Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis***

Authors

  • Alessia Bersagliere,

    1. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
    2. Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
    Search for more papers by this author
    • *

      These authors contributed equally to this work.

  • Iolanda D. Raduazzo,

    1. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
    Search for more papers by this author
    • *

      These authors contributed equally to this work.

  • Mariateresa Nardi,

    1. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
    Search for more papers by this author
  • Sami Schiff,

    1. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
    Search for more papers by this author
  • Angelo Gatta,

    1. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
    Search for more papers by this author
  • Piero Amodio,

    1. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
    Search for more papers by this author
  • Peter Achermann,

    1. Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland
    2. Neuroscience Center Zurich, University and ETH Zurich, Zurich, Switzerland
    3. Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
    Search for more papers by this author
    • **

      Joint senior authorship.

  • Sara Montagnese

    Corresponding author
    1. Department of Clinical and Experimental Medicine, University of Padua, Padua, Italy
    • Dipartimento di Medicina Clinica e Sperimentale, Via Giustiniani, 2, 35128 Padova, Italia
    Search for more papers by this author
    • **

      Joint senior authorship.

    • fax: +39 049 8754179


  • Potential conflict of interest: Nothing to report.

  • Supported by grants from the University of Padova to P.Am. and by the Swiss National Science Foundation (grant 320030-130766 to P.Ac.).

Abstract

In patients with cirrhosis, hyperammonemia and hepatic encephalopathy are common after gastrointestinal bleeding and can be simulated by an amino acid challenge (AAC), or the administration of a mixture of amino acids mimicking the composition of hemoglobin. The aim of this study was to investigate the clinical, psychometric, and wake-/sleep-electroencephalogram (EEG) correlates of induced hyperammonemia. Ten patients with cirrhosis and 10 matched healthy volunteers underwent: (1) 8-day sleep quality/timing monitoring; (2) neuropsychiatric assessment at baseline/after AAC; (3) hourly ammonia/subjective sleepiness assessment for 8 hours after AAC; (4) sleep EEG recordings (nap opportunity: 17:00-19:00) at baseline/after AAC. Neuropsychiatric performance was scored according to age-/education-adjusted Italian norms. Sleep stages were scored visually for 20-second epochs; power density spectra were calculated for consecutive 20-second epochs and average spectra determined for consolidated episodes of non-rapid eye movement (non-REM) sleep of minimal common length. The AAC resulted in: (i) an increase in ammonia concentrations/subjective sleepiness in both patients and healthy volunteers; (ii) a worsening of neuropsychiatric performance (wake EEG slowing) in two (20%) patients and none of the healthy volunteers; (iii) an increase in the length of non-REM sleep in healthy volunteers [49.3 (26.6) versus 30.4 (15.6) min; P = 0.08]; (iv) a decrease in the sleep EEG beta power (fast activity) in the healthy volunteers; (v) a decrease in the sleep EEG delta power in patients. Conclusion: AAC led to a significant increase in daytime subjective sleepiness and changes in the EEG architecture of a subsequent sleep episode in patients with cirrhosis, pointing to a reduced ability to produce restorative sleep. (HEPATOLOGY 2012)

Ancillary