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Potential Non-Hypoxic/Ischemic Causes of Increased Cerebral Interstitial Fluid Lactate/Pyruvate Ratio: A Review of Available Literature

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Abstract

Microdialysis, an in vivo technique that permits collection and analysis of small molecular weight substances from the interstitial space, was developed more than 30 years ago and introduced into the clinical neurosciences in the 1990s. Today cerebral microdialysis is an established, commercially available clinical tool that is focused primarily on markers of cerebral energy metabolism (glucose, lactate, and pyruvate) and cell damage (glycerol), and neurotransmitters (glutamate). Although the brain comprises only 2% of body weight, it consumes 20% of total body energy. Consequently, the ability to monitor cerebral metabolism can provide significant insights during clinical care. Measurements of lactate, pyruvate, and glucose give information about the comparative contributions of aerobic and anaerobic metabolisms to brain energy. The lactate/pyruvate ratio reflects cytoplasmic redox state and thus provides information about tissue oxygenation. An elevated lactate pyruvate ratio (>40) frequently is interpreted as a sign of cerebral hypoxia or ischemia. However, several other factors may contribute to an elevated LPR. This article reviews potential non-hypoxic/ischemic causes of an increased LPR.

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Abbreviations

CBF:

Cerebral blood flow

CMD:

Cerebral microdialysis

ETC:

Electron transport chain

G6P:

Glucose-6-phosphate

Gln:

Glutamine

Glu:

Glutamate

ICP:

Intracranial pressure

LDH:

Lactate dehydrogenase

LPR:

Lactate/pyruvate ratio

LPS:

Lipopolysaccharide

MAS:

Malate-aspartate shuttle

NMR:

Nuclear magnetic resonance

PDH:

Pyruvate dehydrogenase

PG:

Propylene glycol

SAH:

Subarachnoid hemorrhage

TBI:

Traumatic brain injury

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Acknowledgments

The authors gratefully acknowledge the helpful and insightful suggestions of Julien F. Biebuyck, David F. Wilson, Gretchen L. Redline, Marilyn G. Larach, and Sarah M. Gibbs in the preparation of the manuscript. DBL received financial support from the Clinical Neurosciences Training Program (CNST) Summer Research Fellowship program of the University of Pennsylvania School of Medicine.

Disclosure

PLR has received support and research funding from Integra LifeSciences (Plainsboro, NJ) and CMA Microdialysis (Solna, Sweden). WAK has received support and research funding from Covidien (Mansfield, MA) and the U.S. Public Health Service.

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Authors and Affiliations

  1. Department of Neurosurgery, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    W. Andrew Kofke & Peter Le Roux

  2. Department of Anesthesiology and Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    W. Andrew Kofke

  3. University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Daniel B. Larach

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  1. Daniel B. Larach
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Correspondence to Daniel B. Larach.

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Larach, D.B., Kofke, W.A. & Le Roux, P. Potential Non-Hypoxic/Ischemic Causes of Increased Cerebral Interstitial Fluid Lactate/Pyruvate Ratio: A Review of Available Literature. Neurocrit Care 15, 609–622 (2011). https://doi.org/10.1007/s12028-011-9517-8

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