Blood Glucose Control in the Intensive Care Unit: Benefits and Risks

Abnormal blood glucose levels are common during critical illness and are associated with outcomes that correspond to a J‐shaped curve, the lowest risk associated with normoglycemia. Three proof‐of‐concept randomized‐controlled‐trials performed in the surgical, medical, and pediatric intensive care units of the Leuven University Hospital in Belgium demonstrated that maintaining strict age‐adjusted normal fasting levels of glycemia (80–110 mg/dl in adults, 70–100 mg/dl in children, 50–80 mg/dl in infants) with intensive insulin therapy reduced morbidity and mortality as compared with tolerating stress hyperglycemia as a potentially beneficial response. Recently, concern has risen about the safety of this intervention, as a multicenter adult study reported an, as yet unexplained, increased mortality with targeting normoglycemia as compared with an intermediate blood glucose level of around 140 mg/dl. This apparent contradiction may be explained by several methodological differences among studies, comprising, among others, different glucose target ranges in the control groups, different feeding policies, and variable accuracy of tools used for glucose measurement and insulin infusion. Hence, efficacy and safety of intensive insulin therapy may be affected by patient‐related and ICU setting‐related variables. Therefore, no single optimal blood glucose target range for ICU patients can be advocated. It appears safe not to embark on targeting “age‐normal” levels in intensive care units (ICUs) that are not equipped to accurately and frequently measure blood glucose, and have not acquired extensive experience with intravenous insulin administration using a customized guideline. A simple fallback position could be to control blood glucose levels as close to normal as possible without evoking unacceptable blood glucose fluctuations, hypoglycemia, and hypokalemia.

[1]  G. Van den Berghe,et al.  Hyperglycemic kidney damage in an animal model of prolonged critical illness. , 2009, Kidney international.

[2]  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.

[3]  Xiangtong Zhang,et al.  Intensive insulin therapy on infection rate, days in NICU, in-hospital mortality and neurological outcome in severe traumatic brain injury patients: a randomized controlled trial. , 2009, International journal of nursing studies.

[4]  H. Krumholz,et al.  Relationship between spontaneous and iatrogenic hypoglycemia and mortality in patients hospitalized with acute myocardial infarction. , 2009, JAMA.

[5]  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.

[6]  G. Van den Berghe,et al.  Tissue-specific glucose toxicity induces mitochondrial damage in a burn injury model of critical illness , 2009, Critical care medicine.

[7]  Stephane Heritier,et al.  Intensive versus conventional glucose control in critically ill patients. , 2009, The New England journal of medicine.

[8]  Roberto Delfini,et al.  Safety and Efficacy of Intensive Insulin Therapy in Critical Neurosurgical Patients , 2009, Anesthesiology.

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

[10]  M. Ihnat,et al.  Clinical review 2: The "metabolic memory": is more than just tight glucose control necessary to prevent diabetic complications? , 2009, The Journal of clinical endocrinology and metabolism.

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

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

[13]  L. Foubert,et al.  Tight perioperative glucose control is associated with a reduction in renal impairment and renal failure in non-diabetic cardiac surgical patients , 2008, Critical care.

[14]  Ziad A Memish,et al.  Intensive versus conventional insulin therapy: A randomized controlled trial in medical and surgical critically ill patients* , 2008, Critical care medicine.

[15]  R. Gerkin,et al.  Impact of a patient care pathway protocol on surgical site infection rates in cardiothoracic surgery patients. , 2008, American journal of surgery.

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

[17]  Intensive insulin therapy is associated with reduced infectious complications in burn patients. , 2008, Surgery.

[18]  J. Donado,et al.  Strict glycaemic control in patients hospitalised in a mixed medical and surgical intensive care unit: a randomised clinical trial , 2008, Critical care.

[19]  G. Van den Berghe,et al.  Tight blood glucose control is renoprotective in critically ill patients. , 2008, Journal of the American Society of Nephrology : JASN.

[20]  A. Slater,et al.  Glucose control, organ failure, and mortality in pediatric intensive care* , 2008, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[21]  H. Krumholz,et al.  Glucometrics in Patients Hospitalized With Acute Myocardial Infarction: Defining the Optimal Outcomes-Based Measure of Risk , 2008, Circulation.

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

[23]  K. Kouzekanani,et al.  Impact of Postoperative Hyperglycemia following Surgical Repair of Congenital Cardiac Defects , 2008, Pediatric Cardiology.

[24]  N. Tofil,et al.  Is hyperglycemia really harmful? A critical appraisal of “Persistent hyperglycemia in critically ill children” by Faustino and Apkon (J Pediatr 2005; 146:30–34) , 2007, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[25]  D. Dent,et al.  Intensive insulin protocol improves glucose control and is associated with a reduction in intensive care unit mortality. , 2007, Journal of the American College of Surgeons.

[26]  G. Van den Berghe,et al.  Impact of intensive insulin therapy on neuromuscular complications and ventilator dependency in the medical intensive care unit. , 2007, American journal of respiratory and critical care medicine.

[27]  J. Ligtenberg,et al.  Practical aspects of implementing tight glucose control in the ICU. , 2007, Current opinion in clinical nutrition and metabolic care.

[28]  I. Vanhorebeek,et al.  Therapy Insight: the effect of tight glycemic control in acute illness , 2007, Nature Clinical Practice Endocrinology &Metabolism.

[29]  Amy Callahan,et al.  Accuracy of bedside capillary blood glucose measurements in critically ill patients , 2006, Intensive Care Medicine.

[30]  Anthony N Thomas,et al.  Evaluation of short-term consequences of hypoglycemia in an intensive care unit. , 2007, Critical care medicine.

[31]  Yingxing Wu,et al.  Eliminating the diabetic disadvantage: the Portland Diabetic Project. , 2006, Seminars in thoracic and cardiovascular surgery.

[32]  J. Krinsley Glycemic control, diabetic status, and mortality in a heterogeneous population of critically ill patients before and during the era of intensive glycemic management: six and one-half years experience at a university-affiliated community hospital. , 2006, Seminars in thoracic and cardiovascular surgery.

[33]  Miet Schetz,et al.  Strict blood glucose control with insulin during intensive care after cardiac surgery: impact on 4-years survival, dependency on medical care, and quality-of-life. , 2006, European heart journal.

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

[35]  Rinaldo Bellomo,et al.  Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients , 2006, Anesthesiology.

[36]  P. Finn,et al.  Proteolytic and lipolytic responses to starvation. , 2006, Nutrition.

[37]  Bruce Buckingham,et al.  Association of Hypoglycemia, Hyperglycemia, and Glucose Variability With Morbidity and Death in the Pediatric Intensive Care Unit , 2006, Pediatrics.

[38]  G. Van den Berghe,et al.  Intensive insulin therapy in the medical ICU. , 2006, The New England journal of medicine.

[39]  G. Van den Berghe,et al.  Survival benefits of intensive insulin therapy in critical illness: impact of maintaining normoglycemia versus glycemia-independent actions of insulin. , 2006, Diabetes.

[40]  G. Van den Berghe,et al.  Expression of glucose transporters in critical illness , 2006, Critical Care.

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

[42]  R. Tasker,et al.  Glucose level and risk of mortality in pediatric septic shock* , 2005, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[43]  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.

[44]  C. Wolf‐peeters,et al.  Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients , 2005, The Lancet.

[45]  M. Apkon,et al.  Persistent hyperglycemia in critically ill children. , 2005, The Journal of pediatrics.

[46]  James Stephen Krinsley,et al.  Effect of an intensive glucose management protocol on the mortality of critically ill adult patients. , 2004, Mayo Clinic proceedings.

[47]  V. Nadkarni,et al.  Association of timing, duration, and intensity of hyperglycemia with intensive care unit mortality in critically ill children , 2004, Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.

[48]  G. Van den Berghe How does blood glucose control with insulin save lives in intensive care? , 2004, The Journal of clinical investigation.

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

[50]  B. Bistrian,et al.  Intensive insulin therapy in critically ill patients. , 2002, The New England journal of medicine.

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

[52]  G. Van den Berghe,et al.  Five-day pulsatile gonadotropin-releasing hormone administration unveils combined hypothalamic-pituitary-gonadal defects underlying profound hypoandrogenism in men with prolonged critical illness. , 2001, The Journal of clinical endocrinology and metabolism.

[53]  G. Van den Berghe,et al.  Reactivation of pituitary hormone release and metabolic improvement by infusion of growth hormone-releasing peptide and thyrotropin-releasing hormone in patients with protracted critical illness. , 1999, The Journal of clinical endocrinology and metabolism.