Why is hepatic encephalopathy a complication of diuretic use?

Hepatic Encephalopathy as a Complication of Diuretic Use

Diuretics can precipitate hepatic encephalopathy in cirrhotic patients through multiple mechanisms including electrolyte disturbances, dehydration, and worsening of liver function. 1

Mechanisms of Diuretic-Induced Hepatic Encephalopathy

• Diuretic therapy is classically considered a precipitating factor of hepatic encephalopathy in cirrhotic patients, though the exact mechanism is not fully understood 1
• Intravascular volume depletion from excessive diuretic therapy can lead to renal dysfunction and precipitate hepatic encephalopathy 1
• Hypokalemia, particularly from loop diuretics like furosemide, disrupts the body's ability to manage ammonia levels, which is the primary pathogenic material in hepatic encephalopathy 2, 3
• Hyponatremia from diuretic therapy can worsen hepatic encephalopathy by causing cerebral edema and increasing brain volume 4
• Sudden alterations of fluid and electrolyte balance in patients with cirrhosis may precipitate hepatic coma, as noted in the FDA label for furosemide 3
• Spironolactone can cause sudden alterations of fluid and electrolyte balance which may precipitate impaired neurological function and worsen hepatic encephalopathy in patients with hepatic disease 5

Clinical Recognition and Diagnosis

• Diuretic-induced hepatic encephalopathy is defined as "the development of encephalopathy in the absence of any other precipitating factor" 1
• It is one of the diagnostic criteria for diuretic-intractable ascites, which is ascites that cannot be mobilized because of diuretic-induced complications 1
• Clinical manifestations range from subtle cognitive changes (covert HE) to more obvious neurological dysfunction (overt HE) 6
• Regular monitoring of serum creatinine, sodium, and potassium concentration should be performed during diuretic therapy, particularly during the first weeks of treatment 1

Prevention and Management

• Diuretic dosage should be adjusted to achieve a rate of weight loss of no greater than 0.5 kg/day in patients without peripheral edema and 1 kg/day in those with peripheral edema to prevent diuretic-induced complications 1
• Once refractoriness of ascites has been ascertained due to diuretic-induced complications like hepatic encephalopathy, diuretics should be discontinued 1
• Supplemental potassium chloride and, if required, an aldosterone antagonist are helpful in preventing hypokalemia and metabolic alkalosis that can precipitate hepatic encephalopathy 3
• Plasma volume expansion with albumin infusion has been shown to improve diuretic-induced hepatic encephalopathy by reducing plasma ammonia concentration and oxidative stress 7
• Non-absorbable disaccharides such as lactulose are the primary treatment for hepatic encephalopathy once it develops 1

Risk Factors and Special Considerations

• Patients with advanced liver disease are at higher risk for developing diuretic-induced hepatic encephalopathy 1
• Transjugular intrahepatic portosystemic shunt (TIPS) placement, often used for refractory ascites, increases the risk of hepatic encephalopathy, occurring in 30-50% of patients 1, 6
• Patients with refractory ascites who undergo TIPS have a higher frequency of encephalopathy compared to those treated with large volume paracentesis 1
• In patients with cirrhosis and ascites, furosemide therapy is best initiated in the hospital setting to monitor for complications 3
• In hepatic coma and in states of electrolyte depletion, diuretic therapy should not be instituted until the basic condition is improved 3

Practical Recommendations

• Identify and correct precipitating factors such as dehydration, electrolyte abnormalities, and excessive diuretic use 1, 2
• Monitor for early signs of hepatic encephalopathy in cirrhotic patients receiving diuretics 1
• Consider albumin infusion rather than other colloids for volume expansion in diuretic-induced hepatic encephalopathy 7
• In patients with diuretic-induced complications, consider alternative methods for managing ascites, such as large-volume paracentesis with albumin administration 1
• Educate patients and caregivers about the early signs of hepatic encephalopathy and actions to take if symptoms develop 1