Van den Berghe et al. (2001) specifically investigated intensive glycemic control, defined as blood glucose levels ranging from 80 to 110 mg/dL, in patients in a surgical intensive care unit (SICU) setting that were critically ill. In this study, for every 20 mg over 100 mg/dL, mortality increased 30%. The intensive glycemic control group had marked reductions in mortality (4.6–8.0%), multiorgan failure (34%), systemic infection/sepsis (40%), acute renal failure (41%), and required blood transfusions (50%); the authors concluded that these findings supported the implementation of tight glycemic control (Van den Berghe et al., 2001). Severe hypoglycemia (blood glucose levels less than 40 mg/dL) did occur more frequently in the intensive glycemic control group (5%), as opposed to the control group (0.78%); however, increased mortality was not clearly indicated as a direct result of the severe hypoglycemic episodes for patients in the SICU.
In contrast, when Van den Berghe et al. (2006) replicated this study in a medical ICU (MICU) setting, the findings were vastly different, and more importantly, severe hypoglycemia was found to be a predictor of increased mortality. Comparable evidence was noted in 523 MICU patients with admission blood glucose levels of 110 mg/dL (Arabi, Tamim, & Rishu, 2009). According to Arabi et al. (2009), there was a significant increase of hypoglycemia in the intensive insulin therapy group and increased mortality was strongly associated with severe hypoglycemia. Recent evidence from the NICE-SUGAR study, a large international study of 6104 critically ill patients admitted to both SICU and MICU. With a length of stay greater than 3 days, revealed contrasting evidence regarding detectable differences by ICU settings. When comparing the intensive control group (81–108 mg/dL) to conventional management (a target of 180 mg/dL or less), increased mortality was noted in the intensive control group, with no observable differences in patients regardless of ICU setting (Finfer et al., 2009). Other studies have shown equitable safety concerns associated with intensive control, such as the Glucontrol Trial, or no overall benefit in this type of regimen (Preiser et al., 2009). The Glucontrol Trial was a randomized, single-blinded study with an intensive control group (80–110 mg/dL) and conventional therapy group (140–180 mg/dL). Again, increased risk of severe hypoglycemia (≤ 40 mg/dL) occurred more frequently in the intensive control group with no apparent benefit; moreover, there were no significant differences in all-cause mortality and length of stay (Preiser et al., 2009). Given the ambiguity of the evidence related to setting specific differences (MICU vs. SICU) and intensive glycemic control, NPs should critically review the evidence relevant to their practice settings and populations and consider the confounding effect of nutritional status, end-of-life stage, and pre-existing chronic disease processes within ICU settings to explain the observed differences in the aforementioned studies (Arabi et al., 2009; Finfer et al., 2009; Mesotten & Van den Berghe, 2009; Van den Berghe et al., 2001, 2006; Zander, Boldt, Engelmann, Mertzluff, Sirtl, & Stuttmann, 2007).