Marcus J. Dortch

A Computerized Insulin Infusion Titration Protocol Improves Glucose Control With Less Hypoglycemia Compared to a Manual Titration Protocol in a Trauma Intensive Care Unit

BACKGROUND Previous studies reflect reduced morbidity and mortality with intensive blood glucose control in critically ill patients. Unfortunately, implementation of such protocols has proved challenging. This study evaluated the degree of glucose control using manual paper-based vs computer-based insulin protocols in a trauma intensive care unit. METHODS Of 1455 trauma admissions from May 31 to December 31, 2005, a cohort of 552 critically ill patients met study entry criteria. The patients received intensive blood glucose management with IV insulin infusions. Using Fishers exact test, the authors compared patients managed with a computerized protocol vs a paper-based insulin protocol with respect to the portion of glucose values in a target range of 80-110 mg/dL, the incidence of hyperglycemia (> or =150 mg/dL), and the incidence of hypoglycemia (< or =40 mg/dL). RESULTS Three hundred nine patients were managed with a manual paper-based protocol and 243 were managed with a computerized protocol. The total number of blood glucose values across both groups was 21,178. Mean admission glucose was higher in the computer-based protocol group (170 vs 152 mg/dL; p < .001, t-test). Despite this finding by Fishers exact test, glucose control was superior in the computerized group; a higher portion of glucose values was in range 80-110 mg/dL (41.8% vs 34.0%; p < .001), less hyperglycemia occurred (12.8% vs 15.1%; p < .001), and less hypoglycemia occurred (0.2% vs 0.5%; p < .001). CONCLUSIONS A computerized insulin titration protocol improves glucose control by (1) increasing the percentage of glucose values in range, (2) reducing hyperglycemia, and (3) reducing severe hypoglycemia.

Infection reduction strategies including antibiotic stewardship protocols in surgical and trauma intensive care units are associated with reduced resistant gram-negative healthcare-associated infections.

BACKGROUND Resistance to broad-spectrum antibiotics by gram-negative organisms is increasing. Resistance demands more resource utilization and is associated with patient morbidity and death. We describe the implementation of infection reduction protocols, including antibiotic stewardship, and assess their impact on multi-drug-resistant (MDR) healthcare-acquired gram-negative infections. METHODS Combined infection reduction and antibiotic stewardship protocols were implemented in the surgical and trauma intensive care units at Vanderbilt University Hospital beginning in 2002. The components of the program were: (1) Protocol-specific empiric and therapeutic antibiotics for healthcare-acquired infections; (2) surgical antibiotic prophylaxis protocols; and (3) quarterly rotation/limitation of dual antibiotic classes. Continuous healthcare-acquired infection surveillance was conducted by independent practitioners using National Heath Safety Network criteria. Linear regression analysis was used to estimate trends in MDR gram-negative healthcare-acquired infections. RESULTS A total of 1,794 gram-negative pathogens were isolated from healthcare-acquired infections during the eight-year observation period. The proportion of healthcare-acquired infections caused by MDR gram-negative pathogens decreased from 37.4% (2001) to 8.5% (2008), whereas the proportion of healthcare-acquired infections caused by pan-sensitive pathogens increased from 34.1% to 53.2%. The rate of total healthcare-associated infections per 1,000 patient-days that were caused by MDR gram-negative pathogens declined by -0.78 per year (95% confidence interval [CI] -1.28, -0.27). The observed rate of healthcare-acquired infections per 1,000 patient days attributable to specific MDR gram-negative pathogens decreased over time: Pseudomonas -0.14 per year (95% CI -0.20, -0.08), Acinetobacter-0.49 per year (95% CI -0.77, -0.22), and Enterobacteriaceae -0.14 per year (95% CI -0.26, -0.03). CONCLUSION Implementation of an antibiotic stewardship protocol as a component of an infection reduction campaign was associated with a decrease in resistant gram-negative healthcare-acquired infections in intensive care units. These results further support widespread implementation of such initiatives.

CLINICALLY SIGNIFICANT PSYCHOTROPIC DRUG-DRUG INTERACTIONS IN THE PRIMARY CARE SETTING

In recent years, the growing numbers of patients seeking care for a wide range of psychiatric illnesses in the primary care setting has resulted in an increase in the number of psychotropic medications prescribed. Along with the increased utilization of psychotropic medications, considerable variability is noted in the prescribing patterns of primary care providers and psychiatrists. Because psychiatric patients also suffer from a number of additional medical comorbidities, the increased utilization of psychotropic medications presents an elevated risk of clinically significant drug interactions in these patients. While life-threatening drug interactions are rare, clinically significant drug interactions impacting drug response or appearance of serious adverse drug reactions have been documented and can impact long-term outcomes. Additionally, the impact of genetic variability on the psychotropic drug’s pharmacodynamics and/or pharmacokinetics may further complicate drug therapy. Increased awareness of clinically relevant psychotropic drug interactions can aid clinicians to achieve optimal therapeutic outcomes in patients in the primary care setting.

Severe hypoglycemia while on intensive insulin therapy is not an independent predictor of death after trauma.

BACKGROUND Fear of the adverse effects of hypoglycemia has limited the widespread application of intensive insulin therapy (goal, 80-110 mg/dL) in the trauma population. We hypothesized that severe hypoglycemia (SH; <or=40 mg/dL) was not an independent predictor of mortality in the trauma population. METHODS An analysis of critically ill trauma patients treated with intensive insulin therapy from November 2005 to May 2008 was performed. The primary outcomes of interest were any episode of SH (<40 mg/dL) and all-cause inhospital mortality. Multivariate logistic regression was used to estimate the independent relationship between hypoglycemia and death. RESULTS : Fifty-seven thousand two hundred eighty-four data entries (1,824 patients) from the euglycemia protocol were analyzed (mortality = 16.0%). Median glucose was 119 mg/dL, with 43% of values between 80 mg/dL and 110 mg/dL, 81% between 80 mg/dL and 150 mg/dL, and 0.3% <40 mg/dL. There were 126 severe hypoglycemic episodes in 111 patients (6.1% of the patients). Multivariate logistic regression revealed that SH was not independently associated with death after adjusting for other known risk factors (odds ratio, 1.244; 95% confidence interval, 0.853-1.816; p = 0.257). CONCLUSION Hypoglycemia may be an unavoidable byproduct of tight glucose control with 6.1% of the patients experiencing a severe hypoglycemic event (<40 mg/dL). Hypoglycemia is not an independent predictor of death. Hypoglycemia is a statistical probability of time spent on protocol rather than an event leading to death. These data suggest that lower glucose ranges should be targeted in the trauma population without fear of hypoglycemias adverse effect on mortality.

Insulin Resistance Despite Tight Glucose Control Is Associated With Mortality in Critically Ill Surgical Patients

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.

Risk factors for treatment failure in patients receiving vancomycin for hospital-acquired methicillin-resistant Staphylococcus aureus pneumonia.

BACKGROUND The rate of vancomycin failure in patients with hospital-acquired pneumonia (HAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) has exceeded 40% in several studies. This observation was attributed initially to the lack of weight-based dosing and targeting of lower trough concentrations. However, a subsequent study demonstrated no additional benefit in patients who achieved trough vancomycin concentrations >15 mg/L compared with patients with concentrations between 5 and 15 mg/L. We sought to identify contributors to vancomycin failure in patients with MRSA HAP. METHODS This was a retrospective study of patients in a surgical intensive care unit with MRSA HAP who received vancomycin between January 1, 2005, and July 31, 2007. Clinical outcomes, microbiological data, prior antibiotic exposure, ventilator days, co-morbidities, and demographics were compared in patients with clinical success and those with treatment failure. Their characteristics were compared using a two-sided Fisher exact test or Mann-Whitney U test, as appropriate for nominal or continuous data. RESULTS More patients in the treatment failure group had received one or more doses of vancomycin within 90 days leading up to MRSA HAP (84% vs. 47%; p = 0.04). In addition, the duration of prior vancomycin exposure was significantly longer among patients in the treatment failure group (6 vs. 0 days; p < 0.05). There were no statistically significant differences in the percentages of patients who achieved a vancomycin trough concentrations > or =15 mg/dL within the first 48 h (28% vs. 17%; p = 0.69), 72 h (44% vs. 39%; p = 1.0), or 96 h (56% vs. 44%; p = 0.74) after starting treatment. Patients in the failure group had a significantly higher overall mortality rate (32% vs. 0; p = 0.02). CONCLUSIONS These data suggest that patients who have recent exposure to vancomycin are at high risk for vancomycin failure and may benefit from an appropriate alternative when a diagnosis of MRSA HAP is made.

Insulin resistance heralds positive cultures after severe injury.

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.