Trauma and Acute Care Surgery

Unfractionated heparin attenuates histone-mediated cytotoxicity in vitro and prevents intestinal microcirculatory dysfunction in histone-infused rats Abstract: Background Extracellular histones are major mediators of organ dysfunction and death in sepsis, and they may cause microcirculatory dysfunction. Heparins have beneficial effects in sepsis and have been reported to bind to histones and neutralize their cytotoxicity. The aim of this study was to investigate the impact of histones on intestinal microcirculation and the intestinal endothelium and to discuss the protective effect of unfractionated heparin (UFH) on the endothelial cytotoxicity and microcirculatory dysfunction induced by histones. Methods Anesthetized rats were infused with 30 mg/kg calf thymus histones, and UFH was administered intravenously at a concentration of 100 IU/kg/hour. The intestinal microcirculation was visualized and measured with incident dark field microscope. Plasma von Willebrand factor (vWF) and soluble thrombomodulin (sTM) were detected, and structural changes in the rat intestinal microvascular endothelium were examined. The effects of histones and UFH on cell survival rates, vWF release and calcium influx were investigated in human intestinal microvascular endothelial cells (HIMECs). Results Histone infusion caused severe intestinal microcirculatory dysfunction in the absence of obvious hemodynamic changes, and UFH protected intestinal microcirculation in histone-infused rats. Concentrations of the plasma endothelial injury markers vWF and sTM were elevated, and structural abnormalities were found in the intestinal microvascular endothelium in the histone-infused rats. These events were attenuated by UFH. In vitro, UFH significantly reduced the histone-induced cytotoxicity of HIMECs, reduced the release of vWF from the cytoplasm into the culture medium, and inhibited calcium influx into HIMECs. Conclusions Histones induce intestinal microcirculatory dysfunction followed by direct injury to the endothelial cells; UFH protects the intestinal microcirculation partly by antagonizing the endothelial toxicity of histones. Level of evidence This is a basic science paper; it does not require a level of evidence. Corresponding author at: Department of Critical Care Medicine, The First Affiliated Hospital, China Medical University, North Nanjing Street 155, Shenyang 110001, Liaoning Province, China. E-mail address:icusubscript@hotmail.com (Xiaochun Ma). Telephone number: 86-13504998906. Fax: 86-24-83282631 Level of Evidence: not applicable (pre-clinical study) Conflicts of Interest: The authors declare that they have no conflict of interest. Funding: The research was supported by the National Nature Science Foundation of China (Grant No.81671936) Meeting presentations: None © 2019 Lippincott Williams & Wilkins, Inc.

The Role of Psychological Support Interventions in Trauma Patients on Mental Health Outcomes: A Systematic Review and Meta-Analysis Background The recovery and rehabilitation of trauma survivors may be long and challenging. Patients may be prone to psychiatric disorders, cognitive impairments, and decreased quality of life. The objective of this review was to determine whether there is a role for psychological interventions in reducing the incidence and severity of psychiatric sequelae in trauma survivors. Methods MEDLINE, PubMed, SCOPUS, and Google Scholar were searched for published articles. We searched for articles published between 1990 and 2018 with adult subjects, and limited our search to articles published in English. Randomized controlled trials that evaluated various psychiatric interventions in trauma patients on the effects of psychiatric outcomes were included for analysis. The articles were independently reviewed for eligibility by two different reviewers. A meta-analysis was performed on nine studies with similar interventions, outcomes measured, and patient populations. Results Nine hundred thirty-four articles were identified [830 articles identified through database search, and 107 through article references]. Sixty-nine full-text articles were reviewed for eligibility. Of these, 33 were included for qualitative analysis. Thirteen studies evaluating the effect of cognitive-behavioral therapy (CBT)-based interventions on the severity of PTSD, anxiety, and depression symptoms underwent meta-analysis. While CBT-treated patients experienced clinically significant decreases in symptom severity, there were no statistically significant differences between treatment and control groups at follow-up for PTSD, anxiety, and depression. Conclusions Compared to usual care, CBT-based interventions may not be effective in decreasing or preventing PTSD, anxiety, or depression symptoms in trauma survivors. Level of Evidence Systematic Review, level III Conflict of Interest: There are no conflicts of interest. Meetings: None Disclosure of Funding: None. Corresponding Author: Catherine M. Kuza, MD, Keck School of Medicine of the University of Southern California, Department of Anesthesiology, 1450 San Pablo Street, Suite 3600, Los Angeles, CA 90033, (323) 442-7400, (323) 442-7411, E-mail: Catherine.kuza@med.usc.edu © 2019 Lippincott Williams & Wilkins, Inc.

Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) Induced Myocardial Injury is Mitigated by Endovascular Variable Aortic Control (EVAC) Background The cardiac effects of resuscitative endovascular balloon occlusion of the aorta (REBOA) are largely unknown. We hypothesized that increased afterload from REBOA would lead to cardiac injury, and that partial flow using endovascular variable aortic control (EVAC) would mitigate this injury. Methods Eighteen anesthetized swine underwent controlled 25% blood volume hemorrhage. Animals were randomized to either Zone 1 REBOA, Zone 1 EVAC, or no intervention (control) for 45 minutes. Animals were then resuscitated with shed blood, observed during critical care, and euthanized after a six-hour total experimental time. Left ventricular function was measured with a pressure-volume catheter and blood samples were drawn at routine intervals. Results The average cardiac output during the intervention period was higher in the REBOA group [9.3 (8.6-15.4) L/min] compared to the EVAC group [7.2 (5.8-8.0) L/min, P=0.01] and the control group [6.8 (5.8-7.7) L/min, P<0.01]. At the end of the intervention, the preload recruitable stroke work (PRSW) was significantly higher in both the REBOA and EVAC groups compared to the control group [111.2 (102.5-148.6) and 116.7 (116.6-141.4) versus 67.1 (62.7-87.9), P=0.02 and P<0.01, respectively]. The higher PRSW was maintained throughout the experiment in the EVAC group, but not in the REBOA group. Serum troponin concentrations after six hours were higher in the REBOA group compared to both the EVAC and control groups (6.26±5.35 ng/mL versus 0.92±0.61 ng/mL and 0.65±0.38 ng/mL, P=0.05 and P=0.03, respectively). Cardiac intramural hemorrhage was higher in the REBOA group compared to the control group (1.67±0.46 vs 0.17±0.18, P=0.03), but not between the EVAC and control groups. Conclusions In a swine model of hemorrhagic shock, complete aortic occlusion resulted in cardiac injury, although there was no direct decrease in cardiac function. EVAC mitigated the cardiac injury and improved cardiac performance during resuscitation and critical care. Level of Evidence not applicable for basic science study Name and address for correspondence: Carl A Beyer, 2315 Stockton Boulevard, Room OP 512, Sacramento, CA 95817, 916-734-2724 | Fax: 916-734-5633, E-mail: cbeyer@ucdavis.edu Disclaimer: The views expressed in this material are those of the authors and do not reflect the official policy of the US Government, the Department of Defense, the Department of the Air Force, the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the University of California Davis, or Wake Forest University. Meetings: Awarded second prize at the 16th biennial Strandness Symposium, March 3-7, 2019, Wailea, HI. © 2019 Lippincott Williams & Wilkins, Inc.

Point-of-care Resuscitation Research: From Extreme to Mainstream: Trauma Association of Canada Fraser Gurd Lecture 2019 The Gurd Family surgical legacy was deeply intertwined with National service in both World Wars. My own personal research mission has attempted to emulate such service, by enhancing the tools and techniques available to facilitate point-of-care (POC) diagnosis and resuscitation in extreme and adverse environments. Our efforts involving POC diagnosis/resuscitation and the telementored guidance of those remotely responding to catastrophic injury have included collaborations with NASA, the Canadian Space Agency, the Canadian Forces, its democratic allies, and non-governmental surgical organizations. Research has been conducted in resuscitative suites and operating theatres, research laboratories, parabolic flight aircraft, on humanitarian surgical missions, and from ski-hills and firehalls. The initial phases of these efforts involved inaugural studies in resuscitative sonography including defining the EFAST examination. Although the original work was commissioned for Space Medicine, generalization to mainstream practice further justifies space medicine research. Iterative steps in advancing telementored resuscitation have subsequently involved the maturation of space mandated telementored ultrasound support (TMUS), exploration of TMUS in terrestrial clinical practice, and the creation of increasingly mobile (hand-held) TMUS solutions. Subsequently it was recognized that tele-ultrasound is simply one informatic dimension of remote telemedicine, and current efforts are focused in a Program known as TeleMentored Ultrasound Supported Medical Interactions (TMUSMI) of remote responders required to intervene with catastrophic trauma. While this research program has yielded many techniques and findings that have benefited mainstream terrestrial practice, these investigations are currently ongoing, and we hope to demonstrate that TMUSMI may benefit all Canadians especially those in remote areas, as well as potentially every global inhabitant without immediate access to care. Further, we propose that to abstract fully utilize these techniques, a new specialty, that of the remote medical mentor will be required, a new specialty that will require the creation and scientific validation of its principles and techniques. Address for Correspondence AW Kirkpatrick Regional Trauma Services EG 23 Foothills Medical Services 1403 29 ST NW Calgary, Alberta T2N 2T9 This manuscript was an invited Podium Presentation at the Annual Scientific Meeting of the Trauma Association of Canada, as the named Fraser Gurd Lecture 2019. Conflict of Interest No funding of any kind was provided to prepare this manuscript. AW Kirkpatrick continues to serve in the Canadian Forces Medical Services. AW Kirkpatrick has consulted for the Acelity and Innovative Trauma Care Corporations. © 2019 Lippincott Williams & Wilkins, Inc.

Ketamine Infusion for Pain Control in Adult Patients with Multiple Rib Fractures No abstract available

Promotility Agents For The Treatment Of Ileus In Adult Surgical Patients: A Practice Management Guideline From The Eastern Association For The Surgery Of Trauma Background Ileus is a common challenge in adult surgical patients with estimated incidence to be 17%-80%. The main mechanisms of the postoperative ileus pathophysiology are fluid overload, exogenous opioids, neurohormonal dysfunction, gastrointestinal stretch and inflammation. Management includes addressing the underlying cause and supportive care. Multiple medical interventions have been proposed, but effectiveness is uncertain. A working group of the Eastern Association for the Surgery of Trauma (EAST) aimed to evaluate the effectiveness of metoclopramide, erythromycin, and early enteral nutrition (EEN) on ileus in adult surgical patients and to develop recommendations applicable in a daily clinical practice. Methods Literature search identified 45 papers appropriate for inclusion. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was applied to evaluate the effect of metoclopramide, erythromycin, and EEN on the resolution of ileus in adult surgical patients based on selected outcomes: return of normal bowel function, attainment of enteral feeding goal, and hospital length of stay (LOS). The recommendations were made based on the results of a systematic review, a meta-analysis, and evaluation of levels of evidence. Results The level of evidence for all PICOs was assessed as low. Neither metoclopramide nor erythromycin were effective in expediting the resolution of ileus. Analyses of 32 randomized controlled trials showed that EEN facilitates return of normal bowel function, achieving enteral nutrition goals, and reducing hospital LOS. Conclusion In patients who have undergone abdominal surgery, we strongly recommend EEN to expedite resolution of Ileus, but we cannot recommend for or against the use of either metoclopramide or erythromycin to hasten the resolution of ileus in these patients. Level of Evidence Level II Type of Study Therapeutic Corresponding Author: Nikolay Bugaev, MD, Division of Trauma & Acute Care Surgery, Tufts Medical Center, Tufts University School of Medicine, Boston, MA, nbugaev@tuftsmedicalcenter.org, 800 Washington St, #4488, Boston, MA, 02111, Tel. 617-636-4488, Fax 617-636-8172 Conflict of Interests: no conflicts to disclose The manuscript was presented as a podium presentation at the 31st Eastern Association for the Surgery of Trauma (EAST) Annual Scientific Assembly. January 11, 2018: Lake Buena Vista, Florida. Disclosures of Funding: nothing to disclose. © 2019 Lippincott Williams & Wilkins, Inc.

Variability in international normalized ratio and activated partial thromboplastin time after injury are not explained by coagulation factor deficits Introduction Conventional coagulation assays (CCAs), PT/INR (prothrombin time/international normalized ratio) and aPTT (activated partial thromboplastin time), detect clotting factor (CF) deficiencies in hematologic disorders. However, there is controversy about how these CCAs should be used to diagnose, treat and monitor trauma-induced coagulopathy. Study objectives were to determine whether CCA abnormalities are reflective of deficiencies of coagulation factor activity in the setting of severe injury. Methods Patients without previous CF deficiency within a prospective database at an ACS verified Level 1 trauma center had CF activity levels, PT/INR, aPTT, and fibrinogen levels measured upon Emergency Department arrival from 2014-2017. Linear regression assessed how CF activity explained the aPTT and PT/INR variation. Prolonged CCA values were set as INR>1.3 and aPTT>34sec. CF deficiency was defined as <30% activity, except for fibrinogen, defined as <150mg/dL. Results Sixty patients with a mean age of 35.8 (std dev:13.6) years and median new injury severity score (NISS) of 32 (IQR:12-43) were included; 53.3% sustained blunt injuries, 23.3% required massive transfusion, and mortality was 11.67%. Overall, 44.6% of the PT/INR variance and 49.5% of the aPTT variance remained unexplained by CF activity. Deficiencies of CFs were: common pathway 25%; extrinsic pathway 1.7%, and intrinsic pathway 6.7%. The positive predictive value for CF deficiencies were: 1)PT/INR>1.3:4.4% for extrinsic pathway, 56.5% for the common pathway; 2) aPTT>34 sec:16.7% for the intrinsic pathway, 73.7% for the common pathway. Conclusion Almost half of the variances of PT/INR and aPTT were unexplained by CF activity. Prolonged PT/INR and aPTT were poor predictors of deficiencies in the intrinsic or extrinsic pathways, however, they were indicators of common pathway deficiencies. Corresponding Author: Ernest E Moore, MD, Email: ernest.moore@dhha.org Phone: 303-724-2685, Fax: 303-720-2682, Mailing Address: 655 Bannock Street Denver, CO 80203 Disclosure: Research reported in this publication was supported in part by the National Institute of General Medical Sciences grants: T32-GM008315 and P50-GM49222, the National Heart Lung and Blood Institute UM1-HL120877, in addition to the Department of Defense USAMRAA and W81XWH-12-2-0028. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, the National Heart, Lung, and Blood institute, or the Department of Defense. Additional research support was provided by Haemonetics (Haemonetics, Niles, IL, USA) with shared intellectual property. © 2019 Lippincott Williams & Wilkins, Inc.

Blunt Rupture of Two Cardiac Chambers Following a Motor Vehicle Collision No abstract available

Reply to Letter: Observing Pneumothoraces: The 35 Millimeter Rule Is Safe for Both Blunt and Penetrating Chest Trauma No abstract available

A Preliminary Analysis of Level IV Trauma Centers within an Organized Trauma System Background The effect of Level IV trauma center (TC) accreditation within an existing trauma network remains understudied. This study compared pre- to post-accreditation data from Level IV TCs within a mature trauma system in Pennsylvania to determine whether TC designation affected time to and/or rate of transfer to definitive care. Level IV TCs were hypothesized to have a decreased time to transfer following accreditation and improved mortality. Methods The Pennsylvania Trauma Systems Foundation (PTSF) collects pre- and post-designation data from hospitals pursuing accreditation. Data from PTSF between 2012 and 2017 was analyzed. Variables of interest included patient demographics, injury severity, mortality and incidence of surgical interventions pre- to post-credentialing. A multilevel mixed-effects logistic regression model assessed the adjusted impact of Level IV TC accreditation on transfer rate. ArcGIS Desktop was used for geospatial mapping of lives and geographic area covered by the addition of Level IV TCs in Pennsylvania Results Five hospitals underwent Level IV credentialing from 2012-2017, providing data on 5,076 cases (Pre: 2,395 [47.2%]; Post: 2,681 [52.8%]). No significant difference in age, admission Glasgow Coma Scale score, or shock index was observed pre to post-accreditation. A difference in transfer rate was observed after credentialing in unadjusted (62.7% vs. 63.3%; p<0.014) and adjusted analyses (AOR: 1.13, p=0.389). There was a trend toward reduced odds of mortality post-credentialing (AOR: 0.59, p=0.261). Major surgical intervention decreased (Pre: 0.42%, Post: 0.04%; p=0.004). Conclusion Level IV TC accreditation has beneficial effects on increased transfer rates and may improve mortality. It is important to continue to observe the impact of Level IV TCs on patient outcomes within a mature trauma system. Level of Evidence III; prognostic and epidemiological Corresponding Author: Frederick B. Rogers, MD, MS, MA, FACS; Frederick.Rogers@pennmedicine.upenn.edu, 555 N. Duke St., Lancaster, PA 17602, 717-544-5945 (tel), 717-544-5944 (fax) All authors have neither conflict of interest nor disclosure of funding or proprietary interest to declare on the materials or subject matter discussed herein. This study was accepted for a Quick Shot presentation at the 32nd Annual Scientific Assembly of the Eastern Association for the Surgery of Trauma held in Austin, Texas from January 15-19, 2019. © 2019 Lippincott Williams & Wilkins, Inc.

Alexandros Sfakianakis
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