• Mauro Oddo, J Michael Schmidt, Emmanuel Carrera, Neeraj Badjatia, E Sander Connolly, Mary Presciutti, Noeleen D Ostapkovich, Joshua M Levine, Peter Le Roux, and Stephan A Mayer.
• Department of Neurology, Critical Care Division, Columbia University Medical Center, New York, NY, USA. mauro.oddo@chuv.ch
• Crit. Care Med. 2008 Dec 1;36(12):3233-8.

ObjectivesTo analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury.DesignRetrospective analysis of a prospective observational cohort.SettingUniversity hospital neurologic intensive care unit.PatientsTwenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care.InterventionsIntensive insulin therapy (systemic glucose target: 4.4-6.7 mmol/L [80-120 mg/dL]).Measurements And Main ResultsBrain tissue markers of glucose metabolism (cerebral microdialysis glucose and lactate/pyruvate ratio) and systemic glucose were collected hourly. Systemic glucose levels were categorized as within the target "tight" (4.4-6.7 mmol/L [80-120 mg/dL]) vs. "intermediate" (6.8-10.0 mmol/L [121-180 mg/dL]) range. Brain energy crisis was defined as a cerebral microdialysis glucose <0.7 mmol/L with a lactate/pyruvate ratio >40. We analyzed 2131 cerebral microdialysis samples: tight systemic glucose levels were associated with a greater prevalence of low cerebral microdialysis glucose (65% vs. 36%, p < 0.01) and brain energy crisis (25% vs.17%, p < 0.01) than intermediate levels. Using multivariable analysis, and adjusting for intracranial pressure and cerebral perfusion pressure, systemic glucose concentration (adjusted odds ratio 1.23, 95% confidence interval [CI] 1.10-1.37, for each 1 mmol/L decrease, p < 0.001) and insulin dose (adjusted odds ratio 1.10, 95% CI 1.04-1.17, for each 1 U/hr increase, p = 0.02) independently predicted brain energy crisis. Cerebral microdialysis glucose was lower in nonsurvivors than in survivors (0.46 +/- 0.23 vs. 1.04 +/- 0.56 mmol/L, p < 0.05). Brain energy crisis was associated with increased mortality at hospital discharge (adjusted odds ratio 7.36, 95% CI 1.37-39.51, p = 0.02).ConclusionsIn patients with severe brain injury, tight systemic glucose control is associated with reduced cerebral extracellular glucose availability and increased prevalence of brain energy crisis, which in turn correlates with increased mortality. Intensive insulin therapy may impair cerebral glucose metabolism after severe brain injury.

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