Introduction

Severe hypoglycemia (blood glucose level (BGL) <40 mg/dl) is independently associated with an increased risk of mortality in critically ill patients. The impact of milder hypoglycemia (BGL <70 mg/dl) on outcome 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 3,262 patients admitted to Stamford Hospital (ST), 2,063 patients admitted to three institutions in the Netherlands (NL; loose glycemic protocol (L, n = 1,098) and strict glycemic protocol (S, n = 965)) and 914 patients who participated in the GLUCONTROL trial (GL; control arm (C, n = 460) and intensive insulin therapy arm (IIT, n = 454)). The percentage of patients with hypoglycemia varied widely among the different cohorts. Patients with hypoglycemia experienced higher mortality than did those without hypoglycemia within each subgroup (P < 0.0001 for all comparisons), even after stratification by severity of illness or diabetic status. Multivariable logistic regression analysis revealed that hypoglycemia had a greater impact on the mortality of surgical patients than of medical patients. The impact of hypoglycemia on mortality occurred independently of mean glucose level during ICU stay or glycemic variability.

Conclusions

Even a single episode of mild hypoglycemia was associated with a significantly increased risk of mortality in heterogeneous cohorts of critically ill patients, independently of severity of illness, diabetic status, diagnostic category and glycemic variability.