accompany fulminant hepatic failure and can lead to dehydration, hypokalemia, hypochloremia, and metabolic alkalosis. Alkalosis and hypokalemia can each escalate renal ammonia production, contributing to hyperammonemia and HE. Neuroglycopenia can induce neurologic signs that can be confused with and augment HE. Administration of 0.9% NaCl with supplemental vitamins and glucose is usually a safe first option unless portal hypertension and ascites complicate the syndrome. Dextrose (2.5%) and potassium (sliding scale) should be judiciously added to IV fluids, as well as water-soluble vitamins (fortified B-soluble vitamins at 2 ml/L of fluid). Ascites may develop in animals with an acute sinusoidal collapse or acute or chronic fibrosing hepatic injury.

In cats, a B12 injection (250–1,000 mcg total dose, IM or SC) should be considered if severe gut disease, pancreatic disease, or starvation are suspected; a plasma sample for assessment of B12 should be collected before treatment. Definitive assessment of methylmalonic acidemia defines B12 adequacy but cannot be completed in a timely manner for clinical application in emergent liver failure. Thiamine deficiency (B1) can also complicate clinical status, producing neurobehavioral signs overlapping with HE. Although hyperglycemia must be avoided because it can worsen cerebral edema, euglycemia must be established before thiamine administration; otherwise, thiamine-provoked neuroglycopenia may aggravate neurologic injury and clinical signs. Thiamine is especially important in cats and can be supplemented PO or slowly with IV fluids (fortified B-soluble vitamin solution); 25–100 mg/day is recommended.

Animals with acute liver failure have high energy expenditure and protein catabolism. Nutritional support should be attempted enterically with protein intake initially restricted to 2.5 g/kg body wt in dogs and 3.5 g/kg body wt in cats, with overt HE. If neurologic signs are inapparent, protein restriction is not advised.

Broad-spectrum antibiotics should be given empirically if HE, renal failure, or components of the systemic inflammatory response syndrome (SIRS) are identified. As for other suspected bacterial infections involving the liver, a combination of ticarcillin, metronidazole (7.5 mg/kg, PO or IV, every 12 hr), and enrofloxacin are advised.

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, 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.

Initially, vitamin K1 (0.5–1.5 mg/kg, IM or SC) is given in three doses at 12-hr intervals. Repeated dosing may be necessary in animals with overt coagulopathies. However, a balanced hemostatic defect with loss of hepatic procoagulant synthesis paralleled by the loss of hepatically derived anticoagulants results in the lack of an overt coagulopathy. Inhibition of gastric acid secretion with an H2-receptor antagonist (eg, famotidine, faster onset) or HCl pump inhibitor (eg omeprazole, slower onset) is advised. Omeperazole inhibits certain p450 cytochromes and may result in polypharmacy drug interactions. If overt hemorrhagic tendencies are seen, fresh frozen plasma or cryoprecipitate (for vWF and fibrinogen) may be needed. Desmopressin acetate (DDAVP, 0.3 mcg/kg, IV, diluted to 10% in saline) can sometimes arrest serious clinical hemorrhage by improving primary hemostasis. With acute portal hypertension, diapedesis of blood into the enteric lumen may develop before opening of APSSs; this can lead to lethal blood loss and/or aggravate HE. In this scenario, only a whole blood transfusion or administration of packed RBCs and species-specific plasma can replace extracorporeal losses. Concurrent propranolol administration may reduce portal hypertension, which may lessen the rate of blood loss.

The goal of therapeutic strategies in fulminant hepatic failure is to prevent the onset of encephalopathy, limit its severity, and reduce the risk of cerebral edema. Development of cerebral edema is multifactorial, complex, and incompletely understood. Mediators of systemic and local inflammation and circulating neurotoxins (especially ammonia) contribute to its development. HE also can be precipitated by systemic infection, hypotension, and systemic vasodilatation. Altered cerebral endothelial permeability in response to neurotoxins (eg, ammonia) and inflammatory mediators, inflammatory responses, and altered cerebral blood flow are also recognized to trigger or worsen HE.

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, which tends to reduce intracerebral pressure. Hypoxia must be avoided because of its associated cerebral vasodilatory effect. Mannitol (1–1.5 g/kg, IV, once) can help reduce cerebral edema; boluses can be repeated if serum osmolality has 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 infusions are not recommended.

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