Fibrinolysis Resistance After Injury Is a Risk Factor for a Hospital-Acquired Pneumonia-Like Disease Pattern.

Background: Pneumonia is associated with increased morbidity and costs in the intensive care unit (ICU). Its early identification is key for optimal outcomes, but early biomarkers are lacking. Studies suggest that fibrinolysis resistance (FR) after major abdominal surgery is linked to an increased risk of infection. Patients and Methods: Patients in a randomized controlled trial for hemorrhagic shock were evaluated for FR. Fibrinolysis resistance was quantified by thrombelastography with exogenous tissue plasminogen activator (tPA-TEG) at 24- and 48-hours post-injury and measuring LY30 (%). A receiver-operating characteristics (ROC) curve analysis was used to identify a cutoff for increased risk of pneumonia, which was then validated in ICU patients at risk for venous thromboembolism (VTE). Multivariable logistic regression was used to control for confounders. Results: Forty-nine patients in the hemorrhagic shock cohort had tPA-TEGs at 24- and 48-hours (median ISS, 27; 7% pneumonia). A composite tPA-TEG LY30 of less than 4% at 24 and 48 hours was found to be the optimal cutoff for increased risk of pneumonia. This cohort had a seven-fold increased rate of pneumonia (4% vs. 28%; p = 0.048). Eighty-eight patients in the VTE cohort had tPA-TEGs at 24 and 48 hours post-ICU admission (median ISS, 28; 6% pneumonia). The tPA-TEG LY30 of less than 4% was associated with a 10-fold increased rate of pneumonia (19% vs. 1.5%; p = 0.002). In patients with traumatic brain injury, the same association was found (33% vs. 3.2%; p = 0.006). Adjusting for confounders, the tPA-TEG persisted as a substantial risk factor for pneumonia (adjusted odds ratio [OR], 35.7; 95% confidence interval [CI], 1.9-682; p = 0.018). Conclusions: Fibrinolysis resistance quantified by tPA-TEG within 48 hours of ICU admission is associated with an increased risk of pneumonia in patients in hemorrhagic shock and those at risk for VTE. Prospective validation of the tPA-TEG LY30 optimal cutoff for pneumonia and further investigation into whether endogenous FR is a cause of an altered immunity is warranted.

Weight-based enoxaparin thromboprophylaxis in young trauma patients: analysis of the CLOTT-1 registry.

Introduction: Optimal venous thromboembolism (VTE) enoxaparin prophylaxis dosing remains elusive. Weight-based (WB) dosing safely increases anti-factor Xa levels without the need for routine monitoring but it is unclear if it leads to lower VTE risk. We hypothesized that WB dosing would decrease VTE risk compared with standard fixed dosing (SFD). Methods: Patients from the prospective, observational CLOTT-1 registry receiving prophylactic enoxaparin (n=5539) were categorized as WB (0.45-0.55 mg/kg two times per day) or SFD (30 mg two times per day, 40 mg once a day). Multivariate logistic regression was used to generate a predicted probability of VTE for WB and SFD patients. Results: Of 4360 patients analyzed, 1065 (24.4%) were WB and 3295 (75.6%) were SFD. WB patients were younger, female, more severely injured, and underwent major operation or major venous repair at a higher rate than individuals in the SFD group. Obesity was more common among the SFD group. Unadjusted VTE rates were comparable (WB 3.1% vs. SFD 3.9%; p=0.221). Early prophylaxis was associated with lower VTE rate (1.4% vs. 5.0%; p=0.001) and deep vein thrombosis (0.9% vs. 4.4%; p<0.001), but not pulmonary embolism (0.7% vs. 1.4%; p=0.259). After adjustment, VTE incidence did not differ by dosing strategy (adjusted OR (aOR) 0.75, 95% CI 0.38 to 1.48); however, early administration was associated with a significant reduction in VTE (aOR 0.47, 95% CI 0.30 to 0.74). Conclusion: In young trauma patients, WB prophylaxis is not associated with reduced VTE rate when compared with SFD. The timing of the initiation of chemoprophylaxis may be more important than the dosing strategy. Further studies need to evaluate these findings across a wider age and comorbidity spectrum. Level of evidence: Level IV, therapeutic/care management.

Early venous thromboembolism prophylaxis in patients with trauma intracranial hemorrhage: Analysis of the prospective multicenter Consortium of Leaders in Traumatic Thromboembolism study.

BACKGROUND: The optimal time to initiate venous thromboembolism prophylaxis (VTEp) for patients with intracranial hemorrhage (ICH) is controversial and must balance the risks of VTE with potential progression of ICH. We sought to evaluate the efficacy and safety of early VTEp initiation after traumatic ICH. METHODS: This is a secondary analysis of the prospective multicenter Consortium of Leaders in the Study of Thromboembolism study. Patients with head Abbreviated Injury Scale score of > 2 and with immediate VTEp held because of ICH were included. Patients were divided into VTEp ≤ or >48 hours and compared. Outcome variables included overall VTE, deep vein thrombosis (DVT), pulmonary embolism, progression of intracranial hemorrhage (pICH), or other bleeding events. Univariate and multivariate logistic regressions were performed. RESULTS: There were 881 patients in total; 378 (43%) started VTEp ≤48 hours (early). Patients starting VTEp >48 hours (late) had higher VTE (12.4% vs. 7.2%, p = 0.01) and DVT (11.0% vs. 6.1%, p = 0.01) rates than the early group. The incidence of pulmonary embolism (2.1% vs. 2.2%, p = 0.94), pICH (1.9% vs. 1.8%, p = 0.95), or any other bleeding event (1.9% vs. 3.0%, p = 0.28) was equivalent between early and late VTEp groups. On multivariate logistic regression analysis, VTEp >48 hours (odds ratio [OR], 1.86), ventilator days >3 (OR, 2.00), and risk assessment profile score of ≥5 (OR, 6.70) were independent risk factors for VTE (all p < 0.05), while VTEp with enoxaparin was associated with decreased VTE (OR, 0.54, p < 0.05). Importantly, VTEp ≤48 hours was not associated with pICH (OR, 0.75) or risk of other bleeding events (OR, 1.28) (both p = NS). CONCLUSION: Early initiation of VTEp (≤48 hours) for patients with ICH was associated with decreased VTE/DVT rates without increased risk of pICH or other significant bleeding events. Enoxaparin is superior to unfractionated heparin as VTE prophylaxis in patients with severe TBI. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Venous thromboembolism risk after spinal cord injury: A secondary analysis of the CLOTT study.

INTRODUCTION: Patients with spinal cord injury (SCI) are at high risk of venous thromboembolism (VTE). Pharmacologic VTE prophylaxis (VTEppx) is frequently delayed in patients with SCI because of concerns for bleeding risk. Here, we hypothesized that delaying VTEppx until >48 hours would be associated with increased risk of thrombotic events. METHODS: This is a secondary analysis of the 2018 to 2020 prospective, observational, cohort Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study of patients aged 18 to 40 years, at 17 US level 1 trauma centers. Patients admitted for >48 hours with documented SCI were evaluated. Timing of initiation of VTEppx, rates of thrombotic events (deep vein thrombosis [DVT] and pulmonary embolism [PE]), and missed VTEppx doses were analyzed. The primary outcome was VTE (DVT + PE). RESULTS: There were 343 patients with SCI. The mean ± SD age was 29.0 ± 6.6 years, 77.3% were male, and 78.7% sustained blunt mechanism. Thrombotic events occurred in 33 patients (9.6%): 30 DVTs (8.7%) and 3 PEs (0.9%). Venous thromboembolism prophylaxis started at ≤24 hours in 21.3% of patients and 49.3% at ≤48 hours. The rate of VTE for patients started on VTEppx ≤48 hours was 7.1% versus 12.1% if started after 48 hours ( p = 0.119). After adjusting for differences in risk factors between cohorts, starting ≤48 hours was independently associated with fewer VTEs (odds ratio, 0.45; 95% confidence interval, 0.101-0.978; p = 0.044). Unfractionated heparin was associated with a VTE rate of 21.0% versus 7.5% in those receiving enoxaparin as prophylaxis ( p = 0.003). Missed doses of VTEppx were common (29.7%) and associated with increased thrombotic events, although this was not significant on multivariate analysis. CONCLUSION: Rates of thrombotic events in patients with SCI are high. Prompt initiation of VTEppx with enoxaparin and efforts aimed at avoiding missed doses are critical to limit thrombotic events in these high-risk patients. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Tissue plasminogen activator resistance is an early predictor of posttraumatic venous thromboembolism: A prospective study from the CLOTT research group.

BACKGROUND: Venous thromboembolism (VTE) remains a frequent postinjury complication with well established but nonmodifiable risk factors. We hypothesized that fibrinolysis shutdown (SD) as measured by thromboelastography (TEG) would be an independent risk factor for VTE in trauma patients. METHODS: A subgroup of patients enrolled in the CLOTT-2 (Consortium of Leaders in the Study of Traumatic Thromboembolism 2), multicenter prospective cohort study had kaolin TEG and tissue plasminogen activator (tPA)-TEG data at 12 and 24 hours postadmission. Patients underwent a screening duplex venous ultrasound examination during the first week unless clot was already detected on computed tomography. Injury factors associated with early fibrinolysis SD (defined as kaolin TEG Ly30 ≤0.3%) and/or tPA resistance (tPA-R) (defined as kaolin TEG with tPA 75 ng Ly30 <2.1%) were investigated as was the association of the TEG measurements with the development of VTE. RESULTS: A total of 141 patients had both TEG measurements at 24 hours, and 135 had both TEG measurements at 12 hours. Shutdown was evident at 12 hours in 71 of 135 (52.6%) patients and in 62 of 141 (44%) at 24 hours. Tissue plasminogen activator resistance was found in 61 of 135 (45.2%) at 12 hours and in 49 of 141 (34.3%) at 24 hours. Factors significantly associated with SD included receiving >4 U of FFP in the first 24 hours, the presence of a major brain injury or pelvic fracture, and the need for major surgery. In contrast, factors significantly associated with early tPA-R included >4 U of red blood cells transfused in the first 24 hours and the presence of a major chest injury or long bone fracture. Deep vein thrombosis was detected in 15 patients and pulmonary clots in 5 (overall VTE rate, 14.2%). Tissue plasminogen activator resistance at 12 hours was found to be an independent risk factor for VTE (hazard ratio, 5.57; 95% confidence interval, 1.39-22.39). CONCLUSION: Early development of a hypercoagulable state as defined by tPA-R at 12 hours after admission represents a potentially modifiable risk factor for postinjury VTE. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Military-civilian partnerships and the clinical readiness mission: A preliminary study from the Military Health System and the American College of Surgeons.

BACKGROUND: The Blue Book , published in conjunction with the Military Health System Strategic Partnership with the American College of Surgeons, serves as a reference manual for institutions wishing to establish a military-civilian partnership (MCP). To evaluate the applicability of the criteria contained in the Blue Book , we created a survey to be distributed to MCP military surgeons and their civilian host champions. METHODS: E-mail surveys were sent to MCP military surgeons and civilian host champions. Military surgeons were queried about basic demographic information and aspects of the MCP including type, duration of assignment, onboarding, malpractice coverage, and billing for services. We gathered information on the role of military surgeons at the MCP, workload information, and trauma cases. The civilian host champions survey focused on institutional activities including trauma surgical volume, clinical and educational opportunities for the military surgeons, and exposure to research. Military-civilian partnership military surgeons and civilian host champions were questioned on program attributes: administrative support, budget, and profile of the program within the institution. RESULTS: Ten MCP military surgeons and 7 host champions completed surveys. The majority of military surgeons were assigned to the MCP for a 3-year instructor role (90%), and most were trauma surgeons (80%). Clinical activities for the military surgeon were where 60% spent ≥13 weeks annually on trauma. Military surgeons identified host program support in academic growth, deployment preparation, and sense of value at the MCP as positive attributes. Civilian host champions unanimously reported that exposure to research, opportunities to lead trauma teams, dedicated intensive care unit time, and patient volume were positive program attributes. CONCLUSION: This preliminary survey demonstrates that the criteria put forth in the Blue Book align with experiences of MCP military surgeons and host champions. Continued development of this survey and others like it may be useful in the MCP program selection and evaluation process. LEVEL OF EVIDENCE: Therapeutic/care management; Level V.

Postinjury platelet aggregation and venous thromboembolism.

BACKGROUND: Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Furthermore, platelets from injured patients show ex vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that, following injury, impaired ex vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE. METHODS: We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011-2019). Platelet aggregation in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (preresuscitation) and 24 hours (postresuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 hours, and the change (δ) in PA between presentation and 24 hours with development of VTE. RESULTS: The 133 patients were severely injured (median Injury Severity Score, 25), and 14% developed VTE (all >48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 hours, those who subsequently developed VTE had significantly lower platelet counts (126 × 10 9 /L vs. 164 × 10 9 /L, p = 0.01) and lower PA in response to ADP ( p < 0.05), collagen ( p < 0.05), and thrombin ( p = 0.06). Importantly, the magnitude of decrease in PA (δ) from presentation to 24 hours was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: δ-ADP, 1.31 [ p = 0.03]; δ-collagen, 1.36 [ p = 0.01]; δ-thrombin, 1.41 [ p < 0.01]). CONCLUSION: Severely injured patients with decreasing ex vivo measures of PA despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens. LEVEL OF EVIDENCE: Prognostic/Epidemiological; Level III.

Challenging Traditional Paradigms in Posttraumatic Pulmonary Thromboembolism.

Importance: Pulmonary clots are seen frequently on chest computed tomography performed after trauma, but recent studies suggest that pulmonary thrombosis (PT) and pulmonary embolism (PE) after trauma are independent clinical events. Objective: To assess whether posttraumatic PT represents a distinct clinical entity associated with the nature of the injury, different from the traditional venous thromboembolic paradigm of deep venous thrombosis (DVT) and PE. Design, Setting, and Participants: This prospective, observational, multicenter cohort study was conducted by the Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study group. The study was conducted at 17 US level I trauma centers during a 2-year period (January 1, 2018, to December 31, 2020). Consecutive patients 18 to 40 years of age admitted for a minimum of 48 hours with at least 1 previously defined trauma-associated venous thromboembolism (VTE) risk factor were followed up until discharge or 30 days. Exposures: Investigational imaging, prophylactic measures used, and treatment of clots. Main Outcomes and Measures: The main outcomes of interest were the presence, timing, location, and treatment of any pulmonary clots, as well as the associated injury-related risk factors. Secondary outcomes included DVT. We regarded pulmonary clots with DVT as PE and those without DVT as de novo PT. Results: A total of 7880 patients (mean [SD] age, 29.1 [6.4] years; 5859 [74.4%] male) were studied, 277 with DVT (3.5%), 40 with PE (0.5%), and 117 with PT (1.5%). Shock on admission was present in only 460 patients (6.2%) who had no DVT, PT, or PE but was documented in 11 (27.5%) of those with PE and 30 (25.6%) in those with PT. Risk factors independently associated with PT but not DVT or PE included shock on admission (systolic blood pressure <90 mm Hg) (odds ratio, 2.74; 95% CI, 1.72-4.39; P < .001) and major chest injury with Abbreviated Injury Score of 3 or higher (odds ratio, 1.72; 95% CI, 1.16-2.56; P = .007). Factors associated with the presence of PT on admission included major chest injury (14 patients [50.0%] with or without major chest injury with an Abbreviated Injury Score >3; P = .04) and major venous injury (23 [82.1%] without major venous injury and 5 [17.9%] with major venous injury; P = .02). No deaths were attributed to PT or PE. Conclusions and Relevance: To our knowledge, this CLOTT study is the largest prospective investigation in the world that focuses on posttraumatic PT. The study suggests that most pulmonary clots are not embolic but rather result from inflammation, endothelial injury, and the hypercoagulable state caused by the injury itself.

Venous ligation versus venous repair: does the procedure impact venous thromboembolism risk?

BACKGROUND: Traumatic lower extremity venous injuries are most commonly managed with either a vein ligation or repair procedure. Venous injuries are associated with an increased risk of developing venous thromboembolisms (VTE), but little is understood with regard to how specific surgical treatments may impact the risk of developing either a deep vein thrombosis (DVT) or a pulmonary embolism (PE). In this study of lower extremity venous injuries, we hypothesized that venous ligation would be associated with an increased risk of DVT but a lower risk of PE when compared with venous repair. METHODS: Patients were identified from the National Trauma Data Bank (2008 to 2014) with at least one iliac, femoral, popliteal, or tibial venous injury and who received either a vein ligation or repair. The patients were then compared based on the type of procedure and the location of the injury to assess the risk of DVT and PE between the groups. RESULTS: A total of 1214 patients were identified. There was no difference between patients who received a vein ligation versus a repair with respect to age, injury severity score, or initial systolic blood pressure. There was no difference in the odds of developing either a DVT or PE between patients who were treated with vein ligation versus repair. There was also no difference in VTE rates when stratified by the location of the injury. CONCLUSIONS: In individuals with lower extremity venous injuries, there is no difference in the rate of DVT or PE complications when comparing venous repair and ligation procedures. The role of anticoagulation remains to be elucidated following operative treatment. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level IV.

The DISTANCE study: Determining the impact of social distancing on trauma epidemiology during the COVID-19 epidemic-An interrupted time-series analysis.

BACKGROUND: The large-scale social distancing efforts to reduce SARS-CoV-2 transmission have dramatically changed human behaviors associated with traumatic injuries. Trauma centers have reported decreases in trauma volume, paralleled by changes in injury mechanisms. We aimed to quantify changes in trauma epidemiology at an urban Level I trauma center in a county that instituted one of the earliest shelter-in-place orders to inform trauma care during future pandemic responses. METHODS: A single-center interrupted time-series analysis was performed to identify associations of shelter-in-place with trauma volume, injury mechanisms, and patient demographics in San Francisco, California. To control for short-term trends in trauma epidemiology, weekly level data were analyzed 6 months before shelter-in-place. To control for long-term trends, monthly level data were analyzed 5 years before shelter-in-place. RESULTS: Trauma volume decreased by 50% in the week following shelter-in-place (p < 0.01), followed by a linear increase each successive week (p < 0.01). Despite this, trauma volume for each month (March-June 2020) remained lower compared with corresponding months for all previous 5 years (2015-2019). Pediatric trauma volume showed similar trends with initial decreases (p = 0.02) followed by steady increases (p = 0.05). Reductions in trauma volumes were due entirely to changes in nonviolent injury mechanisms, while violence-related injury mechanisms remained unchanged (p < 0.01). CONCLUSION: Although the shelter-in-place order was associated with an overall decline in trauma volume, violence-related injuries persisted. Delineating and addressing underlying factors driving persistent violence-related injuries during shelter-in-place orders should be a focus of public health efforts in preparation for future pandemic responses. LEVEL OF EVIDENCE: Epidemiological study, level III.

How care decisions are made among interdisciplinary providers caring for critically injured patients: A qualitative study.

BACKGROUND: Injury is the leading cause of death in people under 45 years of age in the United States; however, how care decisions occur in critical injury is poorly understood. This exploratory study sought to generate hypotheses about how care decisions are made among interdisciplinary providers caring for patients who have been critically injured. METHODS: This was a qualitative study conducted at two intensive care units in a level 1 trauma center in an urban, teaching, safety-net hospital. Semistructured interviews consisted of case scenarios with competing clinical priorities presented to 25 interdisciplinary providers, elucidating how decisions are approached. Responses were recorded, transcribed, and coded. Thematic analysis was conducted to discover central themes. Category formulation and sorting was done for data reduction and thematic structuring of the data. The range and central tendency of these themes are reported. RESULTS: The central theme for how care decisions are made among interdisciplinary providers was through the distribution of shared responsibility. The distribution of shared responsibility depended on interdisciplinary communication to navigate the two subthemes of time and roles. Time had to be navigated carefully, because it was both an opportunity for data acquisition and consensus building but also a pressure to decisively progress care. Roles were distinct but interchangeable and consisted of experts, actualizers, and questioners. CONCLUSION: Care decisions are made in the context of shared responsibility among interdisciplinary providers. Interdisciplinary communication is a means of establishing roles and navigating time to distribute shared responsibility among interdisciplinary providers.

A Collaborative To Evaluate And Improve The Quality Of Surgical Care Delivered By The Military Health System.

In an effort to improve surgical quality and reduce clinical variability, the Military Health System (MHS) expanded its participation in the National Surgical Quality Improvement Program to all military hospitals beginning in 2015. This expansion and a partnership with the American College of Surgeons laid the foundation for a surgical quality collaborative in the MHS. We review the history of the program in the MHS and the activities that have contributed to developing the collaborative. We also report promising trends in surgical outcomes at hospitals that were already participating in the program in 2014, when a critical MHS review identified areas for improvement in surgical care. We conclude with a discussion of possible lessons for other health systems and challenges ahead for the MHS, now that full enrollment in the program has been completed.