Maria Garrido1, Jelena Skorucak2,3,4, Daniela Raduazzo1,5, Matteo Turco1, Giuseppe Spinelli1,6, Paolo Angeli1, Piero Amodio1, Peter Achermann2,3,4,7, Sara Montagnese8. 1. Department of Medicine, University of Padua, Via Giustiniani, 2, 35128, Padova, Italy. 2. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland. 3. Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland. 4. Center for Interdisciplinary Sleep Research, University of Zurich, Zurich, Switzerland. 5. USO Dipartimentale di Servizio Urgenza ed Emergenza Medica, ULSS 13, Dolo, Regione Veneto, Italy. 6. Department of Psychology, Sapienza University of Rome, Rome, Italy. 7. Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland. 8. Department of Medicine, University of Padua, Via Giustiniani, 2, 35128, Padova, Italy. sara.montagnese@unipd.it.
Abstract
UNLABELLED: Hyperammonaemia/mild hepatic encephalopathy (HE) can be simulated by the oral administration of a so-called amino acid challenge (AAC). This study sought to assess the effects of the AAC alone and in combination with either ammonia-lowering [L-ornithine-L-aspartate (LOLA)] or vigilance-enhancing medication (caffeine). Six patients with cirrhosis (5 males; 61.3 ± 9.2 years; 5 Child A, 1 Child B) and six healthy volunteers (5 males; 49.8 ± 10.6 years) were studied between 08:00 and 19:00 on Monday of three consecutive weeks. The following indices were obtained: hourly capillary ammonia, hourly subjective sleepiness, paper & pencil/computerized psychometry and wake electroencephalography (EEG) at 12:00, i.e. at the time of the maximum expected effect of the AAC. RESULTS: On average, patients had worse neuropsychological performance and slower EEG than healthy volunteers in all conditions but differences did not reach significance. In healthy volunteers, the post-AAC increase in capillary ammonia levels was contained by both the administration of LOLA and of caffeine (significant differences between 10:00 and 14:00 h). The administration of caffeine also resulted in a reduction in subjective sleepiness and in the amplitude of the EEG on several frontal/temporal-occipital sites (p < 0.05; paired t-test). Changes in ammonia levels, subjective sleepiness and the EEG in the three conditions were less obvious in patients. In conclusion, both LOLA and caffeine contained the AAC-induced increase in capillary ammonia, especially in healthy volunteers. Caffeine also counteracted the AAC effects on sleepiness/EEG amplitude. The association of ammonia-lowering and vigilance-enhancing medication in the management of HE is worthy of further study.
UNLABELLED: Hyperammonaemia/mild hepatic encephalopathy (HE) can be simulated by the oral administration of a so-called amino acid challenge (AAC). This study sought to assess the effects of the AAC alone and in combination with either ammonia-lowering [L-ornithine-L-aspartate (LOLA)] or vigilance-enhancing medication (caffeine). Six patients with cirrhosis (5 males; 61.3 ± 9.2 years; 5 Child A, 1 Child B) and six healthy volunteers (5 males; 49.8 ± 10.6 years) were studied between 08:00 and 19:00 on Monday of three consecutive weeks. The following indices were obtained: hourly capillary ammonia, hourly subjective sleepiness, paper & pencil/computerized psychometry and wake electroencephalography (EEG) at 12:00, i.e. at the time of the maximum expected effect of the AAC. RESULTS: On average, patients had worse neuropsychological performance and slower EEG than healthy volunteers in all conditions but differences did not reach significance. In healthy volunteers, the post-AAC increase in capillary ammonia levels was contained by both the administration of LOLA and of caffeine (significant differences between 10:00 and 14:00 h). The administration of caffeine also resulted in a reduction in subjective sleepiness and in the amplitude of the EEG on several frontal/temporal-occipital sites (p < 0.05; paired t-test). Changes in ammonia levels, subjective sleepiness and the EEG in the three conditions were less obvious in patients. In conclusion, both LOLA and caffeine contained the AAC-induced increase in capillary ammonia, especially in healthy volunteers. Caffeine also counteracted the AAC effects on sleepiness/EEG amplitude. The association of ammonia-lowering and vigilance-enhancing medication in the management of HE is worthy of further study.
Authors: P Amodio; P Marchetti; F Del Piccolo; M de Tourtchaninoff; P Varghese; C Zuliani; G Campo; A Gatta; J M Guérit Journal: Clin Neurophysiol Date: 1999-08 Impact factor: 3.708
Authors: E P Casula; P S Bisiacchi; M Corrias; S Schiff; C Merkel; P Amodio; S Montagnese Journal: Metab Brain Dis Date: 2014-07-24 Impact factor: 3.584
Authors: Anna Emilie Kann; Shakoor Ba-Ali; Jakob B Seidelin; Fin Stolze Larsen; Steffen Hamann; Peter Nissen Bjerring Journal: PLoS One Date: 2022-09-28 Impact factor: 3.752