A 20-year retrospective analysis of deep venous thrombosis and pulmonary embolism among combat casualties requiring damage control laparotomy at US Military Role 2 surgical units.

BACKGROUND: Combat casualties receiving damage control laparotomy at forward deployed, resource-constrained US Military Role 2 surgical units (R2) require multiple evacuations, but the added risk of venous thromboembolism (VTE) in this population has not been defined. To fill this gap, we retrospectively analyzed 20 years of Department of Defense Trauma Registry (DoDTR) data to define the VTE rate in this population. METHODS: DoDTR from 2002 to 2023 was queried for US Military combat casualties requiring damage control laparotomy at R2. All deaths were excluded in subsequent analysis. Rates of VTE were assessed, and subgroup analysis was performed on patients requiring massive transfusion. RESULTS: DoDTR (n = 288) patients were young (mean age 25 years), predominantly male (98%) with severe (mean ISS 26), mostly penetrating injury (76%), and high mortality. VTE rate was high: 15.8% (DVT: 10.3% and PE 7.1%). In the massively transfused population, the VTE rate was even higher (26.7% vs 10.2%, p < 0.001). CONCLUSIONS: This is the first report that combat casualties requiring damage control laparotomy at R2 have such high VTE rates. Therefore, for military casualties, we propose screening ultrasound upon arrival to each subsequent capable echelon of care and low threshold for initiating thromboprophylaxis. LEVEL OF EVIDENCE: Prognostic and Epidemiological, Level IV.

Initial Hemorrhage Control Procedure for Splenic Injuries May Affect Risk of Venous Thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE) continues to be a major cause of morbidity in trauma. It is unclear whether the type of hemorrhage control procedure (i.e., splenectomy versus angioembolization) is associated with an increased risk of VTE. We hypothesize that hemodynamically stable patients undergoing angioembolization for blunt high-grade splenic injuries have lower rates of VTE compared to those undergoing splenectomy. METHODS: The American College of Surgeons Trauma Quality Program dataset from 2017 to 2019 was queried to identify all patients with American Association for the Surgery of Trauma grade 3-5 blunt splenic injuries. Outcomes including VTE rates were compared between those who were managed with splenectomy versus angioembolization. Propensity score matching (1:1) was performed adjusting for age, sex, initial vital signs, Injury Severity Score, and splenic injury grade. RESULTS: The analysis included 4698 matched patients (splenectomy [n = 2349] and angioembolization [n = 2349]). The median (interquartile range) age was 41 (27-58) years and 69% were male. Patients were well matched between groups. Angioembolization was associated with significantly lower VTE than splenectomy (2.2% versus 3.4%, P = 0.010) despite less use of VTE chemoprophylaxis (70% versus 80%, P < 0.001), as well as a relative delay in initiation of chemoprophylaxis (44 h versus 33 h, P < 0.001). Hospital and intensive care unit length of stay and mortality were also significantly lower in the angioembolization group. CONCLUSIONS: Angioembolization is associated with a significantly lower incidence of VTE than splenectomy. Thus, angioembolization should be considered for initial management of hemodynamically stable patients with high-grade blunt splenic injuries in whom laparotomy is not otherwise indicated.

Advanced Surgical Skills for Exposure in Trauma (ASSET) course improves military surgeon confidence.

OBJECTIVE: Active duty military surgeons often have limited trauma surgery experience prior to deployment. Consequently, military-civilian training programs have been developed at high-volume trauma centers to evaluate and maintain proficiencies. Advanced Surgical Skills for Exposure in Trauma (ASSET) was incorporated into the predeployment curriculum at the Army Trauma Training Detachment in 2011. This is the first study to assess whether military surgeons demonstrated improved knowledge and increased confidence after taking ASSET. DESIGN: Retrospective cohort study. SETTING: Quaternary care hospital. PATIENTS AND PARTICIPANTS: Attending military surgeons who completed ASSET between July 2011 and October 2020. MAIN OUTCOME MEASURE(S): Pre- and post-course self-reported comfort level with procedures was converted from a five-point Likert scale to a percentage and compared using paired t-tests. RESULTS: In 188 military surgeons, the median time in practice was 3 (1-8) years, with specialties in general surgery (52 percent), orthopedic surgery (29 percent), trauma (7 percent), and other disciplines (12 percent). The completed self-evaluation response rate was 80 percent (n = 151). The self-reported comfort level for all body regions improved following course completion (p < 0.001): chest (27 percent), neck (23 percent), upper extremity (22 percent), lower extremity (21 percent), and abdomen/pelvis (19 percent). The overall score on the competency test improved after completion of ASSET, with averages increasing from 62 ± 18 percent pretest to 71 ± 13 percent post-test (p < 0.001). CONCLUSIONS: After taking the ASSET course, military surgeons demonstrated improved knowledge and increased confidence in the operative skills taught in the course. The ASSET course may provide sustainment of knowledge and confidence if used at regular intervals to maintain trauma skills and deployment readiness.

Management of lower extremity vascular injuries in pediatric trauma patients: 20-year experience at a level 1 trauma center.

Introduction: Pediatric lower extremity vascular injuries (LEVI) are rare but can result in significant morbidity. We aimed to describe our experience with these injuries, including associated injury patterns, diagnostic and therapeutic challenges, and outcomes. Methods: This was a retrospective review at a single level 1 trauma center from January 2000 to December 2019. Patients less than 18 years of age with LEVI were included. Demographics, injury patterns, clinical status at presentation, and intensive care unit (ICU) and hospital length of stay (LOS) were collected. Surgical data were extracted from patient charts. Results: 4,929 pediatric trauma patients presented during the 20-year period, of which 53 patients (1.1%) sustained LEVI. The mean age of patients was 15 years (range 1-17 years), the majority were Black (68%), male (96%), and most injuries were from a gunshot wound (62%). The median Glasgow Coma Scale score was 15, and the median Injury Severity Score was 12. The most commonly injured arteries were the superficial femoral artery (28%) and popliteal artery (28%). Hard signs of vascular injury were observed in 72% of patients and 87% required operative exploration. There were 36 arterial injuries, 36% of which were repaired with a reverse saphenous vein graft and 36% were repaired with polytetrafluoroethylene graft. One patient required amputation. Median ICU LOS was three days and median hospital LOS was 15 days. There were four mortalities. Conclusion: Pediatric LEVIs are rare and can result in significant morbidity. Surgical principles for pediatric vascular injuries are similar to those applied to adults, and this subset of patients can be safely managed in a tertiary specialized center. Level of evidence: Level IV, retrospective study.

When is it safe to start thromboprophylaxis after splenic angioembolization?

BACKGROUND: Thromboprophylaxis after blunt splenic trauma is complicated by the risk of bleeding, but the risk after angioembolization is unknown. We hypothesized that earlier thromboprophylaxis initiation was associated with increased bleeding complications without mitigating venous thromboembolism events. METHODS: All blunt trauma patients who underwent splenic angioembolization within 24 hours of arrival were identified from the American College of Surgeons Trauma Quality Improvement Program datasets from 2017 to 2019. Cases with <24-hour length of stay, other serious injuries, and surgery before angioembolization were excluded. Venous thromboembolism was defined as deep vein thrombosis or pulmonary embolism. Bleeding complications were defined as splenic surgery, additional embolization, or blood transfusion after thromboprophylaxis initiation. Data were compared with χ2 analysis and multivariate logistic regression at P < .05. RESULTS: In 1,102 patients, 84% had American Association for the Surgery of Trauma grade III to V splenic injuries, and 73% received thromboprophylaxis. Splenic surgery after angioembolization was more common in those with thromboprophylaxis initiation within the first 24 hours (5.7% vs 1.7%, P = .007), whereas those with the initiation of thromboprophylaxis after 72 hours were more likely to have a pulmonary embolism (2.3% vs 0.2%, P = .001). Overall, venous thromboembolism increased considerably when thromboprophylaxis was initiated after day 3. In multivariate analysis, time to thromboprophylaxis initiation was associated with bleeding (odds ratio 0.74 [95% confidence interval 0.58-0.94]) and venous thromboembolism complications (odds ratio 1.5 [95% confidence interval 1.20-1.81]). CONCLUSION: This national study evaluates bleeding and thromboembolic risk to elucidate the specific timing of thromboprophylaxis after splenic angioembolization. Initiation of thromboprophylaxis between 24 and 72 hours achieves the safest balance in minimizing bleeding and venous thromboembolism risk, with 48 hours particularly serving as the ideal time for protocolized administration.

Admission to a Verified Pediatric Trauma Center is Associated With Improved Outcomes in Severely Injured Children.

BACKGROUND: Previous studies have shown improved survival for severely injured adult patients treated at American College of Surgeons verified level I/II trauma centers compared to level III and undesignated centers. However, this relationship has not been well established in pediatric trauma centers (PTCs). We hypothesize that severely injured children will have lower mortality at verified level I/II PTCs compared to centers without PTC verification. METHODS: All patients 1-15 years of age with ISS >15 in the 2017-2019 American College of Surgeons Trauma Quality Programs (ACS TQP) dataset were reviewed. Patients with pre-hospital cardiac arrest, burns, and those transferred out for ongoing inpatient care were excluded. Logistic regression models were used to assess the effects of pediatric trauma center verification on mortality. RESULTS: 16,301 patients were identified (64 % male, median ISS 21 [17-27]), and 60 % were admitted to verified PTCs. Overall mortality was 6.0 %. Mortality at centers with PTC verification was 5.1 % versus 7.3 % at centers without PTC verification (p < 0.001). After controlling for injury mechanism, sex, age, pediatric-adjusted shock index (SIPA), ISS, arrival via interhospital transfer, and adult trauma center verification, pediatric level I/II trauma center designation was independently associated with decreased mortality (OR 0.72, 95 % CI 0.61-0.85). CONCLUSIONS: Treatment at ACS-verified pediatric trauma centers is associated with improved survival in critically injured children. These findings highlight the importance of PTC verification in optimizing outcomes for severely injured pediatric patients and should influence trauma center apportionment and prehospital triage. LEVEL OF EVIDENCE: Level IV - Retrospective review of national database.

Short Versus Long Antibiotic Duration for Necrotizing Soft Tissue Infection: A Systematic Review and Meta-Analysis.

Background: Necrotizing soft tissue infections (NSTIs) are rapidly spreading, life-threatening infections that require emergent surgical intervention with immediate antibiotic initiation. However, there is no consensus regarding duration of antibiotic therapy after source control. We hypothesized that a short course of antibiotic therapy is as effective as a long course of antibiotic therapy after final debridement for NSTI. Methods: A systematic review of the literature was performed using PubMed, Embase, and Cochrane Library from inception to November 2022. Observational studies comparing short (≤7 days) versus long (>7 days) antibiotic duration for NSTI were included. Primary outcome was mortality and secondary outcomes included limb amputation and Clostridium difficile infection (CDI). Cumulative analysis was performed with Fisher exact test. Meta-analysis was performed using a fixed effects model and heterogeneity was assessed using Higgins I2. Results: A total of 622 titles were screened and four observational studies evaluating 532 patients met inclusion criteria. Mean age was 52 years, 67% were male, 61% had Fournier gangrene. There was no difference in mortality when comparing short to long duration antibiotic agents on both cumulative analysis (5.6% vs. 4.0%; p = 0.51) and meta-analysis (relative risk, 0.9; 95% confidence interval, 0.8-1.0; I2 0; p = 0.19). There was no significant difference in rates of limb amputation (11% vs. 8.5%; p = 0.50) or CDI (20.8% vs. 13.3%; p = 0.14). Conclusions: Short duration antibiotic therapy may be as effective as longer duration antibiotic therapy for NSTI after source control. Further high-quality data such as randomized clinical trials are required to create evidence-based guidelines.

Burn excision within 48 hours portends better outcomes than standard management: A nationwide analysis.

BACKGROUND: Previous studies have debated the optimal time to perform excision and grafting of second- and third-degree burns. The current consensus is that excision should be performed before the sixth hospital day. We hypothesize that patients who undergo excision within 48 hours have better outcomes. METHODS: The American College of Surgeons Trauma Quality Programs data set was used to identify all patients with at least 10% total body surface area second- and third-degree burns from years 2017 to 2019. Patients with other serious injuries (any Abbreviated Injury Scale, >3), severe inhalational injury, prehospital cardiac arrest, and interhospital transfers were excluded. International Classification of Diseases, Tenth Revision , procedure codes were used to ascertain time of first excision. Patients who underwent first excision within 48 hours of admission (early excision) were compared with those who underwent surgery 48 to 120 hours from admission (standard therapy). Propensity score matching was performed to control for age and total body surface area burned. RESULTS: A total of 2,270 patients (72% male) were included in the analysis. The median age was 37 (23-55) years. Early excision was associated with shorter hospital length of stay (LOS), and intensive care unit LOS. Complications including deep venous thrombosis, pulmonary embolism, ventilator-associated pneumonia, and catheter-associated urinary tract infection were significantly lower with early excision. There was no significant difference in mortality. CONCLUSION: Performance of excision within 48 hours is associated with shorter hospital LOS and fewer complications than standard therapy. We recommend taking patients for operative debridement and temporary or, when feasible, permanent coverage within 48 hours. Prospective trials should be performed to verify the advantages of this treatment strategy. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Improved survival for severely injured patients receiving massive transfusion at US teaching hospitals: A nationwide analysis.

BACKGROUND: Previous studies have shown improved survival for patients treated at American College of Surgeons (ACS)-verified level I trauma centers compared with level II, level III, and undesignated centers. This mortality difference is more pronounced in severely injured patients. However, a survival benefit for severely injured trauma patients has not been established at teaching institutions compared with nonteaching centers. Because massive transfusion (MT) is associated with high mortality, we hypothesize that patients receiving MT have lower mortality at teaching hospitals than at nonteaching hospitals. METHODS: All adult ACS Trauma Quality Improvement Program-eligible patients who underwent MT, defined as >10 U of packed red blood cells in the first 4 hours after arrival, in the 2019 ACS Trauma Quality Programs participant use file were eligible. Patients with severe head injury (head Abbreviated Injury Scale score, ≥3), prehospital cardiac arrest, and interhospital transfers were excluded. Logistic regression models were used to assess the effects of trauma center hospital teaching status on the adjusted odds of 3-hour, 6-hour, and 24-hour mortality. RESULTS: A total of 1,849 patients received MT (81% male; median Injury Severity Score, 26 [18-35]), 72% were admitted to level I trauma centers, and 28% were admitted to level II centers. Overall hospital mortality was 41%; 17% of patients died in 3 hours, 25% in 6 hours, and 33% in 24 hours. Teaching hospitals were associated with decreased 3-hour (odds ratio [OR], 0.45; 95% confidence interval [CI], 0.27-0.75), 6-hour (OR, 0.37; 95% CI, 0.24-0.56), 24-hour (OR, 0.50; 95% CI, 0.34-0.75), and overall mortality (OR, 0.66; 95% CI, 0.44-0.98), compared with nonteaching hospitals, controlling for sex, age, heart rate, injury severity, injury mechanism, and trauma center verification level. CONCLUSION: Severely injured patients requiring MT experience significantly lower mortality at teaching hospitals compared with nonteaching hospitals, independently of trauma center verification level. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Do all cardiac surgery patients benefit from antifibrinolytic therapy?

BACKGROUND: In trauma patients, the recognition of fibrinolysis phenotypes has led to a re-evaluation of the risks and benefits of antifibrinolytic therapy (AF). Many cardiac patients also receive AF, but the distribution of fibrinolytic phenotypes in that population is unknown. The purpose of this hypothesis-generating study was to fill that gap. METHODS: Seventy-eight cardiac surgery patients were retrospectively reviewed. Phenotypes were defined as hypofibrinolytic (LY30 <0.8%), physiologic (0.8%-3.0%), and hyperfibrinolytic (>3%) based on thromboelastogram. RESULTS: The population was 65 ± 10-years old, 74% male, average body mass index of 29 ± 5 kg/m2 . Fibrinolytic phenotypes were distributed as physiologic = 45% (35 of 78), hypo = 32% (25 of 78), and hyper = 23% (18 of 78). There was no obvious effect of age, gender, race, or ethnicity on this distribution; 47% received AF. For AF versus no AF, the time with chest tube was longer (4 [1] vs. 3 [1] days, p = .037), and all-cause morbidity was more prevalent (51% vs. 25%, p = .017). However, when these two groups were further stratified by phenotypes, there were within-group differences in the percentage of patients with congestive heart failure (p = .022), valve disease (p = .024), on-pump surgery (p < .0001), estimated blood loss during surgery (p = .015), transfusion requirement (p = .015), and chest tube output (p = .008), which highlight other factors along with AF that might have affected all-cause morbidity. CONCLUSION: This is the first description of the prevalence of three different fibrinolytic phenotypes and their potential influence on cardiac surgery patients. The use of AF was associated with increased morbidity, but because of the small sample size and treatment allocation bias, additional confirmatory studies are necessary. We hope these present findings open the dialog on whether it is safe to administer AFs to cardiac surgery patients who are normo- or hypofibrinolytic.

The unborn fetus: The unrecognized victim of trauma during pregnancy.

BACKGROUND: Trauma is the leading cause of non-obstetric death in pregnancy. While maternal management is defined, few studies have examined the effects on the fetus. METHODS: Following IRB approval, all pregnant females (2010-2017) at a level-1 trauma center were retrospectively reviewed. Maternal and fetal demographics, interventions, and clinical outcomes were analyzed. RESULTS: There were 188 pregnancies in 5654 females. Maternal demographics were 26 ±â€¯7 years old, gestational age at trauma 21 ±â€¯12 weeks, 81% blunt mechanism, and maternal mortality 6%. Forty-one (22%) fetuses were immediately affected by the trauma including 20 (11%) born alive, 12 (7%) fetal demise, and 9 (5%) stillbirths. Of those that initially survived (n = 20), 5 (25%) expired during neonatal hospitalization. Two mothers returned immediately after trauma discharge with stillbirths for an overall infant mortality of 14% (n = 26). There were 84 patients with complete data to delivery including the 41 born at trauma and 43 born on a subsequent hospitalization. Those born at the time of trauma had significantly more delivery/neonatal complications and worse outcomes. Overall trauma burden to the fetus (preterm delivery, stillbirth, delivery/neonatal complication, or long-term disability) was 66% (56/84). CONCLUSIONS: Trauma during pregnancy has significant immediate mortality and delayed effects on the unborn fetus. This study has uncovered a previously hidden burden and mortality of trauma during pregnancy. LEVEL OF EVIDENCE: Level III.

Hypercoagulability After Resection of Thoracic Malignancy: A Prospective Evaluation.

BACKGROUND: Rates of venous thromboembolism are increased in thoracic malignancy; however, coagulation patterns are not established. We hypothesize that patients with esophageal and lung malignancy have similar hypercoagulable pre- and postoperative profiles as defined by rotational thromboelastometry (ROTEM). METHODS: Prospective study was conducted in 47 patients with esophageal and lung cancer undergoing surgical resection. ROTEM evaluated pre/postoperative coagulation status. RESULTS: Patients with thoracic malignancy were hypercoagulable by ROTEM, but not by conventional coagulation tests. Preoperative hypercoagulability was higher in lung versus esophageal cancer (64 vs. 16%, p = 0.001). Lung cancer patients that were hypercoagulable preoperatively demonstrated decreased maximum clot firmness (MCF) (p = 0.044) and increased clot time (p = 0.049) after surgical resection, suggesting reversal of hypercoagulability. Resection of esophageal cancer increased hypercoagulability (16 vs. 56%, p = 0.002) via elevated MCF (reflecting platelet activity). Hypercoagulability remained at follow-up clinic for both lung and esophageal cancer patients. CONCLUSIONS: Hypercoagulability in patients with lung malignancies reversed following complete surgical resection, whereas hypercoagulability occurred only postoperatively in those with esophageal malignancies. In both, hypercoagulability was associated with fibrin and platelet function.

Risk Factors and Clinical Outcomes Associated With Augmented Renal Clearance in Trauma Patients.

BACKGROUND: Augmented renal clearance (ARC; i.e., creatinine clearance [CLCr] ≥ 130 mL/min) has an incidence of 14%-80% in critically ill patients and has been associated with therapy failures for renally cleared drugs. However, the clinical implications of ARC are poorly defined. We hypothesize that modifiable risk factors that contribute to ARC can be identified in severely injured trauma patients and that these risk factors influence clinical outcome. METHODS: In 207 trauma intensive care unit patients, 24-h CLCr was correlated with clinical estimates of glomerular filtration rate (by Cockroft-Gault, modification of diet in renal disease, or chronic kidney disease epidemiology), and clinical outcomes (infection, venous thromboembolism [VTE], length of stay, and mortality). RESULTS: The population was 45 ± 20 y, 68% male, 77% blunt injury with injury severity score of 24 (17-30). Admission serum creatinine was 1.02 ± 0.35 mg/dL, CLCr was 154 ± 77 mL/min, VTE incidence was 15%, ARC incidence was 57%, and mortality was 11%. Clinical estimates of glomerular filtration rate by Cockroft-Gault, modification of diet in renal disease, chronic kidney disease epidemiology underestimated actual CLCr by 20%, 22%, or 15% (all P < 0.01). CLCr was higher in males and those who survived, and lower in those with hypertension, diabetes, positive cultures, receiving transfusions, or pressors (all P < 0.05). On multivariate analysis, male gender (odds ratio [OR] 2.9 [1.4-6.1]), age (OR 0.97 [0.95-0.99]), and packed red blood cells transfusion (OR 0.31 [0.15-0.66]) were the only independent predictors of ARC. CONCLUSIONS: ARC occurs in more than half of all high-risk trauma intensive care unit patients and is underestimated by standard clinical equations. ARC was not associated with increased incidence of VTE or infection but rather is associated with younger healthier males and reduced mortality. ARC seems to be a beneficial compensatory response to trauma.

Increased risk of fibrinolysis shutdown among severely injured trauma patients receiving tranexamic acid.

BACKGROUND: The association between tranexamic acid (TXA) and fibrinolysis shutdown is unknown. We hypothesize that TXA is associated with fibrinolysis shutdown in critically injured trauma patients. METHODS: Two hundred eighteen critically injured adults admitted to the intensive care unit at an urban Level I trauma center from August 2011 to January 2015 who had thromboelastography performed upon intensive care unit admission were reviewed. Groups were stratified based on fibrinolysis shutdown, which was defined as LY30 of 0.8% or less. Continuous variables were expressed as mean ± standard deviation or median (interquartile range). Poisson regression analysis was used to determine predictors of shutdown. RESULTS: Patients were age 46 ± 18 years, 81% male, 75% blunt trauma, Injury Severity Score of 28 ± 13, 16% received TXA, 64% developed fibrinolysis shutdown, and mortality was 15%. In the first 24 hours, 4 (2-9) units packed red blood cells and 2 (0-6) units fresh frozen plasma were administered. Those with shutdown had worse initial systolic blood pressure (114 ± 38 mm Hg vs. 129 ± 43 mm Hg, p = 0.006) and base deficit (-5 ± 6 mEq/L vs -3 ± 5 mEq/L, p = 0.013); received more packed red blood cells [6 (2-11) vs. 2 (1-5) units, p < 0.0001], and fresh frozen plasma [3 (0-8) vs. 0 (0-4) units, p < 0.0001]; and more often received TXA (23% vs. 4%, p <0.0001). After controlling for confounders, TXA (relative risk, 1.35; 95% confidence interval, 1.10-1.64; p = 0.004) and cryoprecipitate transfusion (relative risk, 1.29; 95% confidence interval, 1.07-1.56; p = 0.007) were independently associated with fibrinolysis shutdown. CONCLUSION: Patients who received TXA were at increased risk of fibrinolysis shutdown compared with patients who did not receive TXA. We recommend that administration of TXA be limited to severely injured patients with evidence of hyperfibrinolysis and recommend caution in those with evidence of fibrinolysis shutdown. LEVEL OF EVIDENCE: Therapeutic, level III.

Association of Anti-Factor Xa-Guided Dosing of Enoxaparin With Venous Thromboembolism After Trauma.

Importance: The efficacy of anti-factor Xa (anti-Xa)-guided dosing of thromboprophylaxis after trauma remains controversial. Objective: To assess whether dosing of enoxaparin sodium based on peak anti-Xa levels is associated with the venous thromboembolism (VTE) rate after trauma. Design, Setting, and Participants: Retrospective review of 950 consecutive adults admitted to a single level I trauma intensive care unit for more than 48 hours from December 1, 2014, through March 31, 2017. Within 24 hours of admission, these trauma patients were screened with the Greenfield Risk Assessment Profile (RAP) (possible score range, 0-46). Patients younger than 18 years and those with VTE on admission were excluded, resulting in a study population of 792 patients. Exposures: The control group received fixed doses of either heparin sodium, 5000 U 3 times a day, or enoxaparin sodium, 30 mg twice a day. The adjustment cohort initially received enoxaparin sodium, 30 mg twice a day. A peak anti-Xa level was drawn 4 hours after the third dose. If the anti-Xa level was 0.2 IU/mL or higher, no adjustment was made. If the anti-Xa level was less than 0.2 IU/mL, each dose was increased by 10 mg. The process was repeated up to a maximum dose of 60 mg twice a day. Main Outcomes and Measures: Rates of VTE were measured. Venous duplex ultrasonography and computed tomographic angiography were used for diagnosis. Results: The study population comprised 792 patients with a mean (SD) age of 46 (19) years and was composed of 598 men (75.5%). The control group comprised 570 patients, was older, and had a longer time to thromboprophylaxis initiation. The adjustment group consisted of 222 patients, was more severely injured, and had a longer hospital length of stay. The mean (SD) RAP scores were 9 (4) for the control group and 9 (5) for the adjustment group (P = .28). The VTE rates were similar for both groups (34 patients [6.0%] vs 15 [6.8%]; P = .68). Prophylactic anti-Xa levels were reached in 119 patients (53.6%) in the adjustment group. No difference in VTE rates was observed between those who became prophylactic and those who did not (7 patients [5.9%] vs 8 [7.8%]; P = .58). To control for confounders, 132 patients receiving standard fixed-dose enoxaparin were propensity matched to 84 patients receiving dose-adjusted enoxaparin. The VTE rates remained similar between the control and adjustment groups (3 patients [2.3%] vs 3 [3.6%]; P = .57). Conclusions and Relevance: Rates of VTE were not reduced with anti-Xa-guided dosing, and almost half of the patients never reached prophylactic anti-Xa levels; achieving those levels did not decrease VTE rates. Thus, other targets, such as platelets, may be necessary to optimize thromboprophylaxis after trauma.

Relation of antifactor-Xa peak levels and venous thromboembolism after trauma.

BACKGROUND: No previous studies have established the optimal antifactor Xa (anti-Xa) level to guide thromboprophylaxis (TPX) dosing with enoxaparin in trauma patients. We hypothesize that achieving 0.2-0.4 IU/mL anti-Xa will decrease venous thromboembolism (VTE) rates after trauma. METHODS: This was a retrospective review of 194 intensive care unit patients sustaining blunt or penetrating trauma from January 2015 to March 2017. All received initial enoxaparin (30 mg BID subcutaneous) and mechanical devices for TPX. Peak anti-Xa levels were drawn after each third dose. The enoxaparin dose was adjusted up to a maximum of 60 mg BID subcutaneous until a peak level of 0.2-0.4 IU/mL was achieved. Data are expressed as mean ± SD if parametric or median (IQR) if not. RESULTS: The Greenfield Risk Assessment Profile score was 9 ± 4, Injury Severity Score 23 ± 14, and hospital length of stay 19 (11-38) days. The overall VTE rate was 7.2% (n = 14), with 10 deep venous thromboses (DVT) and 5 pulmonary emboli (PE). One patient had both a DVT and PE. The median time to VTE diagnosis was 14 (7-17) days. In those diagnosed with a VTE, 50.0% (n = 7) never reached 0.2-0.4 IU/mL anti-Xa and 42.8% (n = 6) were diagnosed with a VTE after achieving these levels. Prophylactic levels were achieved initially in 64 (33.0%) patients, and achieved later in 38 (19.6%) additional patients, giving an overall prophylactic rate of 52.6% (n = 102). There were no differences in VTE (6.9% vs. 7.6%, p = 0.841), DVT (3.9% vs. 6.5%, p = 0.413), or PE (3.9% vs. 1.1%, p = 0.213) rates between those who became prophylactic and those who did not. CONCLUSIONS: There was no difference in VTE incidence between those achieving anti-Xa peak levels of 0.2-0.4 IU/mL and those who did not. Furthermore, these levels were never achieved in some trauma patients despite repeated dosing over a >10-day period. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Global Gene Expression Change Induced by Major Thoracoabdominal Surgery.

OBJECTIVE: To test the hypothesis that major thoracoabdominal surgery induces gene expression changes associated with adverse outcomes. BACKGROUND: Widely different traumatic injuries evoke surprisingly similar gene expression profiles, but there is limited information on whether the iatrogenic injury caused by major surgery is associated with similar patterns. METHODS: With informed consent, blood samples were obtained from 50 patients before and after open transhiatal esophagectomy or pancreaticoduodenectomy. Twelve cases with complicated recoveries (death, infection, venous thromboembolism) were matched with 12 cases with uneventful recoveries. Global gene expression was assayed using human microarray chips. A 2-fold change with a corrected P < 0.05 was considered differentially expressed. RESULTS: In these 24 patients, 522 genes were differentially expressed after surgery; 248 (48%) were upregulated (innate immunity and inflammation) and 274 (52%) were downregulated [adaptive immunity (antigen presentation, T-cell function)]. Hierarchical clustering of the profile reliably predicted pre- and postoperative status. The within-patient change was 3.08 ±â€Š0.91-fold. There was no measurable association with age, malignancy, procedure, surgery length, operative blood loss, or transfusion requirements, but was positively associated with postoperative infection (3.81 ±â€Š0.97 vs 2.79 ±â€Š0.73; P = 0.009) and hospital length of stay (r = 0.583, P = 0.003). Venous thromboembolism and mortality each occurred in one patient, thus no associations were possible. CONCLUSIONS: Major surgery induces a quantifiable pattern of gene expression change that is associated with adverse outcome. This could reflect early impaired adaptive immunity and suggests potential therapeutic targets to improve postoperative recovery.