Glycemic Targets and Approaches to Management of the Patient with Critical Illness

Hyperglycemia during critical illness is associated with adverse outcome. The proof-of-concept Leuven studies assessed causality, and revealed that targeting strict normoglycemia (80–110 mg/dL) with insulin improved outcome compared with tolerating hyperglycemia to the renal threshold (215 mg/dL). A large multicenter trial (NICE-SUGAR [Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation]) found an intermediate blood glucose target (140–180 mg/dL) safer than targeting normoglycemia. Differences in design and in execution of glycemic control at the bedside may have contributed to these results. In NICE-SUGAR (Normoglycaemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation), the blood-glucose target range in the control group was lower, there were problems to reach and maintain normoglycemia in the intervention group, and inaccurate handheld blood glucose meters and variable blood sampling sites were allowed. Inaccurate tools led to insulin-dosing errors with consequently (undetected) hypoglycemia and unacceptable blood glucose variability. Also, the studies were done superimposed upon different nutritional strategies. Thus, such differences do not allow simple, evidence-based recommendations for daily practice, but an intermediate blood glucose target may be preferable while awaiting better tools to facilitate safely reaching normoglycemia.

[1]  W. L. Howell,et al.  Achieving tight glycemic control in the operating room: lessons learned from 12 years in the trenches of a paradigm shift in anesthetic care. , 2006, Seminars in thoracic and cardiovascular surgery.

[2]  Stephen Daniel,et al.  Intensive insulin therapy and mortality in critically ill patients , 2008, Critical care.

[3]  Michael Bailey,et al.  Hypoglycemia and outcome in critically ill patients. , 2010, Mayo Clinic proceedings.

[4]  S. V. Cromphaut,et al.  Hyperglycaemia as part of the stress response: the underlying mechanisms. , 2009 .

[5]  M Schetz,et al.  Intensive insulin therapy in critically ill patients. , 2001, The New England journal of medicine.

[6]  Could Susceptibility to Low Hematocrit Interference Have Compromised the Results of the NICE-SUGAR Trial ? , 2010 .

[7]  David B Sacks,et al.  Tight glucose control in the intensive care unit: are glucose meters up to the task? , 2009, Clinical chemistry.

[8]  G. Wells,et al.  A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. , 1999, The New England journal of medicine.

[9]  R. A. Forse,et al.  Hypocaloric total parenteral nutrition: Effectiveness in prevention of hyperglycemia and infectious complications—A randomized clinical trial , 2000, Critical care medicine.

[10]  G. Van den Berghe,et al.  Glucose dysregulation and neurological injury biomarkers in critically ill children. , 2010, The Journal of clinical endocrinology and metabolism.

[11]  Steven E Wolf,et al.  Glycemic Control in the Burn Intensive Care Unit: Focus on the Role of Anemia in Glucose Measurement , 2009, Journal of diabetes science and technology.

[12]  H. Krumholz,et al.  Glucose normalization and outcomes in patients with acute myocardial infarction. , 2009, Archives of internal medicine.

[13]  R. Bellomo,et al.  Management of blood glucose in the critically ill in Australia and New Zealand: a practice survey and inception cohort study , 2006, Intensive Care Medicine.

[14]  H. Krumholz,et al.  Admission Glucose and Mortality in Elderly Patients Hospitalized With Acute Myocardial Infarction: Implications for Patients With and Without Recognized Diabetes , 2005, Circulation.

[15]  Soumitra R. Eachempati,et al.  Randomized, double-blind, placebo-controlled trial of effects of enteral iron supplementation on anemia and risk of infection during surgical critical illness. , 2009, Surgical infections.

[16]  C. Wade,et al.  Hematocrit causes the most significant error in point of care glucometers. , 2009, Critical care medicine.

[17]  Y. Arabi,et al.  Hypoglycemia with intensive insulin therapy in critically ill patients: Predisposing factors and association with mortality* , 2009, Critical care medicine.

[18]  R. Bellomo,et al.  Early blood glucose control and mortality in critically ill patients in Australia* , 2009, Critical care medicine.

[19]  George G Klee,et al.  Glucose meter performance criteria for tight glycemic control estimated by simulation modeling. , 2010, Clinical chemistry.

[20]  Brian Hutton,et al.  Reliability of point-of-care testing for glucose measurement in critically ill adults* , 2005, Critical care medicine.

[21]  Deborah J. Cook,et al.  Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data , 2009, Canadian Medical Association Journal.

[22]  G. Van den Berghe,et al.  Intensive insulin therapy in the intensive care unit , 2009, Canadian Medical Association Journal.

[23]  J. Daly Early versus late Parenteral Nutrition in Critically Ill Adults , 2012 .

[24]  Eileen White,et al.  Autophagy and Metabolism , 2010, Science.

[25]  I. Hirsch,et al.  Should minimal blood glucose variability become the gold standard of glycemic control? , 2005, Journal of diabetes and its complications.

[26]  G. Fick,et al.  Estimates of Total Analytical Error in Consumer and Hospital Glucose Meters Contributed by Hematocrit, Maltose, and Ascorbate , 2010, Journal of diabetes science and technology.

[27]  Greet Van den Berghe,et al.  Intensive insulin therapy for patients in paediatric intensive care: a prospective, randomised controlled study , 2009, The Lancet.

[28]  Miet Schetz,et al.  Intensive Insulin Therapy in Mixed Medical/Surgical Intensive Care Units , 2006, Diabetes.

[29]  G. Van den Berghe,et al.  Effect of intensive insulin therapy on the somatotropic axis of critically ill children. , 2011, The Journal of clinical endocrinology and metabolism.

[30]  S. V. Van Cromphaut Hyperglycaemia as part of the stress response: the underlying mechanisms. , 2009, Best practice & research. Clinical anaesthesiology.

[31]  Liu Xinbing,et al.  Intensive insulin therapy for the critically ill patients with stress hyperglycemia , 2008 .

[32]  E. de Jonge,et al.  Evaluation of short-term consequences of hypoglycemia in an intensive care unit* , 2006, Critical care medicine.

[33]  P. Raskin,et al.  Hyperglycemia and Acute Coronary Syndrome: A Scientific Statement from the American Heart Association Diabetes Committee of the Council on Nutrition, Physical Activity, and Metabolism , 2008, Anesthesiology.

[34]  R. Bellomo,et al.  Glycemic control in the ICU. , 2011, Chest.

[35]  Miet Schetz,et al.  Intensive Insulin Therapy in Critically Ill Patients: NICE-SUGAR or Leuven Blood Glucose Target? , 2009 .

[36]  C. Wade,et al.  Anemia causes hypoglycemia in intensive care unit patients due to error in single-channel glucometers: Methods of reducing patient risk* , 2010, Critical care medicine.

[37]  R. Maser,et al.  Use of arterial blood with bedside glucose reflectance meters in an intensive care unit: Are they accurate? , 1994, Critical care medicine.

[38]  P. Marik,et al.  Original ResearchCritical Care MedicineToward Understanding Tight Glycemic Control in the ICU: A Systematic Review and Metaanalysis , 2010 .

[39]  Scott K Aberegg,et al.  Intensive insulin therapy in the medical ICU. , 2006, The New England journal of medicine.

[40]  Jan Gunst,et al.  Insufficient activation of autophagy allows cellular damage to accumulate in critically ill patients. , 2011, The Journal of clinical endocrinology and metabolism.

[41]  Brian P. Kavanagh,et al.  Glycemic Control in the ICU , 2010 .

[42]  Johan Groeneveld,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 , 2009, Intensive Care Medicine.

[43]  J. Krinsley,et al.  Glycemic variability: A strong independent predictor of mortality in critically ill patients* , 2008, Critical care medicine.

[44]  Á. Avezum,et al.  Association of elevated fasting glucose with increased short-term and 6-month mortality in ST-segment elevation and non-ST-segment elevation acute coronary syndromes: the Global Registry of Acute Coronary Events. , 2009, Archives of internal medicine.

[45]  O. Tanner Intensive versus Conventional Glucose Control in Critically Ill Patients , 2009 .

[46]  Rolf Rossaint,et al.  Intensive insulin therapy and pentastarch resuscitation in severe sepsis. , 2008, The New England journal of medicine.

[47]  Marcus J Schultz,et al.  Predisposing factors for hypoglycemia in the intensive care unit* , 2006, Critical care medicine.

[48]  Guido Kroemer,et al.  Autophagy in the Pathogenesis of Disease , 2008, Cell.