Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared to standard care resuscitation in patients with hemorrhagic shock. SUMMARY BACKGROUND DATA: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at five U.S. trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days vs. standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared to 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P=0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences.

Risk-stratified thromboprophylaxis effects of aspirin versus low-molecular-weight heparin in orthopedic trauma patients: A secondary analysis of the PREVENT CLOT trial.

BACKGROUND: The PREVENT CLOT trial concluded that thromboprophylaxis with aspirin was noninferior to low-molecular-weight heparin (LMWH) in preventing death after orthopedic trauma. However, it was unclear if these results applied to patients at highest risk of thrombosis. Therefore, we assessed if the effect of aspirin versus LMWH differed based on patients' baseline risk of venous thromboembolism (VTE). METHODS: The PREVENT CLOT trial enrolled 12,211 adult patients with fractures. This secondary analysis stratified the study population into VTE risk quartiles: low (<1%) to high (>10%) using the Caprini score. We assessed stratum-specific treatment effects using the win ratio method, in which each patient assigned to aspirin was paired with each assigned to LMWH. In each pair, we compared outcomes hierarchically, starting with death, then pulmonary embolism, deep vein thrombosis, and bleeding. The secondary outcome added patients' medication satisfaction as a fifth composite component. RESULTS: In the high-risk quartile (n = 3052), 80% had femur fracture, pelvic, or acetabular fractures. Thoracic (47%) and head (37%) injuries were also common. In the low risk quartile (n = 3053), most patients had a tibia fracture (67%), 5% had a thoracic injury, and less than 1% had head or spinal injuries. Among high risk patients, thromboembolic events did not differ statistically between aspirin and LMWH (win ratio, 0.94; 95% confidence interval [CI], 0.82-1.08, p = 0.42). This result was consistent in the low (win ratio, 1.15; 95% CI, 0.90-1.47, p = 0.27), low-medium (win ratio, 1.05; 95% CI, 0.85-1.29, p = 0.68), and medium-high risk quartiles (win ratio, 0.94; 95% CI, 0.80-1.11, p = 0.48). When medication satisfaction was considered, favorable outcomes were 68% more likely with aspirin (win ratio, 1.68; 95% CI, 1.60-1.77; p < 0.001). CONCLUSION: Thromboembolic outcomes were similar with aspirin or LMWH, even among patients at highest risk of VTE. Aspirin was favored if medication satisfaction was also considered. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Increased platelet mitochondrial function correlates with clot strength in a rodent fracture model.

BACKGROUND: Thromboelastographic measures of clot strength increase early after injury, portending higher risks for thromboembolic complications during recovery. Understanding the specific role of platelets is challenging because of a lack of clinically relevant measures of platelet function. Platelet mitochondrial respirometry may provide insight to global platelet function but has not yet been correlated with functional coagulation studies. METHODS: Wistar rats underwent anesthesia and either immediate sacrifice for baseline values (n = 6) or (1) bilateral hindlimb orthopedic injury (n = 12), versus (2) sham anesthesia (n = 12) with terminal phlebotomy/hepatectomy after 24 hours. High-resolution respirometry was used to measure basal respiration, mitochondrial leak, maximal oxidative phosphorylation, and Complex IV activity in intact platelets; Complex I- and Complex II-driven respiration was measured in isolated liver mitochondria. Results were normalized to platelet number and protein mass, respectively. Citrated native thromboelastography (TEG) was performed in triplicate. RESULTS: Citrated native TEG maximal amplitude was significantly higher (81.0 ± 3.0 vs. 73.3 ± 3.5 mm, p < 0.001) in trauma compared with sham rats 24 hours after injury. Intact platelets from injured rats had higher basal oxygen consumption (17.7 ± 2.5 vs. 15.1 ± 3.2 pmol O 2 /[s × 10 8 cells], p = 0.045), with similar trends in mitochondrial leak rate ( p = 0.19) when compared with sham animals. Overall, platelet basal respiration significantly correlated with TEG maximal amplitude ( r = 0.44, p = 0.034). As a control for sex-dependent systemic mitochondrial differences, females displayed higher liver mitochondria Complex I-driven respiration (895.6 ± 123.7 vs. 622.1 ± 48.7 mmol e - /min/mg protein, p = 0.02); as a control for systemic mitochondrial effects of injury, no liver mitochondrial respiration differences were seen. CONCLUSION: Platelet mitochondrial basal respiration is increased after injury and correlates with clot strength in this rodent hindlimb fracture model. Several mitochondrial-targeted therapeutics exist in common use that are underexplored but hold promise as potential antithrombotic adjuncts that can be sensitively evaluated in this preclinical model.

Survey of venous thromboembolism prophylaxis in trauma patients: current prescribing practices and concordance with clinical practice guidelines.

Objectives: Pharmacological venous thromboembolism (VTE) prophylaxis is recommended in the vast majority of trauma patients. The purpose of this study was to characterize current dosing practices and timing of initiation of pharmacological VTE chemoprophylaxis at trauma centers. Methods: This was an international, cross-sectional survey of trauma providers. The survey was sponsored by the American Association for the Surgery of Trauma (AAST) and distributed to AAST members. The survey included 38 questions about practitioner demographics, experience, level and location of trauma center, and individual/site-specific practices regarding the dosing, selection, and timing of initiation of pharmacological VTE chemoprophylaxis in trauma patients. Results: One hundred eighteen trauma providers responded (estimated response rate 6.9%). Most respondents were at level 1 trauma centers (100/118; 84.7%) and had >10 years of experience (73/118; 61.9%). While multiple dosing regimens were used, the most common dose reported was enoxaparin 30 mg every 12 hours (80/118; 67.8%). The majority of respondents (88/118; 74.6%) indicated adjusting the dose in patients with obesity. Seventy-eight (66.1%) routinely use antifactor Xa levels to guide dosing. Respondents at academic institutions were more likely to use guideline-directed dosing (based on the Eastern Association of the Surgery of Trauma and the Western Trauma Association guidelines) of VTE chemoprophylaxis compared with those at non-academic centers (86.2% vs 62.5%; p=0.0158) and guideline-directed dosing was reported more often if the trauma team included a clinical pharmacist (88.2% vs 69.0%; p=0.0142). Wide variability in initial timing of VTE chemoprophylaxis after traumatic brain injury, solid organ injury, and spinal cord injuries was found. Conclusions: A high degree of variability exists in prescribing and monitoring practices for the prevention of VTE in trauma patients. Clinical pharmacists may be helpful on trauma teams to optimize dosing and increase prescribing of guideline-concordant VTE chemoprophylaxis.

Association of Patient Belief About Success of Antibiotics for Appendicitis and Outcomes: A Secondary Analysis of the CODA Randomized Clinical Trial.

Importance: A patient's belief in the likely success of a treatment may influence outcomes, but this has been understudied in surgical trials. Objective: To examine the association between patients' baseline beliefs about the likelihood of treatment success with outcomes of antibiotics for appendicitis in the Comparison of Outcomes of Antibiotic Drugs and Appendectomy (CODA) trial. Design, Setting, and Participants: This was a secondary analysis of the CODA randomized clinical trial. Participants from 25 US medical centers were enrolled between May 3, 2016, and February 5, 2020. Included in the analysis were participants with appendicitis who were randomly assigned to receive antibiotics in the CODA trial. After informed consent but before randomization, participants who were assigned to receive antibiotics responded to a baseline survey including a question about how successful they believed antibiotics could be in treating their appendicitis. Interventions: Participants were categorized based on baseline survey responses into 1 of 3 belief groups: unsuccessful/unsure, intermediate, and completely successful. Main Outcomes and Measures: Three outcomes were assigned at 30 days: (1) appendectomy, (2) high decisional regret or dissatisfaction with treatment, and (3) persistent signs and symptoms (abdominal pain, tenderness, fever, or chills). Outcomes were compared across groups using adjusted risk differences (aRDs), with propensity score adjustment for sociodemographic and clinical factors. Results: Of the 776 study participants who were assigned antibiotic treatment in CODA, a total of 425 (mean [SD] age, 38.5 [13.6] years; 277 male [65%]) completed the baseline belief survey before knowing their treatment assignment. Baseline beliefs were as follows: 22% of participants (92 of 415) had an unsuccessful/unsure response, 51% (212 of 415) had an intermediate response, and 27% (111 of 415) had a completely successful response. Compared with the unsuccessful/unsure group, those who believed antibiotics could be completely successful had a 13-percentage point lower risk of appendectomy (aRD, -13.49; 95% CI, -24.57 to -2.40). The aRD between those with intermediate vs unsuccessful/unsure beliefs was -5.68 (95% CI, -16.57 to 5.20). Compared with the unsuccessful/unsure group, those with intermediate beliefs had a lower risk of persistent signs and symptoms (aRD, -15.72; 95% CI, -29.71 to -1.72), with directionally similar results for the completely successful group (aRD, -15.14; 95% CI, -30.56 to 0.28). Conclusions and Relevance: Positive patient beliefs about the likely success of antibiotics for appendicitis were associated with a lower risk of appendectomy and with resolution of signs and symptoms by 30 days. Pathways relating beliefs to outcomes and the potential modifiability of beliefs to improve outcomes merit further investigation. Trial Registration: ClinicalTrials.gov Identifier: NCT02800785.

Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.

Viscoelastic Hemostatic Assays for Orthopedic Trauma and Elective Procedures.

The application of viscoelastic hemostatic assays (VHAs) (e.g., thromboelastography (TEG) and rotational thromboelastometry (ROTEM)) in orthopedics is in its relative infancy when compared with other surgical fields. Fortunately, several recent studies describe the emerging use of VHAs to quickly and reliably analyze the real-time coagulation and fibrinolytic status in both orthopedic trauma and elective orthopedic surgery. Trauma-induced coagulopathy-a spectrum of abnormal coagulation phenotypes including clotting factor depletion, inadequate thrombin generation, platelet dysfunction, and dysregulated fibrinolysis-remains a potentially fatal complication in severely injured and/or hemorrhaging patients whose timely diagnosis and management are aided by the use of VHAs. Furthermore, VHAs are an invaluable compliment to common coagulation tests by facilitating the detection of hypercoagulable states commonly associated with orthopedic injury and postoperative status. The use of VHAs to identify hypercoagulability allows for an accurate venous thromboembolism (VTE) risk assessment and monitoring of VTE prophylaxis. Until now, the data have been insufficient to permit an individualized approach with regard to dosing and duration for VTE thromboprophylaxis. By incorporating VHAs into routine practice, orthopedic surgeons will be better equipped to diagnose and treat the complete spectrum of coagulation abnormalities faced by orthopedic patients. This work serves as an educational primer and up-to-date review of the current literature on the use of VHAs in orthopedic surgery.

Weight Bias: Examining Achalasia Therapy in the Obese Patient.

We hypothesize that obesity is a common diagnosis in those with achalasia at our institution but time to diagnosis and treatment is longer compared to normal weight counterparts due to implicit bias. We retrospectively reviewed all adult patients between 1/1/2013 and 6/31/2020 with a diagnosis of achalasia. Demographics, comorbidities, Eckardt scores, interventions, complications, time to consult, duration of symptoms, and follow-up were evaluated. More than half of the patients were seen in the most recent 2 years following POEM introduction and 138 had available BMI data. 46 were obese (33%) and 92 were non-obese (67%). Obese patients reported a shorter duration of symptoms prior to seeking treatment 12 versus 24 months. There was no difference in time to intervention or procedure offered. There was a non-significant trend toward higher leak (11 vs 5%) and overall complication rate (19 vs 17%) in obese patients. In follow-up 98 patients had BMI data. There was a a significant difference in mean BMI change -1.2 +/- 4.2 kg/m2 in obese patients and +0.1 +/- 2.1 kg/m2 in normal weight patients. One year follow-up was available in 16 (47%) obese and 25 (33%) non-obese patients and showed a non-significant trend toward greater weight gain in the normal/overweight group (+3.2 +/- 1.1 kg/m2) compared to obese (+2.0 +/- 3.5 kg/m2). Obese patients with achalasia have unique considerations. Duration of symptoms may be shorter in the obese patient with esophageal dysphagia. We noted trends toward greater weight gain following interventions in non-obese patients with equivalent complication rates.

The effects of increased donor support time from organ donation referral to donor procurement on heart transplant recipient survival.

INTRODUCTION: Given the known deleterious cardiac effects of brain death (BD) physiology, we hypothesized that time from cardiac donation referral to procurement (donor support time [DST]), would negatively impact cardiac transplant recipient survival. METHODS: The United Network for Organ Sharing database was queried from 2007 to 2018, identifying 22,593 donor hearts for analysis. Multivariate logistic models for 30-day and 1-year survival, as well as Cox models for overall survival and posttransplant rejection, were used to assess adjusted outcomes. RESULTS: median DST was 3 days (interquartile range: 2-5 days). Ischemic time; distance between donor and recipient hospitals; and recipient age, creatinine, waitlist time, and length of stay were adjusted predictors of survival and rejection. DST was not associated with either outcome in aggregate; however, differential association by donor race was identified, with DST in any race recipient associated with 4% higher odds of 1-year mortality (p = .001; p value for interaction .005) but only a trend towards worse overall mortality (p = .064; p value for interaction .046). CONCLUSION: Thus, duration of exposure to BD physiology may have a differential impact on recipient outcomes based on donor race, suggesting that additional research is needed on donor immunologic, socioeconomic, and healthcare access factors that may impact cardiac transplant recipient outcomes.

Circulating Total Cell-Free DNA Levels Are Increased in Hypertensive Disorders of Pregnancy and Associated with Prohypertensive Factors and Adverse Clinical Outcomes.

Previous studies have described increased circulating cell-free DNA (cfDNA) in hypertensive disorders of pregnancy (HDP). Here, we aimed first to confirm this information using a simple, but sensible fluorescent assay, and second to investigate whether total cfDNA is associated with circulating factors known to be linked to the pathophysiology of HDP as well as with poor maternal-fetal outcomes. We studied 98 women with healthy pregnancies (HP), 88 with gestational hypertension (GH), and 91 with preeclampsia (PE). Total DNA was extracted from plasma using the QIAamp DNA blood mini kit and quantified using Quant-iT™ PicoGreen® dsDNA fluorescent detection kit. We found higher total cfDNA levels in GH and PE (197.0 and 174.2 ng/mL, respectively) than in HP (140.5 ng/mL; both p < 0.0001). Interestingly, total cfDNA levels were elevated in both male and female-bearing pregnancies diagnosed with either HDP, and in more severe versus less severe HDP cases, as classified according to responsiveness to antihypertensive therapy. In addition, total cfDNA was independently associated with HDP, and a cutoff concentration of 160 ng/mL provided appropriate sensitivity and specificity values for diagnosing GH and PE compared to HP (70-85%, both p < 0.0001). Moreover, high total cfDNA was associated with adverse clinical outcomes (high blood pressure, low platelet count, preterm delivery, fetal growth restriction) and high prohypertensive factors (sFLT-1, sEndoglin, MMP-2). These findings represent a step towards to the establishment of cfDNA as a diagnostic tool and the need to understand its role in HDP.

A Randomized Trial Comparing Antibiotics with Appendectomy for Appendicitis.

BACKGROUND: Antibiotic therapy has been proposed as an alternative to surgery for the treatment of appendicitis. METHODS: We conducted a pragmatic, nonblinded, noninferiority, randomized trial comparing antibiotic therapy (10-day course) with appendectomy in patients with appendicitis at 25 U.S. centers. The primary outcome was 30-day health status, as assessed with the European Quality of Life-5 Dimensions (EQ-5D) questionnaire (scores range from 0 to 1, with higher scores indicating better health status; noninferiority margin, 0.05 points). Secondary outcomes included appendectomy in the antibiotics group and complications through 90 days; analyses were prespecified in subgroups defined according to the presence or absence of an appendicolith. RESULTS: In total, 1552 adults (414 with an appendicolith) underwent randomization; 776 were assigned to receive antibiotics (47% of whom were not hospitalized for the index treatment) and 776 to undergo appendectomy (96% of whom underwent a laparoscopic procedure). Antibiotics were noninferior to appendectomy on the basis of 30-day EQ-5D scores (mean difference, 0.01 points; 95% confidence interval [CI], -0.001 to 0.03). In the antibiotics group, 29% had undergone appendectomy by 90 days, including 41% of those with an appendicolith and 25% of those without an appendicolith. Complications were more common in the antibiotics group than in the appendectomy group (8.1 vs. 3.5 per 100 participants; rate ratio, 2.28; 95% CI, 1.30 to 3.98); the higher rate in the antibiotics group could be attributed to those with an appendicolith (20.2 vs. 3.6 per 100 participants; rate ratio, 5.69; 95% CI, 2.11 to 15.38) and not to those without an appendicolith (3.7 vs. 3.5 per 100 participants; rate ratio, 1.05; 95% CI, 0.45 to 2.43). The rate of serious adverse events was 4.0 per 100 participants in the antibiotics group and 3.0 per 100 participants in the appendectomy group (rate ratio, 1.29; 95% CI, 0.67 to 2.50). CONCLUSIONS: For the treatment of appendicitis, antibiotics were noninferior to appendectomy on the basis of results of a standard health-status measure. In the antibiotics group, nearly 3 in 10 participants had undergone appendectomy by 90 days. Participants with an appendicolith were at a higher risk for appendectomy and for complications than those without an appendicolith. (Funded by the Patient-Centered Outcomes Research Institute; CODA ClinicalTrials.gov number, NCT02800785.).

A rat model of orthopedic injury-induced hypercoagulability and fibrinolytic shutdown.

BACKGROUND: Postinjury hypercoagulability occurs in >25% of injured patients, increasing risk of thromboembolic complications despite chemoprophylaxis. However, few clinically relevant animal models of posttraumatic hypercoagulability exist. We aimed to evaluate a rodent model of bilateral hindlimb injury as a preclinical model of postinjury hypercoagulability. METHODS: Forty Wistar rats were anesthetized with isoflurane: 20 underwent bilateral hindlimb fibula fracture, soft tissue and muscular crush injury, and bone homogenate injection intended to mimic the physiological severity of bilateral femur fracture. Twenty sham rats underwent anesthesia only. Terminal citrated blood samples were drawn at 0, 6, 12, and 24 hours (n = 5 per timed group) for analysis by native thromboelastography in the presence and absence of taurocholic acid to augment fibrinolysis. Plasminogen activator inhibitor 1 and α-2 antiplasmin levels in plasma were assessed via enzyme-linked immunosorbent assay. RESULTS: Injured rats became hypercoagulable relative to baseline by 6 hours based on thromboelastography maximal amplitude (MA) and G (p < 0.005); sham rats became hypercoagulable to a lesser degree by 24 hours (p < 0.005). Compared with sham animals, injured rats were hypercoagulable by MA and G within 6 hours of injury, remained hypercoagulable by MA and G through at least 24 hours (all p < 0.01), and showed impaired fibrinolysis by taurocholic acid LY30 at 12 hours (p = 0.019) and native LY30 at 24 hours (p = 0.045). In terms of antifibrinolytic mediators, α-2 antiplasmin was elevated in trauma animals at 24 hours (p = 0.009), and plasminogen activator inhibitor 1 was elevated in trauma animals at 6 hours (p = 0.004) and 12 hours (p < 0.001) when compared with sham. CONCLUSIONS: Orthopedic injury in rodents induced platelet and overall hypercoagulability within 6 hours and fibrinolytic impairment by 12 to 24 hours, mimicking postinjury hypercoagulability in injured patients. This rodent model of orthopedic injury may serve as a preclinical testing ground for potential therapies to mitigate hypercoagulability, maintain normal fibrinolysis, and prevent thromboembolic complications.

Contemporary management of traumatic cervical and thoracic esophageal perforation: The results of an Eastern Association for the Surgery of Trauma multi-institutional study.

BACKGROUND: Traumatic esophageal perforation is rare and associated with significant morbidity and mortality. There is substantial variability in diagnosis and treatment. Esophageal stents have been increasingly used for nontraumatic perforation; however, stenting for traumatic perforation is not yet standard of care. The purpose of this study was to evaluate current management of traumatic esophageal perforation to assess the frequency of and complications associated with esophageal stenting. METHODS: This was an Eastern Association for the Surgery of Trauma multi-institutional retrospective study from 2011 to 2016 of patients with traumatic cervical or thoracic esophageal injury admitted to one of 11 participating trauma centers. Data were collected and sent to a single institution where it was analyzed. Patient demographics, injury characteristics, initial management, complications, and patient mortality were collected. Primary outcome was mortality; secondary outcomes were initial treatment, esophageal leak, and associated complications. RESULTS: Fifty-one patients were analyzed. Esophageal injuries were cervical in 69% and thoracic in 31%. Most patients were initially managed with operative primary repair (61%), followed by no intervention (19%), esophageal stenting (10%), and wide local drainage (10%). Compared with patients who underwent operative primary repair, patients managed with esophageal stenting had an increased rate of esophageal leak (22.6% vs. 80.0%, p = 0.02). Complication rates were higher in blunt compared with penetrating mechanisms (100% vs. 31.8%, p = 0.03) despite similar Injury Severity Score and neck/chest/abdomen Abbreviated Injury Scale. Overall mortality was 9.8% and did not vary based on location of injury, mechanism of injury, or initial management. CONCLUSION: Most patients with traumatic esophageal injuries still undergo operative primary repair; this is associated with lower rates of postoperative leaks as compared with esophageal stenting. Patients who have traumatic esophageal injury may be best managed by direct repair and not esophageal stenting, although further study is needed. LEVEL OF EVIDENCE: Therapeutic, level IV.

Outcomes in patients with gunshot wounds to the brain.

INTRODUCTION: Gunshot wounds to the brain (GSWB) confer high lethality and uncertain recovery. It is unclear which patients benefit from aggressive resuscitation, and furthermore whether patients with GSWB undergoing cardiopulmonary resuscitation (CPR) have potential for survival or organ donation. Therefore, we sought to determine the rates of survival and organ donation, as well as identify factors associated with both outcomes in patients with GSWB undergoing CPR. METHODS: We performed a retrospective, multicenter study at 25 US trauma centers including dates between June 1, 2011 and December 31, 2017. Patients were included if they suffered isolated GSWB and required CPR at a referring hospital, in the field, or in the trauma resuscitation room. Patients were excluded for significant torso or extremity injuries, or if pregnant. Binomial regression models were used to determine predictors of survival/organ donation. RESULTS: 825 patients met study criteria; the majority were male (87.6%) with a mean age of 36.5 years. Most (67%) underwent CPR in the field and 2.1% (n=17) survived to discharge. Of the non-survivors, 17.5% (n=141) were considered eligible donors, with a donation rate of 58.9% (n=83) in this group. Regression models found several predictors of survival. Hormone replacement was predictive of both survival and organ donation. CONCLUSION: We found that GSWB requiring CPR during trauma resuscitation was associated with a 2.1% survival rate and overall organ donation rate of 10.3%. Several factors appear to be favorably associated with survival, although predictions are uncertain due to the low number of survivors in this patient population. Hormone replacement was predictive of both survival and organ donation. These results are a starting point for determining appropriate treatment algorithms for this devastating clinical condition. LEVEL OF EVIDENCE: Level II.

Early versus late venous thromboembolism: A secondary analysis of data from the PROPPR trial.

BACKGROUND: Factors predicting timing of post-traumatic venous thromboembolism (VTE) remain incompletely understood. Because the balance between hemorrhage and thrombosis is dynamic during a patient's hospital course, early and late VTE may be physiologically discrete processes. This secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial aims to explore whether certain risk factors are associated with early versus late VTE. METHODS: The PROPPR trial investigated post-traumatic resuscitation with platelets, plasma, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio. Multinomial regression based on a threshold determined by cubic spline analysis tested the association of clinical variables with early or late VTE, a composite of deep vein thrombosis and pulmonary embolus, adjusting for predetermined confounders. RESULTS: Of the 87 patients (13%) with VTE, pulmonary embolus was predominant in the first 72 hours. A statistically determined threshold at 12 days corresponded to change in odds of early versus late events. Variables associated with early VTE included plasma transfusion (risk ratio [RR] 1.14; 95% confidence interval, 1.00, 1.30; P = .05), sepsis (RR 0.05; 95% confidence interval, 1.40, 6.64; P = .01), pelvic or femur fracture (RR 2.62; 95% confidence interval, 1.00, 6.90; P = .05). Late VTE was associated with dialysis (RR 7.37; 95% confidence interval, 1.59, 34.14; P = .01), older age (RR 1.02; 95% confidence interval 1.00, 1.04; P = .05), and delayed resuscitation approaching ratios of 1:1:1 among patients randomized to 1:1:2 therapy (RR 2.06; 95% confidence interval, 0.28, 3.83; P = .02). Cyroprecipitate increased risk of early (RR 1.04, 95% confidence interval, 1.00,1.08; P < .03) and late VTE (1.05; 95% confidence interval, 1.01, 1.09; P = .01). Prolonged lagtime (coeffcient 0.06, 95% confidence interval, 0.02, 0.10; P < .01) and time-to-peak thrombin generation (coeffcient 0.04, 95% confidence interval, 0.02, 0.07; P < .01) were associated with increased risk of early VTE. CONCLUSION: Early and late VTE may differ in their risk factors. Defining temporal trends in VTE may allow for a more individualized approach to thromboprophylaxis.

Predisposed to failure? The challenge of rescue in the medical intensive care unit.

BACKGROUND: Medical intensive care unit (MICU) patients develop acute surgical processes that require operative intervention. There are limited data addressing outcomes of emergency general surgery (EGS) in this population. The aim of our study was to characterize the breadth of surgical consults from the MICU and assess mortality after abdominal EGS cases. METHODS: All MICU patients with an EGS consult in an academic medical center between January 2010 and 2016 were identified from an electronic medical record-based registry. Charts were reviewed to determine reason for consult, procedures performed, and to obtain additional clinical data. A multivariate logistic regression was used to determine patient factors associated with patient mortality. RESULTS: Of 911 MICU patients seen by our service, 411(45%) required operative intervention, with 186 patients undergoing an abdominal operation. The postoperative mortality rate after abdominal operations was 37% (69/186), significantly higher than the mortality of 16% (1833/11192) for all patients admitted to the MICU over the same period (p < 0.05). Damage-control procedures were performed in 64 (34%) patients, with 46% mortality in this group. The most common procedures were bowel resections, with mortality of 42% (28/66) and procedures for severe clostridium difficile, mortality of 38% (9/24). Twenty-seven patients met our definition of surgical rescue, requiring intervention for complications of prior procedures, with mortality of 48%. Need for surgical rescue was associated with increased admission mortality (odds ratio, 13.07; 95% confidence interval, 2.86-59.77). Twenty-six patients had pathology amenable to surgical intervention but did not undergo operation, with 100% mortality. In patients with abdominal pathology at the time of operation, in-hospital delay was associated with increased mortality (odds ratio, 5.13; 95% confidence interval, 1.11-23.77). CONCLUSION: Twenty percent of EGS consults from the MICU had an abdominal process requiring an operative intervention. While the MICU population as a whole has a high baseline mortality, patients requiring abdominal surgical intervention are an even higher risk. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

Tranexamic acid administration is associated with an increased risk of posttraumatic venous thromboembolism.

BACKGROUND: Tranexamic acid (TXA) is used as a hemostatic adjunct for hemorrhage control in the injured patient and reduces early preventable death. However, the risk of venous thromboembolism (VTE) has been incompletely explored. Previous studies investigating the effect of TXA on VTE vary in their findings. We performed a propensity matched analysis to investigate the association between TXA and VTE following trauma, hypothesizing that TXA is an independent risk factor for VTE. METHODS: This retrospective study queried trauma patients presenting to a single Level I trauma center from 2012 to 2016. Our primary outcome was composite pulmonary embolism or deep vein thrombosis. Mortality, transfusion, intensive care unit and hospital lengths of stay were secondary outcomes. Propensity matched mixed effects multivariate logistic regression was used to determine adjusted odds ratio (aOR) and 95% confidence intervals (95% CI) of TXA on outcomes of interest, adjusting for prespecified confounders. Competing risks regression assessed subdistribution hazard ratio of VTE after accounting for mortality. RESULTS: Of 21,931 patients, 189 pairs were well matched across propensity score variables (standardized differences <0.2). Median Injury Severity Score was 19 (interquartile range, 12-27) and 14 (interquartile range, 8-22) in TXA and non-TXA groups, respectively (p = 0.19). Tranexamic acid was associated with more than threefold increase in the odds of VTE (aOR, 3.3; 95% CI, 1.3-9.1; p = 0.02). Tranexamic acid was not significantly associated with survival (aOR, 0.86; 95% CI, 0.23-3.25; p = 0.83). Risk of VTE remained elevated in the TXA cohort despite accounting for mortality (subdistribution hazard ratio, 2.42; 95% CI, 1.11-5.29; p = 0.03). CONCLUSION: Tranexamic acid may be an independent risk factor for VTE. Future investigation is needed to identify which patients benefit most from TXA, especially given the risks of this intervention to allow a more individualized treatment approach that maximizes benefits and mitigates potential harms. LEVEL OF EVIDENCE: Therapeutic, level III.

Surgical rescue: The next pillar of acute care surgery.

BACKGROUND: The evolving field of acute care surgery (ACS) traditionally includes trauma, emergency general surgery, and critical care. However, the critical role of ACS in the rescue of patients with a surgical complication has not been explored. We here describe the role of "surgical rescue" in the practice of ACS. METHODS: A prospective, electronic medical record-based ACS registry spanning January 2013 to May 2014 at a large urban academic medical center was screened by ICD-9 codes for acute surgical complications of an operative or interventional procedure. Long-term outcomes were derived from the Social Security Death Index. RESULTS: Of 2,410 ACS patients, 320 (13%) required "surgical rescue": most commonly, from wound complications (32%), uncontrolled sepsis (19%), and acute obstruction (15%). The majority of complications (85%) were related to an operation; 15% were related to interventional procedures. The most common rescue interventions required were bowel resection (23%), wound debridement (18%), and source control of infection (17%); 63% of patients required operative intervention, and 22% required surgical critical care. Thirty-six percent of complications occurred in ACS primary patients ("local"), whereas 38% were referred from another surgical service ("institutional") and 26% referred from another institution ("regional"). Hospital length of stay was longer, and in-hospital and 1-year mortalities were higher in rescue patients compared with those without a complication. Outcomes were equivalent between "local" and "institutional" patients, but hospital length of stay and discharge to home were significantly worse in "institutional" referrals. CONCLUSION: We here describe the distinct role of the acute care surgeon in the surgical management of complications; this is an additional pillar of ACS. In this vital role, the acute care surgeon provides crucial support to other providers as well as direct patient care in the "surgical rescue" of surgical and procedural complications. LEVEL OF EVIDENCE: Epidemiological study, level III; therapeutic/care management study, level IV.

Emergency preservation and resuscitation for cardiac arrest from trauma.

The advent of cardiopulmonary resuscitation (CPR) revolutionized the care of patients with cardiac arrest, now allowing survival of up to 30% after out-of-hospital arrest due to arrhythmia; however, outcomes for cardiac arrest after trauma remain dismal, with less than 10% survival despite the most aggressive modern resuscitation techniques. The short time interval between cardiac arrest and brain ischemia, the reduced efficacy of CPR in the patient with profound hypovolemia due to hemorrhage, and the speed of exsanguination from major vascular injury all conspire to limit the effectiveness of standard CPR in the critically injured patient. Beginning in the 1980s, researchers began to harness the effects of profound hypothermia in order to extend the window of survivability after traumatic arrest, allowing the critical time needed to obtain surgical hemostasis in otherwise lethal exsanguinating injuries. These studies have culminated in the emergency preservation and resuscitation (EPR) of the trauma patient. Rapid central arterial access is obtained and profound (<10 °C) hypothermia induced with aortic infusion of cold saline. During this window of up to 1 h, damage control surgical techniques are applied to control hemorrhage and repair injuries, followed by controlled rewarming and reperfusion using cardiopulmonary bypass. In this review, we trace these techniques from their early theoretical development, through refinement in clinically relevant animal models, and into their present application in a currently-enrolling human clinical trial of EPR for cardiac arrest from trauma (EPR-CAT), as well as examine current topics, ongoing challenges, and future directions for emergency preservation and resuscitation research.