Independent Association of Glucose Variability With Hospital Mortality in Adult Intensive Care Patients: Results From the Australia and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Binational Registry

Wide variations in blood glucose excursions in critically ill patients may influence adverse outcomes such as hospital mortality. However, whether blood glucose variability is independently associated with mortality or merely captures the excess risk attributable to hyperglycemic and hypoglycemic episodes is not established. We investigated whether blood glucose variability independently predicted hospital mortality in nonhyperglycemic critical care patients. DESIGN: Retrospective, registry data analyses of outcomes. SETTING: Large, binational registry (Australia and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database repository) of 176 ICUs across Australia and New Zealand. PATIENTS: We used 10-year data on nonhyperglycemic patients registered in the Australia and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation Adult Patient Database repository (n = 290,966). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Glucose variability was captured using glucose width defined as the difference between highest and lowest blood glucose concentration within first 24 hours of ICU admission. We used hierarchical, mixed effects logistic regression models that accounted for ICU variation and several fixed-effects covariates. Glucose width was specifically and independently associated with hospital mortality. The association of blood glucose variability with mortality remained significant (odds ratio for highest vs lowest quartile of glucose, 1.43; 95% CI, 1.32–1.55; p < 0.001) even after adjusting for the baseline risk of mortality, midpoint blood glucose level, occurrence of hypoglycemia and inter-ICU variation. Mixed effects modeling showed that there was a statistically significant variation in this association across ICUs. CONCLUSIONS: Our study demonstrates that glucose variability is independently associated with hospital mortality in critically ill adult patients. Inclusion of correction for glucose variability in glycemic control protocols needs to be investigated in future studies.