Association of Blood Glucose Level and Glycemic Variability With Mortality in Sepsis Patients During ICU Hospitalization

Abstract

Background: There was considerable debate regarding the effect of mean blood glucose (MBG) and glycemic variability (GV) on the mortality of septic patients. This retrospective cohort study aimed to assess the association between MBG and GV with ICU mortality of sepsis patients and to explore the optimal MBG range.

Methods: Sepsis patients were enrolled from the Medical Information Mart for Intensive Care IV database (MIMIC-IV). MBG and glycemic coefficient of variation (Glu_CV) were, respectively, calculated to represent the overall glycemic status and GV during ICU stay. The associations between MBG, Glu_CV, and ICU mortality of the septic patients were assessed by using multivariate logistic regression in different subgroups and the severity of sepsis. Restricted cubic splines evaluated the optimal MBG target.

Results: A total of 7,104 adult sepsis patients were included. The multivariate logistic regression results showed that increased MBG and Glu_CV were significantly correlated with ICU mortality. The adjusted odds ratios were 1.14 (95% CI 1.09-1.20) and 1.05 (95% CI 1.00-1.12). However, there was no association between hyperglycemia and ICU mortality among diabetes, liver disease, immunosuppression, and hypoglycemia patients. And the impact of high Glu_CV on ICU mortality was not observed in those with diabetes, immunosuppression, liver disease, and non-septic shock. The ICU mortality risk of severe hyperglycemia (≧200 mg/dl) and high Glu_CV (>31.429%), respectively, elevated 2.30, 3.15, 3.06, and 2.37, 2.79, 3.14-folds in mild (SOFA ≦ 3), middle (SOFA 3-7), and severe group (SOFA ≧ 7). The MBG level was associated with the lowest risk of ICU mortality and hypoglycemia between 120 and 140 mg/dl in the subgroup without diabetes. For the diabetic subset, the incidence of hypoglycemia was significantly reduced when the MBG was 140-190 mg/dl, but a glycemic control target effectively reducing ICU mortality was not observed.

Conclusion: MBG and Glu_CV during the ICU stay were associated with all-cause ICU mortality in sepsis patients; however, their harms are not apparent in some particular subgroups. The impact of hyperglycemia and high GV on death increased with the severity of sepsis. The risk of ICU mortality and hypoglycemia in those with no pre-existing diabetes was lower when maintaining the MBG in the range of 120-140 mg/dl.

Keywords: glucose metabolism disorders; glycemic control; mortality; restricted cubic splines regression; sepsis.

Figure 1

Forest plot depicting ICU mortality risk in septic patients with and without diabetes. Adjustment factors are the same as those in Model 3.

Figure 2

Multivariable-adjusted odds ratios for ICU mortality according to the levels of the mean blood glucose (MBG) on a continuous scale. Solid red lines are multivariable-adjusted odds ratios, with dashed bold lines showing 95% confidence intervals derived from restricted cubic spline regressions with five knots. Reference lines for no association are indicated by the black dashed lines at a hazard ratio of 1.0, and the reference knot set at 140 mg/dl. Purple regions indicate the fraction of the population with different levels of MBG. Adjustment factors are the same as those in Model 3 of Table 2.