Undifferentiated non-hepatic hyperammonemia in the ICU: Diagnosis and management

Abstract

Hyperammonemia occurs frequently in the critically ill but is largely confined to patients with hepatic dysfunction or failure. Non-hepatic hyperammonemia (NHHA) is far less common but can be a harbinger of life-threatening diagnoses that warrant timely identification and, sometimes, empiric therapy to prevent seizures, status epilepticus, cerebral edema, coma and death; in children, permanent cognitive impairment can result. Subsets of patients are at particular risk for developing NHHA, including the organ transplant recipient. Unique etiologies include rare infections, such as with Ureaplasma species, and unmasked inborn errors of metabolism, like urea cycle disorders, must be considered in the critically ill. Early recognition and empiric therapy, including directed therapies towards these rare etiologies, is crucial to prevent catastrophic demise. We review the etiologies of NHHA and highlight the first presentation of it associated with a concurrent Ureaplasma urealyticum and Mycoplasma hominis infection in a previously healthy individual with polytrauma. Based on this clinical review, a diagnostic and treatment algorithm to identify and manage NHHA is proposed.

Keywords: Ammonia; Cerebral edema; Critical illness; Metabolism; Non-hepatic hyperammonemia; Status epilepticus; Urea cycle defect.