Treating Hyperglycemia in Neurocritical Patients: Benefits and Perils (original) (raw)

• Alberti O, Becker R, Benes L, Wallenfang T, Bertalanffy H. Initial hyperglycemia as an indicator of severity of the ictus in poor-grade patients with spontaneous subarachnoid hemorrhage. Clin Neurol Neurosurg. 2000;102(2):78–83.
  Article CAS PubMed Google Scholar
• Badjatia N, Topcuoglu MA, Buonanno FS, Smith EE, Nogueira RG, Rordorf GA, et al. Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid hemorrhage. Crit Care Med. 2005;33(7):1603–9.
  Article PubMed Google Scholar
• Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke. 2001;32(10):2426–32.
  Article CAS PubMed Google Scholar
• Fogelholm R, Murros K, Rissanen A, Avikainen S. Admission blood glucose and short term survival in primary intracerebral haemorrhage: a population based study. J Neurol Neurosurg Psychiatry. 2005;76(3):349–53.
  Article CAS PubMed Google Scholar
• Frontera JA, Fernandez A, Claassen J, Schmidt M, Schumacher HC, Wartenberg K, et al. Hyperglycemia after SAH: predictors, associated complications, and impact on outcome. Stroke. 2006;37(1):199–203.
  Article PubMed Google Scholar
• Garg R, Chaudhuri A, Munschauer F, Dandona P. Hyperglycemia, insulin, and acute ischemic stroke: a mechanistic justification for a trial of insulin infusion therapy. Stroke. 2006;37(1):267–73.
  Article CAS PubMed Google Scholar
• Godoy DA, Pinero GR, Svampa S, Papa F, Di Napoli M. Hyperglycemia and short-term outcome in patients with spontaneous intracerebral hemorrhage. Neurocrit Care. 2008;9(2):217–29.
  Article CAS PubMed Google Scholar
• Jeremitsky E, Omert LA, Dunham CM, Wilberger J, Rodriguez A. The impact of hyperglycemia on patients with severe brain injury. J Trauma. 2005;58(1):47–50.
  Article CAS PubMed Google Scholar
• Lam AM, Winn HR, Cullen BF, Sundling N. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg. 1991;75(4):545–51.
  Article CAS PubMed Google Scholar
• Lanzino G, Kassell NF, Germanson T, Truskowski L, Alves W. Plasma glucose levels and outcome after aneurysmal subarachnoid hemorrhage. J Neurosurg. 1993;79(6):885–91.
  Article CAS PubMed Google Scholar
• Liu-Deryke X, Collingridge DS, Orme J, Roller D, Zurasky J, Rhoney DH. Clinical impact of early hyperglycemia during acute phase of traumatic brain injury. Neurocrit Care. 2009;11(2):151–7.
  Article PubMed Google Scholar
• Melamed E. Reactive hyperglycaemia in patients with acute stroke. J Neurol Sci. 1976;29(2–4):267–75.
  Article CAS PubMed Google Scholar
• Rovlias A, Kotsou S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery. 2000;46(2):335–42.
  Article CAS PubMed Google Scholar
• van Kooten F, Hoogerbrugge N, Naarding P, Koudstaal PJ. Hyperglycemia in the acute phase of stroke is not caused by stress. Stroke. 1993;24(8):1129–32.
  PubMed Google Scholar
• Weir CJ, Murray GD, Dyker AG, Lees KR. Is hyperglycaemia an independent predictor of poor outcome after acute stroke? Results of a long-term follow up study. BMJ. 1997;314(7090):1303–6.
  CAS PubMed Google Scholar
• Gray CS, Hildreth AJ, Alberti GK, O’Connell JE. Poststroke hyperglycemia: natural history and immediate management. Stroke. 2004;35(1):122–6.
  Article CAS PubMed Google Scholar
• Scott JF, Robinson GM, French JM, O’Connell JE, Alberti KG, Gray CS. Prevalence of admission hyperglycaemia across clinical subtypes of acute stroke. Lancet. 1999;353(9150):376–7.
  Article CAS PubMed Google Scholar
• Williams LS, Rotich J, Qi R, Fineberg N, Espay A, Bruno A, et al. Effects of admission hyperglycemia on mortality and costs in acute ischemic stroke. Neurology. 2002;59(1):67–71.
  CAS PubMed Google Scholar
• Woo E, Ma JT, Robinson JD, Yu YL. Hyperglycemia is a stress response in acute stroke. Stroke. 1988;19(11):1359–64.
  CAS PubMed Google Scholar
• Yang SY, Zhang S, Wang ML. Clinical significance of admission hyperglycemia and factors related to it in patients with acute severe head injury. Surg Neurol. 1995;44(4):373–7.
  Article CAS PubMed Google Scholar
• Kimura K, Iguchi Y, Inoue T, Shibazaki K, Matsumoto N, Kobayashi K, et al. Hyperglycemia independently increases the risk of early death in acute spontaneous intracerebral hemorrhage. J Neurol Sci. 2007;255(1–2):90–4.
  Article CAS PubMed Google Scholar
• Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology. 2003;61(10):1351–6.
  PubMed Google Scholar
• Sala F, Menna G, Bricolo A, Young W. Role of glycemia in acute spinal cord injury. Data from a rat experimental model and clinical experience. Ann N Y Acad Sci. 1999;890:133–54.
  Article CAS PubMed Google Scholar
• Oddo M, Schmidt JM, Carrera E, Badjatia N, Connolly ES, Presciutti M, et al. Impact of tight glycemic control on cerebral glucose metabolism after severe brain injury: a microdialysis study. Crit Care Med. 2008;36(12):3233–8.
  Article CAS PubMed Google Scholar
• Prakash A, Matta BF. Hyperglycaemia and neurological injury. Curr Opin Anaesthesiol. 2008;21(5):565–9.
  Article PubMed Google Scholar
• Vespa P, Boonyaputthikul R, McArthur DL, Miller C, Etchepare M, Bergsneider M, et al. 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(3):850–6.
  Article CAS PubMed Google Scholar
• Zauner A, Daugherty WP, Bullock MR, Warner DS. Brain oxygenation and energy metabolism: part I—biological function and pathophysiology. Neurosurgery. 2002;51(2):289–301.
  Article PubMed Google Scholar
• Benarroch EE. Glycogen metabolism: metabolic coupling between astrocytes and neurons. Neurology. 2010;74(11):919–23.
  Article CAS PubMed Google Scholar
• Oz G, Kumar A, Rao JP, Kodl CT, Chow L, Eberly LE, et al. Human brain glycogen metabolism during and after hypoglycemia. Diabetes. 2009;58(9):1978–85.
  Article CAS PubMed Google Scholar
• Simpson IA, Carruthers A, Vannucci SJ. Supply and demand in cerebral energy metabolism: the role of nutrient transporters. J Cereb Blood Flow Metab. 2007;27(11):1766–91.
  Article CAS PubMed Google Scholar
• Hamlin GP, Cernak I, Wixey JA, Vink R. Increased expression of neuronal glucose transporter 3 but not glial glucose transporter 1 following severe diffuse traumatic brain injury in rats. J Neurotrauma. 2001;18(10):1011–8.
  Article CAS PubMed Google Scholar
• Gjedde A, Crone C. Blood–brain glucose transfer: repression in chronic hyperglycemia. Science. 1981;214(4519):456–7.
  Article CAS PubMed Google Scholar
• Laron Z. Insulin and the brain. Arch Physiol Biochem. 2009;115(2):112–6.
  CAS PubMed Google Scholar
• Kum W, Zhu SQ, Ho SK, Young JD, Cockram CS. Effect of insulin on glucose and glycogen metabolism and leucine incorporation into protein in cultured mouse astrocytes. Glia. 1992;6(4):264–8.
  Article CAS PubMed Google Scholar
• Schulingkamp RJ, Pagano TC, Hung D, Raffa RB. Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci Biobehav Rev. 2000;24(8):855–72.
  Article CAS PubMed Google Scholar
• Seaquist ER, Damberg GS, Tkac I, Gruetter R. The effect of insulin on in vivo cerebral glucose concentrations and rates of glucose transport/metabolism in humans. Diabetes. 2001;50(10):2203–9.
  Article CAS PubMed Google Scholar
• Bingham EM, Hopkins D, Smith D, Pernet A, Hallett W, Reed L, et al. The role of insulin in human brain glucose metabolism: an 18fluoro-deoxyglucose positron emission tomography study. Diabetes. 2002;51(12):3384–90.
  Article CAS PubMed Google Scholar
• Hutchinson PJ, O’Connell MT, Seal A, Nortje J, Timofeev I, Al Rawi PG, et al. A combined microdialysis and FDG-PET study of glucose metabolism in head injury. Acta Neurochir. 2009;151(1):51–61.
  Article Google Scholar
• Bergsneider M, Hovda DA, Shalmon E, Kelly DF, Vespa PM, Martin NA, et al. Cerebral hyperglycolysis following severe traumatic brain injury in humans: a positron emission tomography study. J Neurosurg. 1997;86(2):241–51.
  Article CAS PubMed Google Scholar
• Marcoux J, McArthur DA, Miller C, Glenn TC, Villablanca P, Martin NA, et al. 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(10):2871–7.
  Article CAS PubMed Google Scholar
• Vespa P, Bergsneider M, Hattori N, Wu HM, Huang SC, Martin NA, et al. 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(6):763–74.
  Article CAS PubMed Google Scholar
• Oddo M, Schmidt JM, Mayer SA, Chiolero RL. Glucose control after severe brain injury. Curr Opin Clin Nutr Metab Care. 2008;11(2):134–9.
  Article PubMed Google Scholar
• Strong AJ. The management of plasma glucose in acute cerebral ischaemia and traumatic brain injury: more research needed. Intensive Care Med. 2008;34(7):1169–72.
  Article PubMed Google Scholar
• Tomlinson DR, Gardiner NJ. Glucose neurotoxicity. Nat Rev Neurosci. 2008;9(1):36–45.
  Article CAS PubMed Google Scholar
• Higashi Y, Noma K, Yoshizumi M, Kihara Y. Endothelial function and oxidative stress in cardiovascular diseases. Circ J. 2009;73(3):411–8.
  Article CAS PubMed Google Scholar
• Mohanty P, Hamouda W, Garg R, Aljada A, Ghanim H, Dandona P. Glucose challenge stimulates reactive oxygen species (ROS) generation by leucocytes. J Clin Endocrinol Metab. 2000;85(8):2970–3.
  Article CAS PubMed Google Scholar
• Kamada H, Yu F, Nito C, Chan PH. Influence of hyperglycemia on oxidative stress and matrix metalloproteinase-9 activation after focal cerebral ischemia/reperfusion in rats: relation to blood–brain barrier dysfunction. Stroke. 2007;38(3):1044–9.
  Article CAS PubMed Google Scholar
• Anderson RE, Tan WK, Martin HS, Meyer FB. Effects of glucose and PaO2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra. Stroke. 1999;30(1):160–70.
  CAS PubMed Google Scholar
• Clausen T, Khaldi A, Zauner A, Reinert M, Doppenberg E, Menzel M, et al. Cerebral acid–base homeostasis after severe traumatic brain injury. J Neurosurg. 2005;103(4):597–607.
  Article PubMed Google Scholar
• Li PA, Shuaib A, Miyashita H, He QP, Siesjo BK, Warner DS. Hyperglycemia enhances extracellular glutamate accumulation in rats subjected to forebrain ischemia. Stroke. 2000;31(1):183–92.
  CAS PubMed Google Scholar
• Krinsley JS, Grover A. Severe hypoglycemia in critically ill patients: risk factors and outcomes. Crit Care Med. 2007;35(10):2262–7.
  Article PubMed Google Scholar
• Egi M, Bellomo R, Stachowski E, French CJ, Hart GK, Taori G, et al. Hypoglycemia and outcome in critically ill patients. Mayo Clin Proc. 2010;85(3):217–24.
  Article PubMed Google Scholar
• Siesjo BK, Ingvar M, Pelligrino D. Regional differences in vascular autoregulation in the rat brain in severe insulin-induced hypoglycemia. J Cereb Blood Flow Metab. 1983;3(4):478–85.
  CAS PubMed Google Scholar
• Brown AM, Ransom BR. Astrocyte glycogen and brain energy metabolism. Glia. 2007;55(12):1263–71.
  Article PubMed Google Scholar
• Choi IY, Seaquist ER, Gruetter R. Effect of hypoglycemia on brain glycogen metabolism in vivo. J Neurosci Res. 2003;72(1):25–32.
  Article CAS PubMed Google Scholar
• Gruetter R. Glycogen: the forgotten cerebral energy store. J Neurosci Res. 2003;74(2):179–83.
  Article CAS PubMed Google Scholar
• Oz G, Seaquist ER, Kumar A, Criego AB, Benedict LE, Rao JP, et al. Human brain glycogen content and metabolism: implications on its role in brain energy metabolism. Am J Physiol Endocrinol Metab. 2007;292(3):E946–51.
  Article CAS PubMed Google Scholar
• Suh SW, Hamby AM, Swanson RA. Hypoglycemia, brain energetics, and hypoglycemic neuronal death. Glia. 2007;55(12):1280–6.
  Article PubMed Google Scholar
• Holbein M, Bechir M, Ludwig S, Sommerfeld J, Cottini SR, Keel M, et al. Differential influence of arterial blood glucose on cerebral metabolism following severe traumatic brain injury. Crit Care. 2009;13(1):R13.
  Article PubMed Google Scholar
• Meierhans R, Bechir M, Ludwig S, Sommerfeld J, Brandi G, Haberthur 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.
  Article PubMed Google Scholar
• Schlenk F, Nagel A, Graetz D, Sarrafzadeh AS. Hyperglycemia and cerebral glucose in aneurysmal subarachnoid hemorrhage. Intensive Care Med. 2008;34(7):1200–7.
  Article CAS PubMed Google Scholar
• Parkin M, Hopwood S, Jones DA, Hashemi P, Landolt H, Fabricius M, et al. Dynamic changes in brain glucose and lactate in pericontusional areas of the human cerebral cortex, monitored with rapid sampling on-line microdialysis: relationship with depolarisation-like events. J Cereb Blood Flow Metab. 2005;25(3):402–13.
  Article CAS PubMed Google Scholar
• Feuerstein D, Manning A, Hashemi P, Bhatia R, Fabricius M, Tolias C, et al. Dynamic metabolic response to multiple spreading depolarizations in patients with acute brain injury: an online microdialysis study. J Cereb Blood Flow Metab. 2010;30(7):1343–55.
  Article CAS PubMed Google Scholar
• Helbok R, Schmidt JM, Kurtz P, Hanafy KA, Fernandez L, Stuart RM, et al. Systemic glucose and brain energy metabolism after subarachnoid hemorrhage. Neurocrit Care. 2010;12(3):317–23.
  Article CAS PubMed Google Scholar
• Vespa PM, McArthur D, O’Phelan K, Glenn T, Etchepare M, Kelly D, et al. 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(7):865–77.
  Article CAS PubMed Google Scholar
• McCowen KC, Malhotra A, Bistrian BR. Stress-induced hyperglycemia. Crit Care Clin. 2001;17(1):107–24.
  Article CAS PubMed Google Scholar
• McIntosh TK, Yu T, Gennarelli TA. Alterations in regional brain catecholamine concentrations after experimental brain injury in the rat. J Neurochem. 1994;63(4):1426–33.
  Article CAS PubMed Google Scholar
• Mechanick JI. Metabolic mechanisms of stress hyperglycemia. JPEN J Parenter Enter Nutr. 2006;30(2):157–63.
  Article CAS Google Scholar
• Rosner MJ, Newsome HH, Becker DP. Mechanical brain injury: the sympathoadrenal response. J Neurosurg. 1984;61(1):76–86.
  Article CAS PubMed Google Scholar
• Chrousos GP. The hypothalamic–pituitary–adrenal axis and immune-mediated inflammation. N Engl J Med. 1995;332(20):1351–62.
  Article CAS PubMed Google Scholar
• Barth E, Albuszies G, Baumgart K, Matejovic M, Wachter U, Vogt J, et al. Glucose metabolism and catecholamines. Crit Care Med. 2007;35(9 Suppl):S508–18.
  Article CAS PubMed Google Scholar
• Allport LE, Butcher KS, Baird TA, MacGregor L, Desmond PM, Tress BM, et al. Insular cortical ischemia is independently associated with acute stress hyperglycemia. Stroke. 2004;35(8):1886–91.
  Article PubMed Google Scholar
• Christensen H. Insular lesions and hyperglycemia in acute stroke revisited. Stroke. 2005;36(2):229–30.
  Article PubMed Google Scholar
• Moreton FC, McCormick M, Muir KW. Insular cortex hypoperfusion and acute phase blood glucose after stroke: a CT perfusion study. Stroke. 2007;38(2):407–10.
  Article PubMed Google Scholar
• Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab. 2002;87(3):978–82.
  Article CAS PubMed Google Scholar
• Alvarez-Sabin J, Molina CA, Ribo M, Arenillas JF, Montaner J, Huertas R, et al. Impact of admission hyperglycemia on stroke outcome after thrombolysis: risk stratification in relation to time to reperfusion. Stroke. 2004;35(11):2493–8.
  Article PubMed Google Scholar
• Baird TA, Parsons MW, Phanh T, Butcher KS, Desmond PM, Tress BM, et al. Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. Stroke. 2003;34(9):2208–14.
  Article CAS PubMed Google Scholar
• Bruno A, Levine SR, Frankel MR, Brott TG, Lin Y, Tilley BC, et al. Admission glucose level and clinical outcomes in the NINDS rt-PA Stroke Trial. Neurology. 2002;59(5):669–74.
  CAS PubMed Google Scholar
• Leigh R, Zaidat OO, Suri MF, Lynch G, Sundararajan S, Sunshine JL, et al. Predictors of hyperacute clinical worsening in ischemic stroke patients receiving thrombolytic therapy. Stroke. 2004;35(8):1903–7.
  Article CAS PubMed Google Scholar
• McCormick MT, Muir KW, Gray CS, Walters MR. Management of hyperglycemia in acute stroke: how, when, and for whom? Stroke. 2008;39(7):2177–85.
  Article PubMed Google Scholar
• Parsons MW, Barber PA, Desmond PM, Baird TA, Darby DG, Byrnes G, et al. Acute hyperglycemia adversely affects stroke outcome: a magnetic resonance imaging and spectroscopy study. Ann Neurol. 2002;52(1):20–8.
  Article PubMed Google Scholar
• Saposnik G, Young B, Silver B, Di Legge S, Webster F, Beletsky V, et al. Lack of improvement in patients with acute stroke after treatment with thrombolytic therapy: predictors and association with outcome. JAMA. 2004;292(15):1839–44.
  Article CAS PubMed Google Scholar
• Godoy DA, Di Napoli M. Hyperglycemia in acute phase of spontaneous intracerebral hemorrhage (sICH). J Neurol Sci. 2007;263(1–2):228–9.
  Article PubMed Google Scholar
• Godoy DA, Pinero GR, Svampa S, Papa F, Di Napoli M. Early hyperglycemia and intravenous insulin—the rationale and management of hyperglycemia for spontaneous intracerebral hemorrhage patients: is time for change? Neurocrit Care. 2009;10(1):150–3.
  Article PubMed Google Scholar
• Kruyt ND, Roos YW, Dorhout Mees SM, van den Bergh WM, Algra A, Rinkel GJ, et al. High mean fasting glucose levels independently predict poor outcome and delayed cerebral ischaemia after aneurysmal subarachnoid haemorrhage. J Neurol Neurosurg Psychiatry. 2008;79(12):1382–5.
  Article CAS PubMed Google Scholar
• Kruyt ND, Biessels GJ, de Haan RJ, Vermeulen M, Rinkel GJ, Coert B, et al. Hyperglycemia and clinical outcome in aneurysmal subarachnoid hemorrhage: a meta-analysis. Stroke. 2009;40(6):e424–30.
  Article PubMed Google Scholar
• Salim A, Hadjizacharia P, Dubose J, Brown C, Inaba K, Chan LS, et al. Persistent hyperglycemia in severe traumatic brain injury: an independent predictor of outcome. Am Surg. 2009;75(1):25–9.
  PubMed Google Scholar
• Stead LG, Gilmore RM, Bellolio MF, Mishra S, Bhagra A, Vaidyanathan L, et al. Hyperglycemia as an independent predictor of worse outcome in non-diabetic patients presenting with acute ischemic stroke. Neurocrit Care. 2009;10(2):181–6.
  Article PubMed Google Scholar
• Fuentes B, Castillo J, San Jose B, Leira R, Serena J, Vivancos J, et al. The prognostic value of capillary glucose levels in acute stroke: the GLycemia in Acute Stroke (GLIAS) study. Stroke. 2009;40(2):562–8.
  Article CAS PubMed Google Scholar
• Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology. 2004;63(6):1059–64.
  CAS PubMed Google Scholar
• Stead LG, Jain A, Bellolio MF, Odufuye A, Gilmore RM, Rabinstein A, et al. Emergency department hyperglycemia as a predictor of early mortality and worse functional outcome after intracerebral hemorrhage. Neurocrit Care. 2010;13(1):67–74.
  Article CAS PubMed Google Scholar
• McGirt MJ, Woodworth GF, Ali M, Than KD, Tamargo RJ, Clatterbuck RE. Persistent perioperative hyperglycemia as an independent predictor of poor outcome after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2007;107(6):1080–5.
  Article CAS PubMed Google Scholar
• Juvela S, Siironen J, Kuhmonen J. Hyperglycemia, excess weight, and history of hypertension as risk factors for poor outcome and cerebral infarction after aneurysmal subarachnoid hemorrhage. J Neurosurg. 2005;102(6):998–1003.
  Article PubMed Google Scholar
• Sato M, Nakano M, Asari J, Watanabe K. Admission blood glucose levels and early change of neurological grade in poor-grade patients with aneurysmal subarachnoid haemorrhage. Acta Neurochir. 2006;148(6):623–6.
  Article CAS Google Scholar
• Schlenk F, Vajkoczy P, Sarrafzadeh A. Inpatient hyperglycemia following aneurysmal subarachnoid hemorrhage: relation to cerebral metabolism and outcome. Neurocrit Care. 2009;11(1):56–63.
  Article CAS PubMed Google Scholar
• Cochran A, Scaife ER, Hansen KW, Downey EC. Hyperglycemia and outcomes from pediatric traumatic brain injury. J Trauma. 2003;55(6):1035–8.
  Article PubMed Google Scholar
• Griesdale DE, Tremblay MH, McEwen J, Chittock DR. Glucose control and mortality in patients with severe traumatic brain injury. Neurocrit Care. 2009;11(3):311–6.
  Article CAS Google Scholar
• Liu-Deryke X, Collingridge DS, Orme J, Roller D, Zurasky J, Rhoney DH. Clinical impact of early hyperglycemia during acute phase of traumatic brain injury. Neurocrit Care. 2009;11(2):151–7.
  Article PubMed Google Scholar
• Rovlias A, Kotsou S. Classification and regression tree for prediction of outcome after severe head injury using simple clinical and laboratory variables. J Neurotrauma. 2004;21(7):886–93.
  Article CAS PubMed Google Scholar
• Steyerberg EW, Mushkudiani N, Perel P, Butcher I, Lu J, McHugh GS, et al. Predicting outcome after traumatic brain injury: development and international validation of prognostic scores based on admission characteristics. PLoS Med. 2008;5(8):e165.
  Article PubMed Google Scholar
• Perel P, Arango M, Clayton T, Edwards P, Komolafe E, Poccock S, et al. Predicting outcome after traumatic brain injury: practical prognostic models based on large cohort of international patients. BMJ. 2008;336(7641):425–9.
  Article PubMed Google Scholar
• Murray GD, Butcher I, McHugh GS, Lu J, Mushkudiani NA, Maas AI, et al. Multivariable prognostic analysis in traumatic brain injury: results from the IMPACT study. J Neurotrauma. 2007;24(2):329–37.
  Article PubMed Google Scholar
• LeMay DR, Neal S, Neal S, Zelenock GB, D’Alecy LG. Paraplegia in the rat induced by aortic cross-clamping: model characterization and glucose exacerbation of neurologic deficit. J Vasc Surg. 1987;6(4):383–90.
  Article CAS PubMed Google Scholar
• Hemmila MR, Zelenock GB, D’Alecy LG. Postischemic hyperglycemia worsens neurologic outcome after spinal cord ischemia. J Vasc Surg. 1993;17(4):661–8.
  Article CAS PubMed Google Scholar
• Voll CL, Auer RN. Insulin attenuates ischemic brain damage independent of its hypoglycemic effect. J Cereb Blood Flow Metab. 1991;11(6):1006–14.
  CAS PubMed Google Scholar
• Hamilton MG, Tranmer BI, Auer RN. Insulin reduction of cerebral infarction due to transient focal ischemia. J Neurosurg. 1995;82(2):262–8.
  Article CAS PubMed Google Scholar
• Yuan ZR, Liu B, Zhang Y, Yuan L, Muteliefu G, Lu J. Upregulated expression of neuronal nitric oxide synthase by insulin in both neurons and astrocytes. Brain Res. 2004;1008(1):1–10.
  Article CAS PubMed Google Scholar
• Jain SK, Nagi DK, Slavin BM, Lumb PJ, Yudkin JS. Insulin therapy in type 2 diabetic subjects suppresses plasminogen activator inhibitor (PAI-1) activity and proinsulin-like molecules independently of glycaemic control. Diabet Med. 1993;10(1):27–32.
  Article CAS PubMed Google Scholar
• Davi G, Catalano I, Averna M, Notarbartolo A, Strano A, Ciabattoni G, et al. Thromboxane biosynthesis and platelet function in type II diabetes mellitus. N Engl J Med. 1990;322(25):1769–74.
  Article CAS PubMed Google Scholar
• van den BG, Wouters P, Weekers F, Verwaest C, Bruyninckx F, Schetz M, et al. Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;345(19):1359–67.
  Article Google Scholar
• Arabi YM, Dabbagh OC, Tamim HM, Al Shimemeri AA, Memish ZA, Haddad SH, et al. Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med. 2008;36(12):3190–7.
  Article CAS PubMed Google Scholar
• Treggiari MM, Karir V, Yanez ND, Weiss NS, Daniel S, Deem SA. Intensive insulin therapy and mortality in critically ill patients. Crit Care. 2008;12(1):R29.
  Article PubMed Google Scholar
• Griesdale DE, de Souza RJ, van Dam RM, Heyland DK, Cook DJ, Malhotra A, et al. Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data. CMAJ. 2009;180(8):821–7.
  PubMed Google Scholar
• Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A, Ragaller M, Weiler N, et al. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. N Engl J Med. 2008;358(2):125–39.
  Article CAS PubMed Google Scholar
• Bagshaw SM, Bellomo R, Jacka MJ, Egi M, Hart GK, George C, et al. The impact of early hypoglycemia and blood glucose variability on outcome in critical illness. Crit Care. 2009;13(3):R91.
  Article PubMed Google Scholar
• Finfer S, Chittock DR, Su SY, Blair D, Foster D, Dhingra V, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. 2009;360(13):1283–97.
  Article PubMed Google Scholar
• Hermans G, Wilmer A, Meersseman W, Milants I, Wouters PJ, Bobbaers H, et al. Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. Am J Respir Crit Care Med. 2007;175(5):480–9.
  Article CAS PubMed Google Scholar
• 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(8):1348–53.
  PubMed Google Scholar
• Gentile NT, Seftchick MW, Huynh T, Kruus LK, Gaughan J. Decreased mortality by normalizing blood glucose after acute ischemic stroke. Acad Emerg Med. 2006;13(2):174–80.
  Article PubMed Google Scholar
• Walters MR, Weir CJ, Lees KR. A randomised, controlled pilot study to investigate the potential benefit of intervention with insulin in hyperglycaemic acute ischaemic stroke patients. Cerebrovasc Dis. 2006;22(2–3):116–22.
  Article CAS PubMed Google Scholar
• Gray CS, Hildreth AJ, Sandercock PA, O’Connell JE, Johnston DE, Cartlidge NE, et al. Glucose–potassium–insulin infusions in the management of post-stroke hyperglycaemia: the UK Glucose Insulin in Stroke Trial (GIST-UK). Lancet Neurol. 2007;6(5):397–406.
  Article CAS PubMed Google Scholar
• Bruno A, Kent TA, Coull BM, Shankar RR, Saha C, Becker KJ, et al. Treatment of hyperglycemia in ischemic stroke (THIS): a randomized pilot trial. Stroke. 2008;39(2):384–9.
  Article CAS PubMed Google Scholar
• McCormick M, Hadley D, McLean JR, Macfarlane JA, Condon B, Muir KW. Randomized, controlled trial of insulin for acute poststroke hyperglycemia. Ann Neurol. 2010;67(5):570–8.
  Article CAS PubMed Google Scholar
• Quinn TJ, Lees KR. Hyperglycaemia in acute stroke—to treat or not to treat. Cerebrovasc Dis. 2009;27(Suppl 1):148–55.
  Article PubMed Google Scholar
• Kreisel SH, Berschin UM, Hammes HP, Leweling H, Bertsch T, Hennerici MG, et al. Pragmatic management of hyperglycaemia in acute ischaemic stroke: safety and feasibility of intensive intravenous insulin treatment. Cerebrovasc Dis. 2009;27(2):167–75.
  Article PubMed Google Scholar
• Kim N, Jhang Y, Park JM, Kim BK, Kwon O, Lee J, et al. Aggressive glucose control for acute ischemic stroke patients by insulin infusion. J Clin Neurol. 2009;5(4):167–72.
  Article PubMed Google Scholar
• Kruyt ND, Biessels GJ, Vriesendorp TM, Devries JH, Hoekstra JB, Elbers PW, et al. Subjecting acute ischemic stroke patients to continuous tube feeding and an intensive computerized protocol establishes tight glycemic control. Neurocrit Care. 2010;12(1):62–8.
  Article CAS PubMed Google Scholar
• 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(3):156–60.
  Article PubMed Google Scholar
• Latorre JG, Chou SH, Nogueira RG, Singhal AB, Carter BS, Ogilvy CS, et al. Effective glycemic control with aggressive hyperglycemia management is associated with improved outcome in aneurysmal subarachnoid hemorrhage. Stroke. 2009;40(5):1644–52.
  Article CAS PubMed Google Scholar
• Naidech AM, Levasseur K, Liebling S, Garg RK, Shapiro M, Ault ML, et al. Moderate Hypoglycemia is associated with vasospasm, cerebral infarction, and 3-month disability after subarachnoid hemorrhage. Neurocrit Care. 2010;12(2):181–7.
  Article PubMed Google Scholar
• Bilotta F, Caramia R, Cernak I, Paoloni FP, Doronzio A, Cuzzone V, et al. Intensive insulin therapy after severe traumatic brain injury: a randomized clinical trial. Neurocrit Care. 2008;9(2):159–66.
  Article CAS PubMed Google Scholar
• Meier R, Bechir M, Ludwig S, Sommerfeld J, Keel M, Steiger P, et al. Differential temporal profile of lowered blood glucose levels (3.5 to 6.5 mmol/l versus 5 to 8 mmol/l) in patients with severe traumatic brain injury. Crit Care. 2008;12(4):R98.
  Article PubMed Google Scholar
• Vespa PM. Intensive glycemic control in traumatic brain injury: what is the ideal glucose range? Crit Care. 2008;12(5):175.
  Article PubMed Google Scholar
• Bilotta F, Caramia R, Paoloni FP, Delfini R, Rosa G. Safety and efficacy of intensive insulin therapy in critical neurosurgical patients. Anesthesiology. 2009;110(3):611–9.
  Article CAS PubMed Google Scholar
• Kanji S, Jones E, Goddard R, Meggison HE, Neilipovitz D. Efficiency and safety of a standardized protocol for intravenous insulin therapy in ICU patients with neurovascular or head injury. Neurocrit Care. 2010;12(1):43–9.
  Article CAS PubMed Google Scholar
• Brain Trauma Foundation. Guidelines for the management of severe traumatic brain injury. J Neurotrauma. 2007;24(Suppl 1):S1–106.
  Google Scholar
• Adams HP Jr, Del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, et al. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007;38(5):1655–711.
  Article PubMed Google Scholar
• European Stroke Organization Writing Committee. Guidelines for management of ischaemic stroke, transient ischaemic attack. Cerebrovasc Dis. 2008;25(5):457–507.
  Article Google Scholar
• Steiner T, Kaste M, Forsting M, Mendelow D, Kwiecinski H, Szikora I, et al. Recommendations for the management of intracranial haemorrhage—part I: spontaneous intracerebral haemorrhage. The European Stroke Initiative Writing Committee and the Writing Committee for the EUSI Executive Committee. Cerebrovasc Dis. 2006;22(4):294–316.
  Article PubMed Google Scholar
• Broderick J, Connolly S, Feldmann E, Hanley D, Kase C, Krieger D, et al. Guidelines for the management of spontaneous intracerebral hemorrhage in adults: 2007 update: a guideline from the American Heart Association/American Stroke Association Stroke Council, High Blood Pressure Research Council, and the Quality of Care and Outcomes in Research Interdisciplinary Working Group. Stroke. 2007;38(6):2001–23.
  Article PubMed Google Scholar
• Bederson JB, Connolly ES Jr, Batjer HH, Dacey RG, Dion JE, Diringer MN, et al. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke. 2009;40(3):994–1025.
  Article PubMed Google Scholar