Severe and multiple hypoglycemic episodes are associated with increased risk of death in ICU patients

Abstract

Introduction: In a randomized controlled trial comparing tight glucose control with a computerized decision support system and conventional protocols (post hoc analysis), we tested the hypothesis that hypoglycemia is associated with a poor outcome, even when controlling for initial severity.

Methods: We looked for moderate (2.2 to 3.3 mmol/L) and severe (<2.2 mmol/L) hypoglycemia, multiple hypoglycemic events (n ≥3) and the other main components of glycemic control (mean blood glucose level and blood glucose coefficient of variation (CV)). The primary endpoint was 90-day mortality. We used both a multivariable analysis taking into account only variables observed at admission and a multivariable matching process (greedy matching algorithm; caliper width of 10(-5) digit with no replacement).

Results: A total of 2,601 patients were analyzed and divided into three groups: no hypoglycemia (n =1,474), moderate hypoglycemia (n =874, 34%) and severe hypoglycemia (n =253, 10%). Patients with moderate or severe hypoglycemia had a poorer prognosis, as shown by a higher mortality rate (36% and 54%, respectively, vs. 28%) and decreased number of treatment-free days. In the multivariable analysis, severe (odds ratio (OR), 1.50; 95% CI, 1.36 to 1.56; P =0.043) and multiple hypoglycemic events (OR, 1.76, 95% CI, 1.31 to 3.37; P <0.001) were significantly associated with mortality, whereas blood glucose CV was not. Using multivariable matching, patients with severe (53% vs. 35%; P <0.001), moderate (33% vs. 27%; P =0.029) and multiple hypoglycemic events (46% vs. 32%, P <0.001) had a higher 90-day mortality.

Conclusion: In a large cohort of ICU patients, severe hypoglycemia and multiple hypoglycemic events were associated with increased 90-day mortality.

Trial registration: Clinicaltrials.gov Identifier: NCT01002482 . Registered 26 October 2009.

Figure 1

Flowchart of the study.

Figure 2

Distribution of the number of hypoglycemic events per patient. (A) Severe (<2.2 mmol/L). (B) Moderate (2.2 to 3.3 mmol/L). (C) Any type (<3.3 mmol/L).

Figure 3

Subgroup analysis. Odds ratio (OR) and 95% confidence interval (CI) for death at 90 days associated with moderate (filled squares) or severe (filled circles) hypoglycemia or multiple (n ≥3) hypoglycemic (filled triangles) events in the total population and in matched subgroups according to treatment assignment (conventional vs. computerized decision support system (CDSS)) and diabetes status (diabetic vs. non-diabetic). Matching was performed using propensity score and a ratio of 2:1 for severe hypoglycemia and 1:1 for moderate hypoglycemia and multiple hypoglycemic events. The size of symbols is related to the number of patients (N) retained in the matching process.