Evaluation of blood glucose values in critically ill patients before and after implementation of an intensive insulin infusion protocol

Baylor University Medical Center Proceedings, July, 2007 by Jennifer M. Roth, Benny Bolin, Robert W. Baird

This retrospective study evaluated the effect of an intensive insulin infusion protocol on blood glucose values in five intensive care units at Baylor University Medical Center. The protocol involved an equation in which the hourly blood glucose value and an adjusted multiplier were used to determine the insulin infusion rate. The default target blood glucose range was 90 to 120 mg/dL. Results showed that blood glucose values taken by diabetic fingerstick were significantly better in March 2006, after initiation of the protocol, than in March 2005, before use of the protocol, for the percentage of patients both with a blood glucose value >150 mg/dL (P < 0.001) and with a blood glucose value >120 mg/dL (P < 0.001). The percentage of patients with a blood glucose value [less than or equal to] 80 mg/dL was not significantly different between the two time periods (P > 0.10). The increased number of diabetic fingerstick values within a desired range was achieved without a significantly higher number of blood glucose values [less than or equal to] 80 mg/dL. It can be theorized that wide use of the protocol was at least partly responsible for the significant change in blood glucose values.

**********

Hyperglycemia in critically ill patients is caused by a number of factors. Stress-induced hyperglycemia, commonly defined as blood glucose value >200 mg/dL, is an endogenous process resulting from the inflammatory response that occurs in critical illness. Hyperglycemia can also be triggered by exogenous substances, including pharmacologic agents such as corticosteroids, immunosuppressants, sympathomimetics, and dextrose infusions, as well as parenteral and enteral nutrition (1).

The current focus on tight blood glucose control in critically ill patients began with a now landmark trial by Van den Berghe and colleagues published in late 2001 (2). Numerous studies since then, in various populations of intensive care unit (ICU) patients, have sought to prove, or disprove, the idea that tight blood glucose control is beneficial.

In their first study, Van den Berghe and colleagues compared intensive insulin therapy (blood glucose maintained between 80 and 110 mg/dL with insulin infusion) with conventional treatment (insulin infusion initiated only if blood glucose exceeded 215 mg/dL and then maintained between 180 and 200 mg/dL with insulin infusion) in a surgical ICU. Their prospective randomized controlled study included 1548 patients, who were predominantly cardiothoracic surgery patients. In patients who were in the ICU for more than 5 days, intensive insulin therapy resulted in a significantly reduced ICU mortality rate, as well as significant improvement in outcomes such as length of ICU stay, duration of mechanical ventilation, incidence of bloodstream infections, acute renal failure requiring dialysis, critical illness polyneuropathy, and hyperbilirubinemia. The study was not blinded for logistical reasons (2).

In 2003, Krinsley published results of a retrospective review of 1826 consecutive ICU patients (heterogeneous population), which further reinforced the idea that elevated blood glucose values during critical illness were associated with increased morbidity and mortality. Upon review of blood glucose values, the mean and maximum values were significantly higher in nonsurvivors than in survivors. The lowest mortality rate occurred in the group with mean glucose values between 80 and 99 mg/dL. Hospital mortality increased progressively with each 20-mg/dL increase in glucose range, leading to the conclusion that even modestly elevated blood glucose in the ICU leads to increased hospital mortality in a heterogeneous patient population (3).

The following year, Krinsley published results of a study of 800 consecutive ICU admissions (heterogeneous population) after institution of an intensive glucose management protocol; comparators were 800 historical control patients admitted the year immediately preceding the study period. The intensive intravenous insulin protocol was initiated if two successive glucose values exceeded 200 mg/dL; the protocol maintained glucose values <140 mg/dL. The patients in the intensive glucose management group had significantly decreased hospital mortality rates, length of ICU stay, and incidence of new-onset renal insufficiency and blood transfusion (4).

In 2006, Van den Berghe and colleagues published results of a study of intensive insulin therapy in 1200 medical ICU patients. This study had the same design as their surgical ICU study. The mortality rate was significantly reduced in patients who received intensive insulin therapy who were in the ICU for more than 3 days; however, in patients whose ICU stay was <3 days, the mortality rate in the intensive insulin group was increased. According to the post hoc analysis, the intensive insulin therapy likely did not cause harm. The authors hypothesized that patients staying in the ICU <3 days may have had higher mortality due to withdrawal of treatment for medical futility. Morbidity was significantly decreased in all patients in the intensive insulin therapy group, resulting in a decreased incidence of acute kidney injury, duration of mechanical ventilation, length of ICU stay, and length of hospital stay. As in the previous study, treatment groups were not blinded (5).

In recognition of a need for intensive insulin therapy at Baylor University Medical Center (BUMC), a multidisciplinary group was formed in late 2004 to address the issue. After review of numerous insulin infusion protocols, one was selected for pilot study in the ICUs. The protocol chosen involves an equation in which the hourly blood glucose value and an adjusted multiplier are used to determine the insulin infusion rate. The target blood glucose range can be determined by the prescriber on an individual basis. After a pilot study, minor changes were made to enhance the safety of the protocol, including changing the default target blood glucose range from 80-120 mg/dL to 90-120 mg/dL, thereby potentially avoiding blood glucose values below the desirable range. In addition, the treatment threshold for low blood glucose values was changed from 70 mg/dL, which had been the institutional standard value to trigger treatment for hypoglycemia, to 60 mg/dL. After research and discussion, it was decided that if tight glucose control was the ultimate goal, treating a blood glucose value of 70 mg/dL with dextrose in an asymptomatic patient would not be clinically useful. Following the changes, a second phase of the pilot study was done, which showed the protocol to be efficacious at maintaining blood glucose values within a desirable range (80-120 mg/dL), with an acceptable rate of hypoglycemia. Based on the pilot study results, the protocol was adopted as the standard insulin infusion in all ICUs at BUMC.