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The American Diabetes Association (ADA) defines inpatient hyperglycemia as a fasting blood glucose (BG) >126 mg/dL or a random BG >200 mg/dL that reverts to normal after discharge.1 The prevalence of hyperglycemia in the acutely ill patient in the intensive care unit (ICU) has been shown to be as high as 83%.2 Hyperglycemia in critical illness may occur due to stress-related surges in counterregulatory hormones, preexisting diabetes, impaired glucose tolerance, and insulin resistance. Whether it is a condition necessitating intervention or a marker of disease severity, hyperglycemia has been shown to be an independent risk factor for increased mortality in the ICU.3 Despite this association, tight glycemic control (TGC) has not been shown to consistently improve patient outcomes and, surprisingly, may cause more harm than good in some subgroups. This chapter examines the historical background, essential pathogenesis, associations, key clinical studies, current protocols, and recommendations regarding hyperglycemia in the critically ill.


Hyperglycemia was first detected as glucosuria in etheranesthetized patients 150 years ago. In 1877, Bernard described hyperglycemia in a canine model of hemorrhagic shock.4 For many years, hyperglycemia in the critically ill was considered an adaptation to stress and was not treated. In fact, some early ICU practitioners recognized insulin resistance and believed that elevated glucose levels (160–200 mg/dL) would promote cellular glucose uptake. In 2001, Van den Berghe demonstrated a statistically significant mortality benefit with TGC in surgical ICU patients.4 Subsequently, many professional societies, including the Surviving Sepsis Campaign (SSC), endorsed TGC in 2004.5 The Leuven (Van den Berghe et al.) medical trial in 2006,6 VISEP (Efficacy of Volume Substitution and Insulin Therapy in Severe Sepsis, Brunkhorst et al.) trial in 2008,7 and NICE-SUGAR (Normoglycemia in Intensive Care Evaluation—Survival Using Glucose Algorithm Regulation, Finfer et al.)8 and Glucontrol (Preiser et al.)9 trials published in 2009 have contributed most to the continuously evolving issue of glucose management in the critically ill patient.


Risk factors for the development of hyperglycemia include preexisting diabetes mellitus, advanced age, infusion of catecholamine pressors, glucocorticoids, obesity, excessive dextrose resuscitation, sepsis, hypothermia, hypoxia, uremia, and cirrhosis.10 These proven risk factors highlight the multifactorial pathogenetic mechanisms underlying ICU hyperglycemia.

In the critically ill patient, hyperglycemia can be explained by increased glucose production (glycogenolysis and gluconeogenesis) and decreased peripheral uptake (insulin resistance; Figure 41-1).


Effect of critical illness on glucose metabolism. Critical illness leads to decreased glucose uptake in adipose, skeletal, and peripheral tissue despite normal or high insulin levels, so-called insulin resistance. Counterregulatory hormones stimulate lipolysis, proteolysis, and glycolysis. The endproducts glycerol, alanine, and lactate are then used in the liver for gluconeogenesis. The simultaneous hormone-induced glycogenolysis further contributes to the ensuing hyperglycemic state.

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