What is the appropriate treatment for an adult patient with hyperammonemia and a history of liver disease?

Treatment of Ammonia Level of 109 μmol/L

For an ammonia level of 109 μmol/L in an adult patient with liver disease, initiate lactulose therapy immediately at 30-45 mL orally three to four times daily, targeting 2-3 soft stools per day, while investigating and treating precipitating factors for hepatic encephalopathy. 1

Initial Assessment and Diagnosis

• Confirm the diagnosis of hepatic encephalopathy (HE) as the cause of hyperammonemia, as a normal ammonia level has high negative predictive value for HE, but an elevated level at 109 μmol/L supports the diagnosis in the context of liver disease 2

• Assess the patient's mental status using the West Haven criteria (Grades 0-4) or Glasgow Coma Scale to determine severity of encephalopathy 2

• Investigate precipitating factors immediately, including infections (start empiric antibiotics if high suspicion), gastrointestinal bleeding, electrolyte disorders, acute kidney injury, dehydration, constipation, and use of sedating medications 2

• Brain imaging (CT or MRI) is not routinely indicated unless this is the first episode of altered mental status, there are new focal neurological signs, seizures, or inadequate response to treatment of precipitating factors and HE therapy 2

Medical Management

Lactulose Therapy (First-Line Treatment)

• Start lactulose 30-45 mL orally three to four times daily (containing 20-30 grams per dose), adjusting every 1-2 days to produce 2-3 soft stools daily 1

• For rapid laxation in acute presentations, hourly doses of 30-45 mL may be used initially until laxative effect is achieved, then reduce to standard dosing 1

• If oral administration is not possible due to impending coma or aspiration risk, administer 300 mL lactulose mixed with 700 mL water or saline as a retention enema for 30-60 minutes, repeating every 4-6 hours 1

• Clinical improvement may occur within 24 hours but can take up to 48 hours or longer 1

Rifaximin as Add-On Therapy

• Consider adding rifaximin to lactulose therapy, though its role in acute-on-chronic liver failure warrants further investigation 2

Monitoring and Follow-Up

• Do not routinely recheck ammonia levels to monitor treatment response, as ammonia lowering is inconsistently associated with clinical improvement and levels are not used to guide ongoing therapy 2

• Monitor clinical response based on improvement in mental status and reduction in HE grade 2

• Continue long-term lactulose therapy to prevent recurrence of portal-systemic encephalopathy 1

When to Escalate Care

• Consider ICU admission if the patient progresses to Grade 3 or 4 HE (stupor, coma) or Glasgow Coma Scale <8 2

• Kidney replacement therapy is NOT indicated at an ammonia level of 109 μmol/L unless there is rapidly deteriorating neurological status with coma or cerebral edema (which would require levels typically >150-300 μmol/L) 3, 4

Common Pitfalls to Avoid

• Do not delay treatment while waiting for ammonia results or brain imaging in patients with known liver disease and altered mental status consistent with prior HE episodes 2

• Do not over-rely on ammonia levels for diagnosis or treatment monitoring—HE is a clinical diagnosis, and ammonia may remain elevated after clinical resolution 2

• Ensure proper ammonia sampling technique if levels are checked: use free-flowing venous or arterial blood, transport on ice, and process within 15 minutes to avoid false elevations 3, 4

• Do not forget to treat precipitating factors—infections, GI bleeding, electrolyte abnormalities, and constipation are common triggers that must be addressed for successful HE management 2