How Intensive Insulin Therapy May Benefit Cardiac Surgery Patients

Interest in the effects of insulin on the heart came with the recognition that hyperglycemia in the context of myocardial infarction is associated with increased risks of mortality, congestive heart failure, or cardiogenic shock.1–3 More recently, instigated by research findings on stress hyperglycemia in critical illness, this interest has been extended to the influence of insulin on clinical outcome after cardiac surgery. Even in nondiabetic individuals, stress hyperglycemia commonly occurs as a key metabolic response to critical illness, eg, after surgical trauma. It is recognized as a major pathophysiological feature of organ dysfunction in the critically ill. The condition stems from insulin resistance brought about by dysregulation of key homeostatic processes, which implicates immune/inflammatory, endocrine, and metabolic pathways.4 It has been associated with adverse clinical outcomes, including increased mortality, increased duration of mechanical ventilation, increased intensive care unit (ICU) and hospital stay, and increased risk of infection.5–8 Hyperglycemia in critical illness is managed with exogenous insulin as standard treatment; however, there is considerable disagreement among experts in the field as to what target blood glucose level is optimal for the critically ill patient. Conventionally, the aim of insulin therapy has been to maintain blood glucose levels below the renal threshold, typically 220 mg/dL (12.2 mmol/L). In recent years, some have advocated tight glycemic control (TGC) with intensive insulin therapy (IIT) to normalize blood glucose levels to within the euglycemic range, typically 80 to 110 mg/dL (4.4–6.1 mmol/L). Current evidence on the applicability of TGC to critical illness in general is inconclusive. Although early studies showed that IIT reduced mortality and morbidity in the ICU,9–11 more recent systematic studies and meta-analyses have largely failed to support some or all of these findings, with some suggesting that IIT may increase the risk of hypoglycemia.12 These differences in outcomes may be ascribed in part to differences in study design, including insulin administration protocol, target glycemic level, method of blood glucose measurement, and patient feeding. Alternatively, they may indicate that TGC may not be equally beneficial in all manner of critical illnesses, such that the heterogeneity of the study populations has made identification of outcome benefits difficult. Indeed, a meta-analysis of 26 studies has suggested that TGC appears to benefit surgical ICU patients but not those in medical ICU or mixed ICU settings.13 The present review focuses on the benefits that cardiac surgery patients may derive from TGC/IIT.