Role of determination of partial pressure of ammonia in cirrhotic patients with and without hepatic encephalopathy Francesca Nicolao, Cesare Efrati, Andrea Masini, Manuela Merli, Adolfo Francesco Attili, Oliviero Riggio * Divisione di Gastroenterologia, Dipartimento di Medicina Clinica, Universita ` degli Studi di Roma ‘La Sapienza’, Viale Dell’Universita ` 37, 00185 Rome, Italy Background/Aims: To compare venous, arterial and partial pressure of ammonia (pNH 3 ) in 27 consecutive cirrhotics with hepatic encephalopathy, 15 cirrhotics without hepatic encephalopathy and nine controls; to reevaluate all para- meters after the improvement of encephalopathy. Methods: Patients were studied by clinical examination and psychometric testing. pNH 3 was calculated from arterial ammonia and pH. Results: In patients with encephalopathy, each form of ammonia was higher than in both controls and patients without encephalopathy. The correlation with the severity of hepatic encephalopathy was similar for venous ðr ¼ 0:72Þ, arterial ammonia ðr ¼ 0:76Þ and pNH 3 ðr ¼ 0:75Þ. The sensitivity and specificity of each variable in correctly classifying the patients as having or not having hepatic encephalopathy was also similar. Each form of ammonia decreased after the resolution or amelioration of symptoms. However, even in the 17 patients with complete resolution of hepatic encephalopathy, all three ammonia determinations resulted unchanged or increased in some patients. Conclusions: Despite the significant correlation between pNH 3 and hepatic encephalopathy, our study suggests that neither pNH 3 nor arterial ammonia are, from a clinical point of view, more useful than venous ammonia: all three determinations being limited both for the diagnosis of hepatic encephalopathy and for the clinical management of the patients. q 2003 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. Keywords: Hepatic coma; Liver failure; Cirrhosis; Portal-systemic encephalopathy 1. Introduction Hepatic encephalopathy is a neuropsychiatric syndrome occurring in patients with severe liver disease and/or portal- systemic shunting [1,2]. Hepatic encephalopathy is charac- terized by a wide spectrum of clinical manifestations, ranging from subclinical alterations in the psychometric performance to stupor and coma [2,3]. The exact pathogen- esis of hepatic encephalopathy is still not completely under- stood but there is a general consensus about the importance of gut-derived nitrogenous substances escaping hepatic detoxification and affecting the central nervous system func- tion [4–6]. Ammonia is one of these substances, produced both in the colon and in the small bowel and extensively metabolized in the liver. In case of liver failure and/or portal-systemic shunt, blood ammonia concentration may increase and exert its toxic activity on the brain [5,7]. Although ammonia levels are almost always invariably higher in patients with acute or chronic liver failure, the correlation with the severity of hepatic encephalopathy is often variable and inaccurate [7,8]. Ammonia determina- tions, therefore, do not permit reliable identification of patients with hepatic encephalopathy or the distinction from other forms of coma, which may be observed in patients with severe liver disease. For the same reason, ammonia cannot be utilized as a reliable parameter for monitoring patients with hepatic encephalopathy submitted to treatment. This might be due to the fact that in biological samples, ammonia is usually assayed as total ammonia, without distinguishing between ammonium ions ðNH 1 4 Þ Journal of Hepatology 38 (2003) 441–446 0168-8278/03/$30.00 q 2003 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. doi:10.1016/S0168-8278(02)00436-1 www.elsevier.com/locate/jhep Received 23 August 2002; received in revised form 25 November 2002; accepted 4 December 2002 * Corresponding author. Tel.: 139-06-499-72001; fax: 139-06-445- 3319. E-mail address: origgio@pelagus.it (O. Riggio).