The Effects of Missed Doses of Antibiotics on Hospitalized Patient Outcomes.

BACKGROUND: Missing doses of antibiotics in hospitalized patients is a well-described but inadequately recognized issue. We hypothesized that missing doses of antibiotics decreases quality of care. METHODS: Retrospective study on patients admitted to the Shock Trauma ICU from February to June 2015. Patients prescribed a multidose course of antibiotics were evaluated. A missed antibiotic dose was one ordered but never given (a completely missed dose) or a dose that was not given within an hour before or after the planned time (an off-schedule missed dose). Patient outcomes included a positive culture, ventilator, ICU and hospital length of stay (LOS), and mortality. Multiple statistical methods were used as appropriate; significance was set as P < 0.05. RESULTS: For the 5-mo study period, 280 patients were admitted and 200 met inclusion criteria. Eight percent of patients (16/200) did not miss any antibiotic doses, 39% (77/200) had only off-schedule doses, 2% (4/200) had only completely missed doses, and 51% (103/200) had both off-schedule and completely missed doses. For the 200 patients, 8167 doses were ordered and 2096 (26%) were missed. Adjusting for age, gender, BMI, injury severity score, and doses of antibiotics showed that those who miss doses off-schedule had longer LOS than those who do not miss doses of antibiotics. There was a significant nonlinear relationship between LOS and frequency of early (P-value = 0.02) and late (P-value = 0.01) doses. CONCLUSIONS: To reduce length of hospital stay and optimize quality, methods to improve compliance with antibiotic dosing schedules should be investigated.

Coagulopathy as a predictor of mortality after penetrating traumatic brain injury.

STUDY HYPOTHESIS: Traumatic brain injury (TBI) is a leading cause of mortality with penetrating TBI (p-TBI) patients having worse outcomes. These patients are more likely to be coagulopathic than blunt TBI (b-TBI) patients, thus we hypothesize that coagulopathy would be an early predictor of mortality. METHODS: We identified highest-level trauma activation patients who underwent an admission head CT and had ICU admission orders from August 2009-May 2013, excluding those with polytrauma and anticoagulant use. Rapid thrombelastography (rTEG) was obtained after emergency department (ED) arrival and coagulopathy was defined as follows: ACT≥128s, KT≥2.5s, angle≤56°, MA≤55mm, LY-30≥3.0% or platelet count≤150,000/µL. Regression modeling was used to assess the association of coagulopathy on mortality. RESULTS: 1086 patients with head CT scans performed and ICU admission orders were reviewed. After exclusion criteria were met, 347 patients with isolated TBI were analyzed-99 (29%) with p-TBI and 248 (71%) with b-TBI. Patients with p-TBI had a higher mortality (41% vs. 10%, p<0.0001) and a greater incidence of coagulopathy (64% vs. 51%, p<0.003). After dichotomizing p-TBI patients by mortality, patients who died were younger and were more coagulopathic. When adjusting for factors available on ED arrival, coagulopathy was found to be an early predictor of mortality (OR 3.99, 95% CI 1.37, 11.72, p-value=0.012). CONCLUSIONS: This study demonstrates that p-TBI patients with significant coagulopathy have a poor prognosis. Coagulopathy, in conjunction with other factors, can be used to earlier identify p-TBI patients with worse outcomes and represents a possible area for intervention.

Trends in potentially preventable trauma deaths between 2005-2006 and 2012-2013.

BACKGROUND: Most studies of trauma deaths include non-preventable deaths, potentially limiting successful intervention efforts. In this study we aimed to compare the potentially preventable trauma deaths between 2 time periods at our institution. METHODS: Trauma patients who died in our hospital in 2005-2006 or 2012-2013 were included, non-preventable deaths were excluded from analysis. The Mann-Whitney and chi square test were used to compare variables between both time periods. RESULTS: 80% of deaths were non-preventable. Between the study time periods there was a decrease in potentially preventable deaths, from 29% to 12%, p < 0.001. Head injury deaths significantly decreased (40.6%-24.6%, p = 0.03), while hemorrhage deaths were stable during both time periods (47.6%-43.1%, p = 0.55). CONCLUSION: Potentially preventable trauma deaths decreased during the study period. Hemorrhage remains constant as the leading cause of potentially preventable deaths. Continued research to improve survival from hemorrhage is warranted.

Absences of Endothelial Microvesicle Changes in the Presence of the Endotheliopathy of Trauma.

INTRODUCTION: Severe trauma is accompanied by endothelial glycocalyx disruption, which drives coagulopathy, increasing transfusion requirements and death. This syndrome has been termed endotheliopathy of trauma (EOT). Some have suggested EOT results from endothelial cellular damage and apoptosis. Endothelial microvesicles (EMVs) represent cellular damage. We hypothesized that EOT is associated with endothelial damage and apoptosis resulting in an increase in circulating EMVs. METHODS: Prospective, observational study enrolling severely injured patients. Twelve patients with EOT, based on elevated Syndecan-1 levels, were matched with 12 patients with lower levels, based on Injury Severity Score (ISS), abbreviated injury scale profile, and age. Thrombelastography and plasma levels of biomarkers indicative of cellular damage were measured from blood samples collected on admission. EMVs were determined by flow cytometry using varied monoclonal antibodies associated with endothelial cells. Significance was set at P < 0.05. RESULTS: Admission physiology and ISS (29 vs. 28) were similar between groups. Patients with EOT had higher Syndecan-1, 230 (158, 293) vs. 19 (14, 25) ng/mL, epinephrine, and soluble thrombomodulin levels. Based on thrombelastography, EOT had reductions in clot initiation, amplification, propagation and strength, and a greater frequency of transfusion, 92% vs. 33%. There were no differences in EMVs irrespective of the antibody used. Plasma norepinephrine, sE-selectin, sVE-cadherin, and histone-complexed DNA fragments levels were similar. CONCLUSION: In trauma patients presenting with EOT, endothelial cellular damage or apoptosis does not seem to occur based on the absence of an increase in EMVs and other biomarkers. Thus, this suggests endothelial glycocalyx disruption is the underlying primary cause of EOT.

Early Identification of the Patient with Endotheliopathy of Trauma by Arrival Serum Albumin.

OBJECTIVE: Traumatic endotheliopathy (EoT) is associated with glycocalyx breakdown and capillary leak resulting in the extravasation of proteins. We hypothesized that lower serum albumin levels are associated with EoT, poor outcomes, and can be used for early EoT screening in trauma patients. METHODS: We enrolled severely injured trauma patients with serum albumin levels available on admission. Syndecan-1 and soluble thrombomodulin were quantified from plasma by ELISA. Demographic and clinical data were obtained. We evaluated the association of serum albumin and EoT+ (syndecan-1 level ≥40 ng/mL), followed by dichotomization by serum albumin level, and subgroup comparisons. RESULTS: Of the 258 patients enrolled 92 (36.0%) were EoT+ (syndecan-1 ≥ 40 ng/mL). Median albumin levels in the EoT+ group were 3.4 g/dL, and 3.8 g/dL in EoT- patients, P < 0.05. In a multifactorial analysis, lower albumin levels were inversely associated with the likelihood of EoT+. With receiver characteristic curve analysis, we determined a cutoff albumin level < 3.6 g/dL for EoT+ prediction (area under the curve 0.70; 95% CI: 0.63, 0.77). After dichotomizing by albumin <3.6 or ≥3.6 g/dL, 51.5% of patients had low albumin. Low albumin patients were more likely to have EoT+, as well as higher soluble thrombomodulin (both P < 0.05). Furthermore, they required more frequently blood transfusions, had fewer hospital-free days and higher mortality rate than those with normal albumin. CONCLUSIONS: EoT is a syndrome associated with leakage of albumin from the intravascular compartment, which re-emphasizes that arrival albumin may be a novel and timely approach to the identification of patients needing endothelial rescue therapy.

Abnormalities of laboratory coagulation tests versus clinically evident coagulopathic bleeding: results from the prehospital resuscitation on helicopters study (PROHS).

BACKGROUND: Laboratory-based evidence of coagulopathy (LC) is observed in 25-35% of trauma patients, but clinically-evident coagulopathy (CC) is not well described. METHODS: Prospective observational study of adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers in 2015. Patients meeting predefined highest-risk criteria were divided into CC+ (predefined as surgeon-confirmed bleeding from uninjured sites or injured sites not controllable by sutures) or CC-. We used a mixed-effects, Poisson regression with robust error variance to test the hypothesis that abnormalities on rapid thrombelastography (r-TEG) and international normalized ratio (INR) were independently associated with CC+. RESULTS: Of 1,019 highest-risk patients, CC+ (n=41, 4%) were more severely injured (median ISS 32 vs 17), had evidence of LC on r-TEG and INR, received more transfused blood products at 4 hours (37 vs 0 units), and had greater 30-day mortality (59% vs 12%) than CC- (n=978, 96%). The overall incidence of LC was 39%. 30-day mortality was 22% vs 9% in those with and without LC. In two separate models, r-TEG K-time >2.5 min (RR 1.3, 95% CI 1.1-1.7), r-TEG mA <55 mm (RR 2.5, 95% CI 2.0-3.2), platelet count <150 x 109/L (RR 1.2, 95% CI 1.1-1.3), and INR >1.5 (RR 5.4, 95% CI 1.8-16.3) were independently associated with CC+. A combined regression model was not generated because too few patients underwent both r-TEG and INR. CONCLUSION: CC was rare compared to LC. CC was associated with poor outcomes and impairment of both clotting factor and platelet-mediated coagulation components.

Trends in 1029 trauma deaths at a level 1 trauma center: Impact of a bleeding control bundle of care.

BACKGROUND: Over the last decade the age of trauma patients and injury mortality has increased. At the same time, many centers have implemented multiple interventions focused on improved hemorrhage control, effectively resulting in a bleeding control bundle of care. The objective of our study was to analyze the temporal distribution of trauma-related deaths, the factors that characterize that distribution and how those factors have changed over time at our urban level 1 trauma center. METHODS: Records at an urban Level 1 trauma center were reviewed. Two time periods (2005-2006 and 2012-2013) were included in the analysis. Mortality rates were directly adjusted for age, gender and mechanism of injury. The Mann-Whitney and chi square tests were used to compare variables between periods, with significance set at 0.05. RESULTS: 7080 patients (498 deaths) were examined in 2005-2006, while 8767 patients (531 deaths) were reviewed in 2012-2013. The median age increased 6 years, with a similar increase in those who died. In patients that died, no differences by gender, race or ethnicity were observed. Fall-related deaths are now the leading cause of death. Traumatic brain injury (TBI) and hemorrhage accounted for >91% of all deaths. TBI (61%) and multiple organ failure or sepsis (6.2%) deaths were unchanged, while deaths associated with hemorrhage decreased from 36% to 25% (p<0.01). Across time periods, 26% of all deaths occurred within one hour of hospital arrival, while 59% occurred within 24h. Unadjusted mortality dropped from 7.0% to 6.1 (p=0.01) and in-hospital mortality dropped from 6.0% to 5.0% (p<0.01). Adjusted mortality dropped 24% from 7.6% (95% CI: 6.9-8.2) to 5.8% (95% CI: 5.3-6.3) and in-hospital mortality decreased 30% from 6.6% (95% CI: 6.0-7.2) to 4.7 (95% CI: 4.2-5.1). CONCLUSIONS: Over the same time frame of this study, increases in trauma death across the globe have been reported. This single-site study demonstrated a significant reduction in mortality, attributable to decreased hemorrhagic death. It is possible that efforts focused on hemorrhage control interventions (a bleeding control bundle) resulted in this reduction. These changing factors provide guidance on future prevention and intervention efforts.

Early plasma transfusion is associated with improved survival after isolated traumatic brain injury in patients with multifocal intracranial hemorrhage.

BACKGROUND: Plasma-based resuscitation improves outcomes in trauma patients with hemorrhagic shock, while large-animal and limited clinical data suggest that it also improves outcomes and is neuroprotective in the setting of combined hemorrhage and traumatic brain injury. However, the choice of initial resuscitation fluid, including the role of plasma, is unclear for patients after isolated traumatic brain injury. METHODS: We reviewed adult trauma patients admitted from January 2011 to July 2015 with isolated traumatic brain injury. "Early plasma" was defined as transfusion of plasma within 4 hours. Purposeful multiple logistic regression modeling was performed to analyze the relationship of early plasma and inhospital survival. After testing for interaction, subgroup analysis was performed based on the pattern of brain injury on initial head computed tomography: epidural hematoma, intraparenchymal contusion, subarachnoid hemorrhage, subdural hematoma, or multifocal intracranial hemorrhage. RESULTS: Of the 633 isolated traumatic brain injury patients included, 178 (28%) who received early plasma were injured more severely coagulopathic, hypoperfused, and hypotensive on admission. Survival was similar in the early plasma versus no early plasma groups (78% vs 84%, P = .08). After adjustment for covariates, early plasma was not associated with improved survival (odds ratio 1.18, 95% confidence interval 0.71-1.96). On subgroup analysis, multifocal intracranial hemorrhage was the largest subgroup with 242 patients. Of these, 61 (25%) received plasma within 4 hours. Within-group logistic regression analysis with adjustment for covariates found that early plasma was associated with improved survival (odds ratio 3.34, 95% confidence interval 1.20-9.35). CONCLUSION: Although early plasma transfusion was not associated with improved in-hospital survival for all isolated traumatic brain injury patients, early plasma was associated with increased in-hospital survival in those with multifocal intracranial hemorrhage.

Syndecan-1: A Quantitative Marker for the Endotheliopathy of Trauma.

BACKGROUND: Endothelial glycocalyx breakdown elicits syndecan-1 shedding and endotheliopathy of trauma (EoT). We hypothesized that a cutoff syndecan-1 level can identify patients with endothelial dysfunction who would have poorer outcomes. STUDY DESIGN: We conducted a prospective observational study. Trauma patients with the highest level of activation admitted from July 2011 through September 2013 were eligible. We recorded demographics, injury type/severity (Injury Severity Score), physiology and outcomes data, and quantified syndecan-1 and soluble thrombomodulin from plasma with ELISAs. With receiver operating characteristic curve analysis, we defined EoT+ as the syndecan-1 cutoff level that maximized the sum of sensitivity and specificity (Youden index) in predicting 24-hour in-hospital mortality. We stratified by this cutoff and compared both groups. Factors associated with 30-day in-hospital mortality were assessed with multivariable logistic regression (adjusted odds ratios and 95% CIs reported). RESULTS: From receiver operating characteristic curve analysis (area under the curve = 0.71; 95% CI 0.58 to 0.84), we defined EoT+ as syndecan-1 level ≥40 ng/mL (sensitivity = 0.62, specificity = 0.73). Of the 410 patients evaluated, 34% (n = 138) were EoT+ patients, who presented with higher Injury Severity Scores (p < 0.001) and blunt trauma frequency (p = 0.016) than EoT- patients. Although EoT+ patients had lower systolic blood pressure (median 119 vs 128 mmHg; p < 0.001), base excess and hemoglobin were similar between groups. The proportion of transfused (EoT+ 71.7% vs EoT- 36.4%; p < 0.001) and deceased EoT+ patients (EoT+ 24.6% vs EoT- 12.1%; p < 0.001) was higher. EoT+ was significantly associated with 30-day in-hospital mortality (adjusted odds ratio = 2.23; 95% CI 1.22 to 4.04). CONCLUSIONS: A syndecan-1 level ≥40 ng/mL identified patients with significantly worse outcomes, despite admission physiology similar to those without the condition.

Multicenter retrospective study of noncompressible torso hemorrhage: Anatomic locations of bleeding and comparison of endovascular versus open approach.

BACKGROUND: Rational development of technology for rapid control of noncompressible torso hemorrhage (NCTH) requires detailed understanding of what is bleeding. Our objectives were to describe the anatomic location of truncal bleeding in patients presenting with NCTH and compare endovascular (ENDO) management versus open (OPEN) management. METHODS: This is a retrospective study of adult trauma patients with NCTH admitted to four urban Level I trauma centers in the Houston and San Antonio metropolitan areas in 2008 to 2012. Inclusion criteria include named axial torso vessel disruption, Abbreviated Injury Scale chest or abdomen score of 3 or higher with shock (base excess, <-4) or truncal operation in 90 minutes or less, or pelvic fracture with ring disruption. Exclusion criteria include isolated hip fractures, falls from standing, or prehospital cardiopulmonary resuscitation. After dichotomizing into OPEN, ENDO, and resuscitative thoracotomy (RT) groups based on the initial approach to control NCTH, a mixed-effects Poisson regression with robust error variance (controlling for age, mechanism, Injury Severity Score, shock, hypotension, and severe head injury as fixed effects and site as a random effect) was used to test the hypothesis that ENDO was associated with reduced in-hospital mortality in NCTH patients. RESULTS: Five hundred forty-three patients with NCTH underwent ENDO (n = 166, 31%), OPEN (n = 309, 57%), or RT (n = 68, 12%). Anatomic bleeding locations were 25% chest, 41% abdomen, and 31% pelvis. ENDO was used to treat relatively few types of vascular injuries, whereas OPEN and RT injuries were more diverse. ENDO patients had more blunt trauma (95% vs. 34% vs. 32%); severe injuries (median Injury Severity Score, 34 vs. 27 vs. 21), and increased time to intervention (median, 298 vs. 92 vs. 51 minutes) compared with OPEN and RT. Mortality was 15% versus 20% versus 79%. ENDO was associated with decreased mortality compared to OPEN (relative risk, 0.58; 95% confidence interval, 0.46-0.73). CONCLUSION: Although ENDO may reduce mortality in NCTH patients, significant group differences limit the generalizability of this finding. LEVEL OF EVIDENCE: Therapeutic, level V.

Multicenter observational prehospital resuscitation on helicopter study.

BACKGROUND: Earlier use of in-hospital plasma, platelets, and red blood cells (RBCs) has improved survival in trauma patients with severe hemorrhage. Retrospective studies have associated improved early survival with prehospital blood product transfusion (PHT). We hypothesized that PHT of plasma and/or RBCs would result in improved survival after injury in patients transported by helicopter. METHODS: Adult trauma patients transported by helicopter from the scene to nine Level 1 trauma centers were prospectively observed from January to November 2015. Five helicopter systems had plasma and/or RBCs, whereas the other four helicopter systems used only crystalloid resuscitation. All patients meeting predetermined high-risk criteria were analyzed. Patients receiving PHT were compared with patients not receiving PHT. Our primary analysis compared mortality at 3 hours, 24 hours, and 30 days, using logistic regression to adjust for confounders and site heterogeneity to model patients who were matched on propensity scores. RESULTS: Twenty-five thousand one hundred eighteen trauma patients were admitted, 2,341 (9%) were transported by helicopter, of which 1,058 (45%) met the highest-risk criteria. Five hundred eighty-five of 1,058 patients were flown on helicopters carrying blood products. In the systems with blood available, prehospital median systolic blood pressure (125 vs 128) and Glasgow Coma Scale (7 vs 14) was significantly lower, whereas median Injury Severity Score was significantly higher (21 vs 14). Unadjusted mortality was significantly higher in the systems with blood products available, at 3 hours (8.4% vs 3.6%), 24 hours (12.6% vs 8.9%), and 30 days (19.3% vs 13.3%). Twenty-four percent of eligible patients received a PHT. A median of 1 unit of RBCs and plasma were transfused prehospital. Of patients receiving PHT, 24% received only plasma, 7% received only RBCs, and 69% received both. In the propensity score matching analysis (n = 109), PHT was not significantly associated with mortality at any time point, although only 10% of the high-risk sample were able to be matched. CONCLUSION: Because of the unexpected imbalance in systolic blood pressure, Glasgow Coma Scale, and Injury Severity Score between systems with and without blood products on helicopters, matching was limited, and the results of this study are inconclusive. With few units transfused to each patient and small outcome differences between groups, it is likely large, multicenter, randomized studies will be required to detect survival differences in this important population. LEVEL OF EVIDENCE: Level II.

Predicting progressive hemorrhagic injury from isolated traumatic brain injury and coagulation.

BACKGROUND: Progressive hemorrhagic injury (PHI) in traumatic brain injury (TBI) patients is associated with poor outcomes. Early prediction of PHI is difficult yet vital. We hypothesize that TBI subtype and coagulation would be predictors of PHI. METHODS: This was a retrospective analysis of highest level activation adult trauma patients with evidence of TBI (head Abbreviated Injury Scale ≥3). Coagulopathy was determined using rapid thrombelastography (r-TEG), complete blood counts, and conventional coagulation tests obtained on arrival. Patients were dichotomized into PHI and stable groups based on head computerized CT. Subtypes of TBI included subdural hematoma, intraparenchymal contusions (IPC), subarachnoid hemorrhage, epidural hematoma, and combined. Data are reported as median values with interquartile range (IQR). Multivariate logistic regression was used to assess the effect of subtype and coagulation on PHI. RESULTS: We included 279 isolated TBI patients who met study criteria. There were 157 patients (56%) who experienced PHI; 122 (44%) were stable on repeat CT. Patients with PHI were older, had fewer hospital-free days, and higher mortality (all P < .001). No differences were noted in r-TEG parameters between groups; however, coagulopathy and age were independent predictors of progression in all subtypes (odds ratio [OR], 1.81; 95% CI, 1.09-3.01 [P = .021]; OR, 1.02, 95% CI, 1.01-1.04 [P = .006]). Controlling for age, Glasgow Coma Scale score, and coagulopathy, patients with IPC were more likely to experience PHI (OR, 4.49; 95% CI, 2.24-8.98; P < .0001). CONCLUSION: This study demonstrates that older patients with coagulation abnormalities and IPC on admission are more likely to experience PHI, identifying a target population for earlier therapies.

Variability in the management of superficial venous thrombophlebitis among phlebologists and vascular surgeons.

INTRODUCTION: This study aimed to compare management patterns of patients with superficial venous thrombophlebitis (SVT) among phlebologists and vascular surgeons. METHODS: A survey was provided to practitioners who attended the American Venous Forum meeting in 2011. Statistical analysis included descriptive statistics, unpaired t tests, and Friedman's test for correlation. RESULTS: There were 354 US or Canadian health care providers of whom 169 were phlebologists and 185 were vascular surgeons. There was a significant different in anticoagulation administration and duration (P = .034, P = .032, respectively). Friedman's test for correlation between multiple surgical treatments showed no correlation between surgical treatments tested with all treatments having an equal distribution in our data. Follow-up differed between groups with vascular surgeons following up with imaging more than phlebologists (P = .03). CONCLUSION: Our data indicate that there is no consensus between or among phlebologists or vascular surgeons as to the surgical management of superficial venous thrombophlebitis, duration of follow-up, and anticoagulation parameters.