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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.

Skeletal muscle myosin (SkM) molecules are procoagulant both in vitro and in vivo. The association of plasma SkM isoforms with blood coagulability and hemostatic capacity has not been defined.We hypothesized that coagulopathy in acutely injured patients is associated with procoagulant plasma SkM heavy chain levels.To test this hypothesis, citrated whole blood and plasma from 104 trauma patients were collected and studied to obtain data for rapid thrombelastography, international normalized ratios, and plasma SkM levels. Coagulability parameters were dichotomized by the threshold for the hypercoagulable trauma-induced coagulopathy.Lower plasma full-length SkM heavy chain (full-SkM) levels were associated with higher international normalized ratio values (1.3) (p = .03). The full-SkM levels were also associated with a lower rate of clot propagation (thrombelastography angle65°) (p = .004), and plasma full-SkM levels were positively correlated with the thrombelastography angle (rIn acutely injured trauma patients, lower levels of plasma full-SkM levels are linked to hypocoagulability in trauma-induced coagulopathy, implying that SkM plays a role in the hemostatic capacity in trauma patients and may contribute to trauma-induced coagulopathy.

BACKGROUND: Pulmonary vascular microthrombi are a proposed mechanism of COVID-19 respiratory failure. We hypothesized that early administration of tissue plasminogen activator (tPA) followed by therapeutic heparin would improve pulmonary function in these patients. RESEARCH QUESTION: Does tPA improve pulmonary function in severe COVID-19 respiratory failure, and is it safe? STUDY DESIGN AND METHODS: Adults with COVID-19-induced respiratory failure were randomized from May14, 2020 through March 3, 2021, in two phases. Phase 1 (n = 36) comprised a control group (standard-of-care treatment) vs a tPA bolus (50-mg tPA IV bolus followed by 7 days of heparin; goal activated partial thromboplastin time [aPTT], 60-80 s) group. Phase 2 (n = 14) comprised a control group vs a tPA drip (50-mg tPA IV bolus, followed by tPA drip 2 mg/h plus heparin 500 units/h over 24 h, then heparin to maintain aPTT of 60-80 s for 7 days) group. Patients were excluded from enrollment if they had not undergone a neurologic examination or cross-sectional brain imaging within the previous 4.5 h to rule out stroke and potential for hemorrhagic conversion. The primary outcome was Pao2 to Fio2 ratio improvement from baseline at 48 h after randomization. Secondary outcomes included Pao2 to Fio2 ratio improvement of > 50% or Pao2 to Fio2 ratio of ≥ 200 at 48 h (composite outcome), ventilator-free days (VFD), and mortality. RESULTS: Fifty patients were randomized: 17 in the control group and 19 in the tPA bolus group in phase 1 and eight in the control group and six in the tPA drip group in phase 2. No severe bleeding events occurred. In the tPA bolus group, the Pao2 to Fio2 ratio was significantly (P < .017) higher than baseline at 6 through 168 h after randomization; the control group showed no significant improvements. Among patients receiving a tPA bolus, the Pao2 to Fio2 ratio at 48 h (16.9% [interquartile range (IQR), -8.3% to 36.8%] vs 29.8% [IQR, 4.5%-88.7%]; P = .11), the composite outcome (11.8% vs 47.4%; P = .03), VFD (0.0 [IQR, 0.0-9.0] vs 12.0 [IQR, 0.0-19.0]; P = .11), and in-hospital mortality (41.2% vs 21.1%; P = .19) did not reach statistically significant differences when compared with those of control participants. The patients who received a tPA drip did not experience benefit. INTERPRETATION: The combination of tPA bolus plus heparin is safe in severe COVID-19 respiratory failure. A phase 3 study is warranted given the improvements in oxygenation and promising observations in VFD and mortality. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT04357730; URL: www.clinicaltrials.gov.

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 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: Most remote areas have restricted access to healthcare services and are too small andremote to sustain specialist services. In 2017, the World Society of Emergency Surgery (WSES) published guidelines for the management of intra-abdominal infections. Many hospitals, especially those in remote areas, continue to face logistical barriers, leading to an overall poorer adherence to international guidelines. Methods: The aim of this paper is to report and amend the 2017 WSES guidelines for the management of intra-abdominal infections, extending these recommendations for remote areas and low-income countries. A literature search of the PubMed/MEDLINE databases was conducted covering the period up until June 2020. Results: The critical shortages of healthcare workers and material resources in remote areas require the use of a robust triage system. A combination of abdominal signs and symptoms with early warning signs may be used to screen patients needing immediate acute care surgery. A tailored diagnostic step-up approach based on the hospital's resources is recommended. Ultrasound and plain X-ray may be useful diagnostic tools in remote areas. The source of infection should be totally controlled as soon as possible. Conclusions: The cornerstones of effective treatment for intra-abdominal infections in remote areas include early diagnosis, prompt resuscitation, early source control, and appropriate antimicrobial therapy. Standardization in applying the guidelines is mandatory to adequately manage intra-abdominal infections. (c) 2020 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

Highlights • Patients having COVID-19 pneumonia are at risk of venous thromboembolism. • Prophylaxis versus anticoagulation for severely ill patients is currently debated. • No specific guidelines for the management of severe pulmonary embolism exist. • Endovascular pulmonary embolism therapy may play a critical role in severe COVID-19.

Forthcoming article in: Research and Practice in Thrombosis and Haemostatis., Background The COVID‐19 pandemic has caused a large surge of acute respiratory distress syndrome (ARDS). Prior phase I trials (non COVID‐19) demonstrated improvement in pulmonary function in ARDS patients using fibrinolytic therapy. A follow‐up trial using the widely available tissue‐plasminogen activator (alteplase) is now needed to assess optimal dosing and safety in this critically ill patient population. Objective To describe the design and rationale of a Phase IIa trial to evaluate the safety and efficacy of alteplase treatment for moderate/severe COVID‐19‐induced ARDS. Patients/Methods A rapidly adaptive, pragmatic, open label, randomized, controlled, phase IIa clinical trial will be conducted with three groups: intravenous(IV) alteplase 50mg, IV alteplase 100mg, and control (standard‐of‐care). Inclusion criteria are known/suspected COVID‐19 infection with PaO2/FiO2 ratio4 hours despite maximal mechanical ventilation management. Alteplase will be delivered through an initial bolus of 50mg or 100mg followed by heparin infusion for systemic anticoagulation, with alteplase re‐dosing if there is a >20% PaO2/FiO2 improvement not sustained by 24 hours. Results The primary outcome is improvement in PaO2/FiO2 at 48 hours post‐randomization. Other outcomes include: ventilator‐ and ICU‐free‐days, successful extubation (no reintubation ≤3 days after initial extubation), and mortality. Fifity eligible patients will be enrolled in a rapidly adaptive, modified stepped‐wedge design with four looks at the data. Conclusion Findings will provide timely information on the safety, efficacy and optimal dosing of tPA to treat moderate/severe COVID‐19‐induced ARDS, which can be rapidly adapted to a phase III trial., National Institutes of Health (Grant UL1 RR025780)

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.

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.

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: Pulmonary vascular microthrombi have been proposed as a mechanism of COVID19 respiratory failure. We hypothesized that early administration of tissue-plasminogen activator(tPA) followed by therapeutic heparin would improve pulmonary function in these patients. Methods: Adults with COVID-19-induced respiratory failure were randomized May14, 2020-March 3, 2021 in two phases: Phase-1(n=36): control (standard-of-care) vs tPA-Bolus (50mg tPA IV-bolus followed by 7 days of heparin (goal aPTT=60-80s); Phase-2(n=14): control vs tPA-Drip (50 mg of tPA IV-bolus, followed by tPA drip 2mg/hr plus heparin 500U/hour over 24 hours, then heparin to maintain aPTT 60-80s/7 days). The primary outcome was PaO2/FiO2 improvement at 48 hours post-randomization. Secondary outcomes included: PaO2/FiO2 improvement>50% or PaO2/FiO2>=200 at 48hrs(COMPOSITE), ventilator-free days(VFD) and mortality. Findings: Fifty patients were randomized: Phase 1:17 control, 19 tPA-Bolus; Phase 2: 8 control, 6 tPA-Drip. There were no severe bleeding events in intervention groups. In tPA-Bolus patients, PaO2/FiO2 was significantly(p

Background Post-traumatic lung injury following trauma and hemorrhagic shock (T/HS) is associated with significant morbidity. Leukotriene-induced inflammation has been implicated in the development of post-traumatic lung injury through a mechanism that is only partially understood. Postshock mesenteric lymph returning to the systemic circulation is rich in arachidonic acid, the substrate of 5-lipoxygenase (ALOX5). ALOX5 is the rate-limiting enzyme in leukotriene synthesis and, following T/HS, contributes to the development of lung dysfunction. ALOX5 colocalizes with its cofactor, 5-lipoxygenase–activating protein (ALOX5AP), which is thought to potentiate ALOX5 synthetic activity. We hypothesized that T/HS results in the molecular association and nuclear colocalization of ALOX5 and ALOX5AP, which ultimately increases leukotriene production and potentiates lung injury. Materials and methods To examine these molecular interactions, a rat T/HS model was used. Post-T/HS tissue was evaluated for lung injury through both histologic analysis of lung sections and biochemical analysis of bronchoalveolar lavage fluid. Lung tissue was immunostained for ALOX5 and ALOX5AP with association and colocalization evaluated by fluorescence resonance energy transfer. In addition, rats undergoing T/HS were treated with MK-886, a known ALOX5AP inhibitor. Results ALOX5 levels increase and ALOX5/ALOX5AP association occurred after T/HS, as evidenced by increases in total tissue fluorescence and fluorescence resonance energy transfer signal intensity, respectively. These findings coincided with increased leukotriene production and with the histological changes characteristic of lung injury. ALOX5/ALOX5AP complex formation, leukotriene production, and lung injury were decreased after inhibition of ALOX5AP with MK-886. Conclusions These results suggest that the association of ALOX5/ALOX5AP contributes to leukotriene-induced inflammation and predisposes the T/HS animal to lung injury.

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.

Summary Background Plasma is integral to haemostatic resuscitation after injury, but the timing of administration remains controversial. Anticipating approval of lyophilised plasma by the US Food and Drug Administration, the US Department of Defense funded trials of prehospital plasma resuscitation. We investigated use of prehospital plasma during rapid ground rescue of patients with haemorrhagic shock before arrival at an urban level 1 trauma centre. Methods The Control of Major Bleeding After Trauma Trial was a pragmatic, randomised, single-centre trial done at the Denver Health Medical Center (DHMC), which houses the paramedic division for Denver city. Consecutive trauma patients in haemorrhagic shock (defined as systolic blood pressure [SBP] ≤70 mm Hg or 71–90 mm Hg plus heart rate ≥108 beats per min) were assessed for eligibility at the scene of the injury by trained paramedics. Eligible patients were randomly assigned to receive plasma or normal saline (control). Randomisation was achieved by preloading all ambulances with sealed coolers at the start of each shift. Coolers were randomly assigned to groups 1:1 in blocks of 20 according to a schedule generated by the research coordinators. If the coolers contained two units of frozen plasma, they were defrosted in the ambulance and the infusion started. If the coolers contained a dummy load of frozen water, this indicated allocation to the control group and saline was infused. The primary endpoint was mortality within 28 days of injury. Analyses were done in the as-treated population and by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01838863. Findings From April 1, 2014, to March 31, 2017, paramedics randomly assigned 144 patients to study groups. The as-treated analysis included 125 eligible patients, 65 received plasma and 60 received saline. Median age was 33 years (IQR 25–47) and median New Injury Severity Score was 27 (10–38). 70 (56%) patients required blood transfusions within 6 h of injury. The groups were similar at baseline and had similar transport times (plasma group median 19 min [IQR 16–23] vs control 16 min [14–22]). The groups did not differ in mortality at 28 days (15% in the plasma group vs 10% in the control group, p=0·37). In the intention-to-treat analysis, we saw no significant differences between the groups in safety outcomes and adverse events. Due to the consistent lack of differences in the analyses, the study was stopped for futility after 144 of 150 planned enrolments. Interpretation During rapid ground rescue to an urban level 1 trauma centre, use of prehospital plasma was not associated with survival benefit. Blood products might be beneficial in settings with longer transport times, but the financial burden would not be justified in an urban environment with short distances to mature trauma centres. Funding US Department of Defense.

Thrombelastography platelet mapping is a useful assay to assess antiplatelet therapy. Inhibited response to the adenosine diphosphate receptor on platelets occurs early after injury, but recent work suggests this alteration occurs even with minor trauma. However, the utility of thrombelastography platelet mapping, specifically the percent of adenosine diphosphate receptor inhibition, in predicting outcomes and guiding platelet transfusion in trauma-induced coagulopathy remains unknown We assessed the role of percent of adenosine diphosphate-inhibition in predicting survival, requirement for massive transfusion or platelet transfusion in patients at risk for trauma-induced coagulopathy.Thrombelastography platelet mapping was assessed in 303 trauma activation patients from 2014-2016 and in 89 healthy volunteers. Percent of adenosine diphosphate-inhibition is presented as median and interquartile range. We compared the area under the receiver operating characteristic curve of percent of adenosine diphosphate-inhibition, platelet count, and rapid thrombelastography maximum amplitude for in-hospital mortality, massive transfusion (10 red blood cells or death/6 hours), and platelet transfusion (0 platelet units or death/6 hour).Overall, 35 (11.5%) patient died, 27 (8.9%) required massive transfusion and 46, platelet transfusions (15.2%). Median percent of adenosine diphosphate-inhibition was 42.5% (interquartile range: 22.4-69.1%), compared with 4.3 % (interquartile range: 0-13.5%) in healthy volunteers (P .0001). Patients that died, had a massive transfusion, or platelet transfusion had higher percent of adenosine diphosphate-inhibition than those that did not (P .05 for all). However, percent of adenosine diphosphate-inhibition did not add significantly to the predictive performance of maximum amplitude or platelet count for any of the 3 outcomes, after adjustment for confounders. Subgroup analyses by severe traumatic brain injury, severe injury and requirement of red blood cells showed similar results.Adenosine diphosphate receptor inhibition did not add predictive value to predicting mortality, massive transfusion, or platelet transfusion. Thus, the role of thrombelastography platelet mapping as a solitary tool to guide platelet transfusions in trauma requires continued refinement.

Tranexamic acid (TXA) administration after trauma has not been proven to improve survival in the United States. Trauma patients were presented to the hospital with a spectrum of fibrinolytic activity, in which physiological levels of fibrinolysis are associated with the lowest mortality. We hypothesize that trauma patients who present to the hospital with physiological levels of fibrinolysis will have increased mortality if they receive TXA.Severely injured trauma patients, followed prospectively from 2014 to 2016, were included in the analysis. The patient's first thrombelastography was used to stratify patients into fibrinolysis phenotypes which included fibrinolysis shutdown, physiological fibrinolysis, and systemic hyperfibrinolysis. The primary outcome was in-hospital mortality.A total of 232 patients were analyzed (11% received TXA) with an overall mortality rate of 20%. TXA administration was associated with a higher new injury severity score (49 versus 28; P = 0.001), massive transfusion rate (69% versus 12%; P 0.001), and mortality (52% versus 17%; P 0.001). Hyperfibrinolysis and shutdown had higher mortality rates than physiological group (24% versus 30% versus 14%; P = 0.050). The effect of TXA within phenotypes was not significant for shutdown (28% versus 38%; P = 0.604) but was significant in the physiological group (11% versus 63%; P 0.001) and systemic hyperfibrinolysis (19% versus 55%; P = 0.023). After adjusting for new injury severity score, TXA remained a significant predictor of mortality for patients with physiological fibrinolysis (P = 0.018).There was no clear benefit of receiving TXA in this study, and patients who present to the hospital with physiologic levels of fibrinolysis, who received TXA, had the highest mortality. The role of TXA in mature trauma systems remains unclear, and emerging data supports it may have adverse effects.

Background Thrombelastography (TEG) has been used to characterize the coagulation changes associated with injury and shock. Animal models developed to investigate trauma-induced coagulopathy (TIC) have failed to produce excessive bleeding. We hypothesize that a native TEG will demonstrate marked differences in humans compared with these experimental models, which explains the difficulties in reproducing a clinically relevant coagulopathy in animal models. Methods Whole blood was collected from 138 healthy human volunteers, 25 swine and 66 Sprague–Dawley rats before experimentation. Citrated native TEGs were conducted on each whole blood sample within 2 h of collection. The clot initiation (R-time, minutes), angle (degrees), maximum amplitude (MA; millimeter), and lysis 30 min after MA (LY30; percentage) were analyzed and contrasted between species with data represented as the median and 25 th to 75 th quartile range. Difference between species was conducted with a Kruskal–Wallis test with alpha adjusted with a Bonferroni correction for multiple comparisons (alpha = 0.016). Results Median R-time (clot initiation) was 14.65 min (IQR: 13.2-16.3 min) for humans, 5.7 min (4.9-8.8) for pigs, and 5.2 min (4.4-6) for rodents. Humans had longer R-times than both pigs ( P P P = 0.4439). Angle (fibrin cross-linking) was 42.3° (interquartile range [IQR]: 37.5-50.2) for humans, 71.7° (64.3-75.6) for pigs, and 61.8° (56.8-66.7) for rats. Humans had reduced angle compared with both pigs ( P P P = 0.6052). MA (clot strength) was 55.5 mm (IQR: 52.0-59.5) for humans, 72.5 mm (70.4-75.5) for pigs, and 66.5 mm (56.5-68.6) for rats. Humans had reduced MA compared with both pigs ( P P P = 0.0161). LY30 (fibrinolysis) was 1.5% (IQR: 0.975-2.5) for humans, 3.3% (1.9-4.3) for pigs, and 0.5% (0.1-1.2) for rats. Humans had a lesser LY30 than pigs ( P = 0.0062) and a greater LY30 than rats ( P P Conclusions Humans, swine, and rodents have distinctly different coagulation systems, when evaluated by citrated native TEG. Animals are hypercoagulable with rapid clotting times and clots strengths nearly 50% stronger than humans. These coagulation differences indicate the limitations of previous models of trauma-induced coagulopathy in producing coagulation abnormalities associated with increased bleeding. The inherent hypercoagulable baseline tendencies of these animals may result in subclinical biochemical changes that are not detected by conventional TEG and should be taken into consideration when extrapolated to clinical medicine.

The development of organ dysfunction (OD) is related to the intensity and balance between trauma-induced simultaneous, opposite inflammatory responses. Early proinflammation via innate immune system activation may cause early OD, while anti-inflammation, via inhibition of the adaptive immune system and apoptosis, may induce immunoparalysis, impaired healing, infections, and late OD. Patients discharged with low level OD may develop the persistent inflammation-immunosuppression catabolism syndrome (PICS). Although the incidence of multiple organ failure (MOF) has decreased over time, it remains morbid, lethal and resource-intensive. Single OD, especially acute lung injury, however, remains frequent. At this time, treatment is limited, and prevention remains the mainstay strategy.

Background Open pelvic fractures are life-threatening injuries. Preperitoneal pelvic packing (PPP) has been suggested to be ineffective for hemorrhage control in open pelvic fractures. We hypothesize that PPP is effective at hemorrhage control in patients with open pelvic fractures and reduces mortality. Methods Patients undergoing PPP from 2005 to 2015 were analyzed. Patients with open pelvic fractures were defined as direct communication of the bony injury with overlying soft tissue, vagina, or rectum. Results During the 10-year study, 126 patients underwent PPP; 14 (11%) sustained an open pelvic fracture. After PPP, 1 patient (7%) underwent angioembolization with a documented arterial blush. PPP controlled pelvic hemorrhage in all patients. Overall mortality rate was 7% with one death due to traumatic brain injury. Conclusions PPP is effective for hemorrhage control in patients with open pelvic fractures. PPP should be used in a standard protocol for hemodynamically unstable patients with pelvic fractures regardless of associated perineal injuries.

Background We implemented expanded screening criteria for blunt cerebrovascular injuries (BCVIs) in an attempt to capture the remaining 20% of patients not historically identified with earlier protocols. We hypothesized that these expanded criteria would capture the additional 20% of BCVI patients not previously identified. Methods Screening criteria for BCVI were expanded in 2011 after identifying new injury patterns. The study population included 4 years prior (2007 to 2010; classic) and following (2011 to 2014; expanded) implementation of expanded criteria. Results BCVIs were identified in 386 patients: 150 during the classic period (2.36% incidence) and 236 in the expanded period (2.99% incidence). In the expanded period, 155 patients were imaged based on classic screening criteria, 62 on expanded criteria (21 complex skull fractures, 20 upper rib fractures, 6 mandible fractures, 2 scalp degloving, 1 great vessel injury, and 12 combination), and 19 for other injuries and symptoms. Conclusions There was a significant increase in the identification of BCVI following the adoption of expanded screening criteria, resulting in a substantial reduction of missed injuries. Expanded criteria should be adopted when screening for BCVI.

Summary Background Systemic hyperfibrinolysis is a lethal phenotype of trauma-induced coagulopathy. Its pathogenesis is poorly understood. Recent studies have support a central role of platelets in hemostasis and in fibrinolysis regulation, implying that platelet impairment is integral to the development of postinjury systemic hyperfibrinolysis. Objective The objective of this study was to identify if platelet function is associated with blood clot sensitivity to fibrinolysis. We hypothesize that platelet impairment of the ADP pathway correlates with fibrinolysis sensitivity in trauma patients. Methods A prospective observational study of patients meeting the criteria for the highest level of activation at an urban trauma center was performed. Viscoelastic parameters associated with platelet function (maximum amplitude [MA]) were measured with native thrombelastography (TEG), and TEG platelet mapping of the ADP pathway (ADP-MA). The contribution of fibrinogen to clotting was measured with TEG (angle) and the TEG functional fibrinogen (FF) assay (FF-MA). Another TEG assay containing tissue-type plasminogen activator (t-PA) (75 ng mL−1) was used to assess clot sensitivity to an exogenous fibrinolytic stimulus by use of the TEG lysis at 30 min (LY30) variable. Multivariate linear regression was used to identify which TEG variable correlated with t-PA-LY30 (quantification of fibrinolysis sensitivity). Results Fifty-eight trauma patients were included in the analysis, with a median injury severity score of 17 and a base deficit of 6 mEq L−1. TEG parameters that significantly predicted t-PA-LY30 were related to platelet function (ADP-MA, P = 0.001; MA, P < 0.001) but not to fibrinogen (FF-MA, P = 0.773; angle, P = 0.083). Clinical predictors of platelet ADP impairment included calcium level (P = 0.001), base deficit (P = 0.001), and injury severity (P = 0.001). Results and Conclusions Platelet impairment of the ADP pathway is associated with increased sensitivity to t-PA. ADP pathway inhibition in platelets may be an early step in the pathogenesis of systemic hyperfibrinolysis.

Introduction Systemic hyperfibrinolysis (accelerated clot degradation) and fibrinolysis shutdown (impaired clot degradation) are associated with increased mortality compared with physiologic fibrinolysis after trauma. Animal models have not reproduced these changes. We hypothesize rodents have a shutdown phenotype that require an exogenous profibrinolytic to differentiate mechanisms that promote or inhibit fibrinolysis. Methods Fibrinolysis resistance was assessed by thrombelastography (TEG) using exogenous tissue plasminogen activator (tPA) titrations in whole blood. There were 3 experimental groups: (1) tissue injury (laparotomy/bowel crush), (2) shock (hemorrhage to mean arterial pressure of 20 mmHg), and (3) control (arterial cannulation and tracheostomy). Baseline and 30-minute postintervention blood samples were collected, and assayed with TEG challenged with taurocholic acid (TUCA). Results Rats were resistant to exogenous tPA; the percent clot remaining 30 minutes after maximum amplitude (CL30) at 150 ng/mL ( P = .511) and 300 ng/mL ( P = .931) was similar to baseline, whereas 600 ng/mL ( P = .046) provoked fibrinolysis. Using the TUCA challenge, the percent change in CL30 from baseline was increased in tissue injury compared with control ( P = .048.), whereas CL30 decreased in shock versus control ( P = .048). tPA increased in the shock group compared with tissue injury ( P = .009) and control ( P = .012). Conclusion Rats have an innate fibrinolysis shutdown phenotype. The TEG TUCA challenge is capable of differentiating changes in clot stability with rats undergoing different procedures. Tissue injury inhibits fibrinolysis, whereas shock promotes tPA-mediated fibrinolysis.

Background Thrombelastography (TEG) is a viscoelastic hemostatic assay. We have observed that end-stage renal disease (ESRD) and trauma-induced coagulopathy (TIC) produce distinctive TEG tracings. We hypothesized that rigorously definable TEG patterns could discriminate between healthy controls and patients with ESRD and TIC. Methods TEG was performed on blood from ESRD patients (n = 54) and blood from trauma patients requiring a massive blood transfusion (n = 16). Plots of independent TEG parameters were analyzed for patterns coupled to disease state, compared with controls. Decision trees for taxonomic classification were then built using the “R-Project” statistical software. Results Minimally overlapping clusters of TEG results were observed for the three patient groups when coordinate pairs of maximum amplitude (MA) and TEG-activated clotting time (ACT) were plotted on orthogonal axes. Based on these groupings, a taxonomical classification tree was constructed using MA and TEG ACT. Branch points were set at an ACT of 103 s, and these branches subdivided for MA at 60.8 mm for the high ACT branch and 72.6 mm for the low ACT branch, providing a correct classification rate of 93.4%. Conclusions ESRD and TIC demonstrate distinct TEG patterns. The coagulopathy of ESRD is typified by a prolonged enzymatic phase of clot formation, with normal-to-elevated final clot strength. Conversely, TIC is typified by prolonged clot formation and weakened clot strength. Our taxonomic categorization constitutes a rigorous system for the algorithmic interpretation of TEG based on cluster analysis. This will form the basis for clinical decision support software for viscoelastic hemostatic assays.

Background Up to 25% of severely injured patients develop trauma-induced coagulopathy. To study interventions for this vulnerable population for whom consent cannot be obtained easily, the Food and Drug Administration issued regulations for emergency research with an exception from informed consent (ER-EIC). We describe the community consultation and public disclosure (CC/PD) process in preparation for an ER-EIC study, namely the Control Of Major Bleeding After Trauma (COMBAT) study. Methods The CC/PD was guided by the four bioethical principles. We used a multimedia approach, including one-way communications (newspaper ads, brochures, television, radio, and web) and two-way communications (interactive in-person presentations at community meetings, printed and online feedback forms) to reach the trials catchment area (Denver County's population: 643,000 and the Denver larger metro area where commuters reside: 2.9 million). Particular attention was given to special-interests groups (eg, Jehovah Witnesses, homeless) and to Spanish-speaking communities (brochures and presentations in Spanish). Opt-out materials were available during on-site presentations or via the COMBAT study website. Results A total of 227 community organizations were contacted. Brochures were distributed to 11 medical clinics and 3 homeless shelters. The multimedia campaign had the potential to reach an estimated audience of 1.5 million individuals in large metro Denver area, the majority via one-way communication and 1900 in two-way communications. This resource intensive process cost more than $84,000. Conclusion The CC/PD process is resource-intensive, costly, and complex. Although the multimedia CC/PD reached a large audience, the effectiveness of this process remains elusive. The templates can be helpful to similar ER-EIC studies.

Proteomics has identified potential pathways involved in platelet storage lesions, which correlate with untoward effects in the recipient, including febrile non-haemolytic reactions. We hypothesize that an additional pathway involves protein mediators that accumulate in the platelet supernatants during routine storage in a donor gender-specific fashion. Apheresis platelet concentrates were collected from 5 healthy males and 5 females and routinely stored. The 14 most abundant plasma proteins were removed and the supernatant proteins from days 1 and 5 were analyzed via 1D-SDS-PAGE/nanoLC-MS/MS, before label-free quantitative proteomics analyses. Findings from a subset of 18 proteins were validated via LC-SRM analyses against stable isotope labeled standards. A total of 503 distinct proteins were detected in the platelet supernatants from the 4 sample groups: female or male donor platelets, either at storage day 1 or 5. Proteomics suggested a storage and gender-dependent impairment of blood coagulation mediators, pro-inflammatory complement components and cytokines, energy and redox metabolic enzymes. The supernatants from female donors demonstrated increased deregulation of structural proteins, extracellular matrix proteins and focal adhesion proteins, possibly indicating storage-dependent platelet activation. Routine storage of platelet concentrates induces changes in the supernatant proteome, which may have effects on the transfused patient, some of which are related to donor gender. Biological significance The rationale behind this study is that protein components in platelet releasates have been increasingly observed to play a key role in adverse events and impaired homeostasis in transfused recipients. In this view, proteomics has recently emerged as a functional tool to address the issue of protein composition of platelet releasates from buffy coat-derived platelet concentrates in the blood bank. Despite early encouraging studies on buffy coat-derived platelet concentrates, platelet releasates from apheresis platelets have not been hitherto addressed by means of extensive proteomics technologies. Indeed, apheresis platelets are resuspended in donors' plasma, which hampers detection of less abundant proteins, owing to the overwhelming abundance of albumin (and a handful of other proteins), and the dynamic range of protein concentrations of plasma proteins. In order to cope with these issues, we hereby performed an immuno-affinity column-based depletion of the 14 most abundant plasma proteins. Samples were thus assayed via GeLC-MS, a workflow that allowed us to cover an unprecedented portion of the platelet supernatant proteome, in comparison to previous transfusion medicine-oriented studies in the literature. Finally, we hereby address the issue of biological variability, by considering the donor gender as a key factor influencing the composition of apheresis platelet supernatants. As a result, we could conclude that platelet supernatants from male and female donors are not only different in the first place, but they also store differently. This conclusion has been so far only suggested by classic transfusion medicine studies, but has been hitherto unsupported by actual biochemistry/proteomics investigations. In our opinion, the main strengths of this study are related to the analytical workflow (immunodepletion and GeLC-MS) and proteome coverage, the translational validity of the results (from a transfusion medicine standpoint) and the biological conclusion about the intrinsic (and storage-dependent) gender-related differences of platelet supernatants.

Postinjury abdominal compartment syndrome (ACS) is an example of a deadly clinical occurrence that was eliminated by strategic research and focused preventions. In the 1990s, the syndrome emerged with the widespread use of damage control surgery and aggressive crystalloid-based resuscitation. Patients who previously exsanguinated on the operating table made it to intensive care units, but then developed highly lethal hyperacute respiratory, renal, and cardiac failure due to increased abdominal pressure. Among many factors, delayed haemorrhage control and preload driven excessive use of crystalloid resuscitation were identified as modifiable predictors. The surrogate effect of preventive strategies, including the challenge of the 40-year-old standard of large volume crystalloid resuscitation for traumatic shock, greatly reduced cases of ACS. The discoveries were rapidly translated to civilian and military trauma surgical practices and fundamentally changed the way trauma patients are resuscitated today with substantially improved outcomes.

BackgroundThe optimal time to initiate venous thromboembolism pharmacoprophylaxis after blunt abdominal solid organ injury is unknown.MethodsPostinjury coagulation status was characterized using thromboelastography (TEG) in trauma patients with blunt abdominal solid organ injuries; TEG was divided into 12-hour intervals up to 72 hours.ResultsForty-two of 304 patients (13.8%) identified underwent multiple postinjury thromboelastographic studies. Age (P = .45), gender (P = .45), and solid organ injury grade (P = .71) were similar between TEG and non-TEG patients. TEG patients had higher Injury Severity Scores compared with non-TEG patients (33.2 vs 18.3, respectively, P < .01). Among the TEG patients, the shear elastic modulus strength and maximum amplitude values began in the normal range within the first 12-hour interval after injury, increased linearly, and crossed into the hypercoagulable range at 48 hours (15.1 ± 1.9 Kd/cs and 57.6 ± 1.6 mm, respectively; P < .01, analysis of variance).ConclusionsPatients sustaining blunt abdominal solid organ injuries transition to a hypercoagulable state approximately 48 hours after injury. In the absence of contraindications, pharmacoprophylaxis should be considered before this time for effective venous thromboembolism prevention.

A child's risk of developing cancer from radiation exposure associated with computed tomography (CT) imaging is estimated to be as high as 1/500. Chest CT (CCT), often as part of a "pan-scan," is increasingly performed after blunt trauma in children. We hypothesized that routine CCT for the initial evaluation of blunt injured children does not add clinically useful information beyond chest radiograph (CXR) and rarely changes management.Pediatric (15 y) trauma team evaluations over 6 y at an academic Level I trauma center were reviewed. Demographic data, injuries, imaging, and management were identified for all patients undergoing CT. Effective radiation dose in milliSieverts (mSv) was calculated using age-adjusted scales.Fifty-seven of 174 children (33%) undergoing CT imaging had a CCT; 55 (97%) of these had a CXR. Pathology was identified in significantly fewer CXRs compared with CCTs (51% versus 83%, P0.001). All 7/57 (12%) emergent or urgent chest interventions were based on information from CXR. In 53 children (93%), the CCT was ordered as part of a pan-scan, resulting in a radiation dose of 37.69 ± 7.80 mSv from initial CT scans. Radiation dose was significantly greater from CCT than from CXR (8.7 ± 1.1 mSv versus 0.017 ± 0.002 mSv, P0.001).Clinically useful information found on CCT had good correlation to information obtained from CXR and did not change patient management, however, did add significantly to the radiation exposure of initial imaging. We recommend selective use of CCT, particularly in the presence of an abnormal mediastinal silhouette on CXR after a significant deceleration injury.

Intense debate continues in the search of the optimal ratio of blood components to deliver preemptively in the critically injured patient anticipated to require a massive transfusion. A major challenge is distinguishing patients with refractory coagulopathy versus those with overwhelming injuries who will perish irrespective of blood component administration. The hypothesis of this clinical study is that a predominant number of early deaths from hemorrhage are irretrievable despite an aggressive transfusion policy.During the 7-y period ending in December 2009, there were 772 in-hospital trauma deaths. Each of these deaths had been assigned a cause of death via concurrent review by the multidisciplinary hospital trauma quality improvement committee. Emergency department deaths and patients arriving from outside facilities were excluded from this study.Of the 382 patients (49.5% of total) who died secondary to acute blood loss, 84 (22.0%) survived beyond the ED; of these 84, 68 (81%) were male, mean age was 31 y, and 30 (36%) sustained blunt trauma. Cause of death was determined to be exsanguination in 63 (75%), coagulopathy in 13 (15%), metabolic failure in 5 (6%), and indeterminate in 3 patients (4%).These data indicate that 75% of patients who succumb to postinjury acute blood loss are bleeding because they are dying rather than dying because they are bleeding. Conversely, only 13 (2%) of the hospital deaths were attributed to refractory coagulopathy. These critical facts need to be considered in designing studies to determine optimal massive transfusion protocols.

Nearly all critically ill surgical patients are anemic within 72 hours of intensive care unit (ICU) admission.1 Although most anemic ICU patients receive a packed red blood cell (pRBC) transfusion, such transfusions are associated independently with worse outcomes and have been shown to afford questionable benefit in terms of oxygen consumption.2 Many of the adverse effects of pRBC transfusions are believed to be the result of a storage lesion, which is characterized by time-dependent accumulation of inflammatory mediators as well as depletion of essential nutrients such as adenosine triphosphate and 2,3-diphosphoglycerate. Storage of pRBCs also impairs both erythrocyte deformability and oxygen offloading, as well as results in time-dependent hemolysis.3 Based on these experimental findings, we sought to investigate the relationship between the age of transfused blood and the resultant change in recipient hematocrit level among critically ill surgical patients. Because the primary goal of pRBC transfusion is to increase oxygen delivery via an increase in the hematocrit level, this relationship is of clinical relevance. However, despite numerous investigations concerning the adverse effects of the storage lesion, the specific relationship between age of blood and change in hematocrit level has not been investigated among critically ill patients. The hypothesis of this study was that transfusion of older blood, as compared with newer blood, results in a lesser increment in the hematocrit level. Furthermore, to assess the clinical relevance of the increment in hematocrit, we hypothesized that a lesser increment in post-transfusion hematocrit level would be associated with the need for a subsequent pRBC transfusion.

Background/Purpose Early postinjury death after packed red blood cell (pRBC) transfusion is attributed to uncontrolled hemorrhage and coagulopathy. The adverse immunomodulatory effects of blood transfusion are implicated in subsequent morbidity. We hypothesized that injured children requiring pRBC transfusion demonstrate patterns in outcome similar to those observed in adults. Methods Our prospectively collected trauma registry was queried for demographics, treatment, and outcome (2006-2009). Outcomes of children who received pRBC transfusion were compared with those of age- and Injury Severity Score (ISS)–matched children who did not receive pRBC transfusion by both univariate and multivariable analysis. Results Eight percent (43/512) of injured children received a pRBC transfusion: 20 early and 23 late. The likelihood of pRBC transfusion increased with increasing ISS (ISS 25, 72%). One-half of injured children who received an early pRBC transfusion died; however, most deaths were because of central nervous system injury. Both ventilator and intensive care unit days were increased in children who received pRBC transfusion as compared with those who did not. Conclusion Early pRBC transfusion is associated with a high mortality in children. Late blood transfusion is associated with worse outcomes, although this relationship may not be causal. This pilot study provides evidence of an association between pRBC transfusion, morbidity, and mortality among injured children that warrants refinement in larger, prospective investigations.

Arachidonic acid (AA, and its leukotriene derivatives, e.g., LTB(4)) is an inflammatory mediator in post-shock mesenteric lymph that appears to act as an agonist on G-protein coupled receptors (GPCRs). These mediators prime neutrophils (PMNs) for an increased production of superoxide, implicated in the development of acute lung injury (ALI). Hypertonic saline (HTS) has also been shown to have immunomodulatory effects such as attenuation of PMN priming by precluding appropriate clathrin-mediated endocytosis of activated GPCRs, thereby potentially attenuating ALI. We hypothesize that HTS inhibits priming of the PMN oxidase by these lipid mediators.After PMNs were isolated from healthy donors, incubation was done in either isotonic buffer (control) or HTS (180 mmol/L) for 5 min at 37°C. The PMNs were then primed for 10 min with AA [5 μM] or 5 min with LTB(4) [1 μM] and the oxidase was activated with 200 ng/mL of phorbol 12-myristate 13-acetate (PMA), a non-GPCR activator, and superoxide anion generation was measured via reduction of cytochrome c.Both AA [5 μM] and LTB(4) [1 μM] significantly primed the PMA activated respiratory burst (P 0.05, ANOVA, Newman-Keuls, n = 4). HTS inhibited both AA and LTB(4) priming of the respiratory burst.These data indicate that HTS reduces the cytotoxicity of PMNs stimulated by these lipid mediators in vitro and further support the immunomodulatory effects of HTS.

The acute coagulopathy of trauma is multifactorial, but generally believed to be aggravated by coexisting acidosis, hypothermia, and hemodilution. While acidosis and hypothermia have been extensively evaluated, there is a paucity of data on the independent role of hemodilution in this scenario. We therefore hypothesized that hemodilution will impair coagulation following experimental trauma and hemorrhagic shock.Adult male Spraque-Dawley rats underwent trauma and hemorrhagic shock, followed by resuscitation with 2 × SBV using normal saline (NS). Thrombelastography (TEG) was performed before and after shock.In this trauma model, resuscitation resulted in a hemodilution of 50% (43% ± 4.05% versus 19.8% ± 3.96% Hct pre-shock versus post-shock , P0.0001). Despite the substantial hemodilution, there was no significant change in clot strength (12.96 ± 2.84 versus 11.79 ± 1.28 dynes/cm(2) G pre-shock versus post-shock, P = 0.13). Similarly, the onset of coagulation (R time) was not impaired (1.68 ± 1.74 s versus 1.75 ± 0.63 s R time pre-shock versus post-shock, P = 0.45).In the absence of hypothermia and acidosis, hemodilution (≤ 50%) has a trivial effect on coagulation following trauma and hemorrhagic shock. These data call to question the commonly held belief that hemodilution per se is critical in the development of post-injury coagulopathy.

Postinjury multiple organ failure (MOF) is the net result of a dysfunctional immune response to injury characterized by a hyperactive innate system and a suppressed adaptive system. Acute lung injury (ALI) is the first clinical manifestation of organ failure, followed by renal and hepatic dysfunction. Circulatory shock is integral in the early pathogenesis of MOF, and the gut has been invoked as the motor of MOF. Mesenteric lymph is recognized as the mechanistic link between splanchnic ischemia/reperfusion and distant organ dysfunction, but the specific mediators remain to be defined. Current evidence suggests the lipid fraction of postshock mesenteric lymph is central in the etiology of ALI. Specifically, our recent work suggests that intestinal phospholipase A2 generated arachidonic acid and its subsequent 5-lipoxygenase products are essential in the pathogenesis of ALI. Proteins conveyed via postshock mesenteric lymph also may have an important role. Elucidating these mediators and the timing of their participation in pulmonary inflammation is critical in translating our current knowledge to new therapeutic strategies at the bedside.

Background Guidelines of the National Kidney Foundation recommending aggressive pursuit of autogenous fistulae for dialysis access in lieu of prosthetic arteriovenous grafts have stimulated a renewed interest in transposed brachial-basilic fistulae as an alternative technique for upper arm access in patients who may not be candidates for a lower arm radial-cephalic or forearm brachial-cephalic fistula. We hypothesized that in our safety-net population, where radial-cephalic and brachial-cephalic often are not possible, brachial-basilic would provide patency rates superior to arteriovenous grafts and equivalent to radial-cephalic and brachial-cephalic fistulae. Methods We analyzed retrospectively our most recent 2.5-year experience with dialysis access procedures at our metropolitan safety-net hospital. Procedures were grouped as follows: radial-cephalic, brachial-cephalic, brachial-basilic, and arteriovenous grafts. The access outcomes measured were primary failure, time to use, need for intervention, and primary as well as secondary patency. Differences in age, sex, race, renal function (Modification of Diet in Renal Disease), baseline diagnoses (diabetes mellitus, hypertension, coronary artery disease, and peripheral vascular disease), as well as the number of previous accesses, were adjusted in the analysis. Logistic regression was used to identify independent predictors of primary failure, and Kaplan-Meier plots assessed differences in primary patency rates. A log of the time variables was used to approximate normal distribution. Results In all, 193 patients were included in this study as follows: radial-cephalic, 75 (39%) patients; brachial-cephalic, 35 (18%) patients; brachial-basilic, 33 (17%) patients; and arteriovenous grafts, 50 (26%) patients. Primary patency means differed marginally between groups ( P = .08), and when grafts were excluded from the analysis, no difference was found between primary patency in all autogenous fistula techniques ( P = .88). Kaplan-Meier plots showed that when analyzing the first 35 weeks, a significantly lower primary patency among graft recipients early after the procedure was noted, and a higher performance of BB after 20 weeks was noted (log-rank P = .05, Wilcoxon P = .004). Furthermore, secondary patency did not vary significantly between groups ( P = .62). Radial-cephalic were more likely to fail primarily when compared with the other access groups ( P = .03), and in a univariate analysis, underlying hypertension was associated with a lower risk of primary failure ( P = .01) compared with other diagnoses. A logistic regression stepwise selection showed that the underlying diagnoses of peripheral vascular disease, diabetes mellitus, or coronary artery disease were associated with a greater risk of primary failure compared with those with HTN ( P = .001; odds ratio, 4.05; 95% confidence interval, 1.71–9.59), as well as the presence of a previously failed access ( P = .04; odds ratio, 2.39; 95% confidence interval, 1.08–5.67). Conclusion In a safety-net population, our results suggest that 2-stage brachial-basilic transposition fistulae provide patency rates equivalent to brachial-cephalic and radial-cephalic fistulae and superior to grafts. Although 2 procedures are required, brachial-basilic fistulae provide a reliable access and should be considered the next choice when radial-cephalic and/or brachial-cephalic are not possible.

BACKGROUND: Life-threatening hemorrhage is a rare event in hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. Epidemiologic data are lacking to predict patients at risk for hemorrhage requiring surgical consultation. We sought to identify early clinical predictors of hemorrhagic complications in patients at risk for HELLP syndrome. METHODS: Patients at risk for HELLP syndrome from 1997 to 2007 were identified retrospectively. Variables evaluated in at-risk women were maternal age, gestational history, hepatic transaminase levels, and platelet count. Multiple logistic regression analysis was used to identify independent predictors of poor maternal outcomes, which were defined as hemorrhage requiring transfusion of blood products, need for surgical intervention, hepatic rupture, and death. RESULTS: A total of 109 at-risk women were identified. Adverse outcomes included transfusions (18%), hemorrhage interventions (8%), damage control laparotomy (2.8%), and hepatic rupture (2.8%). Maternal and perinatal mortality were .9% and 3.7%, respectively. Median transfusion requirements for women with hepatic rupture were 56 U of packed red blood cells, 26 U of fresh-frozen plasma, 18 U of platelets, and 6 U of cryoprecipitate. Multiple logistic regression analysis showed previous gestations (P = .002), platelet count (P = .01), and aspartate aminotransferase level increase (P = .04) were independent predictors of life-threatening hemorrhage. Previous gestations increased the risk of adverse outcome 3-fold. CONCLUSIONS: Identifiable risk factors predictive of major hemorrhage are thrombocytopenia (< 100,000 cells/μL), increase of aspartate aminotransferase level greater than 70 IU/L, and previous gestations.

Postinjury multiple organ failure (MOF) became prevalent as the improvements in critical care during the 1970s made it possible to keep trauma patients alive with single organ injury. Enormous efforts invested in laboratory and clinical research made it possible to better understand the epidemiology and pathophysiology of the syndrome. This has translated to improved strategies in prediction, prevention and treatment of MOF. With changes in population demographics and injury mechanisms and improvements in trauma care, changes in the epidemiology of MOF are also becoming evident. Significant improvements in trauma patient management decreased the severity and mortality of MOF, but the syndrome still remains the most significant contributor of late postinjury mortality and intensive care unit resource utilisation. This review defines the essential MOF-related terminology, summarises the changing epidemiology of MOF, describes our current understanding of the pathophysiology, discusses the available strategies for prevention/treatment based on the identified independent predictors and provides future directions for research.

Introduction. Progressive postinjury coagulopathy has become the fundamental rationale for damage control surgery, and the decision to abort operative intervention must occur prior to overt laboratory confirmation of coagulopathy. Current coagulation testing is most commonly performed for monitoring anticoagulation therapy, the results are delayed, and the applicability of these tests in the trauma setting is questionable. Point-of-care (POC) rapid thrombelastography (r-TEG) provides real time analysis of thrombostatic function, which may allow for accurate, goal directed therapy. The test differs from standard thrombelastography (TEG) because the clotting process and subsequent analysis is accelerated by the addition of tissue factor to the whole blood sample, but is limited by the requirement that the analysis be performed within 4 min of blood draw to prevent clot formation. Consequently, citrated specimens have been proposed to obviate this time limitation. We hypothesized that the speed of r-TEG analysis following tissue factor addition to citrated blood might compromise accurate determinations compared with noncitrated whole blood. Additionally, we sought to compare the use of r-TEG with conventional coagulation tests in analysis of postinjury coagulopathy. Methods. We conducted a retrospective study of severely injured patients entered into our trauma database between January and June 2008 who were at risk for postinjury coagulopathy. Patients needed simultaneous conventional coagulation (INR, fibrinogen, platelet count) and r-TEG specimens with either fresh or citrated whole blood for inclusion in the study. κ-Statistics were used to determine the agreement between the tests in predicting hypocoagulability. McNemar's x 2 tests were used to compare theoretical blood product administration between r-TEG and conventional coagulation tests for noncitrated specimens. Therapeutic transfusion triggers were: INR ( >1.5) and r-TEG ACT ( > 125 s) for FFP administration; fibrinogen (

Background Recent guidelines do not support local wound exploration (LWE) or diagnostic peritoneal lavage (DPL) in the evaluation of patients with anterior abdominal stab wounds (AASWs), favoring computed tomography scanning or serial examinations. In patients without immediate indications for laparotomy, we hypothesized that LWE/DPL would identify patients requiring surgery while limiting unnecessary hospital admissions. Methods Patients sustaining penetrating trauma at our level I trauma center over a 3-year period were reviewed. Results During the study period, 139 patients with AASW followed our LWE/DPL algorithm. Fifty-six patients had LWE without fascial penetration: 46 were discharged immediately, 10 required admission. Fifty-eight patients had fascial penetration on LWE but negative DPL: 37 were observed for less than 24 hours, 19 were observed for more than 24 hours, and 2 patients developed peritonitis requiring exploration. Twenty-five patients had positive LWE/DPL: 13 had therapeutic laparotomy, 12 had nontherapeutic laparotomy. Conclusions Only 11% of patients with AASWs without overt indication for laparotomy require surgical care. LWE remains a valid method to exclude intra-abdominal injury and to eliminate hospitalization in more than one third of AASW patients.

Human polymerized hemoglobin (PolyHeme) is a universally compatible oxygen carrier developed for use when red blood cells are unavailable and oxygen-carrying replacement is needed to treat life-threatening anemia. This multicenter phase III trial assessed survival of patients resuscitated with a hemoglobin-based oxygen carrier starting at the scene of injury. Patients resuscitated with PolyHeme had outcomes comparable to those receiving the standard of care including rapid access to stored red blood cells. Although there were more adverse events in the PolyHeme group compared with control patients receiving blood, the observed safety profile is acceptable for the intended population. The benefit-to-risk ratio of PolyHeme is favorable when blood is needed but is not available or an option.