Perspective Article: Hyperammonemia without Liver Failure - Key Considerations for Intensivists.

Abstract

Urea cycle disorders represent the most frequent cause of hyperammonemia in the absence of liver failure and may lead to life-threatening elevations in plasma ammonia, particularly when onset is acute and rapidly progressive. Although the etiologies and management principles of acute liver failure have been extensively addressed elsewhere, hyperammonemia must be recognized in critically ill patients as a potential cause of coma, especially when hepatic failure is not present. Non-hepatic causes, including urea cycle disorders, infectious diseases, drug-induced toxicity, and post-transplant complications, are frequently underrecognized. Management requires prompt neuroprotective measures, short-term protein restriction with appropriate nutritional support, and rapid ammonia removal, preferably using high-dose continuous renal replacement therapy. Early intervention is crucial to prevent cerebral edema and to improve neurological outcomes.