What are the next steps for a 28-year-old non-drinker in the Intensive Care Unit (ICU) with liver failure, who is not responding to Rifaximin (Rifaximin) and Lactulose (Lactulose), and has hyperammonemia (elevated ammonia level)?

From the Guidelines

For a 28-year-old non-drinker with liver failure in the ICU who is failing rifaximin and lactulose therapy with a dangerously high ammonia level of 354, immediate escalation of care is necessary, with the most critical next step being the initiation of continuous renal replacement therapy (CRRT) or hemodialysis to rapidly reduce ammonia levels, as supported by the most recent guidelines 1. The patient's condition necessitates a multi-faceted approach to manage the hyperammonemia and prevent further complications such as cerebral edema or herniation. Key interventions should include:

• Continuous renal replacement therapy (CRRT) or hemodialysis to rapidly decrease ammonia levels, which is crucial given the high risk of cerebral edema and intracranial hypertension associated with ammonia levels greater than 200 umol/L 1.
• Consideration for intubation and mechanical ventilation if the patient shows signs of cerebral edema or altered mental status to protect the airway and ensure adequate oxygenation.
• Intravenous L-ornithine L-aspartate (LOLA) at 20-40g/day to enhance ammonia metabolism, as it has been shown to lower plasma ammonia concentrations and improve symptoms of hepatic encephalopathy 1.
• Neomycin 1g every 6 hours via nasogastric tube as an additional gut decontaminant, although its use should be cautious due to potential side effects.
• Correction of any precipitating factors such as infection, gastrointestinal bleeding, or electrolyte imbalances, which are critical in managing hepatic encephalopathy 1.
• Maintenance of euvolemia, optimization of nutrition with low protein intake initially, and correction of any coagulopathy with vitamin K and fresh frozen plasma as needed.
• Most importantly, urgent evaluation for liver transplantation should be initiated, as it represents the definitive treatment for acute liver failure in a young patient, offering the best chance for survival and recovery 1. These interventions are guided by the principle of prioritizing morbidity, mortality, and quality of life outcomes, and are supported by the most recent and highest quality evidence available 1.

From the FDA Drug Label

The usual adult, oral dosage is 2 to 3 tablespoonfuls (30 mL to 45 mL, containing 20 grams to 30 grams of lactulose) three or four times daily. Hourly doses of 30 mL to 45 mL of lactulose solution may be used to induce the rapid laxation indicated in the initial phase of the therapy of portal-systemic encephalopathy.

The patient is already failing lactulose and rifaximin, and has a high ammonia level of 354.

• Next steps are not explicitly stated in the provided drug labels.
• The labels do provide information on the dosage and administration of lactulose and rifaximin, but do not provide guidance on what to do when these medications are not effective.
• Given the patient's condition, close monitoring and alternative treatments should be considered, but the specific next steps are not specified in the drug labels 2 3.

From the Research

Next Steps for Liver Failure Patient

The patient is a 28-year-old non-drinker in the ICU with liver failure, failing rifaximin and lactulose, and an ammonia level of 354. The next steps for this patient could be:

• Consideration of alternative treatments for hepatic encephalopathy, such as L-ornithine L-aspartate, ornithine phenylacetate, or fecal microbiota transplant, as suggested by 4
• Evaluation of the patient's eligibility for liver transplantation, as this is a major improvement in the management of patients with end-stage liver disease, according to 5
• Implementation of ammonia-targeted therapeutic strategies, such as continuous renal replacement therapy, as mentioned in 6
• Monitoring of the patient's condition, including serum ammonia levels, and adjustment of treatment as needed, as emphasized in 7

Treatment Options

The following treatment options could be considered for this patient:

• L-ornithine L-aspartate, which has been shown to have beneficial effects on hepatic encephalopathy, as reported in 4
• Ornithine phenylacetate, a newer treatment for hepatic encephalopathy that has shown promising results, as mentioned in 4
• Fecal microbiota transplant, which has been shown to have potentially beneficial effects on hepatic encephalopathy, as suggested by 4
• Continuous renal replacement therapy, which can help reduce serum ammonia levels, as mentioned in 6

Monitoring and Management

The patient's condition should be closely monitored, including:

• Serum ammonia levels, as hyperammonemia is associated with worse neurological outcomes, as reported in 6
• Hemodynamic and respiratory parameters, as optimization of these parameters is crucial for patient survival, as emphasized in 7
• Nutritional and metabolic parameters, as controlling nutrient delivery and blood glucose is important for patient management, as mentioned in 7