Evaluating the Significance of Hyperammonemia in Pediatric Patients With Acetaminophen-Induced Liver Injury

The significance of hyperammonemia in pediatric acetaminophen-induced hepatotoxicity is unclear. We hypothesize there is an association between both age and peak serum ammonia, and the primary endpoint of altered mental status (AMS) and a secondary endpoint of overt encephalopathy.

This retrospective review of all pediatric (age <18 years) patients who were admitted to 1 of 6 tertiary care medical centers with a diagnosis of acetaminophen-induced liver injury (AST or ALT > 1000 IU/L). Patients with liver failure from other etiologies as well as those with acetaminophen toxicity with a peak AST/ALT <1000 IU/L were excluded. Patients were considered to have AMS based on documentation in the medical record of either “altered mental status” or “encephalopathy.” A West Haven encephalopathy grade of 0 or 1 was considered “subtle” whereas grades 2-4 were considered “overt.” After using multivariable fractional polynomial techniques to confirm no need for higher order terms, multivariable logistic regression was performed to adjust for age, sex, and time interval from ingestion to initiation of N-acetylcysteine (tNAC). Firth penalized regression was performed.

131 patients were identified. Documentation of mental status was recorded in all cases, and was present in 30 cases (22.9%; 95% CI 16.0-31.1%). Mixed effect logistic regression showed no differences in findings when accounting for clustering based on center. Neither tNAC nor sex were associated with the primary and secondary outcome. Progressing age had a protective effect against developing overt encephalopathy (OR 0.8; 95% CI 0.69-0.93), whereas rising ammonia increased the risk of encephalopathy (OR per 10 unit rise of ammonia 1.03 (95% CI 1.02-1.05; p<0.001).

In this study of pediatric patients admitted with acetaminophen-induced liver injury, increasing age was protective for development of overt encephalopathy, whereas high ammonia levels were associated with the development of overt encephalopathy.