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Cerebral Glutamine Concentration and Lactate–Pyruvate Ratio in Patients with Acute Liver Failure

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Abstract

Aim

Hyperammonemia causes brain edema and high intracranial pressure (ICP) in acute liver failure (ALF) by accumulation of glutamine in brain. Since a high-level glutamine may compromise mitochondrial function, the aim of this study was to determine if the lactate–pyruvate ratio is associated with a rise in the glutamine concentration and ICP.

Patients and Methods

In 13 patients with ALF (8F/5M; median age 46 (range 18–66) years) the cerebral extracellular concentrations of glutamine, lactate, and pyruvate were measured by in vivo brain microdialysis together with ICP and cerebral perfusion pressure (CPP).

Results

The cerebral glutamine concentration was 4,396 (1,011–9,712) μM, lactate 2.15 (1.1–4.45) mM, and pyruvate 101 (43–255) μM. The lactate–pyruvate ratio was 21 (16–40), ICP 20 (2–28) mmHg, and CPP 72 (56–115) mmHg. Cerebral glutamine concentration correlated with the lactate–pyruvate ratio (r = 0.89, P < 0.05). Also the ICP, but not CPP, correlated to the lactate–pyruvate ratio (r = 0.64, P < 0.05).

Conclusion

ICP and the cerebral glutamine concentration in patients with ALF correlate to the lactate–pyruvate ratio. Since CPP was sufficient in all patients the rise in lactate–pyruvate ratio indicates that accumulation of glutamine compromises mitochondrial function and causes intracranial hypertension.

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Abbreviations

ALF:

Acute liver failure

ALT:

Alanine aminotransferase

BBB:

Blood–brain barrier

CPP:

Cerebral perfusion pressure

HE:

Hepatic encephalopathy

ICP:

Intracranial pressure

INR:

International Normalization Ratio

MPT:

Mitochondrial permeability transition

NE:

Norepinephrine

PaCO2 :

Carbon dioxide tension in arterial blood

ROS:

Reactive oxygen species

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Acknowledgments

This work was supported by Rigshospitalet, University of Copenhagen, The Laerdal Foundation for Acute Medicine, Savvaerksejer Jeppe Juhl and wife Ovita Juhls Foundation, The Novo Nordisk Foundation, The AP-Moeller Foundation, The Danish Hospital Foundation for Medical Research – Region of Copenhagen, The Faroe Islands and Greenland and The Danish Medical Association Research Fund.

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Authors and Affiliations

  1. Department of Hepatology, section A-2121, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen O, Denmark

    Peter Nissen Bjerring, Bent Adel Hansen, Flemming Tofteng & Fin Stolze Larsen

  2. Department of Neurosurgery, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen O, Denmark

    John Hauerberg & Linda Jorgensen

  3. Department of Anesthesia, Rigshospitalet, University Hospital of Copenhagen, Blegdamsvej 9, 2100, Copenhagen O, Denmark

    Hans-Jorgen Frederiksen

Authors
  1. Peter Nissen Bjerring
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  2. John Hauerberg
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  3. Hans-Jorgen Frederiksen
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  4. Linda Jorgensen
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  5. Bent Adel Hansen
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  6. Flemming Tofteng
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  7. Fin Stolze Larsen
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Correspondence to Fin Stolze Larsen.

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Bjerring, P.N., Hauerberg, J., Frederiksen, HJ. et al. Cerebral Glutamine Concentration and Lactate–Pyruvate Ratio in Patients with Acute Liver Failure. Neurocrit Care 9, 3–7 (2008). https://doi.org/10.1007/s12028-008-9060-4

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