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Published in: Neurocritical Care 2/2008

01-10-2008 | Original Article

Hyperglycemia and Short-term Outcome in Patients with Spontaneous Intracerebral Hemorrhage

Authors: Daniel A. Godoy, Gustavo R. Piñero, Silvana Svampa, Francesca Papa, Mario Di Napoli

Published in: Neurocritical Care | Issue 2/2008

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Abstract

Background

Hyperglycemia has a detrimental effect in several acute neurological critical illnesses. No consensus exists on the optimal management of hyperglycemia in spontaneous intracerebral hemorrhage (sICH). Our aim was to determine whether blood glucose (BG) would predict 30-day mortality in sICH.

Methods

All patients with a well-defined diagnosis of sICH admitted into 24 h in three primary referred centers were included in this prospective observational follow-up study. Patients had extensive monitoring of BG values and those with BG values >8.29 mmol/l (150 mg/dl) received a variable intravenous insulin dose to maintain BG concentrations during the first 72 h after sICH between 3.32 and 8.29 mmol/l (60–150 mg/dl) using pre-specified insulin dosing schedule protocol.

Results

Between January 1, 2002, and December 31, 2003, 295 consecutive patients (mean ± SD age 66 ± 12 years) were prospectively included. A 1.0 mmol/l (18 mg/dl) increase in the BG concentration at admission was associated with a 33% mortality increase (OR: 1.33; 95%CI: 1.22–1.46; P < 0.0001). Adjusting for demographics, risk factors, stroke severity, and surgery there was no change in the increased risk. During the first 12 h after sICH, the insulin treatment protocol was enabling to reduce mortality (OR: 1.36, 95%CI: 1.14–1.61; P = 0.0005, per 1 IU increase) while thereafter this association was greatly attenuated and not more significant.

Conclusions

Hyperglycemia is a common condition after sICH and may worsen prognosis. Very early insulin therapy apparently does not improve prognosis. These results raise concern about routine clinical practice implementation of this intervention without any evidence from randomized trials.
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Literature
1.
go back to reference Robinson LE, van Soeren MH. Insulin resistance and hyperglycemia in critical illness: role of insulin in glycemic control. AACN Clin Issues 2004;15:45–62.PubMedCrossRef Robinson LE, van Soeren MH. Insulin resistance and hyperglycemia in critical illness: role of insulin in glycemic control. AACN Clin Issues 2004;15:45–62.PubMedCrossRef
2.
go back to reference Lam AM, Winn HR, Cullen BF, Sundling N. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg 1991;75:545–51.PubMed Lam AM, Winn HR, Cullen BF, Sundling N. Hyperglycemia and neurological outcome in patients with head injury. J Neurosurg 1991;75:545–51.PubMed
3.
go back to reference Michaud LJ, Rivara FP, Longstreth WT Jr, Grady MS. Elevated initial blood glucose levels and poor outcome following severe brain injuries in children. J Trauma 1991;31:1356–62.PubMedCrossRef Michaud LJ, Rivara FP, Longstreth WT Jr, Grady MS. Elevated initial blood glucose levels and poor outcome following severe brain injuries in children. J Trauma 1991;31:1356–62.PubMedCrossRef
4.
go back to reference 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;44:373–7.PubMedCrossRef 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;44:373–7.PubMedCrossRef
5.
go back to reference Rovlias A, Kotson S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 2000;46:335–43.PubMedCrossRef Rovlias A, Kotson S. The influence of hyperglycemia on neurological outcome in patients with severe head injury. Neurosurgery 2000;46:335–43.PubMedCrossRef
6.
go back to reference Martini SR, Kent TA. Hyperglycemia in acute ischemic stroke: a vascular perspective. J Cereb Blood Flow Metab 2007;27:435–51.PubMedCrossRef Martini SR, Kent TA. Hyperglycemia in acute ischemic stroke: a vascular perspective. J Cereb Blood Flow Metab 2007;27:435–51.PubMedCrossRef
7.
go back to reference Demchuk AM, Morgenstern LB, Krieger DW, Linda CT, Hu W, Wein TH, et al. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke 1999;30:34–9.PubMed Demchuk AM, Morgenstern LB, Krieger DW, Linda CT, Hu W, Wein TH, et al. Serum glucose level and diabetes predict tissue plasminogen activator-related intracerebral hemorrhage in acute ischemic stroke. Stroke 1999;30:34–9.PubMed
8.
go back to reference 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;59:669–74.PubMed 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;59:669–74.PubMed
9.
go back to reference 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;37:199–203.PubMedCrossRef 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;37:199–203.PubMedCrossRef
10.
go back to reference Capes SE, Hunt D, Maimberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001;32:2426–32.PubMedCrossRef Capes SE, Hunt D, Maimberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: a systematic overview. Stroke 2001;32:2426–32.PubMedCrossRef
11.
go back to reference 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;76:349–53.PubMedCrossRef 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;76:349–53.PubMedCrossRef
12.
go back to reference Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology 2003;61:1351–6.PubMed Passero S, Ciacci G, Ulivelli M. The influence of diabetes and hyperglycemia on clinical course after intracerebral hemorrhage. Neurology 2003;61:1351–6.PubMed
13.
go back to reference 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;255:90–4.PubMedCrossRef 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;255:90–4.PubMedCrossRef
14.
go back to reference Langouche L, Vanhorebeek I, Van den BG. Therapy insight: the effect of tight glycemic control in acute illness. Nat Clin Pract Endocrinol Metab 2007;3:270–8.PubMedCrossRef Langouche L, Vanhorebeek I, Van den BG. Therapy insight: the effect of tight glycemic control in acute illness. Nat Clin Pract Endocrinol Metab 2007;3:270–8.PubMedCrossRef
15.
go back to reference 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;38:1655–711.PubMedCrossRef 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;38:1655–711.PubMedCrossRef
16.
go back to reference 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;6:397–406.PubMedCrossRef 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;6:397–406.PubMedCrossRef
17.
go back to reference 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;38:2001–23.PubMedCrossRef 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;38:2001–23.PubMedCrossRef
18.
go back to reference Broderick JP, Adams HP Jr, Barsan W, Feinberg W, Feldmann E, Grotta J, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1999;30:905–15.PubMed Broderick JP, Adams HP Jr, Barsan W, Feinberg W, Feldmann E, Grotta J, et al. Guidelines for the management of spontaneous intracerebral hemorrhage: A statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 1999;30:905–15.PubMed
19.
go back to reference Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2:81–4.PubMedCrossRef Teasdale G, Jennett B. Assessment of coma and impaired consciousness. A practical scale. Lancet 1974;2:81–4.PubMedCrossRef
20.
go back to reference Hemphill JC III, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001;32:891–7.PubMed Hemphill JC III, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001;32:891–7.PubMed
21.
go back to reference Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23 Suppl 1:S4–19. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 2000;23 Suppl 1:S4–19.
22.
go back to reference Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke 2001;32:917–24.PubMed Di Napoli M, Papa F, Bocola V. C-reactive protein in ischemic stroke: an independent prognostic factor. Stroke 2001;32:917–24.PubMed
23.
go back to reference Godoy DA, Pinero G, Di Napoli M. Predicting mortality in spontaneous intracerebral hemorrhage: can modification to original score improve the prediction? Stroke 2006;37:1038–44.PubMedCrossRef Godoy DA, Pinero G, Di Napoli M. Predicting mortality in spontaneous intracerebral hemorrhage: can modification to original score improve the prediction? Stroke 2006;37:1038–44.PubMedCrossRef
24.
go back to reference 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;59:67–71.PubMed 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;59:67–71.PubMed
25.
go back to reference Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304–5.PubMed Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304–5.PubMed
26.
go back to reference Fogelholm R, Avikainen S, Murros K. Prognostic value and determinants of first-day mean arterial pressure in spontaneous supratentorial intracerebral hemorrhage. Stroke 1997;28:1396–400.PubMed Fogelholm R, Avikainen S, Murros K. Prognostic value and determinants of first-day mean arterial pressure in spontaneous supratentorial intracerebral hemorrhage. Stroke 1997;28:1396–400.PubMed
27.
go back to reference Franke CL, van Swieten JC, Algra A, van Gijn J. Prognostic factors in patients with intracerebral haematoma. J Neurol Neurosurg Psychiatry 1992;55:653–7.PubMed Franke CL, van Swieten JC, Algra A, van Gijn J. Prognostic factors in patients with intracerebral haematoma. J Neurol Neurosurg Psychiatry 1992;55:653–7.PubMed
28.
go back to reference Lee TH, Ryu SJ, Chen ST. The prognostic value of blood glucose in patients with acute stroke. J Formos Med Assoc 1991;90:465–70.PubMed Lee TH, Ryu SJ, Chen ST. The prognostic value of blood glucose in patients with acute stroke. J Formos Med Assoc 1991;90:465–70.PubMed
29.
30.
go back to reference Tuhrim S, Dambrosia JM, Price TR, Mohr JP, Wolf PA, Hier DB, et al. Intracerebral hemorrhage: external validation and extension of a model for prediction of 30-day survival. Ann Neurol 1991;29:658–63.PubMedCrossRef Tuhrim S, Dambrosia JM, Price TR, Mohr JP, Wolf PA, Hier DB, et al. Intracerebral hemorrhage: external validation and extension of a model for prediction of 30-day survival. Ann Neurol 1991;29:658–63.PubMedCrossRef
31.
go back to reference Woo J, Lam CW, Kay R, Wong AH, Teoh R, Nicholls MG. The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke. Arch Neurol 1990;47:1174–7.PubMed Woo J, Lam CW, Kay R, Wong AH, Teoh R, Nicholls MG. The influence of hyperglycemia and diabetes mellitus on immediate and 3-month morbidity and mortality after acute stroke. Arch Neurol 1990;47:1174–7.PubMed
32.
go back to reference Moulin T, Tatu L, Crepin-Leblond T, Chavot D, Berges S, Rumbach T. The Besancon Stroke Registry: an acute stroke registry of 2,500 consecutive patients. Eur Neurol 1997;38:10–20.PubMedCrossRef Moulin T, Tatu L, Crepin-Leblond T, Chavot D, Berges S, Rumbach T. The Besancon Stroke Registry: an acute stroke registry of 2,500 consecutive patients. Eur Neurol 1997;38:10–20.PubMedCrossRef
33.
go back to reference Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004;63:1059–64.PubMed Flibotte JJ, Hagan N, O’Donnell J, Greenberg SM, Rosand J. Warfarin, hematoma expansion, and outcome of intracerebral hemorrhage. Neurology 2004;63:1059–64.PubMed
34.
go back to reference Gray CS, Scott JF, French JM, Alberti KG, O’Connell JE. Prevalence and prediction of unrecognised diabetes mellitus and impaired glucose tolerance following acute stroke. Age Ageing 2004;33:71–7.PubMedCrossRef Gray CS, Scott JF, French JM, Alberti KG, O’Connell JE. Prevalence and prediction of unrecognised diabetes mellitus and impaired glucose tolerance following acute stroke. Age Ageing 2004;33:71–7.PubMedCrossRef
35.
go back to reference Mechanick JI. Metabolic mechanisms of stress hyperglycemia. JPEN J Parenter Enteral Nutr 2006;30:157–63.PubMedCrossRef Mechanick JI. Metabolic mechanisms of stress hyperglycemia. JPEN J Parenter Enteral Nutr 2006;30:157–63.PubMedCrossRef
36.
go back to reference Lu A, Tang Y, Ran R, Ardizzone TL, Wagner KR, Sharp FR. Brain genomics of intracerebral hemorrhage. J Cereb Blood Flow Metab 2006;26:230–52.PubMedCrossRef Lu A, Tang Y, Ran R, Ardizzone TL, Wagner KR, Sharp FR. Brain genomics of intracerebral hemorrhage. J Cereb Blood Flow Metab 2006;26:230–52.PubMedCrossRef
37.
go back to reference Song EC, Chu K, Jeong SW, Jung KH, Kim SH, Kim M, et al. Hyperglycemia exacerbates brain edema and perihematomal cell death after intracerebral hemorrhage. Stroke 2003;34:2215–20.PubMedCrossRef Song EC, Chu K, Jeong SW, Jung KH, Kim SH, Kim M, et al. Hyperglycemia exacerbates brain edema and perihematomal cell death after intracerebral hemorrhage. Stroke 2003;34:2215–20.PubMedCrossRef
38.
go back to reference Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Proinflammatory effects of glucose and anti-inflammatory effect of insulin: relevance to cardiovascular disease. Am J Cardiol 2007;99:15B–26B.PubMedCrossRef Dandona P, Chaudhuri A, Ghanim H, Mohanty P. Proinflammatory effects of glucose and anti-inflammatory effect of insulin: relevance to cardiovascular disease. Am J Cardiol 2007;99:15B–26B.PubMedCrossRef
39.
go back to reference Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab 2007;27:894–908.PubMedCrossRef Wang J, Dore S. Inflammation after intracerebral hemorrhage. J Cereb Blood Flow Metab 2007;27:894–908.PubMedCrossRef
40.
go back to reference Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006;5:53–63.PubMedCrossRef Xi G, Keep RF, Hoff JT. Mechanisms of brain injury after intracerebral haemorrhage. Lancet Neurol 2006;5:53–63.PubMedCrossRef
41.
go back to reference Aljada A, Ghanim H, Mohanty P, Kapur N, Dandona P. Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mononuclear cells (MNC) and reduces plasma tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations. J Clin Endocrinol Metab 2002;87:1419–22.PubMedCrossRef Aljada A, Ghanim H, Mohanty P, Kapur N, Dandona P. Insulin inhibits the pro-inflammatory transcription factor early growth response gene-1 (Egr)-1 expression in mononuclear cells (MNC) and reduces plasma tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) concentrations. J Clin Endocrinol Metab 2002;87:1419–22.PubMedCrossRef
42.
go back to reference Chaudhuri A, Janicke D, Wilson MF, Tripathy D, Garg R, Bandyopadhyay A, et al. Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction. Circulation 2004;109:849–54.PubMedCrossRef Chaudhuri A, Janicke D, Wilson MF, Tripathy D, Garg R, Bandyopadhyay A, et al. Anti-inflammatory and profibrinolytic effect of insulin in acute ST-segment-elevation myocardial infarction. Circulation 2004;109:849–54.PubMedCrossRef
43.
go back to reference Hua Y, Xi G, Keep RF, Wu J, Jiang Y, Hoff JT. Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage. J Cereb Blood Flow Metab 2002;22:55–61.PubMedCrossRef Hua Y, Xi G, Keep RF, Wu J, Jiang Y, Hoff JT. Plasminogen activator inhibitor-1 induction after experimental intracerebral hemorrhage. J Cereb Blood Flow Metab 2002;22:55–61.PubMedCrossRef
44.
go back to reference Kagansky N, Levy S, Knobler H. The role of hyperglycemia in acute stroke. Arch Neurol 2001;58:1209–12.PubMedCrossRef Kagansky N, Levy S, Knobler H. The role of hyperglycemia in acute stroke. Arch Neurol 2001;58:1209–12.PubMedCrossRef
45.
go back to reference Pulsinelli WA, Waldman S, Rawlinson D, Plum F. Moderate hyperglycemia augments ischemic btrain damage: a neuropathologic study in the rat. Neurology 1982;32:1239–46.PubMed Pulsinelli WA, Waldman S, Rawlinson D, Plum F. Moderate hyperglycemia augments ischemic btrain damage: a neuropathologic study in the rat. Neurology 1982;32:1239–46.PubMed
46.
go back to reference Dietrich WD, Alonso O, Busto R. Moderate hyperglycemia worsens acute blood-brain barrier injury after forebrain ischemia in rats. Stroke 1993;24:111–6.PubMed Dietrich WD, Alonso O, Busto R. Moderate hyperglycemia worsens acute blood-brain barrier injury after forebrain ischemia in rats. Stroke 1993;24:111–6.PubMed
47.
go back to reference de Court, Kleinholz M, Holm P, DeVoe G, Schmitt G, Wagner KR, et al. Hemorrhagic infarct conversion in experimental stroke. Ann Emerg Med 1992;21:120–6.CrossRef de Court, Kleinholz M, Holm P, DeVoe G, Schmitt G, Wagner KR, et al. Hemorrhagic infarct conversion in experimental stroke. Ann Emerg Med 1992;21:120–6.CrossRef
Metadata
Title
Hyperglycemia and Short-term Outcome in Patients with Spontaneous Intracerebral Hemorrhage
Authors
Daniel A. Godoy
Gustavo R. Piñero
Silvana Svampa
Francesca Papa
Mario Di Napoli
Publication date
01-10-2008
Publisher
Humana Press Inc
Published in
Neurocritical Care / Issue 2/2008
Print ISSN: 1541-6933
Electronic ISSN: 1556-0961
DOI
https://doi.org/10.1007/s12028-008-9063-1

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