Can sepsis cause hyperammonemia?

Sepsis as a Cause of Hyperammonemia

Yes, sepsis can cause hyperammonemia through multiple mechanisms, even in patients without underlying liver disease. 1, 2

Mechanisms of Sepsis-Induced Hyperammonemia

• Sepsis creates a catabolic state that increases ammonia production through protein breakdown and amino acid catabolism 2
• Septic shock can impair renal function, reducing ammonia excretion 1
• Certain urea-splitting bacteria (particularly in urinary tract infections) can directly produce ammonia 3, 4
• Sepsis may unmask underlying partial urea cycle enzyme deficiencies that were previously compensated 3
• Systemic inflammation and hyperammonemia act synergistically in the development of encephalopathy 1

Clinical Significance and Outcomes

• Non-hepatic hyperammonemia in sepsis is associated with significantly higher mortality rates (59.8% vs. 43.0% hospital mortality) 2
• Patients with sepsis and hyperammonemia show:
  • Lower Glasgow Coma Scale scores 2
  • Higher incidence of delirium (15.9% vs. 8.2%) 2
  • Higher incidence of encephalopathy (37.4% vs. 19.6%) 2
• Hyperammonemia is an independent risk factor for sepsis-associated encephalopathy 5

Diagnostic Considerations

• Consider hyperammonemia in any septic patient with unexplained neurological symptoms, including confusion 1, 6
• Normal ammonia levels are ≤35 μmol/L (≤60 μg/dL) in adults 6
• Hyperammonemia is defined as ≥50 μmol/L (85 μg/dL) in adults 6
• Levels >200 μmol/L (341 μg/dL) are associated with poor neurological outcomes 6, 7

Management Approach for Sepsis-Induced Hyperammonemia

• Treat the underlying sepsis with appropriate antimicrobials and source control 3
• Consider nitrogen scavenger medications (sodium benzoate, sodium phenylacetate) for severe hyperammonemia 1, 3
• For patients with short bowel syndrome and hyperammonemia, arginine supplementation may help correct the condition by supporting the urea cycle 1
• In severe cases with neurological symptoms, renal replacement therapy (hemodialysis) may be necessary to rapidly reduce ammonia levels 1, 3
• Monitor ammonia levels every 3 hours during acute management 1

Special Considerations

• Intestinal infections and urinary tract infections with organisms like Escherichia coli may be particular risk factors for hyperammonemia in sepsis 2, 4
• Patients with short bowel syndrome are at higher risk due to reduced capacity to manufacture citrulline needed for ammonia detoxification 1
• Concomitant renal impairment worsens hyperammonemia as excess ammonia cannot be excreted 1

Early recognition and aggressive management of hyperammonemia in sepsis is crucial to prevent adverse neurological outcomes and improve survival rates 2, 5.