title: Induced hyperammonemia may compromise the ability to generate restful sleep in patients with cirrhosis.
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.
  
  
  CONCLUSIONS
  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.
authors: Institute of Pharmacology and Toxicology, University of Zurich, Zurich, Switzerland.
authors: Alessia
authors: A
authors: Bersagliere
authors: Iolanda D
authors: ID
authors: Raduazzo
authors: Mariateresa
authors: M
authors: Nardi
authors: Sami
authors: S
authors: Schiff
authors: Angelo
authors: A
authors: Gatta
authors: Piero
authors: P
authors: Amodio
authors: Peter
authors: P
authors: Achermann
authors: Sara
authors: S
authors: Montagnese
mesh_terms: D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000009:adverse effects*; D016022:Case-Control Studies; D004569:Electroencephalography; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000139:chemically induced* / Q000150:complications* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D009752:Nutritional Status; D011788:Quality of Life / Q000523:psychology; D012890:Sleep / Q000502:physiology*; D012894:Sleep Stages / Q000502:physiology; D012893:Sleep Wake Disorders / Q000209:etiology* / Q000503:physiopathology; D012895:Sleep, REM / Q000502:physiology
chemical_list: D000596:Amino Acids