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Purpose: Changes in insulin resistance (IR) cause stress-induced hyperglycemia after trauma, but the numerous factors involved in IR have not been delineated clearly. We hypothesized that a statistical model could help determine the relative contribution of different clinical co-variates to IR in critically injured patients., Patients and Methods: We retrospectively studied 726 critically injured patients managed with a computer-assisted glycemic protocol at an academic level I trauma center (639 ventilated controls without pneumonia (VWP) and 87 patients with ventilator-associated pneumonia (VAP). Linear regression using age, gender, body mass index (BMI), diabetes mellitus, pneumonia, and glycemic provision was used to estimate M, a marker of IR that incorporates both the serum blood glucose concentration (BG) and insulin dose., Results: Increasing M (p<0.001) was associated with age (1.62%; 95% confidence interval [CI] 1.27%-1.97% per decade), male gender (9.78%; 95% CI 8.28%-12.6%), BMI (4.32% [95% CI 4.02%-4.62%] per 5 points), diabetes mellitus (21.2%; 95% CI 19.2%-23.2%), pneumonia (10.9%; 95% CI 9.31%-12.6%), and glycemic provision (27.3% [95% CI 6.6%-28.1%] per 100 g of glucose). Total parenteral nutrition was associated with a decrease in M of 10.3%; 95% CI 8.52%-12.1%; p<0.001., Conclusions: Clinical factors can be used to construct a model of IR. Prospective validation might enable early detection and treatment of infection or other conditions associated with increased IR.

Background: Hyperglycemia caused by stress-induced insulin resistance is associated with both infection and mortality in critically injured patients. The onset of infection may increase stress-induced insulin resistance, leading to hyperglycemia. Hyperglycemia has been shown to precede the diagnosis of ventilator-associated pneumonia (VAP) in critically injured adults and has been suggested to have potential diagnostic importance. However, glycemic control (GC) protocols in critically ill patients limit the development of hyperglycemia despite increasing insulin resistance. Our computer-assisted GC protocol achieves excellent GC, limiting infection-related hyperglycemia while capturing prospectively all glucose values, insulin infusion rates, and the multiplier (M) used to calculate the insulin rate. We hypothesized that surrogate measures of insulin resistance, the insulin infusion rate and multiplier M, would increase prior to the clinical suspicion of VAP, even in euglycemic critically injured patients., Methods: All critically injured patients (2,656) on the computerized glycemic control protocol were included in the analysis and categorized by those developing VAP and those without pneumonia on days 3-10 of their intensive care unit (ICU) stay. Median blood glucose concentration (BG), insulin infusion rate (IDR), and multiplier (M) [Insulin Drip Rate=M*(BG-60)] were determined for VAP patients (n=329) and non-infected ventilated (NIV) patients (n=2,327) on each day of mechanical ventilation. The day of VAP diagnosis according to U.S. Centers for Disease Control and Prevention (CDC) criteria was defined as day zero and VAP patients matched with NIV patients according to ventilator day from -10 to +10. Comparisons were conducted using the Mann-Whitney U test., Results: Baseline characteristics between VAP and NIV groups did not differ. Measures of insulin resistance increased from the time of injury in both groups. Patients with VAP had significantly greater change in both measures of insulin resistance, IDR and M, in the 48 hours preceding the diagnosis of VAP. These changes occurred despite the fact that the computer-assisted GC protocol achieved lower glucose values in VAP patients for the majority of study days., Conclusions: Measures of insulin resistance increase in the two days prior to the clinical suspicion of VAP for critically injured patients on the GC protocol. These changes occur despite the protocol maintaining euglycemia. This data suggests that markers of insulin resistance may provide clinically useful information in the early diagnosis of VAP.

Background: Insulin resistance and hyperglycemia are common in acutely injured patients, and associated with poor outcomes. In the era of tight glucose control, measures of insulin responsiveness (IR) may provide a better indicator of patient status than does the serum glucose concentration. We hypothesized that measures of IR during tight glycemic control protocols are associated with infection and may be more predictive than the serum glucose concentration., Methods: All critically injured, mechanically ventilated patients undergo protocolized tight glycemic control with the aid of a computer-based system that calculates the insulin dose using an adapting multiplier (insulin dose = [blood glucose - 60) x M). Consecutive patients on protocol were studied to identify the incidence of positive sterile-site or quantitative bronchoalveolar lavage cultures (>10(4) colony-forming units/mL). Patients were stratified by presence and number of positive cultures and analyzed by both serum glucose measures and measures of IR (average multiplier and average insulin infusion rate)., Results: During the six-month study period, 356 patients were placed on the tight glycemic control protocol. Of these, 101 patients had 192 positive cultures. Patients with positive cultures required significantly more hourly insulin than those without a positive culture (3.7 vs. 2.8 units/h; p = or<0.001). Logistic regression showed the insulin dose (odds ratio 2.1; 95% confidence interval 1.6, 3.0; p = <0.001) and the adapting multiplier to be independent predictors of the patient having a positive culture among other factors associated with nosocomial infection., Conclusions: Insulin resistance, quantified by hourly insulin dose and median multiplier, confers a higher risk of systemic nosocomial infection. Patients with positive cultures actually had lower admission and median blood glucose values over their intensive care unit stays, highlighting the decreased value of this measure as a predictor of outcome in the setting of tight glucose control. A greater insulin requirement suggesting resistance may be used as a marker of a higher risk of nosocomial infection.

Background: The hyperglycemic state following trauma and surgery is related partially to insulin resistance (IR). The objective is to determine if critically ill surgical patients vary in their extent of IR and is IR associated with mortality., Methods: Prospective observational study in trauma and surgical intensive care units. There were 925 ventilated, critically ill surgical patients who were placed on an automated euglycemia protocol. A mathematic multiplier (M) employed by the protocol was used as a measure of IR. Outcome, phenotypic, laboratory, and treatment variables were analyzed., Results: 54,141 entries for glucose (mg/dl) and M were analyzed. Median glucose was 118mg/dL, with 45% of values between 80-110mg/dL, 81% between 80-150 mg/dL, and 0.2% less than 40 mg/ dL. M varied by 42 fold over the entire population, and by an average of 11-fold among individual patients. The median blood glucose was not different between groups (118 mg/dl for survivors and 118 mg/dl for non-survivors, P = 0.36). The median insulin dose and M were significantly higher in non-survivors (4.1 U/hr versus 3.4 U/hr, P = 0.005; 0.061 versus 0.058, P = 0.02)., Conclusions: There was a large amount of variation in insulin resistance, as measured by an adapting multiplier, both across the population and within patients. In the setting of tight glucose control measures of glucose control (median blood glucose and percent in range) do not differentiate between patients who lived and died while measures of insulin resistance (median insulin dose and multiplier) do, suggesting that the insulin resistance is a better predictor of outcome.