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 (ORadj 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.