Chest
Volume 140, Issue 1, July 2011, Pages 212-220
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Recent Advances in Chest Medicine
Glycemic Control in the ICU

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Hyperglycemia is common in critically ill patients, with approximately 90% of patients treated in an ICU developing blood glucose concentrations > 110 mg/dL (6.1 mmol/L). Landmark trials in Leuven, Belgium, suggested that targeting normoglycemia (a blood glucose concentration of 80-110 mg/dL [4.4-6.1 mmol/L]) reduced mortality and morbidity, but other investigators have not been able to replicate these findings. Recently, the international multicenter Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study reported increased mortality with this approach, and recent meta-analyses do not support intensive glucose control for critically ill patients. Although the initial trials in Leuven produced enthusiasm and recommendations for intensive blood glucose control, the results of the NICE-SUGAR study have resulted in the more moderate recommendation to target a blood glucose concentration between 144 mg/dL and 180 mg/dL (8-10 mmol/L). As critical care practitioners pay greater attention to glycemic control, it has become clear that currently used point-of-care measuring systems are not accurate enough to target tight glucose control. Unresolved issues include whether increased blood glucose variability is inherently harmful and whether even moderate hypoglycemia can be tolerated in the quest for tighter blood glucose control. Future research must first address whether intensive glucose control can be delivered safely, and whether computerized decision support systems and newer technologies that allow accurate and continuous or near-continuous measurement of blood glucose can make this possible. Until such time, clinicians would be well advised to abide by the age-old adage to “first, do no harm.”

Section snippets

Intensive Insulin Therapy: The Landmark Trials in Leuven

More recently, recognition that hyperglycemia is independently associated with increased ICU mortality,5, 15, 16, 17, 18, 19, 20, 21 and evidence that better control of blood glucose in acute illness can be beneficial,18 has led to the study of tighter blood glucose control in critical care. The first randomized controlled trial compared intensive insulin therapy (IIT) (target blood glucose concentration between 80 and 110 mg/dL [4.4-6.1 mmol/L]) with conventional insulin therapy (target blood

Confirmatory Studies: IIT in Other Single-Center and Multicenter Trials

The encouraging results from Van den Berghe and colleagues1, 22, 26 led many to accept IIT as a standard of care; others suggested a more cautious approach and had concerns about widespread adoption of the treatment. These concerns included the potential for harm from the increased risk of hypoglycemia, and the possibility of bias because the trials in Leuven were unblinded to the investigators and to the clinicians treating the patients. The general applicability of the results was unclear

The Impact of Hypoglycemia

In the NICE-SUGAR trial, the incidence of severe hypoglycemia (blood glucose concentration ≤ 40 mg/dL [2.2 mmol/L]) was significantly higher with IIT.33 Furthermore, because of the very low incidence of severe hypoglycemia in the control group, the relative risk of severe hypoglycemia was 13.7 in patients assigned to IIT, more than twice that seen in prior randomized controlled trials.1, 22, 32, 34 Although no causal link has yet been demonstrated between hypoglycemia and increased mortality,

The Role of Blood Glucose Variability

Blood glucose concentrations vary markedly in critically ill patients, even when using continuous feeding and insulin infusions.53 Even in the presence of the same mean blood glucose value, blood glucose variability can be quite different (Fig 2).

In a retrospective study of 7,049 critically ill patients treated in four centers in Australia, the SD of blood glucose concentration during ICU stay was used as a marker of blood glucose variability; it was significantly higher in patients who died

The Role of Measurement Error

Even though a more modest target for blood glucose is now accepted, the importance of glucose monitoring and its accuracy has become clearer. Most point-of-care (POC) glucose measuring systems were not developed to guide the administration of insulin in critically ill patients, and it has become clear that they are not accurate enough to guide therapy aimed at keeping blood glucose concentration within a 30 mg/dL (1.7 mmol/L) range (Fig 4).68, 69, 70 Better monitoring systems are needed to

Acute Glucose Control in Critically Ill Patients With Diabetes

Current criteria used for the diagnosis of DM are (1) HbA1c level > 6.5% (National Glycohemoglobin Standardization Program certified methods), (2) fasting glucose concentration > 126 mg/dL (7.0 mmol/L), (3) 2-h plasma glucose concentration > 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test, or (4) classic symptoms of hyperglycemia or hyperglycemic crisis with a random plasma glucose concentration > 200 mg/dL (11.1 mmol/L).82 Although diagnostic criteria based on HbA1c may be

Glucose Control in 2011: Where Are We Now?

Both the initial Leuven trial and the NICE-SUGAR studies demonstrated that ICU mortality is affected by the target for glucose control, but the studies came to opposing conclusions. The initial enthusiasm for tight glucose control that followed the first Leuven trial has been tempered by the unfavorable findings of the NICE-SUGAR study. The available clinical trial data do not support the widespread adoption of intensive glucose control in critically ill patients, but neither do they support

Recommendations for Future Studies

The recommendations for acute glycemic control described here depend on “manual” glycemic control, accompanied by laboratory-based glucose measurements, usually with an insulin infusion titrated according to protocol. Such systems are very expensive in terms of nursing time and are prone to operator error. New technology is emerging that allows accurate and near-continuous measurement of blood glucose. A variety of systems are currently under development but none is yet in widespread clinical

Conclusions

The marked changes in the evidence guiding glucose control in critically ill patients during this decade have once again shown that promising results in single-center studies may be hard to replicate in large, multicenter, randomized controlled trials. The optimum blood glucose target for critically ill patients remains unclear, but a modest target such as that recommended by the American Diabetes Association (144-180 mg/dL [8-10 mmol/L]) with careful monitoring to avoid hypoglycemia and dosing

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

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