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Critical illness-induced dysglycemia and the brain

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Abstract

Purpose

Dysglycemia is a characteristic feature of critical illness associated with adverse outcome. Whether dysglycemia contributes to brain dysfunction during critical illness and long-term neurological complications is unclear. We give an overview of glucose metabolism in the brain and review the literature on critical illness-induced dysglycemia and the brain.

Methods

Medline database search using relevant search terms on dysglycemia, critical illness, acute brain injury/dysfunction, and randomized controlled trial.

Results

Hyperglycemia has been associated with deleterious effects on the nervous system. Underlying mechanisms in critical illness remain largely speculative and are often extrapolated from knowledge in diabetes mellitus. Increased hyperglycemia-induced blood–brain barrier permeability, oxidative stress, and microglia activation may play a role and compromise neuronal and glial cell integrity. Hypoglycemia is feared as critically ill patients cannot recognize or communicate hypoglycemic symptoms, which furthermore are masked by sedation and analgesia. However, observational data on the impact of brief hypoglycemia on the brain in critical illness are controversial. Secondary analysis of two large randomized studies suggested neuroprotection by strict glycemic control with insulin during intensive care, with lowered intracranial pressure, reduction of seizures, and better long-term rehabilitation in patients with isolated brain injury, and reduced incidence of critical illness polyneuromyopathy in the general critically ill patient population. Several subsequent studies failed to reproduce neurological benefit, likely explained by methodological issues, which include divergent achieved glucose levels and inaccurate glucose monitoring tools.

Conclusions

Preventing hyperglycemia during critical illness holds promise as a neuroprotective strategy to preserve brain cell viability and prevent acute brain dysfunction and long-term cognitive impairment in survivors.

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Acknowledgments

Supported by the Foundation for Scientific Research (FWO), Flanders, Belgium (G.0585.09), la Fondation pour la Recherche Médicale (FRM), Journées Neurologiques de Langue Française (JNLF). GVdB, through the University of Leuven, receives long-term structural research financing via the Methusalem program, funded by the Flemish government (METH/08/07) and holds a European Research Council Advanced Grant (AdvG-2012-321670) from the Ideas Programme of the EU FP7.

Conflicts of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Clinical Department and Laboratory of Intensive Care Medicine, Division of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000, Leuven, Belgium

    Romain Sonneville, Ilse Vanhorebeek, Heleen M. den Hertog & Greet Van den Berghe

  2. Service de Réanimation Médicale et Infectieuse and INSERM U1148, Hôpital Bichat-Claude-Bernard, Assistance Publique Hôpitaux de Paris AP-HP, Université Paris Diderot, Sorbonne Paris Cité, Paris, France

    Romain Sonneville

  3. Department of Neurology, Erasmus University Medical Center, Rotterdam, The Netherlands

    Heleen M. den Hertog

  4. Department of Human Histopathology and Experimental Models, Institut Pasteur, Paris, France

    Fabrice Chrétien

  5. Department of Intensive Care Medicine and EA4342, Raymond Poincaré University Hospital, Assistance Publique Hôpitaux de Paris AP-HP, Université Versailles Saint-Quentin, Garches, France

    Djillali Annane & Tarek Sharshar

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  1. Romain Sonneville
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  2. Ilse Vanhorebeek
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  7. Greet Van den Berghe
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Correspondence to Greet Van den Berghe.

Additional information

Take home message: Persistent hyperglycemia is associated with significant neuronal and glial changes during critical illness. Preventing hyperglycemia with insulin infusion during critical illness holds promise as a neuroprotective strategy to prevent acute brain dysfunction as well as long-term cognitive impairment in survivors of critical illness. When occurring, hypoglycemia should be corrected promptly, avoiding overcorrection with excessive glucose reperfusion.

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Sonneville, R., Vanhorebeek, I., den Hertog, H.M. et al. Critical illness-induced dysglycemia and the brain. Intensive Care Med 41, 192–202 (2015). https://doi.org/10.1007/s00134-014-3577-0

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