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Vigilance and wake EEG architecture in simulated hyperammonaemia: a pilot study on the effects of L-Ornithine-L-Aspartate (LOLA) and caffeine

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Abstract

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.

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Abbreviations

AAC:

Amino acid challenge

EEG:

Electroencephalogram

HE:

Hepatic encephalopathy

HÖ:

Horne Östberg

HRQoL:

Health-related quality of life

KSS:

Karolinska sleepiness scale

LOLA:

L-ornithine-L-aspartate

MCS:

Mental component score

PCS:

Physical component score

PHES:

Psychometric hepatic encephalopathy score

PSQI:

Pittsburgh sleep quality index

SF-36:

Medical outcomes short form

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Author notes

  1. Daniela Raduazzo

    Present address: USO Dipartimentale di Servizio Urgenza ed Emergenza Medica, ULSS 13, Dolo, Regione Veneto, Italy

  2. Giuseppe Spinelli

    Present address: Department of Psychology, Sapienza University of Rome, Rome, Italy

Authors and Affiliations

  1. Department of Medicine, University of Padua, Via Giustiniani, 2, 35128, Padova, Italy

    Maria Garrido, Daniela Raduazzo, Matteo Turco, Giuseppe Spinelli, Paolo Angeli, Piero Amodio & Sara Montagnese

  2. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland

    Jelena Skorucak & Peter Achermann

  3. Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland

    Jelena Skorucak & Peter Achermann

  4. Center for Interdisciplinary Sleep Research, University of Zurich, Zurich, Switzerland

    Jelena Skorucak & Peter Achermann

  5. Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland

    Peter Achermann

Authors
  1. Maria Garrido
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  2. Jelena Skorucak
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  9. Sara Montagnese
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Corresponding author

Correspondence to Sara Montagnese.

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Funding

Merz Pharmaceuticals GmbH (Frankfurt am Main, GERMANY) supported the study as an Investigator-Initiated Study and also provided L-ornithine-L-aspartate. Merz Pharmaceuticals GmbH had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

MG holds a research post-doctoral fellowship from Gobierno de Extremadura [jointly financed by the European Regional Development Fund (ERDF); ref. PO14013].

PAc was supported by the Swiss National Science Foundation (grant 32003B_146643) and nano-tera.ch (grant 20NA21_145929).

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Garrido, M., Skorucak, J., Raduazzo, D. et al. Vigilance and wake EEG architecture in simulated hyperammonaemia: a pilot study on the effects of L-Ornithine-L-Aspartate (LOLA) and caffeine. Metab Brain Dis 31, 965–974 (2016). https://doi.org/10.1007/s11011-016-9835-9

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  • DOI: https://doi.org/10.1007/s11011-016-9835-9

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