Reduced Brain/Serum Glucose Ratios Predict Cerebral Metabolic Distress and Mortality After Severe Brain Injury
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The brain is dependent on glucose to meet its energy demands. We sought to evaluate the potential importance of impaired glucose transport by assessing the relationship between brain/serum glucose ratios, cerebral metabolic distress, and mortality after severe brain injury.
We studied 46 consecutive comatose patients with subarachnoid or intracerebral hemorrhage, traumatic brain injury, or cardiac arrest who underwent cerebral microdialysis and intracranial pressure monitoring. Continuous insulin infusion was used to maintain target serum glucose levels of 80–120 mg/dL (4.4–6.7 mmol/L). General linear models of logistic function utilizing generalized estimating equations were used to relate predictors of cerebral metabolic distress (defined as a lactate/pyruvate ratio [LPR] ≥ 40) and mortality.
A total of 5,187 neuromonitoring hours over 300 days were analyzed. Mean serum glucose was 133 mg/dL (7.4 mmol/L). The median brain/serum glucose ratio, calculated hourly, was substantially lower (0.12) than the expected normal ratio of 0.40 (brain 2.0 and serum 5.0 mmol/L). In addition to low cerebral perfusion pressure (P = 0.05) and baseline Glasgow Coma Scale score (P < 0.0001), brain/serum glucose ratios below the median of 0.12 were independently associated with an increased risk of metabolic distress (adjusted OR = 1.4 [1.2–1.7], P < 0.001). Low brain/serum glucose ratios were also independently associated with in-hospital mortality (adjusted OR = 6.7 [1.2–38.9], P < 0.03) in addition to Glasgow Coma Scale scores (P = 0.029).
Reduced brain/serum glucose ratios, consistent with impaired glucose transport across the blood brain barrier, are associated with cerebral metabolic distress and increased mortality after severe brain injury.
- Wartenberg KE, Schmidt JM, Claassen J, Temes RE, Frontera JA, Ostapkovich N, Parra A, Connolly ES, Mayer SA. Impact of medical complications on outcome after subarachnoid hemorrhage. Crit Care Med. 2006;34:617–23.
- Frontera JA, Fernandez A, Claassen J, Schmidt M, Schumacher HC, Wartenberg K, Temes R, Parra A, Ostapkovich ND, Mayer SA. Hyperglycemia after sah: predictors, associated complications, and impact on outcome. Stroke. 2006;37:199–203. CrossRef
- Badjatia N, Topcuoglu MA, Buonanno FS, Smith EE, Nogueira RG, Rordorf GA, Carter BS, Ogilvy CS, Singhal AB. Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid hemorrhage. Crit Care Med. 2005;33:1603–9. CrossRef
- Schlenk F, Nagel A, Graetz D, Sarrafzadeh AS. Hyperglycemia and cerebral glucose in aneurysmal subarachnoid hemorrhage. Intensive Care Med. 2008;34:1200–7. CrossRef
- Van den Berghe G, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, Vlasselaers D, Ferdinande P, Lauwers P, Bouillon R. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345:1359–67. CrossRef
- Van den Berghe G, Wilmer A, Hermans G, Meersseman W, Wouters PJ, Milants I, Van Wijngaerden E, Bobbaers H. Bouillon R). Intensive insulin therapy in the medical ICU. N Engl J Med. 2006;354:449–61. CrossRef
- The NICE-SUGAR Study Investigators. Intensive versus Conventional Glucose Control in Critically Ill Patients. N Engl J Med. 2009;360:1283–97. CrossRef
- Preiser J-C, Devos P, Ruiz-Santana S, Mélot C, Annane D, Groeneveld J, Iapichino G, Leverve X, Nitenberg G, Singer P, et al. A prospective randomised multi-centre controlled trial on tight glucose control by intensive insulin therapy in adult intensive care units: the Glucontrol study. Int Care Med. 2009;10:1738–48. CrossRef
- Qaseem A, Humphrey LL, Chou R, Snow V, Shekelle P. From the clinical guidelines committee of the American College of Physicians. Use of intensive insulin therapy for the management of glycemic control in hospitalized patients: A clinical practice guideline from the American College of Physicians. Ann Int Med. 2011;154:260–7. CrossRef
- Van den Berghe G, Schoonheydt K, Becx P, Bruyninckx F, Wouters PJ. Insulin therapy protects the central and peripheral nervous system of intensive care patients. Neurology. 2005;64:1348–53. CrossRef
- Bilotta F, Caramia R, Cernak I, Paoloni FP, Doronzio A, Cuzzone V, Santoro A, Rosa G. Intensive insulin therapy after severe traumatic brain injury: a randomized clinical trial. Neurocrit Care. 2008;9:159–66. CrossRef
- Bilotta F, Spinelli A, Giovannini F, Doronzio A, Delfini R, Rosa G. The effect of intensive insulin therapy on infection rate, vasospasm, neurologic outcome, and mortality in neurointensive care unit after intracranial aneurysm clipping in patients with acute subarachnoid hemorrhage: a randomized prospective pilot trial. J Neurosurg Anesthesiol. 2007;19:156–60. CrossRef
- Oddo M, Schmidt JM, Carrera E, Badjatia N, Connolly ES, Presciutti M, Ostapkovich ND, Levine JM, Le Roux P, Mayer SA. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study. Crit Care Med. 2008;36:3233–8. CrossRef
- Schlenk F, Graetz D, Nagel A, Schmidt M, Sarrafzadeh AS. Insulin-related decrease in cerebral glucose despite normoglycemia in aneurysmal subarachnoid hemorrhage. Crit Care. 2008;12:R9. CrossRef
- Vespa P, Boonyaputthikul R, McArthur DL, Miller C, Etchepare M, Bergsneider M, Glenn T, Martin N, Hovda D. Intensive insulin therapy reduces microdialysis glucose values without altering glucose utilization or improving the lactate/pyruvate ratio after traumatic brain injury. Crit Care Med. 2006;34:850–6. CrossRef
- Helbok R, Schmidt JM, Kurtz P, Hanafy KA, Fernandez L, Stuart RM, Presciutti M, Ostapkovich ND, Connolly ES, Lee K, Badjatia N, Mayer SA, Claassen J. Serum glucose and brain energy metabolism after subarachnoid hemorrhage. Neurocrit Care. 2010;12:317–23. CrossRef
- Dusick JR, Glenn TC, Lee WN, Vespa PM, Kelly DF, Lee SM, Hovda DA, Martin NA. Increased pentose phosphate pathway flux after clinical traumatic brain injury: a [1,2–13c2] glucose labeling study in humans. J Cereb Blood Flow Metab. 2007;27:1593–602. CrossRef
- Zazulia AR, Videen TO, Powers WJ. Transient focal increase in perihematomal glucose metabolism after acute human intracerebral hemorrhage. Stroke. 2009;40:1638–43. CrossRef
- Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, Glenn TC, McArthur DL, Hovda DA. Metabolic crisis without brain ischemia is common after traumatic brain injury: a combined microdialysis and positron emission tomography study. J Cereb Blood Flow Metab. 2005;25:763–74. CrossRef
- Vespa PM, McArthur D, O’Phelan K, Glenn T, Etchepare M, Kelly D, Bergsneider M, Martin NA, Hovda DA. Persistently low extracellular glucose correlates with poor outcome 6 months after human traumatic brain injury despite a lack of increased lactate: a microdialysis study. J Cereb Blood Flow Metab. 2003;23:865–77. CrossRef
- Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, Phelps ME, McArthur DL, Caron MJ, Kraus JF, Becker DP. Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg. 1997;86:241–51. CrossRef
- Magnoni S, Tedesco C, Carbonara M, Pluderi M, Colombo A, Stocchetti N. Relationship between systemic glucose and cerebral glucose is preserved in patients with severe traumatic brain injury, but glucose delivery to the brain may become limited when oxidative metabolism is impaired: implications for glycemic control. Crit Care Med. 2012;40:1785–91. CrossRef
- Timofeev I, Carpenter KLH, Nortje J, Al-Rawi PG, O’Connell MT, Czosnyka M, et al. Cerebral extracellular chemistry and outcome following traumatic brain injury: a microdialysis study of 223 patients. Brain. 2011;134:484–94. CrossRef
- Badjatia N, Strongilis E, Prescutti M, Fernandez L, Fernandez A, Buitrago M, Schmidt JM, Mayer SA. Metabolic benefits of surface counter warming during therapeutic temperature modulation. Crit Care Med. 2009;2009(37):1893–7. CrossRef
- Badjatia N, Strongilis E, Gordon E, Prescutti M, Fernandez L, Fernandez A, Buitrago M, Schmidt JM, Ostapkovich ND, Mayer SA. Metabolic impact of shivering during therapeutic temperature modulation: the bedside shivering assessment scale. Stroke. 2008;39:3242–7. CrossRef
- Choi HA, Ko SB, Presciutti M, Fernandez L, Carpenter AM, Lesch C, Gilmore E, Malhotra R, Mayer SA, Lee K, Claassen J, Schmidt JM, Badjatia N. Prevention of shivering during therapeutic temperature modulation: the Columbia anti-shivering protocol. Neurocrit Care. 2011;14:389–94. CrossRef
- Vespa PM, O’Phelan K, McArthur D, Miller C, Eliseo M, Hirt D, Glenn T, Hovda DA. Pericontusional brain tissue exhibits persistent elevation of lactate/pyruvate ratio independent of cerebral perfusion pressure. Crit Care Med. 2007;35:1153–60. CrossRef
- Hillered L, Vespa PM, Hovda DA. Translational neurochemical research in acute human brain injury: the current status and potential future for cerebral microdialysis. J Neurotrauma. 2005;22:3–41. CrossRef
- Marcoux J, McArthur DA, Miller C, Glenn TC, Villablanca P, Martin NA, Hovda DA, Alger JR, Vespa PM. Persistent metabolic crisis as measured by elevated cerebral microdialysis lactate-pyruvate ratio predicts chronic frontal lobe brain atrophy after traumatic brain injury. Crit Care Med. 2008;36:2871–7. CrossRef
- Vespa PM, Miller C, McArthur D, Eliseo M, Etchepare M, Hirt D, Glenn TC, Martin N, Hovda D. Nonconvulsive electrographic seizures after traumatic brain injury result in a delayed, prolonged increase in intracranial pressure and metabolic crisis. Crit Care Med. 2007;35:2830–6. CrossRef
- Bellander BM, Cantais E, Enblad P, Hutchinson P, Nordstrom CH, Robertson C, Sahuquillo J, Smith M, Stocchetti N, Ungerstedt U, Unterberg A, Olsen NV. Consensus meeting on microdialysis in neurointensive care. Intensive Care Med. 2004;30:2166–9. CrossRef
- Nordmark J, Rubertsson S, Mortberg E, Nilsson P, Enblad P. Intracerebral monitoring in comatose patients treated with hypothermia after a cardiac arrest. Acta Anaesthesiol Scand. 2009;53:289–98. CrossRef
- Belli A, Sen J, Petzold A, Russo S, Kitchen N, Smith M. Metabolic failure precedes intracranial pressure rises in traumatic brain injury: a microdialysis study. Acta Neurochir (Wien). 2008;150:461–9. CrossRef
- Ko S-B, Choi A, Helbok R, Parikh G, Schmidt JM, Lee K, Badjatia N, Claassen J, Connolly ES, Mayer SA. Multimodality monitoring for cerebral perfusion pressure optimization in comatose patients with intracerebral hemorrhage. Stroke. 2011;42:3087–92. CrossRef
- Schmidt JM, Ko SB, Helbok R, Kurtz P, Stuart RM, Presciutti M, Fernandez L, Lee K, Badjatia N, Connolly ES, Claassen, Mayer SA. Cerebral perfusion pressure thresholds for brain tissue hypoxia and metabolic crisis after poor-grade subarachnoid hemorrhage. Stroke. 2010;42:1531–6.
- Prentice RL, Zhao LP. Estimating equations for parameters in means and covariances of multivariate discrete and continuous responses. Biometrics. 1991;47:825–39. CrossRef
- Pan W. Model selection in estimating equations. Biometrics. 2001;57:529–34. CrossRef
- Nilsson OG, Polito A, Saveland H, Ungerstedt U, Nordstrom CH. Are primary supratentorial intracerebral hemorrhages surrounded by a biochemical penumbra? A microdialysis study. Neurosurgery. 2006;59:521–8. CrossRef
- Maher F, Vannucci SJ, Simpson IA. Glucose transporter proteins in brain. FASEB J. 1994;8:1003–11.
- Hutchinson PJ, O’Connell MT, Seal A, Nortje J, Timofeev I, Al-Rawi PG, Coles JP, Fryer TD, Menon DK, Pickard JD, Carpenter KL. A combined microdialysis and FDG-PET study of glucose metabolism in head injury. Acta Neurochir (Wien). 2009;151:51–61 discussion 61. CrossRef
- Gould GW, Holman GD. The glucose transporter family: structure, function and tissue-specific expression. Biochem J. 1993;295(Pt 2):329–41.
- Meierhans R, Béchir M, Ludwig S, Sommerfeld J, Brandi G, Haberthür C, et al. Brain metabolism is significantly impaired at blood glucose below 6 mM and brain glucose below 1 mM in patients with severe traumatic brain injury. Crit Care. 2010;14(1):R13. CrossRef
- Holbein M, Béchir M, Ludwig S, Sommerfeld J, Cottini SR, Keel M, Stocker F, Stover JF. Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury. Crit Care. 2009;13(1):R13. CrossRef
- Diaz-Parejo P, Ståhl N, Xu W, Reinstrup P, Ungerstedt U, Nordström C-H. Cerebral energy metabolism during transient hyperglycemia in patients with severe brain trauma. Intensive Care Med. 2003;29:544–50.
- Hlatky R, Valadka AB, Goodman JC, Contant CF, Robertson CS. Patterns of energy substrates during ischemia measured in the brain by microdialysis. J Neurotrauma. 2004;21:894–906. CrossRef
- Cesarini KG, Enblad P, Ronne-Engstrom E, Marklund N, Salci K, Nilsson P, Hardemark HG, Hillered L, Persson L. Early cerebral hyperglycolysis after subarachnoid haemorrhage correlates with favourable outcome. Acta Neurochir (Wien). 2002;144:1121–31. CrossRef
- Wartenberg KE, Schmidt JM, Mayer SA. Multimodality monitoring in neurocritical care. Crit Care Clin. 2007;23:507–38. CrossRef
- Reduced Brain/Serum Glucose Ratios Predict Cerebral Metabolic Distress and Mortality After Severe Brain Injury
Volume 19, Issue 3 , pp 311-319
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- Brain injury
- Cerebral microdialysis
- Glucose transport
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- 1. Neurological Intensive Care Unit, Departments of Neurology and Neurosurgery, Columbia University College of Physicians and Surgeons, Milstein Hospital 8 Center, 177 Fort Washington Ave, New York, NY, 10032, USA