Impact of Non-Hepatic Hyperammonemia on Mortality in Intensive Care Unit Patients: A Retrospective Cohort Study

Abstract

Background: The effect of hyperammonemia on the mortality in patients with liver cirrhosis is well documented. However, little is known about the impact of hyperammonemia on mortality in intensive care unit patients without hepatic disease. We aimed to investigate factors associated with non-hepatic hyperammonemia in intensive care unit patients and evaluate the factors related to 90-day mortality. Methods: Between February 2016 and February 2020, 972 cases in 948 intensive care unit patients without hepatic disease were retrospectively enrolled and classified as hyperammonemia grades 0 (≤80 µg/dL; n=585 (60.2%)), 1 (≤160 µg/dL; n=291 (29.9%)), 2 (≤240 µg/dL; n=55 (5.7%)), and 3 (>240 µg/dL; n=41 (4.2%)). Factors associated with hyperammonemia and 90-day mortality were evaluated by multivariate logistic regression analysis and Cox regression analysis, respectively. Kaplan-Meier survival curves for 90-day mortality were constructed.Results: The independent risk factors for hyperammonemia were male sex (odds ratio, 1.517), age (0.984 per year), acute brain failure (2.467), acute kidney injury (1.437), prothrombin time-international normalized ratio (2.272 per unit), and albumin (0.694 per g/dL). The 90-day mortality rate in the entire cohort was 24.3% and gradually increased with increasing hyperammonemia grade at admission (17.9%, 28.2%, 43.6%, and 61.0% in patients with grades 0, 1, 2, and 3, respectively). Additionally, non-hepatic hyperammonemia was an independent predictor of 90-day mortality in intensive care unit patients. Conclusions: Non-hepatic hyperammonemia is common (39.8%) and associated with 90-day mortality in intensive care unit patients. Therefore, clinicians must examine serum ammonia levels in patients before admission to intensive care unit.