Abstract

IntroductionHyperglycemia, hypoglycemia and increased glucose variability are independently associated with increased risk of death in critically ill adults. The relationship between time in targeted blood glucose range (TIR) and mortality is not well described and may be a factor that has confounded the results of the major interventional trials of intensive insulin therapy.MethodsWe conducted a retrospective analysis of prospectively collected data involving 3,297 patients with intensive care unit (ICU) lengths of stay (LOS) of ≥1.0 day who were admitted between 1 January 2009 and 31 December 2013 to a single mixed medical-surgical ICU. We investigated the relationship between TIR 70 to 140 mg/dl with mortality and compared outcomes of non-diabetics (NON) and individuals with diabetes mellitus (DM), including stratifying by TIR above (TIR-hi) and below (TIR-lo) the median value for the NON and DM groups.ResultsThere were 85,799 blood glucose (BG) values for the NON group and 32,651 for the DM group, and we found that 75.5% and 54.8%, respectively, were between 70 and 140 (P <0.0001). The median (interquartile range) TIR (%) values for the NON and DM groups were 80.6% (61.4% to 94.0%) and 55.0% (35.5% to 71.1%), respectively (P <0.0001). For the NON group, mortality was 8.47% and 15.71% for TIR-hi and TIR-lo, respectively (P <0.0001). For the DM group, mortality was 16.09% and 14.44% for TIR-hi and TIR-lo, respectively (P = NS). We observed similar relationships for the NON group when we stratified by ICU LOS or severity of illness, especially in the most severely ill patients. There was a cumulative interaction of indices of hypoglycemia, hyperglycemia or glucose variability with TIR. Multivariable analysis demonstrated, for the NON group, that TIR-hi was independently associated with increased survival (P =0.0019). For the NON group, the observed-to-expected mortality ratios for TIR-hi and TIR-lo, based on Acute Physiology and Chronic Health Evaluation IV methodology, were 0.53 and 0.78, respectively. In contrast, among those in the DM group, there was no clear relationship between TIR 70 to 140 mg/dl and survival.ConclusionsIndependently of ICU LOS and severity of illness, TIR 70 to 140 mg/dl >80% is strongly associated with survival in critically ill patients without diabetes. These findings have implications for the design of clinical protocols for glycemic control in critically ill patients as well for the design of future interventional trials of intensive insulin therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0908-7) contains supplementary material, which is available to authorized users.

Highlights

  • Hyperglycemia, hypoglycemia and increased glucose variability are independently associated with increased risk of death in critically ill adults

  • Time in targeted blood glucose range (TIR)-hi was strongly associated with survival among patients with intensive care unit (ICU) lengths of stay (LOS) of 1 to 3 days; earlier data derived from interventional trials suggested no benefit of glycemic control in a short-stay cohort [1,10]

  • We have shown that TIR 70 to 140 mg/dl is independently associated with survival in a heterogeneous cohort of critically ill patients without diabetes

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Summary

Introduction

Hyperglycemia, hypoglycemia and increased glucose variability are independently associated with increased risk of death in critically ill adults. Chase and coinvestigators have published a series of studies that assessed the association of TIR (referred to as cumulative time in band with organ failure mortality in a 784-patient, before-and-after, single-center cohort evaluation of their Specialized Relative Insulin Nutrition Tables (SPRINT) protocol for IIT [5,6,7]. Okabayashi and colleagues published a single-center RCT demonstrating reduction in surgical site infection with intensive vs moderate BG targets, notable for the very high TIR achieved in the two groups with use of a closed-loop BG monitoring and insulin treatment system [8] Another recent multicenter study in which computerized glucose control was used failed to show any clinical benefit when TIR was low [9]. These data raise the possibility that low TIR may have confounded the results of the major RCT of IIT and may explain their uneven outcomes [1,2,3,10,11]

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