What are the diagnosis and management of encephalopathy?

From the Guidelines

Encephalopathy diagnosis and management should prioritize a comprehensive approach focusing on identifying the underlying cause while providing supportive care, with the most recent guidelines from the European Association for the Study of the Liver (EASL) in 2022 1 serving as the foundation for treatment decisions.

Key Considerations

• Initial evaluation should include a thorough history, physical examination, and laboratory tests including complete blood count, comprehensive metabolic panel, ammonia level, toxicology screen, and blood cultures if infection is suspected.
• Neuroimaging with CT or MRI and electroencephalogram (EEG) are essential diagnostic tools.
• Management depends on the specific etiology but generally involves treating the underlying cause while providing supportive care.

Hepatic Encephalopathy Management

• For hepatic encephalopathy, lactulose (initial dose 25-30 mL orally every 1-2 hours until bowel movement, then 15-30 mL 2-4 times daily) and rifaximin (550 mg twice daily) are first-line treatments 1.
• The diagnosis of hepatic encephalopathy should be made through exclusion of other causes of brain dysfunction, and it should be divided into various stages of severity, reflecting the degree of self-sufficiency and the need for care 1.

Metabolic, Toxic, and Infectious Encephalopathies

• Metabolic encephalopathies require correction of the underlying abnormality, such as glucose for hypoglycemia or sodium correction for hyponatremia (not exceeding 8-10 mEq/L/day to prevent central pontine myelinolysis).
• Toxic encephalopathies necessitate removal of the offending agent and possibly antidotes.
• Infectious causes require appropriate antimicrobials.

Supportive Care

• Supportive care includes airway protection, maintaining adequate oxygenation and perfusion, seizure management with benzodiazepines or antiepileptics, and prevention of complications.
• The pathophysiology of encephalopathy often involves disruption of neurotransmitter systems, particularly increased inhibitory neurotransmission from substances like ammonia or decreased excitatory neurotransmission, leading to altered mental status and neurological dysfunction.

Diagnostic Approaches

• Neurophysiological investigations, such as EEG and evoked potentials, can provide a functional assessment of the nervous system and are useful in the diagnosis and follow-up of hepatic encephalopathy 1.
• These investigations can complement the neurological examination and provide evidence of hepatic encephalopathy in patients with normal consciousness, rule out other causes of disturbances of consciousness, and demonstrate the worsening or improvement of hepatic encephalopathy over time.

From the FDA Drug Label

For the prevention and treatment of portal-systemic encephalopathy, including the stages of hepatic pre-coma and coma. Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; this is generally paralleled by the improvement in the patients’ mental state and by an improvement in EEG patterns. The clinical response has been observed in about 75% of patients, which is at least as satisfactory as that resulting from neomycin therapy.

The diagnosis of encephalopathy is not directly addressed in the provided drug labels. However, the management of portal-systemic encephalopathy can be achieved with lactulose therapy, which has been shown to reduce blood ammonia levels and improve mental state and EEG patterns in about 75% of patients 2.

• The recommended adult oral dosage is 2 to 3 tablespoonfuls (30 mL to 45 mL) three or four times daily 2.
• Continuous long-term therapy is indicated to lessen the severity and prevent the recurrence of portal-systemic encephalopathy 2.
• In severe cases, such as impending coma or coma, lactulose solution may be given as a retention enema via a rectal balloon catheter 2.

From the Research

Encephalopathy Diagnosis

• Encephalopathy refers to dysfunction of the level or contents of consciousness due to brain dysfunction and can result from global brain insults or focal lesions 3
• A practical schema for organizing the differential diagnosis is to group etiologies by their pace of onset and evolution (eg, sudden, acute, subacute, chronic) 3
• The underlying causes of encephalopathy include both primary neurologic and systemic conditions 3

Encephalopathy Management

• Hepatic encephalopathy management varies depending on the acuity of liver failure, but five basic steps in management are critical: stabilization, addressing modifiable precipitating factors, lowering blood ammonia, managing elevated intracranial pressure (ICP), and managing complications of liver failure 4
• In patients with acute liver failure and high-grade encephalopathy, identification of the etiology of acute liver failure is essential to guide treatment and antidote administration 4
• Liver transplantation is the definitive treatment for patients with acute liver failure and hepatic encephalopathy 4
• In patients with chronic hepatic encephalopathy, lactulose and rifaxamin remain a mainstay of therapy 4
• Autoimmune encephalitis is often treatment-responsive when immunotherapy (glucocorticoids, intravenous immune globulin, plasma exchange) is used in various combinations 5

Diagnostic Approaches

• A combination of clinical examination and diagnostic modalities can aid in prompt diagnosis of hepatic encephalopathy 6
• ICP monitoring and transcranial Doppler help diagnose and monitor response to treatment 6
• Neuroimaging combined with a thorough history and examination is often helpful in ruling out stroke and fulminant demyelinating encephalopathies 5
• Obtaining a combined serum and Cerebrospinal fluid (CSF) autoantibody testing will increase the diagnostic yield of autoimmune and paraneoplastic encephalitis 5

Treatment Options

• Transfer to a transplant center and intensive care unit admission with airway management and reduction of CE with hypertonic saline, mannitol, hypothermia, and sedation are recommended as a bridge to liver transplantation 6
• Continuous renal replacement therapy may help lower serum ammonia, treat coexisting uremia, and improve symptoms 4
• Free water restriction and increased dietary sodium are reasonable, cost-effective treatment options for chronic hyponatremia 4