Abstract

Background and aim: In acute liver failure (ALF), the brain is exposed to high levels of ammonia. Human studies defining the clinical significance of ammonia in ALF are lacking. This prospective study evaluated the relationship of arterial ammonia levels at admission to complications and survival among patients with ALF.

Methods: Eighty consecutive ALF patients admitted from March 2001 to December 2003 were followed up until death or complete recovery. All had arterial ammonia estimation at admission (enzymatic method). Logistic regression analysis was performed to identify independent predictors of mortality.

Results: Forty two (52.5%) patients died. Non-survivors had significantly higher median ammonia levels than survivors (174.7 v 105.0 μmol/l; p<0.001). An arterial ammonia level of ⩾ 124 μmol/l was found to predict mortality with 78.6% sensitivity and 76.3% specificity, and had 77.5% diagnostic accuracy. Patients with higher ammonia levels also developed more complications, including deeper encephalopathy (p = 0.055), cerebral oedema (p = 0.020), need for ventilation (p<0.001), and seizures (p = 0.006). Logistic regression analysis showed that pH, presence of cerebral oedema, and arterial ammonia at admission were independent predictors of mortality (odds ratios 6.6, 12.6, and 10.9, respectively). Incorporating these variables, a score predicting mortality risk at admission was derived: 2.53 + 2.91 ammonia + 2.41 oedema + 1.40 pH, where ammonia is scored as 0 (if <124 μmol/l) or 1 (if ⩾124 μmol/l); oedema is scored as 0 (absent) or 1(present); and pH is scored as 1 (if ⩽7.40) or 0 (if >7.40). Levels of partial pressure of ammonia were equally correlated with outcome.

Conclusion: Arterial ammonia at presentation is predictive of outcome and can be used for risk stratification. Ammonia lowering therapies in patients with ALF should be evaluated.