Early versus late intravenous insulin administration in critically ill patients

Objective: To investigate whether timing of intensive insulin therapy (IIT) after intensive care unit (ICU) admission influences outcome. Design and setting: Single-center prospective cohort study in the 14-bed medical ICU of a 1,171-bed tertiary teaching hospital. Patients: The study included 127 patients started on ITT within 48 h of ICU admission (early group) and 51 started on ITT thereafter (late group); the groups did not differ in age, gender, race, BMI, APACHE III, ICU steroid use, admission diagnosis, or underlying comorbidities. Measurements and results: The early group had more ventilator-free days in the first 28 days after ICU admission (median 12 days, IQR 0-24, vs. 1 day, 0-11), shorter ICU stay (6 days, IQR 3-11, vs. 11 days, vs. 7-17), shorter hospital stay (15 days, IQR 9-30, vs. 25 days, 13-43), lower ICU mortality (OR 0.48), and lower hospital mortality (OR 0.27). On multivariate analysis, early therapy was still associated with decreased hospital mortality (OR_adj 0.29). The strength and direction of association favoring early IIT was consistent after propensity score modeling regardless of method used for analysis. Conclusions: Early IIT was associated with better outcomes. Our results raise questions about the assumption that delayed administration of IIT has the same benefit as early therapy. A randomized study is needed to determine the optimal timing of therapy.