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Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: A microdialysis study*

Oddo, Mauro MD; Schmidt, J Michael PhD; Carrera, Emmanuel MD; Badjatia, Neeraj MD, MS; Connolly, E Sander MD; Presciutti, Mary RN; Ostapkovich, Noeleen D. MS; Levine, Joshua M. MD; Roux, Peter Le MD; Mayer, Stephan A. MD, FCCM

doi: 10.1097/CCM.0b013e31818f4026
Neurologic Critical Care

Objectives: To analyze the effect of tight glycemic control with the use of intensive insulin therapy on cerebral glucose metabolism in patients with severe brain injury.

Design: Retrospective analysis of a prospective observational cohort.

Setting: University hospital neurologic intensive care unit.

Patients: Twenty patients (median age 59 yrs) monitored with cerebral microdialysis as part of their clinical care.

Interventions: Intensive insulin therapy (systemic glucose target: 4.4–6.7 mmol/L [80–120 mg/dL]).

Measurements and Main Results: Brain 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).

Conclusions: In 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.

From the Department of Neurology (MO, JMS, EC, NB, MP, NDO, SAM), Critical Care Division, and Department of Neurosurgery (ESC), Columbia University Medical Center, New York, NY; and Department of Neurology and Critical Care (JML), and Department of Neurosurgery (PLR), University of Pennsylvania School of Medicine, Philadelphia, PA.

Supported, in part, by research grants from the SICPA Foundation, Lausanne, Switzerland (to MO and EC), the Swiss National Science Foundation, Grant PBLAB-119620 (to EC), the Integra Foundation (to PLR), the Mary Elizabeth Groff Surgical and Medical Research Trust (to PLR), and the Charles A. Dana Foundation (to SAM).

This work received an Annual Scientific Award at the Society of Critical Care Medicine Congress, February 2–6, 2008, Honolulu, Hawaii.

The authors have not disclosed any potential conflicts of interest.

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© 2008 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins