Postoperative antiplatelet and/or anticoagulation use does not impact complication or reintervention rates after vein repair of arterial injury: A PROOVIT study.

INTRODUCTION: The use of antiplatelet (AP) and anticoagulation (AC) therapy after autogenous vein repair of traumatic arterial injury is controversial. The hypothesis in this study was that there is no difference in early postoperative outcomes regardless of whether AC, AP, both, or neither are used. METHODS: The American Association for the Surgery of Trauma (AAST) PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from November, 2013, to January, 2019, for arterial injuries repaired with a vein graft. Demographics and injury characteristics were compared. Need for in-hospital reoperation was the primary outcome in this four-arm study, assessed with two ordinal logistic regression models (1. no therapy vs. AC only vs. AC and AP; 2. no therapy vs. AP only vs. AC and AP). RESULTS: 373 patients (52 no therapy, 88 AP only, 77 AC only, 156 both) from 19 centers with recorded Injury Severity Scores (ISS) were identified. Patients who received no therapy were younger than those who received AP (27.0 vs. 34.2, p = 0.02), had higher transfusion requirement (p < 0.01 between all groups) and a different distribution of anatomic injury (p < 0.01). After controlling for age, sex, ISS, platelet count, hemoglobin, pH, lactate, INR, transfusion requirement and anatomic location, there was no association with postoperative medical therapy and in-hospital operative reintervention, or any secondary outcome, including thrombosis (p = 0.67, p = 0.22). CONCLUSIONS: Neither AC nor AP alone, nor in combination, impact complication rate after arterial repair with autologous vein. These patients can be safely treated with or without antithrombotics, recognizing that this study did not demonstrate a beneficial effect.

Characterizing Brain Perfusion in a Swine Model of Raised Intracranial Pressure.

INTRODUCTION: Perfusion of the brain is critical, but this can be compromised due to focal space occupying lesions (SOL). SOLs can raise intracranial pressure (ICP), resulting in reduced cerebral blood flow (CBF). Most gyrencephalic models of brain injury focus on parenchymal injury, with few models of acutely elevated ICP. We hypothesized that we could employ a SOL technique to develop a titratable ICP model and sought to quantitate the resulting decrease in brain perfusion. METHODS: Six swine were anesthetized and instrumented. A Fogarty balloon catheter was inserted intracranially. Blood CO2 partial pressure was maintained between 35 and 45 mmHg. The Fogarty balloon was infused with normal saline at 1 mL/min to ICP targets of 10, 20, 30, and 40 mmHg. CBF (mL/100 g/min) were assessed at each ICP level using computed tomography perfusion (CTP). Data are presented as the mean ± standard deviation with all pressures measured in mmHg. CBF values were compared between baseline and each ICP level using analysis of variance. RESULTS: Baseline ICP was 5 ± 2 and systolic blood pressure was 106 ± 7. Balloon volumes (mL) required to achieve each incremental ICP level were 2.4 ± 0.5, 4.9 ± 1.7, 7.6 ± 1.6, and 9.9 ± 1.7. CBF decreased with each raised ICP level, with CBF being significantly less than baseline at ICP values of 30 (56.1 ± 34.7 versus 20.6 ± 11.0, P < 0.05) and 40 (56.1 ± 34.7 versus 6.5 ± 10.6, P < 0.05). CONCLUSIONS: An intracranial balloon catheter can be used to increase ICP, delivering a proportionate reduction in CBF. This model can be used in the future studies to examine adjuncts that manipulate intracranial pressure and their effect on brain perfusion.

The Role of Endovascular Repair of Popliteal Arterial Injuries in the Acute Setting.

BACKGROUND: The role of endovascular surgery in the treatment of popliteal arterial injuries is not well established. As with other popliteal pathology, open repair has traditionally been considered the gold standard. As data has accumulated and technology advanced, however, a reassessment of the role of endovascular surgery is warranted. The aim of this study is to perform a noninferiority comparison of open versus endovascular management of traumatic popliteal injuries. Our hypothesis is that endovascular management is noninferior to open management of traumatic popliteal injuries. METHODS: The National Trauma Data Bank was searched for adult patients from 2002-2016 for isolated popliteal arterial injury. The study used a standard noninferiority methodology to compare rates of amputation and compartment syndrome between endovascular and open surgery. Margins for noninferiority were established using established published rates of complications: 17.1% for amputations and 23.0% for compartment syndrome. Endovascular intervention would be considered noninferior to open surgery if the lower bound confidence of the complication proportion (endo/open complication rate) was greater than the predefined noninferiority margin. RESULTS: A total of 3,698 patients met inclusion criteria, with blunt injury accounting for 2,117 (57%) and penetrating injury accounting for 1,581 (43%). Within the blunt group, 1,976 (93.3%) underwent open and 141 (6.7%) endovascular surgery. The rate of compartment syndrome (percentage and 95% confidence interval) after surgery for open repair was 9.9 (8.6-11.2) and 6.4 (3.2-11.3) for endovascular repair. The complication proportion is 64.6 (59.7-69.5). The rate of amputation for open repair was 15.7 (14.2-17.4) and 14.2 (9.2-20.6) for endovascular repair. The complication proportion is 90.4 (87.4-93.4). Within the penetrating group, 1,525 (96.5%) underwent open repair and 56 (3.5%) endovascular surgery. The rate of compartment syndrome after surgery for open repair was 14.9 (13.2-16.7) and 5.4 (1.5-13.6) for endovascular repair. The complication proportion is 36.2 (31.3-41.1). The rate of amputation for open repair was 4.3 (3.3-5.4) and 3.6 (0.7-11.0) for endovascular repair. The complication proportion is 83.7 (75.3-90.6). CONCLUSIONS: These data suggests that endovascular repair of popliteal artery injury may be noninferior to open repair with respect to limb preservation. Further examination of endovascular repair in popliteal artery injury is warranted.

Development of an Endovascular Model of Pelvic Hemorrhage Using Volumetric Computed Tomography Validation.

PURPOSE: Uncontrolled pelvic hemorrhage from trauma is associated with mortality rates above 30%. The ability of an intervention to reduce blood loss from pelvic trauma is paramount to its success. The objective of this study was to determine if computed tomography volumetric analysis could be used to quantify blood loss in a porcine endovascular pelvic hemorrhage model. MATERIALS AND METHODS: Yorkshire swine under general anesthesia underwent balloon dilation and rupture of the profunda femoris artery, which was confirmed by digital subtraction angiography. Computed tomography angiography and postprocessing segmentation were performed to quantify pelvic hemorrhage volume at 5 and 30 minutes after injury. Continuous hemodynamic and iliofemoral flow data were obtained. Baseline and postinjury hemoglobin, hematocrit and lactate were collected. RESULTS: Of 6 animals enrolled, 5 survived the 30-minute post-injury period. One animal died at 15 minutes. Median volume of pelvic hemorrhage was 141±106 cm3 at 5 minutes and 302±79 cm3 at 30 minutes with a 114% median increase in hematoma volume over 25 minutes (p=0.040). There was a significant decrease in mean arterial pressure (107 to 71 mm Hg, p=0.030) and iliofemoral flow (561 to 122 mL/min, p=0.014) at 30 minutes postinjury, but no significant changes in hemoglobin, hematocrit, or heart rate. CONCLUSION: Computed tomography volumetric analysis can be used to quantify rate and volume of blood loss in a porcine endovascular pelvic hemorrhage model. Future studies can incorporate this approach when evaluating the effect of hemorrhage control interventions associated with pelvic fractures.

Undisclosed financial conflicts of interest in DSM-5-TR: cross sectional analysis.

OBJECTIVE: To assess the extent and types of financial ties to industry of panel and task force members of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, fifth edition, text revision (DSM-5-TR), published in 2022. DESIGN: Cross sectional analysis. SETTING: Open Payments database, USA. PARTICIPANTS: 92 physicians based in the US who served as members of either a panel (n=86) or task force (n=6) on the DSM-5-TR with information recorded in the Centers for Medicare and Medicaid Services Open Payments database during 2016-19. This period was chosen to include the year that development of the DSM-5-TR began and the three years preceding, a time consistent with previous research on conflicts of interest and consistent with the American Psychiatric Association's disclosure requirements for the fifth revision (DSM-5) of the manual. MAIN OUTCOME MEASURES: Type and amount of compensation the panel and task force members of DSM-5-TR received during 2016-19. RESULTS: After duplicate names had been removed, 168 individuals were identified who served as either panel or task force members of the DSM-5-TR. 92 met the inclusion criteria of being a physician who was based in the US and therefore could be included in Open Payments. Of these 92 individuals, 55 (60%) received payments from industry. Collectively, these panel members received a total of $14.2m (£11.2m; €13m). One third (33.3%) of the task force members had payments reported in Open Payments. CONCLUSIONS: Conflicts of interest among panel members of DSM-5-TR were prevalent. Because of the enormous influence of diagnostic and treatment guidelines, the standards for participation on a guideline development panel should be high. A rebuttable presumption should exist for the Diagnostic and Statistical Manual of Mental Disorders to prohibit conflicts of interest among its panel and task force members. When no independent individuals with the requisite expertise are available, individuals with associations to industry could consult to the panels, but they should not have decision making authority on revisions or the inclusion of new disorders.

Partial vs Full Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in a Swine Model of Raised Intracranial Pressure and Hemorrhagic Shock.

BACKGROUND: Partial resuscitative endovascular balloon occlusion of the aorta (pREBOA) is a potential method to mitigate the ischemia observed in full REBOA (fREBOA). However, the effect of pREBOA on cerebral perfusion in the setting of raised intracranial pressure (rICP) is unknown. The aim was to evaluate the effects of no REBOA (nREBOA) vs pREBOA vs fREBOA on cerebral perfusion in a swine model of rICP and hemorrhagic shock. STUDY DESIGN: Anesthetized swine (n = 18) underwent instrumentation. Controlled hemorrhage was performed over 30 minutes. rICP was achieved using an intracranial Fogarty catheter inflated to achieve an ICP of 20 mmHg. Animals underwent intervention for 30 minutes, followed by resuscitation. The primary outcome was cerebral perfusion measured by ICP (millimeters of mercury), cerebral perfusion pressure (CPP; millimeters of mercury), and cerebral blood flow (CBF; milliliters per minute per 100 g) derived from CT perfusion. The secondary outcomes included hemodynamics and lactate (millimoles per liter). RESULTS: The peak ICP of pREBOA animals (22.7 ± 2.5) was significantly lower than nREBOA and fREBOA. pREBOA CPP was significantly higher compared with nREBOA and fREBOA during resuscitation. The pREBOA CBF was greater during intervention and resuscitation compared with nREBOA (p < 0.001). Systolic blood pressure was similar between pREBOA and fREBOA, and coronary perfusion was significantly greater in pREBOA. fREBOA had significantly higher lactate during the intervention (9.3 ± 1.3) and resuscitation (8.9 ± 3.5) compared with nREBOA and pREBOA. CONCLUSION: pREBOA produced greater cerebral perfusion, as demonstrated by more favorable CPP, CBF, and ICP values. fREBOA was associated with metabolic derangement and diminished pressure during resuscitation. pREBOA is superior to fREBOA in a swine model and should be considered over fREBOA for aortic occlusion.

Factors Associated With Increased Mortality in Severe Abdominopelvic Injury.

BACKGROUND: Associated injuries are thought to increase mortality in patients with severe abdominopelvic trauma. This study aimed to identify clinical factors contributing to increased mortality in patients with severe abdominopelvic trauma, with the hypothesis that a greater number of concomitant injuries would result in increased mortality. METHODS: This was a retrospective review of the Trauma Quality Improvement Program (TQIP) database of patients ≥ 18 years with severe abdominopelvic trauma defined as having an abdominal Abbreviated Injury Score (AIS) ≥ 3 with pelvic fractures and/or iliac vessel injury (2015-2017). Primary outcome was in-hospital mortality based on concomitant body region injuries. Secondary outcomes included mortality at 6 h, 6 to 24 h, and after 24 h based on concomitant injuries, procedures performed, and transfusion requirements. RESULTS: A total of 185,257 patients were included in this study. Survivors had more severely injured body regions than non-survivors (4 vs. 3, P < 0.001). Among those who died within 6 h, 28.5% of patients required a thoracic procedure and 43% required laparotomy compared to 6.3% and 22.1% among those who died after 24 h (P < 0.001). Head AIS ≥ 3 was the only body region that significantly contributed to overall mortality (OR 1.26, P < 0.001) along with laparotomy (OR 3.02, P < 0.001), neurosurgical procedures (2.82, P < 0.001) and thoracic procedures (2.28, P < 0.001). Non-survivors who died in < 6 h and 6-24 h had greater pRBC requirements than those who died after 24 h (15.5 and 19.5 vs. 8 units, P < 0.001). CONCLUSION: Increased number of body regions injured does not contribute to greater mortality. Uncontrolled noncompressible torso hemorrhage rather than the burden of concomitant injuries is the major contributor to the high mortality associated with severe abdominopelvic injury.

The Underlying Cardiovascular Mechanisms of Resuscitation and Injury of REBOA and Partial REBOA.

Introduction: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is used for aortic control in hemorrhagic shock despite little quantification of its mechanism of resuscitation or cardiac injury. The goal of this study was to use pressure-volume (PV) loop analysis and direct coronary blood flow measurements to describe the physiologic changes associated with the clinical use of REBOA. Methods: Swine underwent surgical and vascular access to measure left ventricular PV loops and left coronary flow in hemorrhagic shock and subsequent placement of occlusive REBOA, partial REBOA, and no REBOA. PV loop characteristics and coronary flow are compared graphically with PV loops and coronary waveforms, and quantitatively with measures of the end systolic and end pressure volume relationship, and coronary flow parameters, with accounting for multiple comparisons. Results: Hemorrhagic shock was induced in five male swine (mean 53.6 ± 3.6 kg) as demonstrated by reduction of stroke work (baseline: 3.1 vs. shock: 1.2 L*mmHg, p < 0.01) and end systolic pressure (ESP; 109.8 vs. 59.6 mmHg, p < 0.01). ESP increased with full REBOA (178.4 mmHg; p < 0.01), but only moderately with partial REBOA (103.0 mmHg, p < 0.01 compared to shock). End systolic elastance was augmented from baseline to shock (1.01 vs. 0.39 ml/mmHg, p < 0.01) as well as shock compared to REBOA (4.50 ml/mmHg, p < 0.01) and partial REBOA (3.22 ml/mmHg, p = 0.01). Percent time in antegrade coronary flow decreased in shock (94%-71.8%, p < 0.01) but was rescued with REBOA. Peak flow increased with REBOA (271 vs. shock: 93 ml/min, p < 0.01) as did total flow (peak: 2136, baseline: 424 ml/min, p < 0.01). REBOA did not augment the end diastolic pressure volume relationship. Conclusion: REBOA increases afterload to facilitate resuscitation, but the penalty is supraphysiologic coronary flows and imposed increase in LV contractility to maintain cardiac output. Partial REBOA balances the increased afterload with improved aortic system compliance to prevent injury.

A technical and data analytic approach to pressure-volume loops over numerous cardiac cycles.

Cardiac pressure-volume (PV) loop analysis is the reference standard for studying the cardiovascular implications of clinical perturbations (eg, heart failure, aortic occlusion, hypovolemia) and is a benchmark for comparisons with noninvasive alternatives (eg, ultrasound, magnetic resonance imaging). Historically, most PV loop analyses were of individual cardiac cycles for which the options to analyze PV loops using off-the-shelf software were limited, and home-grown analysis software often lacked peer review or code-sharing. Our aim was to describe a start-to-finish implementation of PV loops for determination of hemodynamic parameters in swine, to provide technical advice for vascular access and proceduralization, and to describe data capture, curation, preprocessing, and analysis of raw PV time data. We have provided a novel data analytic method to programmatically analyze raw PV loop data beyond single cardiac cycles and real, raw swine PV loop data and the accompanying MATLAB (MathWorks, Inc, Natick, Mass) code as an example of how to process and analyze raw data directly.

Characterization of cerebral blood flow during open cardiac massage in swine: Effect of volume status.

Introduction: Patients in cardiac arrest treated with resuscitative thoracotomy and open cardiac massage (OCM) have high rates of mortality with poor neurological outcomes. The aim of this study is to quantitate cerebral perfusion during OCM using computed tomography perfusion (CTP) imaging in a swine model of normo- and hypovolemia. Methods: Anesthetized swine underwent instrumentation with right atrial and aortic pressure catheters. A catheter placed in the ascending aorta was used to administer iodinated contrast and CTP imaging acquired. Cerebral blood flow (CBF; ml/100 g of brain) and time to peak (TTP; s) were measured. Animals were then euthanized by exsanguination (hypovolemic group) or potassium chloride injection (normovolemic group) and subjected to a clamshell thoracotomy, aortic cross clamping, OCM, and repeated CTP. Data pertaining to peak coronary perfusion pressure (pCoPP; mmHg) were collected and % CoPP > 15 mmHg (% CoPP; s) calculated post hoc. Results: Normovolemic animals (n = 5) achieved superior pCoPP compared to the hypovolemic animals (n = 5) pCoPP (39.3 vs. 12.3, p < 0.001) and % CoPP (14.5 ± 1.9 vs. 30.9 ± 6.5, p < 0.001). CTP acquisition was successful and TTP elongated from spontaneous circulation, normovolemia to hypovolemia (5.7 vs. 10.8 vs. 14.8, p = 0.01). CBF during OCM was similar between hypovolemic and normovolemic groups (7.5 ± 8.1 vs. 4.9 ± 6.0, p = 0.73) which was significantly lower than baseline values (51.9 ± 12.1, p < 0.001). Conclusion: OCM in normovolemia generates superior coronary hemodynamics compared to hypovolemia. Despite this, neither generates adequate CBF as measured by CTP, compared to baseline. To improve the rate of neurologically intact survivors, novel resuscitative techniques need to be investigated that specifically target cerebral perfusion as existing techniques are inadequate.

A swine model of reproducible timed induction of peripheral arterial shunt failure: Developing warning signs of imminent shunt failure.

Temporary intravascular shunts are used to maintain perfusion in injured vessels, although failure can be unpredictable and lead to significant morbidity. The aim of the present study was to develop a dose- and timing-controlled swine model of intrinsic shunt failure to facilitate the development of a warning system for impending failure. Ten Yorkshire swine (weight, 56.6 ± 4.2 kg) underwent bilateral Argyle shunt (Cardinal Health, Dublin, OH) placement in the external iliac arteries, with proximal cannulation of the circumflex iliac arteries for infusion of thrombin. The thrombin infusion was randomized to the left or right side for 5000 vs 10,000 U/h. The 5000-U/h group required 2.1 times as long as the 10,000-U/h group to reach failure (mean, 21.8 minutes vs 46.4 minutes; P < .0001), as shown by a Kaplan-Meier survival analysis (log-rank P < .0001). However, the 5000-U/h group required the same total amount of thrombin (mean, 3752 ± 856 U; P = .57). Thus, time- and/or thrombin dose-controlled induction of shunt failure is technically feasible. Furthermore, in the final 15 minutes before failure, the flow was similar between the two groups (P > .05), and the slope of the flow curve became more negative the closer the model was to failure. Overall, this model could be used to develop an alert system to predict for impending shunt failure or the need for intervention.

Class of hemorrhagic shock is associated with progressive diastolic coronary flow reversal and diminished left ventricular function.

Introduction: The relationship between coronary artery flow and left ventricular (LV) function during hemorrhagic shock remains unknown. The aim of this study was to quantify coronary artery flow directionality alongside left ventricular function through the four classes of hemorrhage shock. Methods: Following baseline data collection, swine were exsanguinated into cardiac arrest via the femoral artery using a logarithmic bleed, taking each animal through the four classes of hemorrhagic shock based on percent bleed (class I: 15%; class II: 15%-30%; class III: 30%-40%; class IV: >40%). Telemetry data, left ventricular pressure-volume loops, and left anterior descending artery flow tracings over numerous cardiac cycles were collected and analyzed for each animal throughout. Results: Five male swine (mean 72 ± 12 kg) were successfully exsanguinated into cardiac arrest. Mean left ventricular end-diastolic volume, end-diastolic pressure, and stroke work decreased as the hemorrhagic shock class progressed (p < 0.001). The proportion of diastole spent with retrograde coronary flow was also associated with class of hemorrhagic shock (mean 5.6% of diastole in baseline, to 63.9% of diastole in class IV; p < 0.0001), worsening at each class from baseline through class IV. Preload recruitable stroke work (PRSW) decreased significantly in classes II through IV (p < 0.001). Systemic Vascular Resistance (SVR) is associated with class of hemorrhage shock (p < 0.001). Conclusion: With progressive classes of hemorrhagic shock left ventricular function progressively decreased, and the coronary arteries spent a greater proportion of diastole in retrograde flow, with progressively more negative total coronary flow. Preload recruitable stroke work, a load-independent measure of inotropy, also worsened in severe hemorrhagic shock, indicating the mechanism extends beyond the drop in preload and afterload alone.

Whole Blood Selective Aortic Arch Perfusion for Exsanguination Cardiac Arrest: Assessing Myocardial Tolerance to the Duration of Cardiac Arrest.

INTRODUCTION: Selective aortic arch perfusion (SAAP) is an endovascular technique that consists of aortic occlusion with perfusion of the coronary and cerebral circulation. It been shown to facilitate return of spontaneous circulation (ROSC) after exanguination cardiac arrest (ECA), but it is not known how long arrest may last before the myocardium can no longer be durably recovered. The aim of this study is to assess the myocardial tolerance to exsanguination cardiac arrest before successful ROSC with SAAP. METHODS: Male adult swine (n = 24) were anesthetized, instrumented, and hemorrhaged to arrest. Animals were randomized into three groups: 5, 10, and 15 min of cardiac arrest before resuscitation with SAAP. Following ROSC, animals were observed for 60 min in a critical care environment. Primary outcomes were ROSC, and survival at 1-h post-ROSC. RESULTS: Shorter cardiac arrest time was associated with higher ROSC rate and better 1-h survival. ROSC was obtained for 100% (8/8) of the 5-min ECA group, 75% (6/8) of the 10-min group, 43% (3/7) of the 15-min group (P = 0.04). One-hour post-ROSC survival was 75%, 50%, and 14% in 5-, 10-, and 15-min groups, respectively (P = 0.02). One-hour survivors in the 5-min group required less norepinephrine (1.31 mg ±â€Š0.83 mg) compared with 10-SAAP (0.76 mg ±â€Š0.24 mg), P = 0.008. CONCLUSION: Whole blood SAAP can accomplish ROSC at high rates even after 10 min of unsupported cardiac arrest secondary to hemorrhage, with some viability beyond to 15 min. This is promising as a tool for ECA, but requires additional optimization and clinical trials.Animal Use Protocol, IACUC: 0919015.

Resuscitative endovascular balloon occlusion of the aorta associated with improved survival in hemorrhagic shock.

BACKGROUND: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is controversial as a hemorrhage control adjunct due to lack of data with a suitable control group. We aimed to determine outcomes of trauma patients in shock undergoing REBOA versus no-REBOA. METHODS: This single-center, retrospective, matched cohort study analyzed patients ≥16 years in hemorrhagic shock without cardiac arrest (2000-2019). REBOA (R; 2015-2019) patients were propensity matched 2:1 to historic (H; 2000-2012) and contemporary (C; 2013-2019) groups. In-hospital mortality and 30-day survival were analyzed using chi-squared and log rank testing, respectively. RESULTS: A total of 102,481 patients were included (R = 57, C = 88,545, H = 13,879). Propensity scores were assigned using age, race, mechanism, lowest systolic blood pressure, lowest Glasgow Coma Score (GCS), and body region Abbreviated Injury Scale scores to generate matched groups (R = 57, C = 114, H = 114). In-hospital mortality was significantly lower in the REBOA group (19.3%) compared to the contemporary (35.1%; p = 0.024) and historic (44.7%; p = 0.001) groups. 30-day survival was significantly higher in the REBOA versus no-REBOA groups. CONCLUSION: In a high-volume center where its use is part of a coordinated hemorrhage control strategy, REBOA is associated with improved survival in patients with noncompressible torso hemorrhage.

An estrogen (17α-ethinyl estradiol-3-sulfate) reduces mortality in a swine model of multiple injuries and hemorrhagic shock.

BACKGROUND: Although 17α-ethinyl estradiol-3-sulfate (EES) reduces mortality in animal models of controlled hemorrhage, its role in a clinically relevant injury model is unknown. We assessed the impact of EES in a swine model of multiple injuries and hemorrhage. METHODS: The study was performed under Good Laboratory Practice, with 30 male uncastrated swine (25-50 kg) subjected to tibial fracture, pulmonary contusion, and 30% controlled hemorrhage for an hour. Animals were randomized to one of five EES doses: 0 (control), 0.3, 1, 3, and 5 mg/kg, administered postinjury. Subjects received no resuscitation and were observed for 6 hours or until death. Survival data were analyzed using Cox-proportional hazard regression. Left ventricular pressure-volume loops were used to derive preload recruitable stroke work as a measure of cardiac inotropy. Immediate postinjury preload recruitable stroke work values were compared with values at 1 hour post-drug administration. RESULTS: Six-hour survival for the 0, 0.3, 1, 3, and 5 mg/kg groups was 0%, 50%, 33.3%, 16.7%, and 0%, respectively. Following Cox regression, the hazard (95% confidence interval) of death was significantly reduced in the 0.3 (0.22 [0.05-0.93]) and 1 (0.24 [0.06-0.89]) mg/kg groups but not the 3 (0.49 [0.15-1.64]) and 5 (0.46 [0.14-1.47]) mg/kg groups. Mean survival time was significantly extended in the 1 mg/kg group (246 minutes) versus the 0 mg/kg group (96 minutes) (p = 0.04, t test). At 1 hour post-drug administration, inotropy was significantly higher than postinjury values in the 0.3 and 1 mg/kg groups (p = 0.003 and p < 0.001, respectively). Inotropy was unchanged in the 3 and 5 mg/kg groups but significantly depressed in the control (p = 0.022). CONCLUSION: Administration of EES even in the absence of fluid resuscitation reduces mortality and improves cardiac inotropy in a clinically relevant swine model of multiple injuries and hemorrhage. These findings support the need for a clinical trial in human trauma patients.

In-hospital outcomes in autogenous vein versus synthetic graft interposition for traumatic arterial injury: A propensity-matched cohort from PROOVIT.

BACKGROUND: The ideal conduit for traumatic arterial repair is controversial. Autologous vein was compared with synthetic interposition grafts in the acute setting. The primary outcome was in-hospital reoperation or endovascular intervention. METHODS: The American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment registry from November 2013 to January 2019 was queried for arterial injuries requiring interposition vein or graft repair. Patients with no recorded Injury Severity Score were excluded, and multiple imputation was used for other missing data. Patients treated with synthetic grafts (SGs) were propensity matched to patients with vein grafts (VGs) to account for preoperative differences. RESULTS: Four hundred sixty from 19 institutions were identified, with 402 undergoing VG and 58 SG. In the SG group, 45 were PTFE grafts, 5 were Dacron, and 8 had other conduits. The SG group was more severely injured at admission with more gunshot wounds and higher mean Injury Severity Score, lactate, and first-24-hour transfusion requirement. In addition, the SG cohort had significantly lower admission systolic blood pressure, pH, and hemoglobin. After propensity matching, 51 patients with SG were matched with 87 patients with VG. There were no differences in demographics, clinical parameters, or diagnostic evaluation techniques postmatch. The need for reoperation or endovascular intervention between the matched groups was equivalent (18%; p = 0.8). There was no difference in any secondary outcome including thrombosis, stenosis, pseudoaneurysm, infection, or embolic event, and hospital and intensive care unit length of stay were the same. CONCLUSION: American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment registry data demonstrate that SGs are used in more critically ill patients. After controlling for relevant clinical factors and propensity matching, there is no in-hospital difference in rate of reoperation or endovascular intervention, or any secondary outcome between VG and SG. LEVEL OF EVIDENCE: Prognostic and Epidemiolgic, Level III.

Automatic Hemorrhage Detection From Color Doppler Ultrasound Using a Generative Adversarial Network (GAN)-Based Anomaly Detection Method.

Hemorrhage control has been identified as a priority focus area both for civilian and military populations in the United States because exsanguination is the most common cause of preventable death in hemorrhagic injury. Non-compressible torso hemorrhage (NCTH) has high mortality rate and there are currently no broadly available therapies for NCTH outside of a surgical room environment. Novel therapies, which include High Intensity Focused Ultrasound (HIFU) have emerged as promising methods for hemorrhage control as they can non-invasively cauterize bleeding tissue deep within the body without injuring uninvolved regions. A major challenge in the application of HIFU with color Doppler US guidance is the interpretation and optimization of the blood flow images in real-time to identify the hemorrhagic focus. Today, this task requires an expert sonographer, limiting the utility of this therapy in non-clinical environments. In this work, we investigated the feasibility of an automated hemorrhage detection method using a Generative Adversarial Network (GAN) for anomaly detection that learns a manifold of normal blood flow variability and subsequently identifies anomalous flow patterns that fall outside the learned manifold. As an initial feasibility study, we collected ultrasound color Doppler images of femoral arteries in an animal model of vascular injury (N = 11 pigs). Velocity information of the blood flow were extracted from the color Doppler images that were used for training and testing the anomaly detection network. Normotensive images from 8 pigs were used for training, and testing was performed on normotensive, immediately after injury, 10 minutes post-injury and 30 minutes post-injury images from 3 other pigs. The residual images or the reconstructed error maps show promise in detecting hemorrhages with an AUC of 0.90, 0.87, 0.62 immediately, 10 minutes post-injury and 30 minutes post-injury respectively with an overall AUC of 0.83.

The Cardiac Physiology Underpinning Exsanguination Cardiac Arrest: Targets for Endovascular Resuscitation.

ABSTRACT: Exsanguination leading to cardiac arrest is the terminal phase of uncontrolled hemorrhage. Resuscitative interventions have focused on preload and afterload support. Outcomes remain poor due to several factors but poor coronary perfusion undoubtedly plays a role. The aim of this study is to characterize the relationship between arterial pressure and flow during hemorrhage in an effort to better describe the terminal phases of exsanguination.Male swine weighing 60 kg to 80 kg underwent splenectomy and instrumentation followed by a logarithmic exsanguination until asystole. Changes in hemodynamic parameters over time were compared using one-way, repeated measures analysis of variance.Nine animals weighing 69 ±â€Š15 kg were studied. Asystole occurred at 53 ±â€Š13 min when 52 ±â€Š11% of total blood volume has been shed. The greatest fall in mean hemodynamic indices were noted in the first 15 min: SBP (80-42 mm Hg, P = 0.02), left ventricular end-diastolic volume (94-52 mL, P = 0.04), cardiac output (4.8-2.4 L/min, P = 0.03), coronary perfusion pressure (57-30 mm Hg, P = 0.01), and stroke volume (60-25 mL, P = 0.02). This corresponds to the greatest rate of exsanguination. Organized cardiac activity was observed until asystole without arrythmias. Coronary flow was relatively preserved throughout the study, with a precipitous decline once mean arterial pressure was less than 20 mm Hg, leading to asystole.In this model, initial hemodynamic instability was due to preload failure, with asystole occurring relatively late, secondary to failure of coronary perfusion. Future resuscitative therapies need to directly address coronary perfusion failure if effective attempts are to be made to salvage these patients.

Development of a computed tomography perfusion protocol to support large animal resuscitation research.

BACKGROUND: Adequate cerebral perfusion is crucial for a positive neurological outcome in trauma; however, it is difficult to characterize in the acute setting with noninvasive methods. Intra-arterial computed tomography perfusion may offer a solution. The aim of this study was to develop an intra-arterial computed tomography perfusion protocol for resuscitation research. METHODS: The study examined intra-arterial contrast administration for computed tomography perfusion (CTP) acquisition. It consisted of three phases: intra-arterial contrast dose finding, evaluation of reproducibility, and evaluation during hypotension. Blood pressure and laser Doppler flow data were collected. In phase 1, animals underwent CTPs using several intra-arterial contrast injection protocols. In phase 2, animals underwent two CTPs 7 hours apart using the 2.5 mL/s for 3-second protocol. In phase 3, animals underwent CTPs at several pressures following a computer-controlled bleed including euvolemia and at systolic pressures of 60, 40, and 20 mm Hg. Phase 1 CTPs were evaluated for contrast-to-noise ratio. In phase 2, CTPs were compared within each animal and with laser Doppler flow using linear regression. Phase 3 CTPs were graphed against systolic pressure and fitted with a nonlinear fit. RESULTS: The protocol using 2.5mL/s for 3 seconds was optimal, demonstrating a contrast-to-noise ratio of 40.1 and a superior arterial input function curve compared with the 1 mL/s bolus. Cerebral blood flow demonstrated high concordance between baseline and end of study CTPs (R2 = 0.82, p < 0.001). Cerebral blood flow also compared moderately well against laser Doppler flow during 8 (R2 = 0.53, p = 0.03); however, laser Doppler flow did not perform well during hypovolemia, and the favorable concordance was not maintained (R2 = 0.45, p = 0.06). Cerebral blood flow was graphed against systolic blood pressure and fitted with a nonlinear fit (R2 = 0.95, p = 0.003). CONCLUSION: Computed tomography perfusion using intra-arterial contrast injection may offer a novel alternative to traditional CTP protocols that could prove a useful additional tool in the setting of resuscitation research.

Postoperative complications of endovascular blunt thoracic aortic injury repair.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) has become the standard of care for thoracic aortic aneurysms and increasingly for blunt thoracic aortic injury (BTAI). Postoperative complications, including spinal cord ischemia and paraplegia, have been shown to be less common with elective TEVAR than with open thoracic or thoracoabdominal repair. Although small cohort studies exist, the postoperative complications of endovascular repair of traumatic aortic injury have not been described through large data set analysis. METHODS: A retrospective cohort analysis was performed of the American College of Surgeons Trauma Quality Improvement Program registry spanning from 2007 to 2017. All patients with BTAI who underwent TEVAR, as indicated by the Abbreviated Injury Scale or the International Classification of Diseases (ICD-9 or ICD-10), were included. Categorical data were presented as proportions and continuous data as mean and SD. OR was calculated for each postoperative complication. RESULTS: 2990 patients were identified as having undergone TEVAR for BTAI. The postoperative incidence of stroke was 2.8% (83), and 4.7% (140) of patients suffered acute kidney injury or renal failure. The incidence of spinal cord ischemia was 1.9% (58), whereas 0.2% (7) of patients suffered complete paraplegia. Renal events and stroke were found to occur significantly more frequently in those undergoing TEVAR (OR 1.758, 1.449-2.134 and OR 2.489, 1.917-3.232, respectively). Notably, there was no difference between TEVAR and non-operative BTAI incidences of spinal cord ischemia or paraplegia (OR 1.061, 0.799-1.409 and OR 1.698, 0.728-3.961, respectively). DISCUSSION: Postoperative intensive care unit care of patients after BTAI has historically focused on awareness of spinal cord ischemia. Our analysis suggests that after endovascular repair of blunt aortic trauma, care should involve vigilance primarily against postoperative cerebrovascular and renal events. Further study is warranted to develop guidelines for the intensivist managing patients after TEVAR for BTAI. LEVEL OF EVIDENCE: Level III.