eMedicine Specialties > Gastroenterology > Liver

Acute Liver Failure: Follow-up

Author: Gagan K Sood, MD, Associate Professor, Department of Medicine and Surgery, Baylor College of Medicine
Contributor Information and Disclosures

Updated: Jun 25, 2009

Follow-up

Complications

• Hepatic encephalopathy 
  • Manage hepatic encephalopathy in the conventional way, by providing lactulose and avoiding sedatives. In the late stages of encephalopathy, avoid providing lactulose by mouth or nasogastric tube without previous intubation, considering the risk of aspiration.
  • Hepatic encephalopathy is not truly a complication because it is required for the diagnosis of fulminant hepatic failure, but evolution to higher stages of hepatic encephalopathy may result in patients losing their abilities to maintain their airways. 
• Cerebral edema
  • The occurrence of cerebral edema and ICH in patients with acute liver failure is related to the severity of encephalopathy. Cerebral edema is seldom observed in patients with grades I-II encephalopathy. The risk of edema increases to 25-35% with progression to grade III and to 65-75% (or more) in patients reaching grade IV coma.
  • Patients in the advanced stages of encephalopathy require close follow-up care. Monitoring and management of hemodynamic and renal parameters, as well as glucose, electrolytes, and acid/base status, become critical. Frequent neurologic evaluation for signs of elevated ICP should be conducted.
• ICP monitoring
  • ICP monitoring helps in the early recognition of cerebral edema. The clinical signs of elevated ICP, including hypertension, bradycardia, and irregular respirations (Cushing triad), are not uniformly present; these and other neurologic changes, such as papillary dilatation or signs of decerebration, are typically evident only late in the course.
  • CT scanning of the brain does not reliably demonstrate evidence of edema, especially in the early stages. A primary purpose of ICP monitoring is to detect elevations in ICP and reductions in CPP, so that interventions can be made to prevent herniation while preserving brain perfusion.
  • The ultimate goal of such measures is to maintain neurologic integrity and to prolong survival while awaiting receipt of a donor organ or recovery of sufficient functioning hepatocyte mass.
  • Additionally, refractory ICH and/or decreased CPP is considered a contraindication to liver transplantation in many centers.
  • In patients with grade III or IV encephalopathy, consider placement of ICP monitors.
  • Correct coagulopathy and bleeding tendencies with the use of FFP and platelet infusion.
  • If an ICP monitor is placed, ICP should be maintained below 20-25 mm Hg, if possible, with CPP maintained above 50-60 mm Hg. Support of systemic blood pressure may be required to maintain adequate CPP.
• ICH is managed initially by the use of mannitol. Osmotic diuresis with IV mannitol is effective in the short term in decreasing cerebral edema. Administration of IV mannitol (in a bolus dose of 0.5-1 g/kg or 50-100 g) is recommended to treat ICH in acute liver failure. The dose may be repeated once or twice, as needed, provided serum osmolality has not exceeded 320 mOsm/L. Volume overload is a risk with mannitol use in patients with renal impairment and may necessitate the use of dialysis to remove excess fluid.
• Other measures can be used to treat ICH.
  • Hyperventilation may be instituted temporarily in an attempt to acutely lower ICP and to prevent impending herniation, if life-threatening ICH is not controlled with mannitol infusion and other general management as outlined above.
  • Hyperventilation to reduce the partial pressure of carbon dioxide in the blood (PaCO₂) to 25-30 mm Hg is known to quickly lower ICP via vasoconstriction, causing decreased cerebral blood flow, but this effect is short-lived. 
• Other therapies used to decrease ICH but not routinely recommended may be considered in refractory ICH.
  • A controlled trial of administration of 30% hypertonic saline, 5-20 mL/h, to maintain serum sodium levels of 145-155 mmol/L in patients with acute liver failure and severe encephalopathy suggested that induction and maintenance of hypernatremia may be used to prevent the rise in ICP values.
  • Barbiturate agents (thiopental or pentobarbital) may also be considered when severe ICH does not respond to other measures; administration has been shown to effectively decrease ICP. Significant systemic hypotension frequently limits their use and may necessitate additional measures to maintain adequate mean arterial pressure.
    • Thiopental 5-10 mg/kg loading dose followed by 3-5 mg/kg IV infusion.
    • Pentobarbital 3-5 mg/kg IV loading dose followed by 1-3 mg/kg/h infusion.
  • Moderate hypothermia (32-34°C) may prevent or control ICH in patients with acute liver failure. Potential deleterious effects of hypothermia include increased risk of infection, coagulation disturbance, and cardiac arrhythmias. An external cooling blanket may be used to achieve this goal.
• Seizures, which may be seen as a manifestation of the process that leads to hepatic coma and ICH, should be controlled with phenytoin. The use of any sedative is discouraged in light of its effects on the evaluation of mental status. Only minimal doses of benzodiazepines should be used given their delayed clearance by the failing liver. Seizure activity may acutely elevate and may also cause cerebral hypoxia and, thus, contribute to cerebral edema.
• Hemorrhage  
  • This develops as a result of the profoundly impaired coagulation that manifests in these patients.
  • Correct coagulopathy, as earlier outlined.
  • The transfusion requirements for coagulation products (FFP, platelets) may be enormous. Multiple transfusions with packed red blood cells may be needed.
  • Gastrointestinal bleeding may develop from esophageal, gastric, or ectopic varices as a result of portal hypertension. Portal hypertensive gastropathy and stress gastritis may also develop.
  • Any minor trauma may result in extensive percutaneous bleeding or internal hemorrhage.
  • Consider retroperitoneal hemorrhage if large transfusion requirements are not matched by an obvious blood loss.
• Infection prophylaxis and treatment
  • Periodic surveillance cultures should be performed to detect bacterial and fungal infections.
  • Empiric broad-spectrum antibiotics and antifungals should be given in the following circumstances:
    • Progressive encephalopathy (All patients listed for transplantation start antibiotics.)
    • Signs of systemic inflammatory response syndrome (SIRS) (temperature, >38ºC or <36ºC; white blood cell [WBC] count, >12,000/μL or <4000/μL; pulse rate, >90 bpm)
    • Persistent hypotension
  • Zosyn and fluconazole should be the initial choice. In hospital-acquired IV catheter infections, consider vancomycin.
• Renal electrolyte and acid-base imbalances
  • Acute renal failure is a frequent complication in patients with acute liver failure and may be due to dehydration, hepatorenal syndrome, or acute tubular necrosis.
  • Maintain adequate blood pressure, avoid nephrotoxic medications and NSAIDs, and promptly treat infections.
  • When dialysis is needed, continuous (ie, continuous venovenous hemodialysis [CVVHD]) rather than intermittent renal replacement therapy is preferred.
• Metabolic concerns
  • Alkalosis and acidosis occur; identify and treat the underlying cause.
  • Base deficits can be corrected by THAM solution (tromethamine injection), which prevents a rise in carbon dioxide, osmolality, and serum sodium.
  • Severe hypoglycemia occurs in approximately 40% of patients with fulminant hepatic failure. Although hypoglycemia occurs more frequently in children, it needs to be monitored in adult patients as well.
  • Blood sugars should be maintained in the range of 60-200 mg/dL with the infusion. Use 10% dextrose solution and glucose monitoring.
  • Phosphate, magnesium, and potassium levels are low and require frequent supplementation.

Prognosis

• Prognosis is highly dependent on the inciting cause of fulminant hepatic failure. Prognostic indices have been developed to identify patients who require liver transplantation. The development of complications is the other factor that largely determines survival.
• Viral hepatitis
  • Approximately 50-60% of patients with fulminant hepatic failure due to HAV infection survive.
  • These patients account for a substantial proportion (10-20%) of the pediatric liver transplants in some countries, despite the relatively mild infection observed in many children infected with HAV.
  • The outcome for patients with fulminant hepatic failure as the result of other causes of viral hepatitis is much less favorable.
• Acetaminophen toxicity
  • Fulminant hepatic failure due to acetaminophen toxicity generally has a relatively favorable outcome, and prognostic variables permit reasonable accuracy in determining the need for OLT.
  • Patients presenting with deep coma (hepatic encephalopathy grades 3-4) have increased mortality when compared with those with milder encephalopathy.
  • An arterial pH of less than 7.3 and either a PT greater than 100 seconds or serum creatinine greater than 300 mcg/mL (3.4 mg/dL) are independent predictors of a poor prognosis.
• Non–acetaminophen-induced fulminant hepatic failure
  • A PT greater than 100 seconds and any 3 of the following 5 criteria are independent predictors¹⁰ : (1) age younger than 10 years or older than 40 years; (2) fulminant hepatic failure due to non-A, non-B, non-C hepatitis; halothane hepatitis; or idiosyncratic drug reactions; (3) jaundice present longer than 1 week before onset of encephalopathy; (4) PT greater than 50 seconds; or (5) serum bilirubin greater than 300 mmol/L (17.5 mg/dL).
  • Once these patients are identified, arrange appropriate preparations for OLT.
  • The above criteria, developed at King's College Hospital in London, have been validated in other centers; however, significant variability occurs in the patient populations encountered at any center, and this heterogeneity may preclude widespread applicability.
  • Other prognosticating tests have been proposed. Reduced levels of Gc-globulin (a molecule that binds actin) have been reported in fulminant hepatic failure, and a persistently increasing PT portends death. These and other parameters have not been widely validated yet.
• Wilson disease: Wilson disease presenting as fulminant hepatic failure is almost uniformly fatal without OLT.

Miscellaneous

Medicolegal Pitfalls

• Failure to consider a diagnosis of fulminant hepatic failure and/or failure to initiate appropriate timely referral to a liver transplantation center

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Blake A Jones, MD, to the development and writing of this article.

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