Ultradian Variation of Blood Glucose in Intensive Care Unit Patients Receiving Insulin Infusions

Abstract

Treatment of hyperglycemia with an insulin infusion protocol (IIP) has improved outcomes in intensive care unit (ICU) patients (1,2). While morning glucose has been reported, little is known about variation of blood glucose for patients on IIP, causing uncertainty about the optimal treatment of ICU patients (3–5). Our objectives were to test whether morning glucose represented whole-day glucose and to determine whether glucose varied over the course of the day. In ICU patients receiving IIP, glucose was lower in the early morning, correlated poorly with average glucose, and varied with an ultradian pattern. In this prospective, single-center, observational study in the ICUs of a university tertiary care hospital, we recorded all glucose measurements in two cohorts of ICU patients receiving an IIP targeting blood glucose 80–110 mg/dl. Supplementary details are available in an online appendix (available at http://dx.doi.org/10.2337/dc07-0865.). Between 20 May 2006 and 6 August 2006, 141 ICU patients were treated with IIP, 8 of whom received insulin for two periods, resulting in 149 patient episodes. The average duration of insulin use for an episode was 115 ± 9 h (range 5–604). Forty-one percent ( n = 11,670) of glucose measurements during this period were in the target range (80–110 mg/dl) (Fig. 1 A ). In preliminary data acquired between May 2004 and June 2005, the proportion of measurements in the target range increased initially and then stabilized (Fig. 1). Twenty-six percent of patients experienced at least one glucose value <60 mg/dl, and 2.7% had a glucose value <40 mg/dl. The IIP was designed to control glucose within 8 h (1), and slightly more glucose measurements beyond 8 h (42%, n = 10,766) were in range ( P = 0.014) (Fig. 1 B ). The mean and median of this positively skewed, non-Gaussian distribution ( P < 0.0001, Kolmogorov-Smirnov test) were 118.5 …