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There is a paucity of data describing opioid prescribing patterns for trauma patients. We investigated pain medication regimens prescribed at discharge for patients with traumatic rib fractures, as well as potential variables predictive of opioid prescribing.A single-center, retrospective analysis was performed of 337 adult patients presenting with ≥1 traumatic rib fractures between January and December 2019. The primary outcome was oral morphine milligram equivalents (MME) prescribed on discharge. A multivariable logistic regression analysis was performed to determine factors independently associated with above median (150) MME prescription at discharge.The majority of patients were male (68.8%) with a median age of 53 y. Blunt trauma accounted for 97.3% of cases with a median Injury Severity Score(ISS) of 10. Locoregional pain procedures were utilized in 16.9% of patients. Opioids were the most common analgesic prescribed at discharge, and 74.1% of patients prescribed opioids on discharge were also prescribed a non-opioid adjunct. On multivariable analysis, daily MME prescribed during hospitalization (OR 1.01, 95% CI 1.01-1.02, P 0.01) and number of rib fractures (OR 2.26, 95% CI 1.36-3.74, P 0.01) were predictive of high MME prescribed on discharge.For patients with traumatic rib fractures, daily MME during hospitalization and number of rib fractures were predictive of high MME prescribing on discharge. Further prospective studies evaluating strategies for pain management and protocolized approaches to opioid prescribing are needed to reduce unnecessary and inappropriate opioid use in this patient population.

Improvised explosive devices have resulted in a unique polytrauma injury pattern termed dismounted complex blast injury (DCBI), which is frequent in the modern military theater. Dismounted complex blast injury is characterized by extremity amputations, junctional vascular injury, and blast traumatic brain injury (bTBI). We developed a combat casualty relevant DCBI swine model, which combines hemorrhagic shock (HS) and tissue injury (TI) with a bTBI, to study interventions in this unique and devastating military injury pattern.A 50-kg male Yorkshire swine were randomized to the DCBI or SHAM group (instrumentation only). Those in the DCBI group were subjected to HS, TI, and bTBI. The blast injury was applied using a 55-psi shock tube wave. Tissue injury was created with bilateral open femur fractures. Hemorrhagic shock was induced by bleeding from femoral arteries to target pressure. A resuscitation protocol modified from the Tactical Combat Casualty Care guidelines simulated battlefield resuscitation for 240 minutes.Eight swine underwent the DCBI model and five were allocated to the SHAM group. In the DCBI model the mean base excess achieved at the end of the HS shock was -8.57 ± 5.13 mmol·L -1 . A significant coagulopathy was detected in the DCBI model as measured by prothrombin time (15.8 seconds DCBI vs. 12.86 seconds SHAM; p = 0.02) and thromboelastography maximum amplitude (68.5 mm DCBI vs. 78.3 mm in SHAM; p = 0.0003). For the DCBI models, intracranial pressure (ICP) increased by a mean of 13 mm Hg, reaching a final ICP of 24 ± 7.7 mm Hg.We created a reproducible large animal model to study the combined effects of severe HS, TI, and bTBI on coagulation and ICP in the setting of DCBI, with significant translational applications for the care of military warfighters. Within the 4-hour observational period, the swine developed a consistent coagulopathy with a concurrent brain injury evidenced by increasing ICP.

Traumatic brain injury (TBI) in combination with shock has been associated with hypocoagulability. However, recent data suggest that TBI itself can promote a systemic procoagulant state via the release of brain-derived extracellular vesicles. The objective of our study was to identify if TBI was associated with differences in thrombelastography indices when controlling for other variables associated with coagulopathy following trauma. We hypothesized that TBI is independently associated with a less coagulopathic state.Prospective study includes all highest-level trauma activations at an urban Level I trauma center, from 2014 to 2020. Traumatic brain injury was defined as Abbreviated Injury Scale head score greater than 3. Blood samples were drawn at emergency department admission. Linear regression was used to assess the role of independent predictors on trauma induced coagulopathy. Models adjusted for Injury Severity Score (ISS), shock (defined as ED SBP70, or ED SBP90 and ED HR108, or first hospital base deficit10), and prehospital Glasgow Coma Scale score.Of the 1,023 patients included, 291 (28%) suffered a TBI. Traumatic brain injury patients more often were female (26% vs. 19%, p = 0.01), had blunt trauma (83% vs. 43%, p0.0001), shock (33% vs. 25%, p = 0.009), and higher median ISS (29 vs. 10, p0.0001). Fibrinolysis shutdown (25% vs. 18%) was more common in the TBI group (p0.0001). When controlled for the confounding effects of ISS and shock, the presence of TBI independently decreases lysis at 30 minutes (LY30) (beta estimate: -0.16 ± 0.06, p = 0.004). This effect of TBI on LY30 persisted when controlling for sex and mechanism of injury in addition to ISS and shock (beta estimate: -0.13 ± 0.06, p = 0.022).Traumatic brain injury is associated with lower LY30 independent of shock, tissue injury, sex, and mechanism of injury. These findings suggest a propensity toward a hypercoagulable state in patients with TBI, possibly due to fibrinolysis shutdown.Prognostic and Epidemiologic; Level III.

Background: Although surgical stabilization for rib fractures (SSRF) has been adopted widely over the past decade, little information is available regarding the prevalence and outcomes of post-operative surgical site infection (SSI). We hypothesized that SSI after SSRF is uncommon but morbid. Patients and Methods: Patients undergoing SSRF at a level 1 trauma center from 2010-2020 were reviewed. The primary outcome was the prevalence of SSI, documented by clinical examination, radiography, systemic markers of infection, and microbiology. Results: Of 228 patients undergoing SSRF, 167 (73.2%) were male, the median age was 53 years (P25-P75; 41-63 years), injury severity score (ISS) was 19 (P25-P75, 13-26), with a median of eight fractured ribs (P25-P75, 6-11). All stabilization plates were titanium. SSRF was typically performed on post-injury day one (P25-P75, 0-2 days) after trauma. All patients received antibiotic agents within 30 minutes of incision, and a median of four ribs (P25-P75, 3-6) were repaired. Four (1.8%) patients developed an SSI and all underwent implant removal. Two patients required implant removal within 30 days (on post-operative day seven and 17) and two for chronic infection at seven and 17 months after SSRF. The causative organism was methicillin-sensitive Staphylococcus aureus (MSSA) bacteria in all patients. After implant removal, three patients received intravenous and oral antibiotic agents, ranging from two to six weeks, without recurrent infection. No patient required additional SSRF. Conclusions: Surgical site infection after SSRF is rare but morbid and can become symptomatic within one week to 17 months. Implant removal results in complete recovery.

Fibrinogen is the first coagulation factor to decrease after massive hemorrhage. European massive transfusion guidelines recommend early repletion of fibrinogen; however, this practice has not been widely adopted in the US. We hypothesize that hypofibrinogenemia is common at hospital arrival and is an integral component of trauma-induced coagulopathy.This study entailed review of a prospective observational database of adults meeting the highest-level activation criteria at an urban level 1 trauma center from 2014 through 2020. Resuscitation was initiated with 2:1 red blood cell (RBC) to fresh frozen plasma (FFP) ratios and continued subsequently with goal-directed thrombelastography. Hypofibrinogenemia was defined as fibrinogen below 150 mg/dL. Massive transfusion (MT) was defined as more than 10 units RBC or death after receiving at least 1 unit RBC over the first 6 hours of admission.Of 476 trauma activation patients, 70 (15%) were hypofibrinogenemic on admission, median age was 34 years, 78% were male, median New Injury Severity Score (NISS) was 25, and 72 patients died (15%). Admission fibrinogen level was an independent risk factor for MT (odds ratio [OR] 0.991, 95% CI 0.987-0.996]. After controlling for confounders, NISS (OR 1.034, 95% CI 1.017-1.052), systolic blood pressure (OR 0.991, 95% CI 0.983-0.998), thrombelastography angle (OR 0.925, 95% CI 0.896-0.954), and hyperfibrinolysis (OR 2.530, 95% CI 1.160-5.517) were associated with hypofibrinogenemia. Early cryoprecipitate administration resulted in the fastest correction of hypofibrinogenemia.Hypofibrinogenemia is common after severe injury and predicts MT. Cryoprecipitate transfusion results in the most expeditious correction. Earlier administration of cryoprecipitate should be considered in MT protocols.

Severe injury predisposes patients to trauma-induced coagulopathy, which may be subdivided by the state of fibrinolysis. Systemic hyperfibrinolysis (HF) occurs in approximately 25% of these patients with mortality as high as 70%. Severe injury also causes the release of numerous intracellular proteins, which may affect coagulation, one of which is hemoglobin, and hemoglobin substitutes induce HF in vitro. We hypothesize that the α-globin chain of hemoglobin potentiates HF in vitro by augmenting plasmin activity.Proteomic analysis was completed on a pilot study of 30 injured patients before blood component resuscitation, stratified by their state of fibrinolysis, plus 10 healthy controls. Different concentrations of intact hemoglobin A, the α- and β-globin chains, or normal saline (controls) were added to whole blood, and tissue plasminogen activator (tPA)-challenged thrombelastography was used to assess the degree of fibrinolysis. Interactions with plasminogen (PLG) were evaluated using surface plasmon resonance. Tissue plasminogen activator-induced plasmin activity was evaluated in the presence of the α-globin chain.Only the α- and β-globin chains increased in HF patients (p0.01). The α-globin chain but not hemoglobin A or the β-globin chain decreased the reaction time and significantly increased lysis time 30 on citrated native thrombelastographies (p0.05). The PLG and α-globin chain had interaction kinetics similar to tPA:PLG, and the α-globin chain increased tPA-induced plasmin activity.The α-globin chain caused HF in vitro by binding to PLG and augmenting plasmin activity and may represent a circulating "moonlighting" mediator released by the tissue damage and hemorrhagic shock inherent to severe injury.Prognostic, level III.

Background Despite the prevalence of hypocoagulability after injury, the majority of trauma patients paradoxically present with elevated thrombin generation (TG). While several studies have examined plasma TG post-injury, this has not been assessed in whole blood. We hypothesize that whole blood TG is lower in hypocoagulopathy, and TG effectively predicts massive transfusion. Study Design Blood was collected from trauma activation patients at an urban Level-1 trauma center. Whole blood TG was performed with a prototype point-of-care device. Whole blood TG values in healthy volunteers were compared to trauma patients, and TG values were examined in trauma patients with shock and massive transfusion requirement (MT). Results Overall, 118 patients were included (Table 1). Compared to healthy volunteers, trauma patients overall presented with more robust TG; however, those arriving in shock (n=23) had a depressed TG, with significantly lower peak thrombin (88.3 versus 133.0 nM, p=0.01) and slower maximum rate of thrombin generation (27.4 versus 48.3 nM/min, p=0.04). Patients who required massive transfusion (n=26) had significantly decreased TG, with a longer lag time (median 4.8 min versus 3.9 min, p=0.04), decreased peak thrombin (median 71.4 nM versus 124.2 nM, p=0.0003), and lower maximum rate of TG (median 15.8 nM/min versus 39.4 nM/min, p=0.01). AUROC analysis revealed lag time (AUROC 0.6), peak thrombin (AUROC 0.7), and maximum rate of TG (AUROC 0.7) predict early MT. Conclusion These data challenge the prevailing bias that all trauma patients present with elevated TG and highlight that deficient thrombin contributes to the hypocoagulopathic phenotype of trauma-induced coagulopathy. Further, whole blood TG predicts massive transfusion, suggesting point of care whole blood TG may be a useful tool for diagnostic and therapeutic strategies in trauma.

Background Outcomes following pancreatic trauma have not improved significantly over the past two decades. A 2013 Western Trauma Association algorithm highlighted emerging data that might improve the diagnosis and management of high-grade pancreatic injuries (HGPIs; grades III-V). We hypothesized that the use of magnetic resonance cholangiopancreatography, pancreatic duct stenting, operative drainage versus resection, and nonoperative management of HGPIs increased over time. Methods Multicenter retrospective review of diagnosis, management, and outcomes of adult pancreatic injuries from 2010 to 2018 was performed. Data were analyzed by grade and time period (PRE, 2010-2013; POST, 2014-2018) using various statistical tests where appropriate. Results Thirty-two centers reported data on 515 HGPI patients. A total of 270 (53%) had penetrating trauma, and 58% went directly to the operating room without imaging. Eighty-nine (17%) died within 24 hours. Management and outcomes of 426 24-hour survivors were evaluated. Agreement between computed tomography and operating room grading was 38%. Magnetic resonance cholangiopancreatography use doubled in grade IV/V injuries over time but was still low.Overall HGPI treatment and outcomes did not change over time. Resection was performed in 78% of grade III injuries and remained stable over time, while resection of grade IV/V injuries trended downward (56% to 39%, p = 0.11). Pancreas-related complications (PRCs) occurred more frequently in grade IV/V injuries managed with drainage versus resection (61% vs. 32%, p = 0.0051), but there was no difference in PRCs for grade III injuries between resection and drainage.Pancreatectomy closure had no impact on PRCs. Pancreatic duct stenting increased over time in grade IV/V injuries, with 76% used to treat PRCs. Conclusion Intraoperative and computed tomography grading are different in the majority of HGPI cases. Resection is still used for most patients with grade III injuries; however, drainage may be a noninferior alternative. Drainage trended upward for grade IV/V injuries, but the higher rate of PRCs calls for caution in this practice. Level of evidence Retrospective diagnostic/therapeutic study, level III.

BACKGROUND: Venous thromboembolism chemoprophylaxis (VTE-CHEMO) is often delayed in patients with traumatic brain injury because of the concern for intracranial hemorrhage (ICH) progression. We hypothesize that (1) late time to VTE-CHEMO (≥48h) is associated with higher incidence of VTE, and (2) VTE-CHEMO use does not correlate with ICH progression. MATERIALS AND METHODS: This is a multiinstitutional retrospective study of patients with traumatic brain injury admitted between 2014 and 2016. Inclusion criteria were head Abbreviated Injury Code ≥2, ICH present on initial head computed tomography, and two or more head computed tomography scans after admission. The primary outcome was VTE, and the secondary outcome was ICH progression. Patients were classified as receiving VTE-CHEMO early (30 (hazard ratio [HR], 1.05; P = 0.002), Injury Severity Score (HR, 1.004; P < 0.001), pelvic or femur fractures (HR, 1.05; P < 0.0001), spinal cord injury (HR, 1.28; P = 0.02), and missed VTE-CHEMO doses (HR, 1.08; P = 0.01) were significant predictors of VTE. In those who required neurosurgery, late VTE-CHEMO predicted VTE (HR, 1.21; P = 0.0001). Overall, 32% patients experienced ICH progression, which did not correlate with VTE-CHEMO use or timing. CONCLUSIONS: This multicenter study highlights benefits from early VTE-CHEMO and identifies high-risk groups who may benefit from more aggressive prophylaxis. These data also emphasize risk to patients by withholding VTE-CHEMO.

BACKGROUND Knowledge on practice patterns for aortic occlusion (AO) in the setting of severe pelvic fractures is limited. This study aimed to describe clinical outcomes based on number and types of interventions after zone 3 resuscitative endovascular balloon occlusion of the aorta (REBOA) deployment. METHODS A retrospective review of the American Association for the Surgery of Trauma Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery multicenter registry was performed for patients who underwent zone 3 AO from 2013 to 2020. Patients with a blunt mechanism who survived beyond the emergency department were included. Interventions evaluated were preperitoneal pelvic packing (PP), angioembolization (AE), and external fixation (EF) of the pelvis. Management approaches were compared against the primary outcome of mortality. Secondary outcomes included transfusion requirements, overall complications and acute kidney injury (AKI). RESULTS Of 207 patients who underwent zone 3 AO, 160 (77.3%) fit the inclusion criteria. Sixty (37.5%) underwent AO alone, 50 (31.3%) underwent a second hemostatic intervention, and 49 (30.6%) underwent a third hemostatic intervention. Overall mortality was 37.7% (n = 60). There were no differences in mortality based on any number or combination of interventions. On multivariable regression, only EF was associated with a mortality reduction (odds ratio, 0.22; p = 0.011). Increasing number of interventions were associated with higher transfusion and complication rates. Pelvic packing + AE was associated with increased AKI than PP or AE alone (73.3% vs. 29.5% and 28.6%, p = 0.005), and AE was associated with increased AKI resulting in dialysis than PP alone (17.9% vs. 6.8%, p = 0.036). CONCLUSION Zone 3 REBOA can be used as a standalone hemorrhage control technique and as an adjunct in the management of severe pelvic fractures. The only additional intervention associated with a mortality reduction was EF. The benefit of increasing number of interventions must be weighed against more harm. Heterogeneity in practice patterns for REBOA use in pelvic fracture management underscores the need for an evidence base to standardize care. LEVEL OF EVIDENCE Therapeutic, Level IV.

Background Venous thromboembolism (VTE) in patients with major pelvic fractures who undergo preperitoneal pelvic packing (PPP) has not been investigated. We hypothesized that patients who undergo PPP are at high risk for VTE, thus early prophylactic anticoagulation and screening duplex are warranted. Study design All patients requiring PPP from 2015 to 2019 were reviewed. Management and outcomes were analyzed. Results During the study period, 79 patients underwent PPP. Excluding the early deaths, 17 patients had deep venous thrombosis (DVT) and 6 had pulmonary emboli (PE); 4 patients had both DVT/PE. Overall mortality was 15%. Thirty-two patients underwent screening duplex within 72 h of admission and 10 were positive for DVT. Conclusion Patients with complex pelvic trauma undergoing PPP have a 23% incidence of DVT and an additional 8% incidence of PE. 31% of screening ultrasounds are positive. The overall mortality was 15%. With a high incidence of VTE in this patient population, we recommend screening duplex ultrasounds.

Background The aim of this study was to determine the current utilization patterns of resuscitative endovascular balloon occlusion of aorta (REBOA) for hemorrhage control in nontrauma patients. Methods Data on REBOA use in nontrauma emergency general surgery patients from six centers, 2014-2019, was pooled for analysis. We performed descriptive analyses using Fisher's exact, Student's t, chi-squared, or Mann–Whitney U tests as appropriate. Results Thirty-seven patients with acute hemorrhage from nontrauma sources were identified. REBOA placement was primarily performed by trauma attendings (20/37, 54%) and vascular attendings (13/37, 35%). In seven patients (19%), balloons were positioned prophylactically but never inflated. In 24 (65%) of 37 patients, REBOA was placed in the operating room. 28/37 balloons (76%) were advanced to zone 1, 8/37 (22%) were advanced to zone 3, and there was one REBOA use in the inferior vena cava. Most common indications were gastrointestinal and peripartum bleeding. In the 30 cases of balloon inflation, 24 of 30 (80%) resulted in improved hemodynamics. Eleven of 30 patients (37%) died before discharge. One patient developed a distal embolism, but there were no reports of limb loss. Twelve patients (40% of all REBOA inflations and 63% of survivors) were discharged to home. Conclusions REBOA has been used in a range of acutely hemorrhaging emergency general surgery patients with low rates of access-related complications. Mortality is high in this patient population and further research is needed; however, appropriate patient selection and early use may improve survival in these life-threatening cases.

Background Use of the focused assessment with sonography for trauma (FAST) examination in patients with pelvic fractures has been reported as unreliable. We hypothesized that FAST is a reliable method for detecting clinically significant intra-abdominal hemorrhage in patients with pelvic fractures. Methods All patients with pelvic fractures over a 10-year period were reviewed at a Level I trauma center. The predictive ability of FAST was assessed by calculating the sensitivity, specificity, positive predictive value and negative predictive value against the criterion standard of either computed tomography (CT) or laparotomy findings. The FAST examination was considered "false negative" if findings at laparotomy indicated traumatic intra-abdominal hemorrhage. Likewise, the FAST examination was considered "false positive" if either CT or findings at laparotomy indicated no intra-abdominal hemorrhage. Hemodynamic instability scores were calculated for all patients. Results There were 1,456 patients with pelvic fractures and an initial FAST reviewed; 1,219 (83.7%) underwent FAST and either CT or operative exploration. Median age was 43 years (interquartile range, 26-56 years) and mean Injury Severity Score was 18.5 ± 12.3. The sensitivity and specificity for FAST in this group of patients with pelvic fracture was 85.4% and 98.1%, respectively. The positive predictive value and negative predictive value were 78.4% and 98.8%, respectively. Of 21 patients with a false-positive FAST, 15 (71.4%) were confirmed with a negative CT scan, and 6 (28.6%) underwent laparotomy without findings of intra-abdominal hemorrhage. Of 13 patients with a false-negative FAST, all were identified with positive findings at the time of laparotomy. The specificity of the FAST examination remained high regardless of hemodynamic instability score grade. Conclusion The false positive rate of FAST examination for intra-abdominal hemorrhage is 1.1%. These data suggest that a positive FAST in this clinical scenario should be considered to represent intra-abdominal fluid. This series contradicts prior reports that FAST is unreliable in patients with pelvic fracture. Level of evidence Diagnostic, level III.

BACKGROUND Trauma patients with hyperfibrinolysis and depletion of fibrinolytic inhibitors (DFIs) measured by thrombelastography (TEG) gain clot strength with TXA, but TEG results take nearly an hour. We aimed to develop an assay, plasmin TEG (P-TEG), to more expeditiously stratify risk for massive transfusion (MT), mortality, and hyperfibrinolysis. METHODS Trauma patients (N = 148) were assessed using TEG assays without exogenous additives (rapid/native), with exogenous plasmin (P-TEG) or tissue plasminogen activator (tPA TEG). The plasmin dose used does not effect healthy-control clot lysis 30 minutes after maximum amplitude (LY30) but causes shortened reaction time (R time) relative to native TEG (P-TEG R time < native TEG R time considered P-TEG negative). If P-TEG R time is greater than or equal to native TEG R time, the patient was considered P-TEG positive. Each assay's ability to predict MT, mortality, and (risk for) hyperfibrinolysis was determined. χ and Mann-Whitney U tests were used to compare categorical and continuous variables, respectively. Results were reported as median ± interquartile range or n (%). RESULTS Plasmin TEG provided results faster than all other assays (4.7 ± 2.5-9.1 minutes), approximately 11-fold faster than rapid-TEG (rTEG) LY30 (54.2 ± 51.1-58.1 minutes; p < 0.001). Plasmin TEG-positive patients had greater than fourfold higher MT rate (30% vs. 7%; p = 0.0015) with an area under the receiver operating characteristic curve of 0.686 (p = 0.028), greater than fourfold higher 24-hour mortality (33.3% vs. 7.8%; p = 0.0177), greater than twofold higher 30-day mortality (35% vs. 16.4%; p = 0.0483), higher rates of DFI (55% vs. 18%; p < 0.001), and a trend toward elevated D-dimer (19.9 vs. 3.3 μg/mL; p = 0.14). Plasmin TEG was associated with hyperfibrinolysis on rTEG LY30 at the 7.6% threshold (p = 0.04) but not the 3% threshold (p = 0.40). Plasmin TEG performed best in relation to DFI, with a positive predictive value of 58% and negative predictive value of 81%. When combined with tPA TEG time to maximum amplitude, P-TEG outperformed rTEG LY30 for predicting MT (area under the receiver operating characteristic curve, 0.811 vs. 0.708). CONCLUSION Within 5 minutes, P-TEG can stratify patients at highest risk for MT, mortality, and risk for hyperfibrinolysis. In composite with tPA TEG time to maximum amplitude, P-TEG outperforms rTEG LY30 for predicting MT and does so four times faster (12.7 vs. 54.1 minutes). The rapid results of P-TEG may be useful for those who practice selective TXA administration to maximize TXA's time-dependent efficacy. LEVEL OF EVIDENCE Diagnostic test, level V.

Most blunt splenic injuries (BSI) are treated with nonoperative management (NOM) or embolization (EMBO). Little is known about the hematologic changes associated with these treatments. We aim to assess the temporal changes of hematologic markers in trauma patients who undergo splenectomy (SPL), packing and splenorrhaphy (P/S), EMBO, or NOM. We hypothesize that differences in trends of hematologic markers exist in patients undergoing EMBO or SPL, compared to NOM.An 8-year review of adult patients with BSI and underwent SPL, EMBO, P/S, or NOM. White blood cell count (WBC), hematocrit (HCT) and platelet count (PLT) at presentation to 14 days post-admission were analyzed; post-procedural complications were reviewed. Temporal trends were compared using linear mixed-effects models.478 patients sustained BSI, 298 (62.3%) underwent NOM, 100 (29.2%) SPL, 42 (8.8%) EMBO, and 38 (8.0%) P/S. After adjustment for age, ISS and splenic injury grade, SPL patients had a significantly higher upward trend compared to other management strategies (p 0.05). Infection further increased this trend. Starting on day 6, SPL patients with infections had significantly higher WBC than those without infection. SPL and P/S were more likely than NOM to develop infections after adjustment for confounders (HR = 3.64; 95%CI: 1.79-7.39 and HR = 2.59; 95%CI: 1.21-5.55, respectively). Day 6 WBC16,000 cells/ml post-SPL had a positive predictive value (PPV) of 65.2% and negative predictive value (NPV) of 76.9% for infections. Among P/S, Day 6 WBC10,200 cells/ml had a PPV = 50% and NPV = 86.7% for infections.We observed distinct patterns of hematologic markers following BSI managed with SPL, EMBO, P/S, and NOM. Day 6 WBC increases after SPL or P/S should raise suspicion of infections and trigger a diagnostic investigation.

Trauma with hemorrhagic shock causes massive tissue plasminogen activator release, plasmin generation, and hyperfibrinolysis. Tranexamic acid (TXA) has recently been used to treat bleeding in trauma by preventing plasmin generation to limit fibrinolysis. Trauma patients also have increased complement activation that correlates with mortality and organ failure, but the source of activation is not clear, and plasmin has recently been shown to efficiently cleave C3 and C5 to their activated fragments. We hypothesized that trauma patients in hemorrhagic shock with hyperfibrinolysis on thromboelastography (TEG) LY30 would have increased complement activation at early time points, as measured by soluble C5b-9 complex, and TXA would prevent this. Plasma samples were obtained from an unrelated, previously performed IRB-approved prospective randomized study of trauma patients. Three groups were studied with n = 5 patients in each group: patients without hyperfibrinolysis (TEG LY30 3%) (who therefore did not get TXA), patients with hyperfibrinolysis (TEG LY30 3%) who did not get TXA, and patients with hyperfibrinolysis who were then treated with TXA. We found that patients who did not receive TXA, regardless of fibrinolytic phenotype, had elevated soluble C5b-9 levels at 6 h relative to emergency department levels. In contrast, all five patients with initial TEG LY30 more than 3% and were then treated with TXA had reduced soluble C5b-9 levels at 6 h relative to emergency department levels. There were no differences in PF1 + 2, Bb, or C4d levels between groups, suggesting that coagulation and complement activation pathways may not be primarily responsible for the observed differences.

Objective To describe the current use of the ER-REBOA catheter and associated outcomes and complications. Introduction Noncompressible truncal hemorrhage is the leading cause of potentially preventable death in trauma patients. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a novel strategy to obtain earlier temporary hemorrhage control, supporting cardiac, and cerebral perfusion before definitive hemostasis. Methods Prospective, observational study conducted at 6 Level 1 Trauma Centers over 12-months. Inclusion criteria were age >15 years of age with evidence of truncal hemorrhage below the diaphragm and decision for emergent hemorrhage control intervention within 60 minutes of arrival. REBOA details, demographics, mechanism of injury, complications, and outcomes were collected. Results A total of 8166 patients were screened for enrollment. In 75, REBOA was utilized for temporary hemorrhage control. Blunt injury occurred in 80% with a median injury severity score (ISS) 34 (21, 43). Forty-seven REBOAs were placed in Zone 1 and 28 in Zone 3. REBOA inflation increased systolic blood pressure from 67 (40, 83) mm Hg to 108 (90, 128) mm Hg 5 minutes after inflation (P = 0.02). Cardiopulmonary resuscitation was ongoing during REBOA insertion in 17 patients (26.6%) and 10 patients (58.8%) had return of spontaneous circulation after REBOA inflation. The procedural complication rate was 6.6%. Overall mortality was 52%. Conclusion REBOA can be used in blunt and penetrating trauma patients, including those in arrest. Balloon inflation uniformly improved hemodynamics and was associated with a 59% rate of return of spontaneous circulation for patients in arrest. Use of the ER-REBOA catheter is technically safe with a low procedural complication rate.

The coronavirus disease 2019 (COVID-19) pandemic has led to unprecedented stresses on modern medical systems, overwhelming the resource infrastructure in numerous countries while presenting a unique series of pathophysiologic clinical findings. Thrombotic coagulopathy is common in critically ill patients suffering from COVID-19, with associated high rates of respiratory failure requiring prolonged periods of mechanical ventilation. Here, we report a case series of five patients suffering from profound, medically refractory COVID-19-associated respiratory failure who were treated with fibrinolytic therapy using tissue plasminogen activator (tPA; alteplase). All five patients appeared to have an improved respiratory status following tPA administration: one patient had an initial marked improvement that partially regressed after several hours, one patient had transient improvements that were not sustained, and three patients had sustained clinical improvements following tPA administration. LEVEL OF EVIDENCE: Therapeutic, Level V.

INTRODUCTION: Several disease processes trigger prolonged activation of the alternative complement pathway. Crosslinks between complement activation and physiologic changes in platelets and neutrophils have been identified, but how this interplay alters the hemostatic potential in humans remains undefined. We hypothesize that activation of the alternative pathway triggers a hypercoagulable state. METHODS: C3/C5 convertase Cobra Venom Factor (CVF, 10 Units/mL) was employed to activate the alternative complement pathway in whole blood. Complement inhibition was completed with inhibitors for C3/C3b (Compstatin, 25 and 50 μM), C3a receptor (SB290157, 300 nM, C3aR), and C5a receptor (W54011, 6 nM, C5aR). Coagulation was assessed using native thrombelastography which produces the following: reaction time (R time); angle; maximum amplitude (MA); percent fibrinolysis at 30-minutes post-MA (LY30). RESULTS: Inhibition with C3aR and C5aR inhibitors did not alter clot formation (R time, 11.2 vs 11.6 min, p=0.36), clot strength (MA, 52.0 vs 52.3 mm, p=0.43) or fibrinolysis (LY30, 1.6 vs 4.0%, p=0.19). Compstatin did not influence clot formation or clot strength but did induce a dose-dependent increase in fibrinolysis (control LY30 3.0 vs 7.8% and 12.4% for 25 and 50 μM respectively, p=0.0002). CVF increased MA (58.0 vs 62.8 mm, p

BACKGROUND: While tissue injury provokes fibrinolysis shutdown in trauma, the mechanism remains elusive. Cellular death causes release of structural proteins, including actin and myosin, which may interact with clot formation and structure. We hypothesized that tissue injury is associated with high circulating actin and that actin produces a hypercoagulable profile with decreased fibrinolysis in vitro. METHODS: Blood was collected from trauma activation patients at a single Level I trauma center for thrombelastography and proteomics. Proteomic analyses were performed through targeted liquid chromatography coupled with mass spectrometry using isotope-labeled standards for quantification of actin and its endogenous inhibitor gelsolin. Based on the results, we added physiologic concentrations of cytoskeletal G-actin to whole blood from healthy volunteers and analyzed changes in thrombelastography, as well as to plasma and examined clot architecture using confocal microscopy of fluorescently labeled fibrinogen. RESULTS: Overall, 108 trauma patients were included: majority (71%) men, median age of 32.7 years, 66% blunt mechanism, median New Injury Severity Score (NISS) of 41. Compared with patients without severe tissue injury (NISS < 15, n = 10), patients with severe tissue injury (NISS > 15, n = 98) had higher levels of circulating actin (0.0428 vs. 0.0301, p = 0.02). Further, there was a trend toward lower gelsolin levels in patients with fibrinolysis shutdown (0.1844 vs. 0.2052, p = 0.17) and tissue plasminogen activator resistance (0.1676 vs. 0.2188, p = 0.06).Ten healthy volunteers were included in the in vitro experiments (50% male; median age, 31.3 years). Actin significantly increased angle (40.0° to 52.9°, p = 0.002) and decreased fibrinolysis (percent clot lysis 30 minutes after reaching maximum amplitude, 4.0% to 1.6%; p = 0.002), provoking fibrinolytic shutdown in three patients. The addition of actin to control plasma decreased fiber resolvability of fibrin clots, monitored by microscopy, and decreased plasmin-mediated fibrinolysis. CONCLUSION: Actin increases clot propagation and provokes fibrinolysis shutdown in vitro, through a mechanism of plasmin inhibition. High circulating levels of actin are present in trauma patients with severe tissue injury, suggesting actin contributes to fibrinolysis shutdown in the setting of tissue injury.

Supplemental digital content is available in the text., BACKGROUND Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients. METHODS Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices. RESULTS A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05, ρ = 0.9), CFF.MA (ß = 0.99, ρ = 0.95), CK.LY30 (ß = 1.01, ρ = 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06, ρ = 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93, ρ = 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30. CONCLUSION The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing. LEVEL OF EVIDENCE Diagnostic test, level II.

Zone 1 resuscitative endovascular balloon occlusion of the aorta has been recommended for refractory shock after a dismounted complex blast injury for the austere combat scenario. While resuscitative endovascular balloon occlusion of the aorta should enhance coronary perfusion, there is a potential risk of secondary brain injury due to loss of cerebral autoregulation. We developed a combat casualty relevant dismounted complex blast injury swine model to evaluate the effects of resuscitative endovascular balloon occlusion of the aorta zone I on intracranial pressure and cerebral edema. We hypothesized that zone 1 aortic occlusion with resuscitative endovascular balloon occlusion of the aorta would increase mean arterial pressure transmitted in excessive intracranial pressure, thereby worsening brain injury.50 kg male Yorkshire swine were subjected to a combination dismounted complex blast injury model consisting of blast traumatic brain injury (50 psi, ARA Mobile Shock Laboratory), tissue injury (bilateral femur fractures), and hemorrhagic shock (controlled bleeding to a base deficit goal of 10 mEq/L). During the shock phase, pigs were randomized to no aortic occlusion (n = 8) or to 30 minutes of zone 1 resuscitative endovascular balloon occlusion of the aorta (zone 1 aortic occlusion group, n = 6). After shock, pigs in both groups received a modified Tactical Combat Casualty Care-based resuscitation and were monitored for an additional 240 minutes until euthanasia/death for a total of 6 hours. Intracranial pressure was monitored throughout, and brains were harvested for water content. Linear mixed models for repeated measures were used to compare mean arterial pressure and intracranial pressure between zone 1 aortic occlusion and no aortic occlusion groups.After dismounted complex blast injury, the zone 1 group had a significantly higher mean arterial pressure during hemorrhagic shock compared to the control group (41.2 mm Hg vs 16.7 mm Hg, P = .002). During balloon occlusion, intracranial pressure was not significantly elevated in the zone 1 aortic occlusion group vs control, but intracranial pressure was significantly lower in the zone 1 group at the end of the observation period. In addition, the zone 1 aortic occlusion group did not have increased brain water content (zone 1 aortic occlusion: 3.95 ± 0.1g vs no aortic occlusion: 3.95 ± 0.3 g, P = .87). Troponin levels significantly increased in the no aortic occlusion group but did not in the zone 1 aortic occlusion group.Zone 1 aortic occlusion using resuscitative endovascular balloon occlusion of the aorta in a large animal dismounted complex blast injury model improved proximal mean arterial pressure while not significantly increasing intracranial pressure during balloon inflation. Observation up to 240 minutes postresuscitation did not show clinical signs of worsening brain injury or cardiac injury. These data suggest that in a dismounted complex blast injury swine model, resuscitative endovascular balloon occlusion of the aorta in zone 1 may provide neuro- and cardioprotection in the setting of blast traumatic brain injury. However, longer monitoring periods may be needed to confirm that the neuroprotection is lasting.

Aim We aimed to evaluate the knowledge, attitude, and practices in the application of AI in the emergency setting among international acute care and emergency surgeons. Methods An online questionnaire composed of 30 multiple choice and open-ended questions was sent to the members of the World Society of Emergency Surgery between 29th May and 28th August 2021. The questionnaire was developed by a panel of 11 international experts and approved by the WSES steering committee. Results 200 participants answered the survey, 32 were females (16%). 172 (86%) surgeons thought that AI will improve acute care surgery. Fifty surgeons (25%) were trained, robotic surgeons and can perform it. Only 19 (9.5%) were currently performing it. 126 (63%) surgeons do not have a robotic system in their institution, and for those who have it, it was mainly used for elective surgery. Only 100 surgeons (50%) were able to define different AI terminology. Participants thought that AI is useful to support training and education (61.5%), perioperative decision making (59.5%), and surgical vision (53%) in emergency surgery. There was no statistically significant difference between males and females in ability, interest in training or expectations of AI (p values 0.91, 0.82, and 0.28, respectively, Mann–Whitney U test). Ability was significantly correlated with interest and expectations (p p = 0.9, rho − 0.01). Conclusions The implementation of artificial intelligence in the emergency and trauma setting is still in an early phase. The support of emergency and trauma surgeons is essential for the progress of AI in their setting which can be augmented by proper research and training programs in this area.

Background The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. Methods Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. Results A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p p p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p p p p p p p p p Conclusions The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands. Graphical abstract

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 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.

Prehospital identification of the injured patient likely to require emergent care remains a challenge. End-tidal carbon dioxide (ETCO2) has been used in the prehospital setting to monitor respiratory physiology and confirmation of endotracheal tube placement. Low levels of ETCO2 have been demonstrated to correlate with injury severity and mortality in a number of in-hospital studies. We hypothesized that prehospital ETCO2 values would be predictive of mortality and need for massive transfusion (MT) in intubated patients.This was a retrospective multicenter trial with 24 participating centers. Prehospital, emergency department, and hospital values were collected. Receiver operating characteristic curves were created and compared. Massive transfusion defined as10 U of blood in 6 hours or death in 6 hours with at least 1 U of blood transfused.A total of 1,324 patients were enrolled. ETCO2 (area under the receiver operating characteristic curve [AUROC], 0.67; confidence interval [CI], 0.63-0.71) was better in predicting mortality than shock index (SI) (AUROC, 0.55; CI, 0.50-0.60) and systolic blood pressure (SBP) (AUROC, 0.58; CI, 0.53-0.62) (p0.0005). Prehospital lowest ETCO2 (AUROC, 0.69; CI, 0.64-0.75), SBP (AUROC, 0.75; CI, 0.70-0.81), and SI (AUROC, 0.74; CI, 0.68-0.79) were all predictive of MT. Analysis of patients with normotension demonstrated lowest prehospital ETCO2 (AUROC, 0.66; CI, 0.61-0.71), which was more predictive of mortality than SBP (AUROC, 0.52; CI, 0.47-0.58) or SI (AUROC, 0.56; CI, 0.50-0.62) (p0.001). Lowest prehospital ETCO2 (AUROC, 0.75; CI, 0.65-0.84), SBP (AUROC, 0.63; CI, 0.54-0.74), and SI (AUROC, 0.64; CI, 0.54-0.75) were predictive of MT in normotensive patients. ETCO2 cutoff for MT was 26 mm Hg. The positive predictive value was 16.1%, and negative predictive value was high at 98.1%.Prehospital ETCO2 is predictive of mortality and MT. ETCO2 outperformed traditional measures such as SBP and SI in the prediction of mortality. ETCO2 may outperform traditional measures in predicting need for transfusion in occult shock.Diagnostic test, level III.

BACKGROUND The rationale for resuscitative endovascular balloon occlusion of the aorta (REBOA) is to control life-threatening subdiaphragmatic bleeding and facilitate resuscitation; however, incorporating this into the resuscitative practices of a trauma service remains challenging. The objective of this study is to describe the process of successful implementation of REBOA use in an academic urban Level I trauma center. All REBOA procedures from April 2014 through December 2019 were evaluated; REBOA was implemented after surgical faculty attended a required and internally developed Advanced Endovascular Strategies for Trauma Surgeons course. Success was defined by sustained early adoption rates. METHODS An institutional protocol was published, and a REBOA supply cart was placed in the emergency department with posters attached to depict technical and procedural details. A focused professional practice evaluation was utilized for the first three REBOA procedures performed by each faculty member, leading to internal privileging. RESULTS Resuscitative endovascular balloon occlusion of the aorta was performed in 97 patients by nine trauma surgeons, which is 1% of the total trauma admissions during this time. Each surgeon performed a median of 12 REBOAs (interquartile range, 5-14). Blunt (77/97, 81%) or penetrating abdominopelvic injuries (15/97, 15%) comprised the main injury mechanisms; 4% were placed for other reasons (4/97), including ruptured abdominal aortic aneurysms (n = 3) and preoperatively for a surgical oncologic resection (n = 1). Overall survival was 65% (63/97) with a steady early adoption trend that resulted in participation in a Department of Defense multicenter trial. CONCLUSION Strategies for how departments adopt new procedures require clinical guidelines, a training program focused on competence, and a hospital education and privileging process for those acquiring new skills. LEVEL OF EVIDENCE Therapeutic, level V.

Introduction The optimal time to initiate venous thromboembolism (VTE) chemoprophylaxis in blunt solid organ injury (BSOI) patients is debated. We hypothesize that 1) BSOI patients are hypercoagulable within 12 h of injury and 2) hypercoagulability dominates in patients who develop clot complications (CC). Material and methods This is a prospective study of BSOI patients admitted to two Level-1 Trauma Centers’ trauma intensive care units (ICU). Serial kaolin thrombelastography (TEG) and tissue plasminogen activator (tPA)-challenge TEGs were performed. CC included VTE and cerebrovascular accidents. Results On ICU admission, all patients (n = 95) were hypercoagulable, 58% were in fibrinolysis shutdown, and 50% of patients were tPA-resistant. Twelve patients (13%) developed CC. Compared to those without CC, they demonstrated decreased fibrinolysis at 12 h and higher clot strength at 48 h Conclusions BSOI patients are universally hypercoagulable upon ICU admission. VTE chemoprophylaxis should be started immediately in BSOI patients with hypercoagulability on TEG.

Background Trauma patients with hypersensitivity to tissue plasminogen activator mediated fibrinolysis quantified by tissue plasminogen activator thromboelastography are at increased risk of massive transfusion. The tissue plasminogen activator thromboelastography assay has been tested in trauma patients using native thromboelastography with no exogenous activator. We hypothesize that adding an activator will expedite the time to results. Methods Healthy whole blood was assayed with and without exogenous plasmin, which acts to deplete inhibitors of fibrinolysis, mimicking trauma blood. Samples were assessed using native, kaolin, and rapid thromboelastography with and without tissue plasminogen activator. The tissue plasminogen activator thromboelastography indices of time to maximum amplitude and lysis at 30 minutes were contrasted between healthy blood with and without plasmin using the three different activators. The activators were then used with a tissue plasminogen activator thromboelastography in 100 trauma patients to assess performance in predicting massive transfusion. Results In healthy blood, regardless of activator, lysis at 30 minutes did not increase with plasmin alone, but did increase with tissue plasminogen activator (P = .012). Adding tissue plasminogen activator and plasmin increased lysis at 30 minutes (P = .036). Time to maximum amplitude was reduced with tissue plasminogen activator and plasmin compared with tissue plasminogen activator alone (P = .012). Activated thromboelastographies had increased lysis at 30 minutes (P = .002), but no difference in time to maximum amplitude compared with native thromboelastographies. In trauma patients, native tissue plasminogen activator thromboelastography had greater performance in predicting massive transfusion than activated tissue plasminogen activator thromboelastographies with no difference in time to maximum amplitude. Conclusion Adding an activator to tissue plasminogen activator thromboelastography does not expedite time to maximum amplitude in healthy blood depleted of fibrinolysis inhibitors. Activated tissue plasminogen activator thromboelastographies are inferior to native tissue plasminogen activator thromboelastography for predicting massive transfusion and do not reduce the time to results.

Stroke secondary to blunt cerebrovascular injury (BCVI) most often occurs before initiation of antithrombotic therapy. Earlier treatment, especially in multiply injured patients with relative contraindications to antithrombotic agents, could be facilitated with improved risk stratification; furthermore, the relationship between BCVI-attributed stroke and hypercoagulability remains unknown. We hypothesized that patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who do not stroke.Rapid thromboelastography (TEG) was evaluated for patients with BCVI-attributed stroke at an urban Level I trauma center from 2011 to 2018. Contemporary controls who had BCVI but did not stroke were selected for comparison using propensity-score matching with 20% caliper that accounted for age, sex, injury severity, and BCVI location and grade.During the study period, 15,347 patients were admitted following blunt trauma. Blunt cerebrovascular injury was identified in 435 (3%) patients, of whom 28 experienced associated stroke and had a TEG within 24 hours of arrival. Forty-nine patients who had BCVI but did not suffer stroke served as matched controls. Stroke patients formed clots faster as evident in their larger angle (77.5 degrees vs. 74.6 degrees, p = 0.03) and had greater clot strength as indicated by their higher maximum amplitude (MA) (66.9 mm vs. 61.9 mm, p0.01). Activated clotting time was shorter among stroke patients but not significantly (113 seconds vs. 121 seconds, p0.05). Increased angle and elevated MA were significant predictors of stroke with odds ratios of 2.97 for angle greater than 77.3 degrees and 4.30 for MA greater than 63.0 mm.Patients who suffer BCVI-related stroke are hypercoagulable compared with those with BCVI who remain asymptomatic. Increased angle or MA should be considered when assessing the risk of thrombosis and determining the optimal time to initiate antithrombotic therapy in patients with BCVI.Prognostic, Level III.

BACKGROUND: Females are hypercoagulable and have survival benefit in trauma-induced coagulopathy (TIC). The mechanism for this sex-specific hypercoagulability is unknown. Platelets and platelet function are central in providing hemostatic potential and are the largest contributor to clot strength. Ligands (adenosine diphosphate [ADP] and platelet activating factor [PAF]) bind distinct platelet receptors to potentiate activation and aggregation. We hypothesize that female platelets have a differential response to ADP and PAF, resulting in greater aggregation and activation compared to males, and that estradiol pre-treatment of male or female platelets enhances this activity. METHODS: Platelets were collected from healthy volunteers: pre/post-menopausal females (≤54 years old,>54 years old) and similarly aged males. Platelet aggregometry and flow cytometry (fibrinogen binding capacity) were examined. After treatment with ADP or PAF, platelet aggregation was assessed with Chronolog and activation assessed by CD41 receptor surface expression using flow cytometry. Aggregation and activation were again assessed after platelet pre-treatment with estradiol. RESULTS: Healthy volunteers included 12 premenopausal and 13 postmenopausal females and 18 similarly aged males. Female platelets (combined pre- and postmenopausal) had increased aggregation with ADP stimulation, as compared to male platelets. Male and female platelets had differential fibrinogen receptor expression, with female platelets (combined pre- and postmenopausal) demonstrating robust activation with ADP versus male platelets with PAF. In the presence of estradiol incubation, male platelets’ activation with PAF approximated that of females (combined pre- and postmenopausal) and activation with PAF was enhanced in both male and female platelets. CONCLUSIONS: Male and female platelets have differential response to stimuli, suggesting sex-dependent signaling and cellular activation. Female platelets have both increased aggregation and activation potential, and estradiol pre-treatment feminizes male platelets to approximate female platelet activation with PAF. These findings offer potential explanation for sex-based differences in hemostatic potential in TIC and question whether donor sex of transfused platelets should be considered in resuscitation. Estradiol may also serve as a novel therapeutic adjunct in TIC. LEVEL OF EVIDENCE: This is a basic science project and as such, does not require a level of evidence. STUDY TYPE: Original Article.

BackgroundTrauma-induced coagulopathy can present as abnormalities in a conventional or viscoelastic coagulation assay or both. We hypothesized that patients with discordant coagulopathies reflect different clinical phenotypes.MethodsBlood samples were collected prospectively from critically injured patients upon arrival at two urban Level I trauma centers. International normalized ratio (INR), partial thromboplastin time (PTT), thromboelastography (TEG), and coagulation factors were assayed.Results278 patients (median ISS 17, mortality 26%) were coagulopathic: 20% with isolated abnormal INR and/or PTT (CONVENTIONAL), 49% with isolated abnormal TEG (VISCOELASTIC), and 31% with abnormal INR/PTT and TEG (BOTH). Compared with VISCOELASTIC, CONVENTIONAL and BOTH had higher ISS, lower GCS, larger base deficit, and decreased factor activities (all p

Background Conventional coagulation assays (CCAs), prothrombin time (PT)/international normalized ratio (INR) and activated partial thromboplastin time (aPTT), detect clotting factor (CF) deficiencies in hematologic disorders. However, there is controversy about how these CCAs should be used to diagnose, treat, and monitor trauma-induced coagulopathy. Study objectives were to determine whether CCA abnormalities are reflective of deficiencies of coagulation factor activity in the setting of severe injury. Methods Patients without previous CF deficiency within a prospective database at an ACS-verified Level I trauma center had CF activity levels, PT/INR, aPTT, and fibrinogen levels measured upon emergency department arrival from 2014 to 2017. Linear regression assessed how CF activity explained the aPTT and PT/INR variation. Prolonged CCA values were set as INR greater than 1.3 and aPTT greater than 34 seconds. CF deficiency was defined as less than 30% activity, except for fibrinogen, defined as less than 150 mg/dL. Results Sixty patients with a mean age of 35.8 (SD, 13.6) years and median New Injury Severity Score of 32 (interquartile range, 12-43) were included; 53.3% sustained blunt injuries, 23.3% required massive transfusion, and mortality was 11.67%. Overall, 44.6% of the PT/INR variance and 49.5% of the aPTT variance remained unexplained by CF activity. Deficiencies of CFs were: common pathway, 25%; extrinsic pathway, 1.7%; and intrinsic pathway, 6.7%. The positive predictive value for CF deficiencies were: (1) PT/INR greater than 1.3:4.4% for extrinsic pathway, 56.5% for the common pathway; (2) aPTT greater than 34 seconds:16.7% for the intrinsic pathway, 73.7% for the common pathway. Conclusion Almost half of the variances of PT/INR and aPTT were unexplained by CF activity. Prolonged PT/INR and aPTT were poor predictors of deficiencies in the intrinsic or extrinsic pathways; however, they were indicators of common pathway deficiencies. Level of evidence Prognostic, level III.

Traumatic brain injury (TBI) patients present on a spectrum from hypocoagulability to hypercoagulability, depending on the injury complexity, severity, and time since injury. Prior studies have found a unique coagulopathy associated with TBI using conventional coagulation assays such as INR; however, few studies have assessed the association of TBI and coagulopathy using viscoelastic assays that comprehensively evaluate the coagulation in whole blood. This study aims to reevaluate the TBI-specific trauma-induced coagulopathy using arrival thrombelastography. Because brain tissue is high in key procoagulant molecules, we hypothesize that isolated TBI is associated with procoagulant and hypofibrinolytic profiles compared with injuries of the torso, extremities, and polytrauma, including TBI.Data are from the prospective Trauma Activation Protocol study. Activated clotting time (ACT), angle, maximum amplitude (MA), 30-minute percent lysis after MA (LY30), and functional fibrinogen levels (FFLEV) were recorded. Patients were categorized into isolated severe TBI (I-TBI), severe TBI with torso and extremity injuries (TBI + TORSO/EXTREMITIES), and isolated torso and extremity injuries (I-TORSO/EXTREMITIES). Poisson regression was used to adjust for multiple confounders.Overall, 572 patients (48 I-TBI, 45 TBI + TORSO/EXTREMITIES, 479 I-TORSO/EXTREMITIES) were included in this analysis. The groups differed in INR, ACT, angle, MA, and FFLEV but not in 30-minute percent lysis. When compared with I-Torso/Extremities, after adjustment for confounders, severe I-TBI was independently associated with ACT less than 128 seconds (relative risk [RR], 1.5; 95% confidence interval [CI], 1.1-2.2), angle less than 65 degrees (RR, 2.2; 95% CI, 1.4-3.6), FFLEV less than 356 (RR, 1.7; 95% CI, 1.2-2.4) but not MA less than 55 mm, hyperfibrinolysis, fibrinolysis shutdown, or partial thromboplastin time (PTT) greater than 30.Severe I-TBI was independently associated with a distinct coagulopathy with delayed clot formation but did not appear to be associated with fibrinolysis abnormalities. Low fibrinogen and longer ACT values associated with I-TBI suggest that early coagulation factor replacement may be indicated in I-TBI patients over empiric antifibrinolytic therapy. Mechanisms triggering coagulopathy in TBI are unique and warrant further investigation.Retrospective cohort study, prognostic, level III.

Introduction Fibrinolysis was initially defined using rapid thrombelastography (rTEG). The cutoffs for the pathologic extremes of the fibrinolytic system, hyperfibrinolysis and shutdown, were both defined based on association with mortality. We propose to redefine these phenotypes for both TEG and for rotational thrombelastometry, the other commonly used viscoelastic assay. Methods Rotational thrombelastometry, rTEG, and clinical data were prospectively collected on trauma patients admitted to an urban Level I trauma center from 2010 to 2016. Hyperfibrinolysis was defined as the Youden index from EXTEM-clot lysis index 60 minutes after clotting time (CLI60) and rTEG-fibrinolysis 30 minutes after achieving MA (LY30) for predicting massive transfusion (>10 red blood cell units, or death per 6 hours after injury) as a surrogate for severe bleeding. Patients identified as having hyperfibrinolysis were then removed from the data set, and the cutoff for fibrinolysis shutdown was derived as the optimal cutoff for predicting mortality in the remaining patients. Results Overall, 216 patients (median age, 36 years (interquartile range, 27-49 years), 82% men, 58% blunt injury) were included. Of these, 16% required massive transfusion, and 12.5% died. Rapid thrombelastography phenotypes were redefined as hyperfibrinolysis: rTEG-LY30 greater than7.7%, physiologic rTEG-LY30 0.6% to7.6%, and shutdown rTEG-LY30 less than 0.6%. EXTEM-CLI60 fibrinolysis phenotypes were hyperfibrinolysis CLI60 less than 82%, physiologic (CLI60, 82-97.9%), and shutdown (CLI60 > 98%). Weighted kappa statistics revealed moderate agreement between rotational thrombelastometry- and rTEG-defined fibrinolysis (k = 0.51; 95% confidence interval, 0.39-0.63), with disagreement mostly in the shutdown and physiologic categories. Conclusion We confirmed the U-shaped distribution of death related to fibrinolysis system abnormalities. Both rTEG LY30 and EXTEM CLI60 can identify the spectrum of fibrinolytic phenotypes, have moderate agreement, and can be used to guide hemostatic resuscitation. Level of evidence Diagnostic study, level III.

BACKGROUND Both tissue plasminogen activator (tPA) in the circulation and urokinase (uPA) in tissues cleave plasminogen (PLG) to plasmin to promote clot lysis. Tranexamic acid (TXA) blocks both the tPA-dependent generation of plasmin on blood clots as well as active plasmin binding to polymerized fibrin, and is commonly administered for bleeding in trauma to limit fibrinolysis. In addition to lysing clots, however, active plasmin also cleaves complement proteins, potentially enhancing inflammation. Because TXA does not block uPA-dependent plasmin generation from PLG and instead augments it, we hypothesized that administration of TXA could enhance or inhibit proinflammatory C5a formation in a PLG activator-dependent manner. METHODS Citrate platelet-poor plasma (PPP) and PPP depleted of complement protein C3 or PLG were obtained from healthy donors and commercial sources. Platelet-poor plasma was treated ex vivo with or without TXA and either with or without tPA or with or without uPA. Clotting was then induced by calcium and thrombin in clotted PPP experiments, while unclotted PPP experiments were treated with vehicle controls. C5a levels were measured via enzyme-linked immunosorbent assay. Data were expressed as mean ± SEM. RESULTS Plasmin-mediated fibrinolysis by tPA in clotted PPP led to an approximately threefold increase in C5a production (p < 0.0001), which was significantly inhibited by TXA (p < 0.001). Paradoxically, when fibrinolysis was induced by uPA, TXA treatment led to further increases in C5a production beyond uPA alone (p < 0.0001). Furthermore, clotting was not required for C5a generation from uPA + TXA. C3 depletion had no effect on C5a production, while depletion of PLG eliminated it. CONCLUSIONS Tranexamic acid administration can have proinflammatory or anti-inflammatory effects through regulating C5a generation by plasmin, depending on the predominating PLG activator. Tranexamic acid may cause significant inflammatory C5a elevations in injured tissues by augmenting uPA-mediated plasmin generation in a fibrin-independent manner. In contrast, TXA reduces C5a generation during tPA-mediated fibrinolysis that may reduce inflammatory responses. In vivo validation of these novel ex vivo findings is warranted and may have important clinical consequences.

Resuscitative endovascular occlusion of the aorta (REBOA) is used for temporary aortic occlusion of trauma patients in the management of noncompressible hemorrhage. Previous studies have focused on how to properly perform REBOA in the trauma environment to improve survival rates, but high-grade evidence defining the ideal patient population does not yet exist. This post hoc analysis of the Emergent Truncal Hemorrhage Control Study seeks to identify the most important clinical factors for physicians to consider when selecting for REBOA candidates and their potential survival following REBOA.Post hoc analysis of a large, multicenter, prospective observational study conducted at six level 1 trauma centers, 2017 to 2018, was performed. An onsite data collector documented all time points for REBOA patients since admission. Candidate predictors were demographics; injury severity; physiology preprocedure, during procedure, and postprocedure; cardiopulmonary resuscitation; and REBOA-specific variables (time to procedure, procedure-related time intervals, access site, technique, sheath size, catheter length, balloon volume, deployment zone). Predictive models for survival at three different time points along the trauma triage and REBOA process timeline ("Admission," "REBOA Initiation," and "Postaortic Occlusion") were devised by logistic regression.Eighty-eight patients had REBOA placement. The Admission model selected age, Glasgow Coma Scale, and admission systolic blood pressure as significant predictors of survival (area under the receiver operating characteristic curve [AUROC], 0.86; 95% CI, 0.77-0.94). The REBOA Initiation and Postaortic Occlusion models selected age, Glasgow Coma Scale, and the systolic blood pressure measured just before balloon inflation as predictors for survival (AUROC, 0.87 [95% CI, 0.78-0.97] and AUROC, 0.90 [95% CI, 0.81-0.99], respectively). No REBOA procedural variables were identified as predictors of patient survival.Only patient-specific criteria of age, neurologic status, and severity of shock predicted survival. The hemodynamic stability of the patient at the time REBOA is initiated is more important than how REBOA is initiated. These findings suggest that earlier preparation for REBOA placement may be a key to improved survival.Therapeutic, level IV.

Introduction Current guidelines recommend nonoperative management (NOM) of low-grade (American Association for the Surgery of Trauma-Organ Injury Scale Grade I-II) pancreatic injuries (LGPIs), and drainage rather than resection for those undergoing operative management, but they are based on low-quality evidence. The purpose of this study was to review the contemporary management and outcomes of LGPIs and identify risk factors for morbidity. Methods Multicenter retrospective review of diagnosis, management, and outcomes of adult pancreatic injuries from 2010 to 2018. The primary outcome was pancreas-related complications (PRCs). Predictors of PRCs were analyzed using multivariate logistic regression. Results Twenty-nine centers submitted data on 728 patients with LGPI (76% men; mean age, 38 years; 37% penetrating; 51% Grade I; median Injury Severity Score, 24). Among 24-hour survivors, definitive management was NOM in 31%, surgical drainage alone in 54%, resection in 10%, and pancreatic debridement or suturing in 5%. The incidence of PRCs was 21% overall and was 42% after resection, 26% after drainage, and 4% after NOM. On multivariate analysis, independent risk factors for PRC were other intra-abdominal injury (odds ratio [OR], 2.30; 95% confidence interval [95% CI], 1.16-15.28), low volume (OR, 2.88; 1.65, 5.06), and penetrating injury (OR, 3.42; 95% CI, 1.80-6.58). Resection was very close to significance (OR, 2.06; 95% CI, 0.97-4.34) (p = 0.0584). Conclusion The incidence of PRCs is significant after LGPIs. Patients who undergo pancreatic resection have PRC rates equivalent to patients resected for high-grade pancreatic injuries. Those who underwent surgical drainage had slightly lower PRC rate, but only 4% of those who underwent NOM had PRCs. In patients with LGPIs, resection should be avoided. The NOM strategy should be used whenever possible and studied prospectively, particularly in penetrating trauma. Level of evidence Therapeutic Study, level IV.

INTRODUCTION Locoregional analgesia (LRA) remains underused in patients with chest wall injuries. Surgical stabilization of rib fractures (SSRF) offers an opportunity to deliver surgeon-directed LRA under direct visualization at the site of surgical intervention. We hypothesized that a single-dose liposomal bupivacaine (LB) intercostal nerve block provides comparable analgesia to an indwelling, peripheral nerve plane analgesic catheter with continuous bupivacaine infusion (IC), each placed during SSRF. METHODS Noninferiority, single-center, randomized clinical trial (2017-2020) was performed. Patients were randomized to receive either IC or LB during SSRF. The IC was tunneled into the surgical field (subscapular space), and LB involved thoracoscopic intercostal blocks of ribs 3 to 8. The primary outcome was the Sequential Clinical Assessment of Respiratory Function score, measured daily for 5 days postoperatively. Secondary outcomes included daily narcotic equivalents and failure of primary LRA, defined as requiring a second LRA modality. RESULTS Thirty-four patients were enrolled: 16 IC and 18 LB. Age, Injury Severity Score, RibScore, Blunt Pulmonary Contusion Score, and use of nonnarcotic analgesics was similar between groups. Duration of IC was 4.5 days. There were three failures in the IC group versus one in the LB group (p = 0.23). There was no significant difference in Sequential Clinical Assessment of Respiratory Function score between the IC and LB groups. On postoperative days 2 to 4, narcotic requirements were less than half in the LB, as compared with the IC group; however, this difference was not statistically significant. Average wholesale price was US $605 for IC and US $434 for LB. CONCLUSION In this noninferiority trial, LB provided at least comparable and potentially superior LRA as compared with IC among patients undergoing SSRF. LEVEL OF EVIDENCE Therapeutic, level II.

Background We sought to identify opportunities for interventions to mitigate complications of tube thoracostomy (TT). Methods Retrospective review of all trauma patients undergoing TT from 6/30/2016–6/30/2019. Multivariable logistic regression identified independent predictors of complications. Results Out of 451 patients, 171 (37.9%) had at least one TT malpositioning or complication. Placement in the emergency department, placement by emergency medicine physicians, and body mass index >30 kg/m2 were independent predictors of complication. Malpositioning increased the likelihood of early complication (6.5%–53.5%), and early complication increased the likelihood of late complication (4.3%–13.6%). Patients with a late complication had, on average, a 7.56 day longer hospital stay than patients without a late complication. Conclusion TT complications were associated with placement in the emergency department, placement by emergency medicine physicians, and BMI>30 kg/m2. We identified associations between malpositioning, early complications, and late complications, and demonstrated that TT complications impact patient outcomes.

INTRODUCTION: Evidence supports the use of plasma-first resuscitation in the treatment of trauma-induced coagulopathy (TIC). While thawed plasma (TP) has logistical benefits, the ability of plasma proteins to attenuate fibrinolysis and correct TIC remain unknown. We hypothesize that TP etains the ability to inhibit tissue plasminogen activator(tPA)-induced fibrinolysis at 28-day storage. METHODS: Healthy volunteers underwent blood draws followed by 50% dilution of whole blood (WB) with TP at 28-, 21-, 14-, 7-, 5-, and, 0-day storage, normal saline (NS), and WB control. Samples underwent citrated tPA-challenge (75 ng/ml) thromboelastography (TEG). Plasminogen activator inhibitor-1 (PAI-1) and α(2)-antiplasmin (α(2)-AP) concentrations in thawed or stored plasma were determined. RESULTS: In the presence of tPA, 28-day TP inhibited tPA-induced coagulopathy as effectively as WB. 28-day TP had a similar R-time, MA, and fibrinolysis (P > 0·05 for all) compared to WB, while angle was enhanced (P = 0·02) compared to WB. Significant correlations were present between storage time and clot strength (P = 0·04) and storage time and fibrinolysis (P = 0·0029). Active PAI-1 levels in thawed plasma were 1·10 ± 0·54 ng/mL while total PAI-1 levels were 4·79 ± 1·41 ng/mL. There was no difference of α(2)-AP levels in FFP (40·45 ± 3·5 μg/mL) compared to plasma thawed for 14 (36·78 ± 5·39 μg/mL, P = 0·65) or 28 days (45·16 ± 5·61 μg/mL, P = 0·51). DISCUSSION: Thawed plasma retained the ability to inhibit tPA-induced fibrinolysis over 28-day storage at 1–4°C. α(2)-AP levels were maintained in plasma thawed for 28 days and FFP. These in vitro results suggest consideration should be made to increasing the storage life of TP.

Background The lack of an accurate marker of prehospital hemorrhagic shock limits our ability to triage patients to the correct level of care, delays treatment in the emergency department, and inhibits our ability to perform prehospital interventional research in trauma. End-tidal carbon dioxide (ETCO2) is the measurement of alveolar carbon dioxide concentration at end expiration and is measured noninvasively in the ventilator circuit for intubated patients in continuous manner. Several hospital-based studies have been able to demonstrate that either low or decreasing levels of ETCO2 as well as disparities between ETCO2 and plasma carbon dioxide correlate with increasing mortality in trauma. We hypothesized that prehospital ETCO2 values will be predictive of mortality and need for massive transfusion following injury. Methods This is a single-center retrospective study from an urban level 1 trauma center. We reviewed all intubated adult patients transported for injury who had prehospital ETCO2 values available. Unadjusted comparisons of continuous variables were done with the Wilcoxon two-sample test. The predictive performance of prehospital ETCO2, the prehospital shock index, and prehospital systolic blood pressure were assessed and compared using areas under the receiver operating characteristic curves. Optimal cutoffs were estimated by maximizing the Youden index. Massive transfusion was defined as >10 U of blood or death in 24 hours. Results A total of 173 patients were identified with prehospital ETCO2 values during the 2-year study period. Population was 78.5% male with a median age of 37.5 years (interquartile range, 23.5-53.5 years). Injury mechanism was penetrating in 22.8%. This cohort had a median Injury Severity Score of 26 (interquartile range, 17-36), massive transfusion rate of 34.7%, and mortality of 42.1%. In the evaluation of prediction of postinjury mortality and massive transfusion, ETCO2 outperformed systolic blood pressure and shock index, but these differences did not reach statistical significance. Conclusion End-tidal carbon dioxide is a novel prehospital predictor of mortality and massive transfusion after injury. Level of evidence Prognostic/Epidemiologic, level III.

Background Randomized clinical trials (RCTs) support the use of prehospital plasma in traumatic hemorrhagic shock, especially in long transports. The citrate added to plasma binds with calcium, yet most prehospital trauma protocols have no guidelines for calcium replacement. We reviewed the experience of two recent prehospital plasma RCTs regarding admission ionized-calcium (i-Ca) blood levels and its impact on survival. We hypothesized that prehospital plasma is associated with hypocalcemia, which in turn is associated with lower survival. Methods We studied patients enrolled in two institutions participating in prehospital plasma RCTs (control, standard of care; experimental, plasma), with i-Ca collected before calcium supplementation. Adults with traumatic hemorrhagic shock (systolic blood pressure ≤70 mm Hg or 71-90 mm Hg + heart rate ≥108 bpm) were eligible. We use generalized linear mixed models with random intercepts and Cox proportional hazards models with robust standard errors to account for clustered data by institution. Hypocalcemia was defined as i-Ca of 1.0 mmol/L or less. Results Of 160 subjects (76% men), 48% received prehospital plasma (median age, 40 years [interquartile range, 28-53 years]) and 71% suffered blunt trauma (median Injury Severity Score [ISS], 22 [interquartile range, 17-34]). Prehospital plasma and control patients were similar regarding age, sex, ISS, blunt mechanism, and brain injury. Prehospital plasma recipients had significantly higher rates of hypocalcemia compared with controls (53% vs. 36%; adjusted relative risk, 1.48; 95% confidence interval [CI], 1.03-2.12; p = 0.03). Severe hypocalcemia was significantly associated with decreased survival (adjusted hazard ratio, 1.07; 95% CI, 1.02-1.13; p = 0.01) and massive transfusion (adjusted relative risk, 2.70; 95% CI, 1.13-6.46; p = 0.03), after adjustment for confounders (randomization group, age, ISS, and shock index). Conclusion Prehospital plasma in civilian trauma is associated with hypocalcemia, which in turn predicts lower survival and massive transfusion. These data underscore the need for explicit calcium supplementation guidelines in prehospital hemotherapy. Level of evidence Therapeutic, level II.

BACKGROUND: Both hyperfibrinolysis and fibrinolysis shutdown can occur after severe trauma. The subgroup of trauma patients with fibrinolysis shut- down resistant to tissue plasminogen activator (t-PA)-mediated fibrinolysis have increased mortality. Fibrin polymerization and structure may influence fibrinolysis subgroups in trauma, but fibrin architecture has not been characterized in acutely injured subjects. We hypothesized that fibrin polymerization measured in situ will correlate with fibrinolysis subgroups. METHODS: Blood samples were collected from trauma patients and noninjured controls. We selected samples across a range of fibrinolysis phenotypes (shutdown, physiologic, hyperfibrinolysis) and t-PA sensitivities (sensitive, physiologic, resistant) determined by thrombelastography. Plasma clots were created in situ with fluorescent fibrinogen and imaged using confocal microscopy for analysis of clot architecture in three dimensions. For each clot, we quantified the fiber resolvability, a metric of fiber distinctness or clarity, by mapping the variance of fluores- cence intensity relative to background fluorescence. We also determined clot porosity by measuring the size and distribution of the gaps between fibrin fibers in three-dimensional space. We compared these measures across fibrinolysis subgroups. RESULTS: Fiber resolvability was significantly lower in all trauma subgroups compared with controls (n = 35 and 5, respectively; p < 0.05). We observed markedly different patterns of fibrin architecture among trauma patients stratified by fibrinolysis subgroup. Subjects with t-PA–resistant fibrinolysis shutdown exhibited abnormal, densely packed fibrin clots nearly devoid of pores. Individuals with t-PA–hypersensitive fibrinolysis shutdown had highly irregular clots with pores as large as 2500 μm3 to 20,000 μm3, versus 78 μm3 to 1250 μm3 in noninjured controls. CONCLUSION: Fiber resolvability was significantly lower in trauma patients than controls, and subgroups of fibrinolysis differ in the porosity of the fibrin clot structure. The dense fibrin network in the t-PA–resistant group may prevent access to plasmin, suggesting a mechanism for thrombotic morbidity after injury.

Goal-directed hemostatic resuscitation based on thrombelastography (TEG) has a survival benefit compared with conventional coagulation assays such as international normalized ratio, activated partial thromboplastin time, fibrinogen level, and platelet count. While TEG-based transfusion thresholds for patients at risk for massive transfusion (MT) have been defined using rapid TEG, cutoffs have not been defined for TEG using other activators such as kaolin. The purpose of this study was to develop thresholds for blood product transfusion using citrated kaolin TEG (CK-TEG) in patients at risk for MT.CK-TEG was assessed in trauma activation patients at two Level 1 trauma centers admitted between 2010 and 2017. Receiver operating characteristic (ROC) curve analyses were performed to test the predictive performance of CK-TEG measurements in patients requiring MT, defined as10 units of red blood cells or death within the first 6 hours. The Youden Index defined optimal thresholds for CK-TEG-based resuscitation.Of the 825 trauma activations, 671 (81.3%) were men, 419 (50.8%) suffered a blunt injury, and 62 (7.5%) received a MT. Patients who had a MT were more severely injured, had signs of more pronounced shock, and more abnormal coagulation assays. CK-TEG R-time was longer (4.9 vs. 4.4 min, p = 0.0084), angle was lower (66.2 vs. 70.3 degrees, p0.0001), maximum amplitude was lower in MT (57 vs. 65.5 mm, p0.0001), and LY30 was greater (1.8% vs. 1.2%, p = 0.0012) in patients with MT compared with non-MT. To predict MT, R-time yielded an area under the ROC curve (AUROC) = 0.6002 and a cut point of4.45 min. Angle had an AUROC = 0.6931 and a cut point of67 degrees. CMA had an AUROC = 0.7425, and a cut point of60 mm. LY30 had an AUROC = 0.623 with a cut point of4.55%.We have identified CK-TEG thresholds that can guide MT in trauma. We propose plasma transfusion for R-time4.45 min, fibrinogen products for an angle67 degrees, platelet transfusion for MA60 mm, and antifibrinolytics for LY304.55%.Therapeutic study, level V.

Background Resuscitation guided by thrombelastography improves survival after injury. If bleeding is rapid, however, or if no thrombelastography data are available, the optimal strategy remains controversial. Our current practice gives fresh frozen plasma and red blood cells (1:2) empirically in patients with life-threatening hemorrhage, with subsequent administration based on rapid thrombelastography. We identified patients at risk of massive transfusion at 1 hour, examined their initial rapid thrombelastography, and used this value to provide empiric recommendations about transfusions. Methods Massive transfusion was defined as >4 units of red blood cells in the first hour. Patients managed by a trauma activation (2014–2017) had an admission rapid thrombelastography analyzed to determine what proportion met thresholds for administration of cryoprecipitate or platelets. Results Overall, 35 patients received >4 units of red blood cells in the first hour. Based on the admission rapid thrombelastography, 37% met criteria for both platelets and cryoprecipitate, 35% for either platelets or cryoprecipitate and 29% for neither. Kaplan-Meier analysis showed a significant delay in the administration of cryoprecipitate and platelets compared to fresh frozen plasma. Conclusion Patients who require >4 units of red blood cells within the first hour should receive cryoprecipitate and platelets if thrombelastography results are not available. Point-of-care devices are needed for optimal care of trauma-induced-coagulopathy, but these data offer guidance in their absence.

Background Hypercoagulability and malignancy have been linked since the 1860s. However, the impact of different neoplasms on multiple components of the coagulation system remains poorly understood. Thrombelastography (TEG) enables measurement of coagulation incorporating clotting through fibrinolysis. We hypothesize that specific TEG indices that are associated with hypercoagulability can be appreciated in patients with adenocarcinoma undergoing pancreatic resection. Study Design Blood samples were obtained from patients undergoing pancreatic resection before surgical incision and assayed with TEG. The 4 indices of coagulation measured by TEG included in the analysis were R time, angle, maximum amplitude, and lysis at 30 minutes. Patient tumor type, nodal disease, and mass resectability were contrasted with TEG indices. Results One hundred patients were enrolled over 18 months. The majority (63%) of patients had adenocarcinoma. Patients with adenocarcinoma had increased angle compared with other lesions (49 degrees [interquartile range {IQR} 37 to 59 degrees] vs 43 degrees [IQR 32 to 49 degrees]; p = 0.011). When excluding patients that underwent neoadjuvant therapy, patients with adenocarcinoma had shorter R times (13 minutes [IQR 9 to 16 minutes] vs 14 minutes [IQR 12 to 18 minutes]; p = 0.051), steeper angles (49 degrees [IQR 40 to 59 degrees] vs 43 degrees [IQR 32 to 49 degrees]; p = 0.010), and higher maximum amplitude (67 mm [IQR 61 to 69 mm] vs 62 mm [IQR 57 to 67 mm]; p = 0.017). Nodal disease was associated with a significantly increased angle (49 degrees [IQR 42 to 59 degrees] vs 40 degrees [IQR 32 to 50 degrees]; p = 0.002) and maximum amplitude (64 mm [IQR 61 to 69 mm] vs 62 mm [IQR 56 to 67 mm]; p = 0.017). Patients who underwent successful mass resection had longer R times (14 minutes [IQR 11 to 17 minutes] vs 10 minutes [IQR 9 to 15]; p = 0.033) and shorter angles (44 degrees [IQR 35 to 55 degrees] vs 58 degrees [IQR 45 to 66 degrees]; p = 0.025). Conclusions Patients with adenocarcinoma undergoing pancreatic resection have multiple TEG abnormalities consistent with hypercoagulability. These TEG outputs are associated with tumor type, nodal disease, and probability of a successful resection. The use of preoperative TEG has the potential to aid surgeon and patient discussions on anticipated disease burden and prognosis before resection.

BACKGROUND: Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology. METHODS: Blood samples were collected in the field or at Emergency Department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), “eufibrinolytic” (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins. RESULTS: HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared to healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p0.1 and fold change of concentrations of 0.75–1.3). CONCLUSION: HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs. LEVEL OF EVIDENCE: III prognostic.