Mild hypoglycemia is independently associated with increased mortality in the critically ill

Abstract

Introduction: Severe hypoglycemia (blood glucose concentration (BG) < 40 mg/dL) is independently associated with an increased risk of mortality in critically ill patients. The association of milder hypoglycemia (BG < 70 mg/dL) with mortality is less clear.

Methods: Prospectively collected data from two observational cohorts in the USA and in The Netherlands, and from the prospective GLUCONTROL trial were analyzed. Hospital mortality was the primary endpoint.

Results: We analyzed data from 6,240 patients: 3,263 admitted to Stamford Hospital (ST), 2,063 admitted to three institutions in The Netherlands (NL) and 914 who participated in the GLUCONTROL trial (GL). The percentage of patients with hypoglycemia varied from 18% to 65% among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia even after stratification by severity of illness, diagnostic category, diabetic status, mean BG during intensive care unit (ICU) admission and coefficient of variation (CV) as a reflection of glycemic variability. The relative risk (RR, 95% confidence interval) of mortality associated with minimum BG < 40, 40 to 54 and 55 to 69 mg/dL compared to patients with minimum BG 80 to 109 mg/dL was 3.55 (3.02 to 4.17), 2.70 (2.31 to 3.14) and 2.18 (1.87 to 2.53), respectively (all P < 0.0001). The RR of mortality associated with any hypoglycemia < 70 mg/dL was 3.28 (2.78 to 3.87) (P < 0.0001), 1.30 (1.12 to 1.50) (P = 0.0005) and 2.11 (1.62 to 2.74) (P < 0.0001) for the ST, NL and GL cohorts, respectively. Multivariate regression analysis demonstrated that minimum BG < 70 mg/dL, 40 to 69 mg/dL and < 40 mg/dL were independently associated with increased risk of mortality for the entire cohort of 6,240 patients (odds ratio (OR) (95% confidence interval (CI)) 1.78 (1.39 to 2.27) P < 0.0001), 1.29 (1.11 to 1.51) P = 0.0011 and 1.87 (1.46 to 2.40) P < 0.0001) respectively.

Conclusions: Mild hypoglycemia was associated with a significantly increased risk of mortality in an international cohort of critically ill patients. Efforts to reduce the occurrence of hypoglycemia in critically ill patients may reduce mortality.

Figure 1

Relationship between minimum BG during ICU stay and mortality, stratified by subpopulation. BG, blood glucose; GL-C, GLUCONTROL-control arm; GL-I, GLUCONTROL-intensive arm; NL-L, Netherlands-"loose"; NL-S, Netherlands-"strict"; ST, Stamford.

Figure 2

Relationship between minimum BG during ICU stay and mortality, stratified by APACHE II score. APACHE II, Acute Physiology and Chronic Health Evaluation II disease classification system; BG, blood glucose.

Figure 3

Relationship of mean blood glucose-mortality, stratified by presence or absence of hypoglycemia. There were 32 patients with mean BG < 80 mg/dL, 28 with hypoglycemia (51.9% mortality) and 1 without hypoglycemia (25% mortality). BG, blood glucose; HYPO; hypoglycemia BG < 70 mg/dL.

Figure 4

Association of mortality with disturbances in the three domains of glycemic control. There were no patients with Mean BG > 140 mg/dL and CV < 15%. BG, blood glucose; CV, coefficient of variation; HYPO, hypoglycemia BG < 70 mg/dL.