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Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain

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Abstract

Purpose

Experimental evidence suggests that lactate is neuroprotective after acute brain injury; however, data in humans are lacking. We examined whether exogenous lactate supplementation improves cerebral energy metabolism in humans with traumatic brain injury (TBI).

Methods

We prospectively studied 15 consecutive patients with severe TBI monitored with cerebral microdialysis (CMD), brain tissue PO2 (PbtO2), and intracranial pressure (ICP). Intervention consisted of a 3-h intravenous infusion of hypertonic sodium lactate (aiming to increase systemic lactate to ca. 5 mmol/L), administered in the early phase following TBI. We examined the effect of sodium lactate on neurochemistry (CMD lactate, pyruvate, glucose, and glutamate), PbtO2, and ICP.

Results

Treatment was started on average 33 ± 16 h after TBI. A mixed-effects multilevel regression model revealed that sodium lactate therapy was associated with a significant increase in CMD concentrations of lactate [coefficient 0.47 mmol/L, 95 % confidence interval (CI) 0.31–0.63 mmol/L], pyruvate [13.1 (8.78–17.4) μmol/L], and glucose [0.1 (0.04–0.16) mmol/L; all p < 0.01]. A concomitant reduction of CMD glutamate [−0.95 (−1.94 to 0.06) mmol/L, p = 0.06] and ICP [−0.86 (−1.47 to −0.24) mmHg, p < 0.01] was also observed.

Conclusions

Exogenous supplemental lactate can be utilized aerobically as a preferential energy substrate by the injured human brain, with sparing of cerebral glucose. Increased availability of cerebral extracellular pyruvate and glucose, coupled with a reduction of brain glutamate and ICP, suggests that hypertonic lactate therapy has beneficial cerebral metabolic and hemodynamic effects after TBI.

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Acknowledgments

The authors thank Béatrice Pellet, from the Division of Pharmacy, for the preparation of sodium lactate, as well as all neurosurgical fellows, ICU physicians, and ICU nurses for their help and support. This work was supported by grants from the Swiss National Science Foundation (Grant Nr. 320030_138191, to M.O.), the European Critical Care Research Network, European Society of Intensive Care Medicine (to M.O.), and the Gueules Cassées Foundation (to P.B.). This work received the best abstract award at the European Society of Intensive Care Medicine congress in Paris, 2013.

Conflicts of interest

The authors have no conflict of interest to declare.

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Authors and Affiliations

  1. Department of Intensive Care Medicine, Neuroscience Critical Care Research Group, Faculty of Biology and Medicine, University Hospital of Lausanne, Rue du Bugnon 46, 1011, Lausanne, Switzerland

    Pierre Bouzat, Nathalie Sala, Tamarah Suys & Mauro Oddo

  2. Joseph Fourier University, Grenoble, France

    Pierre Bouzat

  3. Department of Radiology, Faculty of Biology and Medicine, University Hospital of Lausanne, 1011, Lausanne, Switzerland

    Jean-Baptiste Zerlauth & Reto Meuli

  4. Faculty of Biology and Medicine, Institute of Social and Preventive Medicine, University Hospital of Lausanne, 1011, Lausanne, Switzerland

    Pedro Marques-Vidal

  5. Division of Clinical Pathophysiology, Department of Internal Medicine, Faculty of Biology and Medicine, University Hospital of Lausanne, 1011, Lausanne, Switzerland

    François Feihl

  6. Division of Neurosurgery, Department of Clinical Neurosciences, Faculty of Biology and Medicine, University Hospital of Lausanne, 1011, Lausanne, Switzerland

    Jocelyne Bloch, Mahmoud Messerer & Marc Levivier

  7. Laboratory of Neuroenergetics and Cellular Dynamics, Faculty of Biology and Medicine, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL), Centre de Neurosciences Psychiatriques, University Hospital of Lausanne, 1011, Lausanne, Switzerland

    Pierre J. Magistretti

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  1. Pierre Bouzat
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  2. Nathalie Sala
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  9. Marc Levivier
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  10. Reto Meuli
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  11. Pierre J. Magistretti
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  12. Mauro Oddo
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Corresponding author

Correspondence to Mauro Oddo.

Additional information

Take-home message: Exogenous systemic supplemental lactate can be efficiently used by the injured human brain with beneficial sparing of cerebral glucose. These clinical interventional study further suggests resuscitation with hypertonic lactate may be a valid therapeutic strategy after TBI.

Clinicaltrials.gov identifier NCT01573507.

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Bouzat, P., Sala, N., Suys, T. et al. Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain. Intensive Care Med 40, 412–421 (2014). https://doi.org/10.1007/s00134-013-3203-6

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  • DOI: https://doi.org/10.1007/s00134-013-3203-6

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