Gastroenterology
Volume 136, Issue 3 , Pages 863-871, March 2009

Low Cerebral Oxygen Consumption and Blood Flow in Patients With Cirrhosis and an Acute Episode of Hepatic Encephalopathy

  • Peter Iversen

      Affiliations

    • PET Centre, Aarhus University Hospital, Aarhus, Denmark
    • Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Michael Sørensen

      Affiliations

    • PET Centre, Aarhus University Hospital, Aarhus, Denmark
    • Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Lasse Kristoffer Bak

      Affiliations

    • Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark
  • ,
  • Helle Sønderby Waagepetersen

      Affiliations

    • Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark
  • ,
  • Manouchehr Seyedi Vafaee

      Affiliations

    • PET Centre, Aarhus University Hospital, Aarhus, Denmark
    • Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Per Borghammer

      Affiliations

    • PET Centre, Aarhus University Hospital, Aarhus, Denmark
    • Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Kim Mouridsen

      Affiliations

    • Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Svend Borup Jensen

      Affiliations

    • PET Centre, Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Hendrik Vilstrup

      Affiliations

    • Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Arne Schousboe

      Affiliations

    • Department of Pharmacology and Pharmacotherapy, Faculty of Pharmaceutical Sciences, University of Copenhagen, Copenhagen, Denmark
  • ,
  • Peter Ott

      Affiliations

    • Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Albert Gjedde

      Affiliations

    • PET Centre, Aarhus University Hospital, Aarhus, Denmark
    • Center of Functionally Integrative Neuroscience (CFIN), Aarhus University Hospital, Aarhus, Denmark
  • ,
  • Susanne Keiding

      Affiliations

    • PET Centre, Aarhus University Hospital, Aarhus, Denmark
    • Department of Medicine V, Aarhus University Hospital, Aarhus, Denmark
    • Corresponding Author InformationReprint requests Address requests for reprints to: Susanne Keiding, MD, Department of Medicine V, Aarhus University Hospital, DK- 8000 Aarhus, Denmark. Phone: +45 8949 3031; fax: +45 8949 3020

Received 22 August 2008; accepted 23 October 2008. published online 03 November 2008.

Background & Aims

It is unclear whether patients with hepatic encephalopathy (HE) have disturbed brain oxygen metabolism and blood flow.

Methods

We measured cerebral oxygen metabolism rate (CMRO2) by using 15O-oxygen positron emission tomography (PET); and cerebral blood flow (CBF) by using 15O-water PET in 6 patients with liver cirrhosis and an acute episode of overt HE, 6 cirrhotic patients without HE, and 7 healthy subjects.

Results

Neither whole-brain CMRO2 nor CBF differed significantly between cirrhotic patients without HE and healthy subjects, but were both significantly reduced in cirrhotic patients with HE (P < .01). CMRO2 was 0.96 ± 0.07 μmol oxygen/mL brain tissue/min (mean ± SEM) in cirrhotic patients with HE, 1.34 ± 0.08 in cirrhotic patients without HE, and 1.35 ± 0.05 in healthy subjects; and CBF was 0.29 ± 0.01 mL blood/mL brain tissue/min in patients with HE, 0.47 ± 0.02 in patients without HE, and 0.49 ± 0.03 in healthy subjects. CMRO2 and CBF were correlated, and both variables correlated negatively with arterial ammonia concentration. Analysis of regional values, using individual magnetic resonance co-registrations, showed that the reductions in CMRO2 and CBF in patients with HE were essentially generalized throughout the brain.

Conclusions

The observations imply that reduced cerebral oxygen consumption and blood flow in cirrhotic patients with an acute episode of overt HE are associated with HE and not cirrhosis as such, and that the primary event in the pathogenesis of HE could be inhibition of cerebral energy metabolism by increased blood ammonia.

Abbreviations used in this paper: CBF, cerebral blood flow, CMRO2, cerebral metabolic rate of oxygen, FDG, 18F-fluoro-deoxyglucose, FWHM, full width at half maximum, HE, hepatic encephalopathy, MR, magnetic resonance, MRI, magnetic resonance imaging, PET, positron emission tomography, pO2, partial pressure of oxygen, pCO2, partial pressure of carbon dioxide, VOI, volume of interest

 

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by the Danish Medical Research Council (271-06-0357, 271-07-0267), the Alfred Benzon Foundation, the Carlsberg Foundation, Aarhus University, and the Helga and Peter Kornings Foundation.

PII: S0016-5085(08)01895-7

doi:10.1053/j.gastro.2008.10.057

Gastroenterology
Volume 136, Issue 3 , Pages 863-871, March 2009