Threshold for toxicity from hyperammonemia in critically ill children.

Abstract

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 7 days after inclusion were collected. The outcome assessed was 28 day 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 28 day mortality rate was 31.1%. Risk of mortality increased according to the ammonemia within 48 h: odds ratio 1.5, 1.9, 3.3, 2.4 for ammonemia above 100, 150, 200, and 300 μmol/L, respectively. Peak ammonemia ≥200 μmol/L within the first 48 h 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 (≥200 μmol/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.

• Authors: Bruno Ozanne, John Nelson, Jocelyne Cousineau, Marie Lambert, Véronique Phan, Grant Mitchell, Fernando Alvarez, Thierry Ducruet, Philippe Jouvet
• Journal: Journal of hepatology (J Hepatol) Vol. 56 Issue 1 Pg. 123-8 (Jan 2012) ISSN: 1600-0641 [Electronic] Netherlands
• PMID: 21703182 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Chemical References

• Ammonia

Topics

• Ammonia (blood)
• Brain Edema (etiology, physiopathology)
• Child
• Child, Preschool
• Critical Illness
• Encephalocele (etiology, physiopathology)
• Female
• Humans
• Hyperammonemia (complications, etiology, mortality, physiopathology)
• Infant
• Kaplan-Meier Estimate
• Liver Failure, Acute (complications, physiopathology)
• Male
• Retrospective Studies
• Risk Factors
• Urea Cycle Disorders, Inborn (complications, physiopathology)