Don’t Sugar Coat It: Glycemic Control in the Intensive Care Unit

Abstract

Stress hyperglycemia is the transient increase in blood glucose as a result of complex hormonal changes that occur during critical illness. It has been described in the critically ill for nearly 200 years; patient harm, including increases in morbidity, mortality, and lengths of stay, has been associated with hyperglycemia, hypoglycemia, and glucose variability. However, there remains a contentious debate regarding the optimal glucose ranges for this population, most notably within the past 15 years. Recent landmark clinical trials have dramatically changed the treatment of stress hyperglycemia in the intensive care unit (ICU). Earlier studies suggested that tight glucose control improved both morbidity and mortality for ICU patients, but later studies have suggested potential harm related to the development of hypoglycemia. Multiple trials have tried to elucidate potential glucose target ranges for special patient populations, including those with diabetes, trauma, sepsis, cardiac surgery, and brain injuries, but there remains conflicting evidence for most of these subpopulations. Currently, most international organizations recommend targeting moderate blood glucose concentration to levels <180 mg/dL for all patients in the intensive care unit. In this review, the history of stress hyperglycemia and its treatment will be discussed including optimal glucose target ranges, devices for monitoring blood glucose, and current professional organizations’ recommendations regarding glucose control in the ICU.

Issues for the management of people with diabetes and COVID-19 in ICU

“…It is well recognized that an optimal glycemic control during the stay in ICU can improve the prognosis [7]. However, the optimal glycemic control, particularly in ICU involves today several aspects.…”

Central metabolic interactions of immune cells and microbes: prospects for defeating infections

“…While sepsis, as many other severe illnesses, is associated with increased blood glucose levels (so-called "stress hyperglycaemia"), sepsis patients might be hyper-susceptible to insulin interventions aimed at reducing glucose levels, which can cause life-threatening hypoglycaemia [114]. While sepsis, as many other severe illnesses, is associated with increased blood glucose levels (so-called "stress hyperglycaemia"), sepsis patients might be hyper-susceptible to insulin interventions aimed at reducing glucose levels, which can cause life-threatening hypoglycaemia [114].…”

“…Presumably this also reflects increased metabolic rates of leucocytes to promote inflammatory response, but this has not been investigated so far. During sepsis, blood glucose levels initially increase but can become hypoglycaemic in patients where glucose control is implemented, which is associated with poor clinical outcomes [114]. For instance, IFN-c was able to restore the immunotolerant phenotype of human monocytes isolated from sepsis patients, which includes increased glycolytic flux as determined by lactate secretion [43].…”

“…Does infection disrupt host glucose homeostasis in vivo? While sepsis, as many other severe illnesses, is associated with increased blood glucose levels (so-called "stress hyperglycaemia"), sepsis patients might be hyper-susceptible to insulin interventions aimed at reducing glucose levels, which can cause life-threatening hypoglycaemia [114]. Interestingly, we have seen an equivalent mechanism in the mouse candidaemia model, whereby C. albicans-infected mice developed severe hypoglycaemia following administration of the glucose-lowering drug metformin, whereas in the absence of infection mice could maintain blood glucose levels when injected with the same dose of metformin [44].…”

“…Blood glucose levels are tightly controlled to maintain tissue homeostasis, but likely also contribute to maintaining immune function. During sepsis, blood glucose levels initially increase but can become hypoglycaemic in patients where glucose control is implemented, which is associated with poor clinical outcomes [114]. In murine infection models with diverse pathogens (bacteria, fungi and viruses), glucose has been shown to have either positive or negative effects on host outcomes (Fig 3).…”