Arterial ammonia with Blood Ammonia Checker II and with indophenol reaction to assess presence of hepatic encephalopathy

Abstract

Hepatic encephalopathy (HE) is associated with elevated arterial ammonia levels. The relationship is variable, in part due to ammonia methodology. One method, based on the indophenol reaction (IPh), is interfered with a number of amino acids including all aromatic amino acids. We have determined arterial ammonia simultaneously with the Blood Ammonia Checker II (BAC) as reference method and with the IPh method. The difference BAC-IPh, μmol/l, was assumed to express the interference in the indophenol method (IFI) by amino acids. It may be positive or negative. The aim was to establish the value of BAC in comparison with IPh in the diagnosis of liver disease and overt HE and to asses any added value of IFI. Of two reference groups without disturbances, A ( n = 39) had not and B ( n = 13) had encephalopathy. Group C consisted of 125 liver patients (34 no cirrhosis, 91 cirrhosis) of which 55 had no manifest HE (C:HE−) and 70 had HE (C:HE+). Median BAC ammonia nitrogen (NH 3N), μmol/l: A 21, B 35, C 80, C:HE−57 and C:HE+98 (A < B < C and A < B < C:HE − < C:HE+, P < 0.001). Median IPh NH 3N, μmol/l: A 27, B 30, C 30, C:HE −25 and C:HE+ 35 μmol/l (A = B = C and C:HE − < C:HE+, P < 0.01). IFI medians: A −6, B 3, C 40, C:HE−29 and C:HE+ 58 μmol/l (A < B ( P < 0.05) < C ( P < 0.0001); A, B < C:HE− and C:HE+; C:HE− < CH:HE+ (all P < 0.0001)). While BAC correlated weakly with IPh in the (sub)groups C, C:HE−, C:HE+ ( r = 0.3, 0.3, 0.4, P < 0.05), it correlated strongly with IFI ( r = 0.9, 0.9, 0.8, P < 0.0001). There was no correlation between IPh and IFI. BAC, as well as IFI, could discriminate all liver patients (C) from both reference groups A and B with 100% positive likelihoods. BAC, IPh and IFI could discriminate between HE− and HE+. To differentiate cirrhosis from non-cirrhosis the specificity of IPh was uniformly high and the sensitivity satisfactory, whereas BAC had a high sensitivity but an insufficient specificity. In conclusion, in blood, BAC is the ammonia determination of choice. It differentiates between reference groups (encephalopathic or not) and liver disease and the more so HE. The combination of BAC and IPh (indicating IFI) may eventually be shown useful to rapidly assess the severity of underlying liver disease in HE patients. In other biological fluids, IPh is excellent when the inhibiting influence of non-protein nitrogen substances is absent or can be eliminated.