Factors Associated With Prolonged Antibiotic Use in the Setting of Suspected Pneumonia and Negative Bronchoalveolar Lavage Cultures.

Background: Diagnostic criterion for pneumonia includes clinical data and bronchoalveolar lavage cultures (BALCx) to identify pathogens. Although ~60% of BALCx are negative, there may be reluctance to discontinue antibiotics, leading to prolonged antibiotic use (PAU). Objective: The purpose of this study is to compare outcomes of subjects with negative BALCx with PAU versus without prolonged antibiotic use (nPAU). Methods: A retrospective cohort study was conducted including subjects admitted to the intensive care unit (ICU), with suspected pneumonia, and negative BALCx. Data were compared based on length of exposure to antibiotics, PAU (antibiotics >4 days) versus nPAU (antibiotics <4 days). Results: A total of 128 subjects were included, 57 in the PAU group and 71 in the nPAU group. Baseline demographics were similar between groups. Severity of illness measured by multiple organ dysfunction scores at time of bronchoalveolar lavage (BAL) collection to final result showed a statistically significant decrease in the PAU group but not in the nPAU group. No differences were found in ICU days, ventilator-free days, or mortality; however, length of stay was longer for PAU (23 vs. 17, p = .04). In the PAU group, there were fewer BALCx results of "no growth" (23% vs. 45%, p = .04), more positive gram stains (83% vs. 60%, p = .01) and more positive non-BALCx (40% vs. 14%, p = .01). In a multivariate analysis, factors associated with PAU were positive BAL gram stains (adjusted odds ratio [aOR] 3.1, p = .037) and positive non-BALCx (aOR 4.7, p = .002). Conclusion: For subjects with suspected pneumonia and negative BALCx, positive non-BALCx and positive BALCx gram stain influenced the length of exposure of antibiotics.

Use of a furosemide drip does not improve earlier primary fascial closure in the open abdomen.

BACKGROUND: The furosemide drip (FD), in addition to improving volume overload respiratory failure, has been used to decrease fluid in attempts to decrease intra-abdominal and abdominal wall volumes to facilitate fascial closure. The purpose of this study is to evaluate the FD and the associated rate of primary fascial closure following trauma damage control laparotomy (DCL). MATERIALS AND METHODS: From January 2004 to September 2008, a retrospective review from a single institution Trauma Registry of the American College of Surgeons dataset was performed. All DCLs greater than 24 h who had a length of stay for 3 or more days were identified. The study group (FD+) and control group (FD-) were compared. Demographic data including age, sex, probability of survival, red blood cell transfusions, initial lactate, and mortality were collected. Primary outcomes included primary fascial closure and primary fascial closure within 7 days. Secondary outcomes included total ventilator days and LOS. RESULTS: A total of 139 patients met inclusion criteria: 25 FD+ and 114 FD-. The 25 FD+ patients received the drug at a median 4 days post DCL. Demographic differences between the groups were not significantly different, except that initial lactate was higher for FD- (1.7 vs 4.0; P=0.03). No differences were noted between groups regarding successful primary fascial closure (FD+ 68.4% vs FD- 64.0%; P=0.669), or closure within 7 days (FD+13.2% vs FD- 28.0%; P=0.066) of original DCL. FD+ patients suffered more open abdomen days (4 [2-7] vs 2 [1-4]; P=0.001). FD+ did not demonstrate an association with primary fascial closure [Odds ratio (OR) 1.5, 95% confidence interval (CI) 0.260-8.307; P=0.663]. FD+ patients had more ventilator days and longer Intensive Care Unit (ICU)/hospital LOS (P<0.01). CONCLUSION: FD use may remove excess volume; however, forced diuresis with an FD is not associated with an increased rate of primary closure after DCL. Further studies are warranted to identify ICU strategies to facilitate fascial closure in DCL.

Failure to achieve euglycemia despite aggressive insulin control signals abnormal physiologic response to trauma.

PURPOSE: We hypothesize that a failure to normalize a patient's glucose on an automated euglycemia protocol signals an adverse response after trauma and that this response can identify patients with an increased mortality. MATERIALS AND METHODS: There were 1246 ventilated, critically ill trauma patients who were placed on an automated euglycemia. All glucose values collected both by laboratory serum measurements and by bedside arterial samples were included in the analysis. RESULTS: Forty six thousand two hundred eighteen data entries for glucose (mg/dL) were analyzed. Time to normalization, defined as the first value in the goal range of 80 to 110 mg/dL, was different between the 2 groups, survivors correcting significantly faster (396 vs 487 minutes; P = .003). Mortality in patients who normalized (80-110 mg/dL) in the first 6 hours of admission was 13.6% vs 18.3% in patients requiring greater than 6 hours (P = .02). Patients who never normalized also required significantly greater insulin doses despite there being no significant difference in demographic data between the 2 groups. CONCLUSIONS: A posttraumatic patient's response to tight glycemic control revealed important prognostic information about the patients' physiologic status. Patients who failed to reach euglycemia in the first 6 hours of admission had an increased hospital mortality. The time to normalization is significantly longer in those patients who died. Patients who did not correct rapidly required significantly higher insulin doses, suggesting insulin resistance.

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.

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;

Glucose metabolism, not obesity, predicts mortality in critically ill surgical patients.

Our hypothesis was to determine if insulin resistance and hyperglycemia, rather than obesity, are predictive of mortality in the surgically critically ill. An observational study of an automated protocol in surgical and trauma intensive care units was performed. Two groups were created based on body mass index (BMI): Obese (OB) defined as BMI > or = 30 (n = 338) and nonobese defined as BMI < 30 (n = 885). Euglycemia was maintained using an automated protocol using an adapting multiplier, which we used as our marker of stress insulin resistance. The primary outcome was hospital mortality. One thousand, two hundred and twenty-three patients met criteria with 73,225 glucose values. The OB group required more insulin (4.5 U/hr vs 3.2 U/hr, P < or = 0.01) and had a higher mean multiplier (0.07 vs 0.06, P < 0.01) reflecting insulin resistance. There was no difference in mortality between OB and nonobese (11.6% vs 11.5%, P = 0.96). Logistic regression showed that insulin dose (odds ratio 0.864; 95% confidence interval 0.772-0.967, P = 0.01), and not BMI, was an independent predictor of survival in this population. Obesity is not an independent risk factor for mortality in the surgical critical care population. Insulin resistance and subsequent hyperglycemia are increased in obesity and are independent predictors of mortality.

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.

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.

Stress insulin resistance is a marker for mortality in traumatic brain injury.

BACKGROUND: Both hyper- and hypoglycemia have been associated with poor outcome in traumatic brain injury (TBI). Neither the risks nor benefit of tight glucose control (goal range, 80-110 mg/dL) have been documented in the TBI population. OBJECTIVE: To analyze whether densely collected blood glucose data, using a computerized algorithm, to maintain tight glycemic control will reveal significant differences in blood glucose control between survivors and nonsurvivors in patients with TBI. METHODS: From October 2005 to April 2006, all ventilated, critically ill surgical patients with TBI Abbreviated Injury Scale score of >or=3 were placed on an automated, euglycemia protocol with every 2-hour blood glucose sampling. Mortalities within 24 hours were excluded. The protocol calculates the insulin rate using a linear equation (rate = blood glucose - 60[M]). M is an adapting multiplier and used here as a marker for insulin resistance (IR). RESULTS: Of 1,636 trauma intensive care unit admissions 160 patients, (median Injury Severity Score 34, mortality 13.1%) had 10,071 samples collected. Median glucose 115.6 mg/dL, with 41% of values between 80 and 110 mg/dL, 81% between 80 and 150 mg/dL, and 0.3% <40 mg/dL. The median blood glucose was statistically different but not clinically different among the patients who lived and died (114; interquartile range, 109-132 vs. 118; 111-136, p = 0.01). The median insulin dose was a unit per hour higher among the patient who died (4.2; 2.7-5.9 vs. 3.2; 2.4-5.0, p = 0.006). A logistic regression model demonstrated insulin rate (odds ratio 0.736, 95% confidence interval, 0.549-0.985, p = 0.039) to be the only independent predictor of mortality among the measures of blood glucose control. CONCLUSION: Nonsurvivors with TBI have significantly higher markers of IR (insulin rate and multiplier). Markers of glucose control (median glucose, hypoglycemic episodes, and the percentage of values in range) did not differ clinically among groups. Despite this stress IR, tight glycemic control appears possible and safe with low levels of hypoglycemic episodes in the TBI population.

Intensive insulin therapy in practice: can we do it?

BACKGROUND: Intensive insulin therapy (IIT) is the standard of care in the ICU, but precise implementation of insulin protocols has been difficult in clinical practice. The authors' objective was to quantify adherence to an IIT protocol in a practice setting, and to describe how adherence impacts overall blood glucose (BG) control. METHODS: A retrospective analysis of a cohort of critically ill patients treated with IIT was performed. Protocol adherence was evaluated by assessing the timing of BG measurements. Each measurement was categorized according to the time from the previous reading: early (<1 hour), on time (1-3 hours), and late (>3 hours). Outcome measures included mean and median BG for each time category as well as the proportion of values within the target range. RESULTS: In 1106 trauma and surgical ICU patients, 54,139 measurements were available for analysis. The overall mean BG (116 mg/dL) was near the target (80-110 mg/dL), but only 46% of values were within this range. There were 45,806 (86%) measurements on time, 2749 (5%) early, and 4478 (9%) were late. BG values of late measurements were less likely to be within range (34% vs 46% for on time measurements, P<.001). Of late measurements, 19% were >200 mg/dL, 13% were 150-200 mg/dL, and 16% were <60 mg/dL. CONCLUSIONS: IIT is difficult to implement precisely in a complex ICU environment. Measurement timing impacts overall BG control, with late measurements more often associated with severe hyperglycemic (BG>150 mg/dL) and hypoglycemic (BG<60 mg/dL) episodes.

Blood glucose variability is associated with mortality in the surgical intensive care unit.

Intensive insulin therapy has widely and rapidly been adopted as the standard of care for the treatment of hyperglycemia in the intensive care unit (ICU). Variability in blood glucose is increasingly recognized as an important factor in outcomes in the chronic diabetic in addition to hemoglobin A1C. We tested the hypothesis that measures of blood glucose variability would be associated with mortality in the surgical ICU. A retrospective analysis of a cohort of ventilated, critically ill surgical and trauma ICU patients placed on an automated insulin protocol was performed. Blood glucose (BG) variability was measured by comparing standard deviation, percentile values, successive changes in blood glucose, and by calculating the triangular index for various glucose-related indices. Eight hundred and fifty-eight patients had 46,474 blood glucose and insulin dose data points. One hundred and twenty-one patients died for an overall mortality rate of 14 per cent. Several measures of blood glucose variability (maximum successive change in BG and the triangular index) were different between the groups despite similar mean BG between survivors (117 mg/dL) and nonsurvivors (118 mg/dL). Increased blood glucose variability is associated with mortality in the surgical ICU. Further studies should focus on the demographic, clinical, and genetic factors responsible for this observation and identify strategies to minimize BG variability.

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 Fisher's 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 Fisher's 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.