Insulin Resistance in Critically Injured Adults: Contribution of Pneumonia, Diabetes, Nutrition, and Acuity.

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.

A pilot study of the noninvasive assessment of the lung microbiota as a potential tool for the early diagnosis of ventilator-associated pneumonia.

BACKGROUND: Ventilator-associated pneumonia (VAP) remains a common complication in critically ill surgical patients, and its diagnosis remains problematic. Exhaled breath contains aerosolized droplets that reflect the lung microbiota. We hypothesized that exhaled breath condensate fluid (EBCF) in hygroscopic condenser humidifier/heat and moisture exchanger (HCH/HME) filters would contain bacterial DNA that qualitatively and quantitatively correlate with pathogens isolated from quantitative BAL samples obtained for clinical suspicion of pneumonia. METHODS: Forty-eight adult patients who were mechanically ventilated and undergoing quantitative BAL (n = 51) for suspected pneumonia in the surgical ICU were enrolled. Per protocol, patients fulfilling VAP clinical criteria undergo quantitative BAL bacterial culture. Immediately prior to BAL, time-matched HCH/HME filters were collected for study of EBCF by real-time polymerase chain reaction. Additionally, convenience samples of serially collected filters in patients with BAL-diagnosed VAP were analyzed. RESULTS: Forty-nine of 51 time-matched EBCF/BAL fluid samples were fully concordant (concordance > 95% by κ statistic) relative to identified pathogens and strongly correlated with clinical cultures. Regression analysis of quantitative bacterial DNA in paired samples revealed a statistically significant positive correlation (r = 0.85). In a convenience sample, qualitative and quantitative polymerase chain reaction analysis of serial HCH/HME samples for bacterial DNA demonstrated an increase in load that preceded the suspicion of pneumonia. CONCLUSIONS: Bacterial DNA within EBCF demonstrates a high correlation with BAL fluid and clinical cultures. Bacterial DNA within EBCF increases prior to the suspicion of pneumonia. Further study of this novel approach may allow development of a noninvasive tool for the early diagnosis of VAP.

Elevated serum creatine phosphokinase is associated with mortality and inotropic requirement in critically injured adults.

BACKGROUND: Hemeproteins such as free myoglobin can undergo autoxidation and catalyse lipid peroxidation, increasing oxidative stress. Creatine phosphokinase (CPK) elevation is a marker for free myoglobin after myocyte damage. Since oxidative injury is a key mechanism of injury-related organ dysfunction, we hypothesised that serum CPK levels correlate with mortality and need for inotropic medication and duration of inotropic support, i.e. shock, among critically injured patients. METHODS: We conducted a retrospective review of 17,847 patients admitted to a single Trauma Intensive Care Unit over 9 years. 2583 patients with serum CPK levels were included in the analysis. Patient data were collected continuously into an electronic ICU repository. Univariate analysis was accomplished using Spearman correlation and the Mann­Whitney U test. Propensity score adjustment models accounting for potential confounders were used to assess the independent effect of CPK level on mortality, need for inotropic support, and duration of inotropic support. RESULTS: Median CPK was significantly higher in patients who died (916 [IQR 332, 2472] vs. 711 [253, 1971], p = 0.004) and in those who required inotropic medications (950 [353, 2525] vs. 469 [188, 1220], p < 0.001). After adjusting for propensity score and potential confounders the odds of mortality increased by 1.10 (95% CI 1.02­1.19, p = 0.020) and the odds of inotropic medication use increased by 1.30 (95% CI 1.22­1.38, p < 0.001) per natural log unit increase in CPK. There was a significant association between CPK level and duration of inotropic support (Spearman's rho .237, p < 0.001) that remained significant in a propensity score-adjusted model. CONCLUSION: In critically injured patients, elevated serum CPK level is independently associated with mortality, need for inotropic medication, and duration of inotropic support. This study is the first to evaluate the relationship of CPK level and mortality in addition to surrogate measures of shock in a population of critically injured patients. If these associations are verified prospectively, there may be a role for treatment with hemeprotein reductants, such as paracetamol, to mitigate the effects of shock and end-organ dysfunction.

Hypocaloric enteral nutrition protects against hypoglycemia associated with intensive insulin therapy better than intravenous dextrose.

Intensive insulin therapy treats hyperglycemia but increases the risk of hypoglycemia. Typically, intravenous dextrose is given to prevent hypoglycemia; however, enteral nutrition is preferred. We hypothesized that the provision of hypocaloric enteral nutrition would protect against hypoglycemia. A retrospective analysis was performed evaluating patients treated with intensive insulin therapy comparing the use of enteral nutrition versus a dextrose-only intravenous solution. Nutrition in the 2 hours before each blood glucose test was assessed, and the association with hypoglycemia (50 mg/dL or less) evaluated. Risk of hypoglycemia as a function of nutrition type and rate was estimated by multivariable regression. A total of 26,140 blood glucose tests were collected on 1289 patients. Hypoglycemia occurred in 6.4 per cent of patients. In regression models, enteral nutrition was the strongest protective factor against hypoglycemia (P < 0.001) with the largest risk reduction (steepest portion of the curve) occurring at 60 per cent goal. Hypocaloric enteral nutrition showed a greater risk reduction than a peripheral dextrose-only intravenous solution alone. In the setting of intensive insulin therapy, the provision of enteral nutrition, even if hypocaloric, is sufficient to protect against hypoglycemia. Future prospective studies should evaluate the efficacy of enteral nutrition in reducing the risk of hypoglycemia and whether lower rates of hypoglycemia correspond to improved outcomes.

Insulin resistance increases before ventilator-associated pneumonia in euglycemic trauma patients.

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.

Non-invasive detection of pulmonary pathogens in ventilator-circuit filters by PCR.

Ventilator associated pneumonia is a common and costly complication in critically ill and injured surgical patients. The diagnosis of pneumonia remains problematic and non-specific. Using clinical criteria, a diagnosis of pneumonia is typically not made until an infection is well established. Semi-quantitative cultures of endotracheal aspirate and broncho-alveolar lavage are employed to improve the accuracy of diagnosis but are invasive and require time for culture results to become available. We report data that show that an inexpensive, rapid and non-invasive alternative may exist. In particular we show that: 1). Bio-aerosols evolved in the breath of ventilated patients and captured in the hygroscopic condenser humidifier filter of the ventilator circuit contain pathogenic micro-organisms. 2). The number (CFU/ml) and identity (Genus, species) of the pathogens in the aerosol samples can rapidly and inexpensively be determined by PCR. 3). Data from a convenience sample of filters correlate with clinical findings from standard microbiological methods such as broncho-alveolar lavage. The evaluation of the bacterial load evolved in exhaled breath by PCR is amenable to repeated sampling. Since increasing bacterial burden is believed to correlate with the establishment of infection, the use of quantitative PCR may provide a method to rapidly, inexpensively, and effectively detect and diagnose the early onset of pneumonia and identify pathogens involved.

Does regionalization of acute care surgery decrease mortality?

BACKGROUND: During the initial development of an Emergency General Surgery (EGS) service, severity of illness (SOI) can be expected to be high and should decrease as the service matures. We hypothesize that a matured regional EGS service would show decreasing mortality and length of stay (LOS) over time. METHODS: We performed a retrospective study of a prospectively collected EGS registry data from 2004 to 2009. Patients were included if they had been discharged from the EGS service and were stratified by year of discharge. Systemic inflammatory response syndrome, sepsis, shock, peritonitis, perforation, and acute renal failure were used as markers of SOI. Patients were defined as high acuity if they had one or more of these SOI markers. Differences in mortality, LOS, intensive care unit admissions, SOI, charges, and distance were compared across and between years using nonparametric statistical tests (Fisher's exact, Wilcoxon rank-sum, and Kruskal-Wallis tests). RESULTS: A total of 3,439 patients met study criteria. The mean age was 47 years ± 17.5 years. The majority of the patients were female (1,813, 47.3%). The overall LOS was 6.4 days ± 9.4 days (median, 4 days). In all, 2,331 (67.8%) of the patients underwent operation. Over the course of the study period, the SOI indicators stabilized at between 13% and 17% of the patient population with at least one indicator. During that time period, mortality steadily decreased from 4.9% to 1.3% (p < 0.5). CONCLUSION: Despite consistently high SOI, a dedicated and matured EGS service demonstrated a decrease in mortality and LOS.

Provision of balanced nutrition protects against hypoglycemia in the critically ill surgical patient.

BACKGROUND: Intensive insulin therapy lowers blood glucose and improves outcomes but increases the risk of hypoglycemia. Typically, insulin protocols require a dextrose solution to prevent hypoglycemia. The authors hypothesized that the provision of balanced nutrition (enteral nutrition [EN] or parenteral nutrition [PN]) would be more protective against hypoglycemia (≤50 mg/dL) than carbohydrate alone. METHODS: A retrospective analysis was performed of patients treated with intensive insulin therapy and surviving ≥24 hours. The computer-based insulin protocol requires infusion of D10W at 30 mL/h if EN or PN is not provided. Nutrition provision was assessed in 2-hour increments, comparing periods of blood glucose control with and without balanced nutrition. The risk of hypoglycemia for each blood glucose measurement was estimated by multivariable regression. RESULTS: In total, 66,592 glucose measurements were collected on 1392 patients. Hypoglycemic events occurred in 5.8/1000 glucose tests after 2 hours without balanced nutrition compared to 2.2/1000 tests when balanced nutrition was given in the preceding 2 hours. In multivariable regression models, balanced nutrition was the strongest protective factor against hypoglycemia. Patients who did not receive balanced nutrition in the preceding 2 hours had a 3 times increase in the odds of a hypoglycemic event at their next glucose check (odds ratio = 3.6, P < .001). Providing carbohydrate alone was not protective. CONCLUSIONS: Balanced nutrition is associated with reduced risk of hypoglycemia. These results suggest that balanced nutrition should be given when insulin therapy is initiated. Future studies should evaluate the efficacy of EN vs PN in preventing hypoglycemia.

Colon anastomosis after damage control laparotomy: recommendations from 174 trauma colectomies.

BACKGROUND: Primary colonic anastomosis in trauma patients has been demonstrated to be safe. However, few studies have investigated this in the setting of damage control laparotomy. We hypothesized that colonic anastomosis for trauma patients requiring an open abdomen (OA) would have a higher anastomotic leak (AL) rate when compared with patients having an immediate abdominal closure following trauma laparotomy. METHODS: We performed a cohort comparison study of all trauma patients who underwent colectomy, between the years 2004 and 2009. Exclusion criteria were mortality within 24 hours of admission or colectomy for indications unrelated to injury. Data collected included age, gender, injury severity score, mechanism, length of stay, and mortality. Multivariable logistic regression was performed to assess the relationship of OA to our primary outcome measure, AL. RESULTS: Totally, 174 patients met study criteria. Fecal diversion was performed in 58 patients, and colonic anastomosis was performed in the remaining 116 patients. Patients with OA had a clinically significant increase in AL rate compared with immediate abdominal closure (6% vs. 27%, p=0.002). Logistic regression demonstrated that OA was independently associated with AL, with OA patients having more than a sixfold increase in odds of AL compared with those who were closed (odds ratio=6.37, p=0.002, area under the receiver operator curve=0.72). Transfusion requirement and left-sided anastomosis were risk factors for leak. CONCLUSIONS: Patients with a colonic anastomosis and an OA have an unacceptably high leak rate compared with those who undergo reconstruction with immediate closure. Given the significant risk of AL, colonic anastomosis should not be routinely performed in patients with OA.

Does hypoxia affect intensive care unit delirium or long-term cognitive impairment after multiple trauma without intracranial hemorrhage?

BACKGROUND: Within the traumatic brain injury population, outcomes are affected by hypoxic events in the early injury period. Previous work shows a high prevalence of cognitive deficits in patients with multiple injuries who do not have intracranial hemorrhage identified on admission head computed tomography scan. We hypothesize that intensive care unit (ICU) delirium and long-term cognitive impairment (LTCI) are more likely in patients who have a hypoxic event within the first 48 hours of ICU admission. METHODS: A total of 173 patients with multiple injuries (Injury Severity Score [ISS] >15) who presented to a Level I trauma center from July 2006 to July 2007 were enrolled in a study on long-term cognitive deficit. Ninety-seven patients required ICU management and all had continuous oxygen saturation data collected. The Confusion Assessment Method for the ICU was collected twice a day on all patients in ICU. Of the total enrolled population, 108 (62%) were evaluated 12 months after discharge by neuropsychological tests. Cognitive impairment was defined as having 2 neuropsychological test scores, 1.5 standard deviations below the mean or 1 neuropsychological test score, and 2 standard deviations below the mean. Demographic data, ISS, initial 24-hour blood requirements, presence of hypoxia (SpO(2) <90% and <85%) or hypotension (systolic blood pressure <90 mm Hg), emergency department (ED) pulse, Glasgow Coma Scale score, ventilator and ICU days were recorded. Significant univariate identification of clinical variables was used for multivariate analysis. RESULTS: Fifty-five of 97 ICU patients (57%) were Confusion Assessment Method-ICU positive for delirium and 59 of 108 (55%) demonstrated cognitive impairment at 12-month follow-up. There was no significant association between hypoxia and ICU delirium (74.5% vs. 74%; p = 0.9) or LTCI (89% vs. 83%; p = 0.5). Ventilator days (8.7 ± 8.9 vs. 2.9 ± 4.6; p < 0.0001), ED pulse (109 ± 28.5 vs. 94 ± 22.8; p = 0.01), and blood transfusions (10 U ± 10.8 U vs. 5 U ± 5.3 U; p = 0.015) were significant independent predictors of delirium. Ventilator days (odds ratio, 1.16; 95% confidence interval, 1.05-1.29; p = 0.004) and ED pulse (odds ratio, 1.02; 95% confidence interval, 1.00-1.04; p = 0.03) remained significant predictors of ICU delirium after adjusting for ISS, hypoxic state, blood transfusions, and ED blood pressure. Among ED Glasgow Coma Scale score (10.5 ± 5.1 vs. 11.4 ±5.5; p = 0.7), ISS (33.3 ± 10.1 vs. 32.2 ± 9.0; p = 0.5), ventilator days (6.5 ± 7.5 vs. 6.2 ± 8.8; p = 0.4), blood transfusions (8.1 ± 6.8 vs. 9.4 ± 8.1; p = 0.4), and delirium (62% vs. 62.5%; p = 0.9), there were no significant univariate associations with LTCI. CONCLUSIONS: Hypoxic events in the ICU do not have a direct correlation with ICU delirium or LTCI in the patients with multiple injuries without evidence of intracranial hemorrhage.

Increasing blood glucose variability heralds hypoglycemia in the critically ill.

BACKGROUND: Control of hyperglycemia improves outcomes, but increases the risk of hypoglycemia. Recent evidence suggests that blood glucose variability (BGV) is more closely associated with mortality than either isolated or mean BG. We hypothesized that differences in BGV over time are associated with hypoglycemia and can be utilized to estimate risk of hypoglycemia (<50 mg/dL). MATERIALS AND METHODS: Patients treated with intravenous insulin in the Surgical Intensive Care Unit of a tertiary care center formed the retrospective cohort. Exclusion criteria included death within 24 h of admission. We describe BGV in patients over time and its temporal relationship to hypoglycemic events. The risk of hypoglycemia for each BG measurement was estimated in a multivariable regression model. Predictors were measures of BGV, infusions of dextrose and vasopressors, patient demographics, illness severity, and BG measurements. RESULTS: A total of 66,592 BG measurements were collected on 1392 patients. Hypoglycemia occurred in 154 patients (11.1%). Patient BGV fluctuated over time, and increased in the 24 h preceding a hypoglycemic event. In crude and adjusted analyses, higher BGV was positively associated with a hypoglycemia (OR 1.41, P < 0.001). Previous hypoglycemic events and time since previous BG measurement were also positively associated with hypoglycemic events. Severity of illness, vasopressor use, and diabetes were not independently associated with hypoglycemia. CONCLUSIONS: BGV increases in the 24 h preceding hypoglycemia, and patients are at increased risk during periods of elevated BG variability. Prospective measurement of variability may identify periods of increased risk for hypoglycemia, and provide an opportunity to mitigate this risk.

Trends in estradiol during critical illness are associated with mortality independent of admission estradiol.

BACKGROUND: We have previously demonstrated that elevated serum estradiol (E(2)) at intensive care unit (ICU) admission is associated with death in the critically ill, regardless of sex. However, little is known about how changes in initial E(2) during the course of care might signal increasing patient acuity or risk of death. We hypothesized that changes from baseline serum E(2) during the course of critical illness are more strongly associated with mortality than a single E(2) level at admission. STUDY DESIGN: A prospective cohort of 1,408 critically ill or injured nonpregnant adult patients requiring ICU care for ≥48 hours with admission and subsequent E(2) levels was studied. Demographics, illness severity, and E(2) levels were examined, and the probability of mortality was modeled with multivariate logistic regression. Changes in E(2) were examined by both analysis of variance and logistic regression. RESULTS: Overall mortality was 14.1% [95% confidence interval (CI) 12.3% to 16%]. Both admission and subsequent E(2) levels were independently associated with mortality [admission E(2) odds ratio 1.1 (CI 1.0 to 1.2); repeat estradiol odds ratio 1.3 (CI 1.2 to1.4)], with subsequent values being stronger. Changes in E(2) were independently associated with mortality [odds ratio 1.1 (CI 1.0 to 1.16)] and improved regression model performance. The regression model produced an area under the receiver operating characteristic curve of 0.80 (CI 0.77 to 0.83). CONCLUSIONS: Although high admission levels of E(2) are associated with mortality, changes from baseline E(2) in critically ill or injured adults are independently associated with mortality. Future studies of E(2) dynamics may yield new indicators of patient acuity and illuminate underlying mechanisms for targeted therapy.

Core temperature variation is associated with heart rate variability independent of cardiac index: a study of 278 trauma patients.

PURPOSE: The purpose of this study is to determine if temperature extremes are associated with reduced heart rate variability (HRV) and "cardiac uncoupling." MATERIALS AND METHODS: This was a retrospective, observational cohort study performed on 278 trauma intensive care unit admissions that had continuous HR, cardiac index (CI), and core temperature data from "thermodilution" Swan-Ganz catheter. Dense (captured second-by-second) physiologic data were divided into 5-minute intervals (N = 136 133; 11 344 hours of data). Mean CI, mean temperature, and integer HR SD were computed for each interval. Critically low HRV was defined as HR SD from 0.3 to 0.6 beats per minute. Temperature extremes were defined as less than 36°C or greater than 39°C. RESULTS: Low HRV and CI vary with temperature. Temperature extremes are associated with increased risk for critically low HRV (odds ratio, >1.8). Cardiac index increases with temperature until hyperthermia (>40°C). At temperature extremes, changes in CI were not explained solely by changes in HR. CONCLUSIONS: The conclusions of this study are (1) temperature extremes are associated with low HRV, potentially reflecting cardiac autonomic dysfunction; (2) CI increases with temperature; and (3) HRV provides additional physiologic information unobtainable via current invasive cardiac monitoring and current vital signs.

Triaging to a regional acute care surgery center: distance is critical.

BACKGROUND: In acute care surgery, predicting mortality is important to determine appropriate patient transfer to a regional emergency general surgery (EGS) center. We hypothesized that distance to a referral center and severity of illness (SOI) would be predictors of death. METHODS: We performed a retrospective analysis of a prospectively collected EGS registry from 2004 to 2008. The study population consisted of all patients discharged from the EGS service with an available home zip code in the registry. Study data included age, gender, length of stay (LOS), intensive care unit (ICU) LOS, distance between our facility and patient home zip code, and need for operative management. Systemic inflammatory response syndrome/sepsis/shock, peritonitis, perforation, and acute renal failure were used as SOI indicators. Mortality at discharge was the primary outcome. Patients were stratified by survival and compared using non-parametric statistical tests. Logistic regression assessed the simultaneous contribution of age, SOI, and distance to risk of death. RESULTS: A total of 3,439 patients met study criteria. Females slightly outnumbered males (1,813, 52.7%) with a median age of 47 years. The overall LOS was 6.4 days±9.3 days, and 2,331 (67.8%) of the patients underwent operation. Mean distance was 41.5 miles±51.2 miles (median, 22.2). Overall mortality was 2.7%. Increasing distance, age, and presence of SOI indicators were associated with mortality in univariable analyses. In multivariable logistic regression controlling for patient age and SOI, increasing distance in miles was related to increased mortality (odds ratio, 1.005; p<0.001). This odds ratio equates to a doubling in odds of death for each 132 miles between our center and the patient's home zip code. CONCLUSION: Age, SOI, and distance from a regional referral center explain much of the variation in mortality and can be used for triage to regional EGS centers.

The genetics of heterotopic ossification: insight into the bone remodeling pathway.

OBJECTIVES: Heterotopic Ossification (HO) is a significant complication after trauma occurring in 12% to 25% of fractures. Although clinical predictors have been studied to determine the likelihood of developing HO, the results have been inconsistent. This study examines genetic predictors of the HO phenotype to identify the "at-risk" patient and increase the understanding of the genetic contribution to the formation of HO. METHODS: We examined the frequency of 61 single nucleotide polymorphisms (SNPs) in 1095 consecutive trauma patients with fractures. Radiographic studies of these patients were examined for HO in follow-up. Ten percent of the patients in the study demonstrated radiographic evidence of HO. Multivariate logistic regression was used to analyze each SNP independently while adjusting for severity of injury (as measured by the Trauma and Injury Severity Score). RESULTS: Three SNPs (beta2-adrenergic receptor, toll-like receptor 4, complement factor H) were identified that were associated with an increased or decreased frequency of HO. The less common polymorphism of the beta2-adrenergic receptor gene was associated with increased risk of HO. For toll-like receptor 4 and complement factor H, the less common polymorphism was associated with a decreased risk of HO. CONCLUSIONS: The SNPs identified as predictors of HO formation are representative of the adrenergic system, immune system, and the alternative complement system. This represents the interplay of multiple pathways that affect bone remodeling, aberrations of which may be found in the genome.

Systems initiatives reduce healthcare-associated infections: a study of 22,928 device days in a single trauma unit.

BACKGROUND: "Implementation research" promotes the systematic conversion of evidence-based principles into routine practice to improve the quality of care. We hypothesized a system-based initiative to reduce nosocomial infection would lower the incidence of ventilator-associated pneumonia (VAP), urinary tract infection (UTI), and bloodstream infection (BSI). METHODS: From January 2006 to April 2008, 7,364 adult trauma patients were admitted, of which 1,953 (27%) were admitted to the trauma intensive care unit and comprised the study group. Tight glycemic control was maintained using a computer algorithm for continuous insulin administration based on every 2-hour blood glucose testing. Centers for Disease Control and Prevention definitions of nosocomial infections were used. Evidence-based infection reduction strategies included the following: a VAP bundle (spontaneous breathing, Richmond Agitation-Sedation Scale, oral hygiene, bed elevation, and deep vein thrombosis/stress ulcer prophylaxis), UTI (expert insertion team and Foley removal/change at 5 days), and BSI (maximum barrier precautions, chlorhexidine skin prep, line management protocol). An electronic dashboard identified the at-risk population, and designated auditors monitored the compliance. Infection rates (events per 1,000 device days) were measured over time and compared annually using Fisher's exact test. RESULTS: The study group had 22,928 device exposure days: 6,482 ventilator days, 9,037 urinary catheter days, and 7,399 central line days. Patient acuity, demographics, and number of device days did not vary significantly year-to-year. Annual infection rates declined between 2006 and 2008, and decreases in UTI and BSI rates were statistically significant (p < 0.05). These decreases pushed UTI and BSI rates below Centers for Disease Control and Prevention norms. CONCLUSIONS: Over 28 months, a systems approach to reducing nosocomial infection rates after trauma decreased nosocomial infections: UTI (76.3%), BSI (74.1%), and VAP (24.9%). Our experience suggests that infection reduction requires (1) an evidence-based plan; (2) MD and staff education/commitment; (3) electronic documentation; and (4) auditors to monitor and ensure compliance.

Acute care surgery program: mentoring fellows and patient outcomes.

BACKGROUND: Acute care surgery programs have demonstrated that trauma patient outcomes have not changed with the addition of emergency general surgery (EGS) responsibilities. EGS patient outcomes and the mentoring of fellows on EGS service have not been previously studied. We hypothesize that EGS patient outcomes would not differ by provider on a service driven by evidence-based medicine (EBM) protocols. PATIENTS AND METHODS: Retrospective study of prospectively collected EGS repository. academic level I trauma center, and regional EGS referral center from 2003 to 2007. There were 14 faculty and seven fellows during the study period. EGS coverage is a full week, with weeknight coverage by the in-house trauma/EGS faculty. Fellows are mentored by designated faculty while on service, who discuss patients, assist in the OR, or assume care if necessary. Data collected included age, gender, LOS, ICU LOS, ventilator days, disposition (home/rehab), and infectious complications(IC) (VAP, BSI, UTI, SSI). Primary outcome was mortality. RESULTS: 1769 patients met study criteria. The mean age was 47.1 (+/-18), 47% were males. The average ICU LOS was 2.9 d (+/-7.9), ventilator d 2.6 (+/-7.6); 82.1% were discharged home and 13.7% were referred to rehab. There was no statistical difference in mortality, LOS, ICU LOS, disposition, ventilator d, and IC between faculty and fellow providers. CONCLUSIONS: An EGS service with EBM protocols assures consistency in patient outcomes independent of provider level: faculty or fellows. Our model for mentoring fellows did not decrease EGS patient outcomes.

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.