Threshold for toxicity from hyperammonemia in critically ill children

Background & Aims: Hyperammonemia results from reduction of hepatocyte function or enzyme of urea cycle deficiency. Hyperammonemia contributes to cerebral edema that may lead to cerebral herniation. The threshold of toxicity of ammonemia is unknown. Methods: We conducted a retrospective observational study in our pediatric intensive care unit. All children who developed hyperammonemia from January 2000 to April 2009 were included. Clinical and laboratory data at admission, specific treatments implemented, and ammonemias the first 7days after inclusion were collected. The outcome assessed was 28day mortality. Risk of mortality was estimated by a logistic regression model. Results: Ninety patients with liver failure (63.3%) and primary or secondary urea cycle defect (23.3%) were included. Patients with urea cycle defects were more likely to receive ammonia scavengers than patients with liver failure (47.6% versus 3.5%). The 28day mortality rate was 31.1%. Risk of mortality increased according to the ammonemia within 48h: odds ratio 1.5, 1.9, 3.3, 2.4 for ammonemia above 100, 150, 200, and 300μmol/L, respectively. Peak ammonemia ⩾200μmol/L within the first 48h was an independent risk factor for mortality, with greater risk found in liver failure than in urea cycle defect. Conclusions: Our study identifies a threshold of exposure to ammonia (⩾200μmol/L) above which mortality increases significantly, especially in liver failure. Specific treatments of hyperammonemia are rarely used in liver failure when compared with urea cycle defect even though use of ammonia scavengers may help to decrease ammonemia. [ABSTRACT FROM AUTHOR]