Step 4: Ammonia Levels

The number-one recommendation on the Choosing Wisely Canada website’s Hepatology page is, “Don’t order serum ammonia to diagnose or manage hepatic encephalopathy.” Elevated serum ammonia levels do not add diagnostic or prognostic value in liver patients suspected of HE because encephalopathy may precede the rise in ammonia levels.³ Ideally, we would like to know how much ammonia enters the brain, not how much is in the blood. A common pitfall is to incorrectly rule out HE via a normal ammonia level—ammonia levels can be normal or near normal in HE. Serial measurements of ammonia may help evaluate the efficacy of ammonia-lowering drugs. But have a low threshold to treat HE on speculation, as this condition is difficult to definitively diagnose in the emergency department. 

Lactulose has been found to significantly reduce mortality and serious complications of HE in a Cochrane review of 38 randomized controlled trials (RCTs). Dosing is 20 g (30 mL) orally and is titrated to three to four soft stools per day.⁴ A common myth is that increasing the dose of lactulose will be effective after standard doses have failed. But overdosing lactulose can lead to worsening volume depletion, aspiration, hypernatremia, and even precipitation of HE.¹ If the patient with HE is rendered NPO, polyethylene glycol (PEG) via nasogastric dosed at 4 L over four hours has been shown to resolve HE more rapidly than lactulose in one small RCT of hospitalized patients.^5,6 

It is important to understand that patients with HE have excess gamma aminobutyric acid (GABA) stimulation. This makes them sensitive to GABAergic medications such as benzodiazepines and propofol. Such medications should be dose-adjusted or avoided whenever possible. When endotracheal intubation is necessary, ketamine may be a better choice of induction agent than propofol for this reason. 

Step 5: Top Off Fluids, Glucose, Potassium 

One way to remember some of the important aspects of treating HE is that everything besides the liver enzymes and liver function tests tends to be low: circulatory volume, serum potassium, and glucose. For fluid replacement, consider albumin in addition to normal saline for patients with a low serum albumin, as there is some RCT evidence (although weak) that it may improve outcomes when added to lactulose in patients with HE.⁷ Intravenous albumin will likely be especially effective in patients with concurrent hepatorenal syndrome and/or acute liver failure. 

It is important to understand that patients with HE have depleted glycogen stores. That’s why a single bolus of D50W is unlikely to achieve normoglycemia for an extended period of time. An ongoing infusion of D10W or D25W is often required to prevent hypoglycemia and worsening LOA. 

Another pitfall is ignoring mild hypokalemia. Treat even the mildest hypokalemia because low potassium contributes to hyperammonemia by decreasing ammonia excretion. Correcting hypokalemia is thought to decrease ammonia levels in patients with HE.⁸ Magnesium also must be corrected if low because failure to address hypomagnesemia will make potassium replacement ineffective.