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

• Published in: Journal of critical care Vol. 70; p. 154042
• Main Authors: Long, Micah T., Coursin, Douglas B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-08-2022; Elsevier Limited
• Subjects: Adenosine; Amino acids; Ammonia; Bacteria; Cerebral edema; Child; Critical care; Critical Illness; Dehydrogenases; Edema; Energy; Etiology; Humans; Hyperammonemia - diagnosis; Hyperammonemia - etiology; Hyperammonemia - therapy; Infections; Intensive Care Units; Kidneys; Kinases; Liver diseases; Medical diagnosis; Metabolism; Mortality; Neurotoxicity; Non-hepatic hyperammonemia; Oxidative stress; Patients; Potassium; Proteins; Signal transduction; Status epilepticus; Urea cycle defect; Ureaplasma; Ureaplasma Infections - complications; Urine; Ammonia; Critical illness; Non-hepatic hyperammonemia; Urea cycle defect; Metabolism; Cerebral edema; Status epilepticus
• ISSN: 0883-9441; 1557-8615
• DOI: 10.1016/j.jcrc.2022.154042

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.
•Non-hepatic hyperammonemia accounts for only 5% of critically ill patients with hyperammonemia, but is underdiagnosed.•Etiologies of nonhepatic hyperammonemia can be grouped into increased production, or decreased clearance of ammonia.•Ammonia metabolism in the brain can result in cerebral edema, seizures, status epilepticus, coma and death.•Brief delays in diagnosis or management of non-hepatic hyperammonemia may result in irreversible patient harm.•Empiric management often includes treatment for certain rare infections and adult-onset inborn errors of metabolism.•The severity of hyperammonemia impacts morbidity. A guide to diagnostic and treatment thresholds is provided.