Hypoglycemia in Critically Ill Patients

Dysglycemia is common in critically ill patients. Both hyperglycemia and hypoglycemia are independent risk factors for increased morbidity and mortality. Hypoglycemia severity may even have a ‘dose-response’ relationship with increased mortality(Bagshaw et al., 2009). Acute hypoglycemia induces a systemic, counter-regulatory stress response that leads to an increase in blood norepinephrine, epinephrine, glucagon, growth hormone, and cortisol concentrations. Risk factors that are associated with the occurrence of hypoglycemia in ICU patients include severity of illness, strict glucose control, continuous veno-venous hemodialysis, decrease of nutrition without adjustment for insulin infusion, a prior diagnosis of diabetes mellitus, sepsis, and need for inotropic support (Arabi et al, 2009;Krinsley & Grover, 2007;Vriesendorp et al. ,2006). The association between hyperglycemia and mortality seems population dependent, with the strongest association in patients in the cardiac, cardiothoracic and neurological ICU(Whitcomb et al., 2005). During acute illness, hyperglycemia might exert an even more deleterious effect on ICU patients without diabetes than among patients with diabetes(Capes et al., 2000;Krinsley 2006;Rady et al., 2005). Unlike nondiabetic patients, diabetic patients show no clear association between hyperglycemia during intensive care unit stay and mortality and markedly lower odds ratios of death at all levels of hyperglycemia. These findings suggest that, in critically patients with diabetes mellitus, hyperglycemia may have different biological and/or clinical implications(Egi et al., 2008). Recently, variability of glucose concentrations has been identified as an additional factor that may contribute to the mortality and morbidity of dysglycemia. A retrospective evaluation of over 7000 patients identified glycemic variability, defined as the standard deviation of each patient’s mean glucose level during ICU stay, as a stronger predictor of mortality than hyperglycemia(Egi et al., 2006). High glucose variability during ICU stay was associated with increased mortality in patients without diabetes, even after adjustment for severity of illness and mean glucose concentration(Krinsley 2009). In contrast, there was no independent association of glucose variability with mortality among patients with diabetes. Glucose variability contributes to ICU mortality and in-hospital death by increasing oxidative stress, neuronal damage, mitochondrial damage, and coagulation activation. The relation between glucose concentration and outcome is complex and not linear. The interaction between glucose concentrations and outcome may arise from independent and synergistic domains of glycemic control including central tendency (such as mean and