Effects of hyperglycemia and insulin therapy on outcome in a hyperglycemic septic model of critical illness.

BACKGROUND The effects of hyperglycemia and insulin therapy on septic outcome have not been well studied. METHODS Septic hyperglycemia was induced by infusion of TPN (254 kcal/kg x d) immediately following cecal ligation and puncture (CLP) surgery in rats. Animals (N = 109) were monitored for blood glucose and followed for survival for 4 days. Separate cohorts (N = 36) were sacrificed at 22 hours post-CLP and analyzed for cytokines/chemokines, hormones, and organ damage markers. The effects of insulin treatment on 4 day survival were also examined (N = 60). RESULTS Hyperglycemic septic animals had significantly higher blood glucose (p < 0.0001), plasma proinflammatory cytokine levels, serum organ damage markers (p < 0.05) and reduced mean survival time (p < 0.001). Insulin treatment (2 IU/kg/hr) resulted in significantly lower blood glucose (p < 0.01) and improved 4 day survival (p < 0.03). CONCLUSIONS Hyperglycemia is associated with greater morbidity and mortality in sepsis. Insulin therapy significantly improved survival suggesting that management of hyperglycemia with insulin may improve outcome in septic patients.

[1]  R. L. Grubbs,et al.  Cecal ligation and puncture with total parenteral nutrition: a clinically relevant model of the metabolic, hormonal, and inflammatory dysfunction associated with critical illness. , 2004, The Journal of surgical research.

[2]  R. Einspanier,et al.  Insulin attenuates the systemic inflammatory response in endotoxemic rats. , 2004, Endocrinology.

[3]  J. Gjedsted,et al.  The roles of insulin and hyperglycemia in sepsis pathogenesis , 2004, Journal of leukocyte biology.

[4]  P. Marik,et al.  Stress-hyperglycemia, insulin and immunomodulation in sepsis , 2004, Intensive Care Medicine.

[5]  Michael F. Wilson,et al.  Anti-Inflammatory and Profibrinolytic Effect of Insulin in Acute ST-Segment–Elevation Myocardial Infarction , 2004, Circulation.

[6]  James Stephen Krinsley,et al.  Association between hyperglycemia and increased hospital mortality in a heterogeneous population of critically ill patients. , 2003, Mayo Clinic proceedings.

[7]  S. Prato,et al.  Hyperglycaemia and cardiovascular risk , 2003, Acta Diabetologica.

[8]  M. Levi,et al.  Infection and inflammation and the coagulation system. , 2003, Cardiovascular research.

[9]  K. Butcher,et al.  Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome. , 2003, Stroke.

[10]  Ning Li,et al.  Influence of acute hyperglycemia in human sepsis on inflammatory cytokine and counterregulatory hormone concentrations. , 2003, World journal of gastroenterology.

[11]  Peter Radermacher,et al.  Metabolic alterations in sepsis and vasoactive drug–related metabolic effects , 2003, Current opinion in critical care.

[12]  F. McAlister,et al.  Diabetes and coronary artery bypass surgery: an examination of perioperative glycemic control and outcomes. , 2003, Diabetes care.

[13]  M. Levy,et al.  2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis Definitions Conference , 2003, Intensive care medicine.

[14]  G. Van den Berghe,et al.  Intensive insulin therapy exerts antiinflammatory effects in critically ill patients and counteracts the adverse effect of low mannose-binding lectin levels. , 2003, The Journal of clinical endocrinology and metabolism.

[15]  M. Cakir,et al.  Hyperglycemia: an independent marker of in-hospital mortality in patients with undiagnosed diabetes. , 2003, The Journal of clinical endocrinology and metabolism.

[16]  Miet Schetz,et al.  Outcome benefit of intensive insulin therapy in the critically ill: Insulin dose versus glycemic control* , 2003, Critical care medicine.

[17]  R. Marfella,et al.  Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress , 2002, Circulation.

[18]  A. Raymond,et al.  Risk factors for stroke and predictors of one-month mortality. , 2002, Singapore medical journal.

[19]  S. Bannai,et al.  Restored vulnerability of cultured endothelial cells to high glucose by iron replenishment. , 2001, Biochemical and biophysical research communications.

[20]  B A Mizock,et al.  Alterations in fuel metabolism in critical illness: hyperglycaemia. , 2001, Best practice & research. Clinical endocrinology & metabolism.

[21]  Jeffrey B. Boord,et al.  Practical management of diabetes in critically ill patients. , 2001, American journal of respiratory and critical care medicine.

[22]  G. V. Berghe,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[23]  G. Clermont,et al.  Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care , 2001, Critical care medicine.

[24]  J. Cornel,et al.  Impaired glucose metabolism predicts mortality after a myocardial infarction. , 2001, International journal of cardiology.

[25]  Derek C. Angus,et al.  Epidemiology of sepsis: An update , 2001, Critical care medicine.

[26]  Y. Mao,et al.  Sustained endotoxemia leads to marked down-regulation of early steps in the insulin-signaling cascade , 2001, Critical care medicine.

[27]  R. Little,et al.  Insulin resistance and substrate utilization in human endotoxemia. , 2000, The Journal of clinical endocrinology and metabolism.

[28]  A. Aljada,et al.  Insulin inhibits the expression of intercellular adhesion molecule-1 by human aortic endothelial cells through stimulation of nitric oxide. , 2000, The Journal of clinical endocrinology and metabolism.

[29]  C. Lang,et al.  Alterations in tissue glucose uptake during the hyperglycemic and hypoglycemic phases of sepsis. , 2000, Shock.

[30]  B. Bistrian,et al.  Metabolic effects of insulin and insulin-like growth factor-I in endotoxemic rats during total parenteral nutrition feeding. , 2000, Metabolism: clinical and experimental.

[31]  R. Balk.  Pathogenesis and management of multiple organ dysfunction or failure in severe sepsis and septic shock. , 2000, Critical care clinics.

[32]  R. Balk.  SEVERE SEPSIS AND SEPTIC SHOCK Definitions, Epidemiology, and Clinical Manifestations , 2000 .

[33]  V. Lagente,et al.  Endotoxin-induced acute lung injury in rats. Role of insulin. , 1999, Pulmonary pharmacology & therapeutics.

[34]  J. Patiño,et al.  Hypocaloric Support in the Critically Ill , 1999, World Journal of Surgery.

[35]  C. Pison,et al.  Glucose modulates hemodynamic, metabolic, and inflammatory responses to lipopolysaccharide in rabbits. , 1997, Journal of applied physiology.

[36]  F. Numano,et al.  Glucose-Dependent Interleukin 6 and Tumor Necrosis Factor Production by Human Peripheral Blood Monocytes In Vitro , 1996, Diabetes.

[37]  A. Ullrich,et al.  Tumor necrosis factor-alpha- and hyperglycemia-induced insulin resistance. Evidence for different mechanisms and different effects on insulin signaling. , 1996, The Journal of clinical investigation.

[38]  B. Angelin,et al.  Growth hormone potentiates the in vivo biological activities of endotoxin in the rat , 1996, European journal of clinical investigation.

[39]  C. Lang,et al.  Insulin-mediated glucose uptake by individual tissues during sepsis. , 1990, Metabolism: clinical and experimental.

[40]  M. Fulop.  Hyperkalemia in diabetic ketoacidosis. , 1990, The American journal of the medical sciences.

[41]  R. Douglas,et al.  Metabolic response to sepsis and trauma , 1989, The British journal of surgery.

[42]  R. Wolfe,et al.  Effect of severe burn injury on substrate cycling by glucose and fatty acids. , 1987, The New England journal of medicine.

[43]  A. Sakurai,et al.  Relationship of hypoglycemia to tumor necrosis factor production and antitumor activity: role of glucose, insulin, and macrophages. , 1985, Journal of the National Cancer Institute.

[44]  R. Sherwin,et al.  Synergistic interactions among antiinsulin hormones in the pathogenesis of stress hyperglycemia in humans. , 1981, Journal of Clinical Endocrinology and Metabolism.

[45]  R. Wolfe,et al.  Glucose metabolism in man: responses to intravenous glucose infusion. , 1979, Metabolism: clinical and experimental.

[46]  A. Malhotra,et al.  Stress-induced hyperglycemia. , 2001, Critical care clinics.

[47]  W. Bode,et al.  Inflammation, sepsis, and coagulation. , 1999, Haematologica.