Perioperative Hyperglycemia Management: An Update.

A substantial body of literature demonstrates a clear association between perioperative hyperglycemia and adverse clinical outcomes.1-3 The risk for post-operative complications and increased mortality relates to both long-term glycemic control and to the severity of hyperglycemia on admission and during the hospital stay.2 The underlying mechanism(s) relating hyperglycemia to poor outcomes is not completely understood. Past and current studies point to physiologic changes that occur in the hyperglycemic state that may contribute to poor outcomes. Elevated blood glucose levels impair neutrophil function, cause an overproduction of reactive oxygen species, free fatty acids and inflammatory mediators. These pathophysiologic changes contribute to direct cellular damage, vascular and immune dysfunction.4 Substantial evidence indicates that correction of hyperglycemia with insulin administration reduces hospital complications and decreases mortality in cardiac5 and general surgery patients.6 However, optimal glucose management during the perioperative period is widely debated. Recent randomized controlled trials targeting conventional targets for glycemic control do not demonstrate the significant risk of hypoglycemia7,8 as seen in prior studies using insulin to maintain tight blood glucose control.9 The pendulum of inpatient care has since moved toward more moderate and individualized glycemic targets. This manuscript reports on the prevalence, diagnosis and pathophysiology of perioperative hyperglycemia and provides a practical outline for the management of surgical patients with diabetes and hyperglycemia. Metabolic Consequences of Surgical Stress and Anesthesia During the fasting state, normal subjects maintain plasma glucose levels between 60-100 mg/dl (3.3-5.5 mmol/l). The stress of surgery and anesthesia alters the finely regulated balance between hepatic glucose production and glucose utilization in peripheral tissues. An increase in the secretion of counterregulatory hormones (catecholamines, cortisol, glucagon, and growth hormone) occurs, causing excessive release of inflammatory cytokines including tumor necrosis factor-α, interleukin-6 and interleukin-1β (Figure 1).10 Cortisol increases hepatic glucose production, stimulates protein catabolism and promotes gluconeogenesis, resulting in elevated blood glucose levels.11 Surging catecholamines increase glucagon secretion and inhibit insulin release by pancreatic β-cells.4 Additionally, the increase in stress hormones leads to enhanced lipolysis and high free fatty acid (FFA) concentrations. Increased FFAs have been shown to inhibit insulin-stimulated glucose uptake12 and limit the intracellular signaling cascade in skeletal muscle responsible for glucose transport activity.13 Evidence also suggests that TNF-α interferes with the synthesis and/or translocation of the glucose transporter GLUT-4 reducing glucose uptake in peripheral tissues.14 These processes result in an altered state of insulin action, leading to a relative state of insulin resistance which is most pronounced on the first postoperative day and may persist for 9-21 days following surgery.15 Open in a separate window Figure 1 The Surgical Stress Response