INTRODUCTION:Traumatic brain injury (TBI) is the leading cause of combat casualties in modern war with an estimated 20% of casualties experiencing head injury. Since the release of the Brain Trauma Foundation's Guidelines for the Management of Severe Traumatic Brain Injury in 1995, recommendations for management of TBI have included the avoidance of routine hyperventilation. However, both published and anecdotal data suggest that many patients with TBI are inappropriately ventilated during transport, thereby increasing the risk of morbidity and mortality from secondary brain injury. MATERIALS AND METHODS:Enlisted Air Force personnel with prior emergency medical technician training completing a 3-week trauma course were evaluated on their ability to provide manual ventilation. Participants provided manual ventilation using either an in-situ endotracheal tube (ETT) or standard face mask on a standardized simulated patient manikin with TBI on the first and last days of the course. Manual ventilation was provided via a standard manual ventilator and a novel manual ventilator designed to limit tidal volume (VT) and respiratory rate (RR). Participants were given didactic and hands-on training on the third day of the course. Half of the participants were given simulator feedback during the hands-on training. All students provided 2 minutes of manual ventilation with each respirator. Data were collected on the breath-to-breath RR, VT, and peak airway pressures generated by the participant for each trial and were averaged for each trial. A minute ventilation (MV) was then derived from the calculated RR and VT. RESULTS:One hundred fifty-six personnel in the trauma course were evaluated in this study. Significant differences were found in the participant's performance with manual ventilation with the novel compared to the traditional ventilator. Before training, MV with the novel ventilator was less than with the traditional ventilator by 2.1 ± 0.4 L/min (P = .0003) and 1.6 ± 0.5 L/min (P = .0489) via ETT and face mask, respectively. This effect persisted after training with a difference between the devices of 1.8 ± 0.4 L/min (P = .0069) via ETT. Both traditional education interventions (didactics with hands-on training) and simulator-based feedback did not make a significant difference in participant's performance in delivering MV. CONCLUSIONS:The use of a novel ventilator that limits RR and VT may be useful in preventing hyperventilation in TBI patients. Didactic education and simulator-based feedback training may not have significant impact on improving ventilation practices in prehospital providers.

Background The impact of the coronavirus disease 2019 (COVID-19) pandemic substantially altered operations at hospitals that support graduate medical education. We examined the impact of the pandemic on an anesthesiology training program with respect to overall case volume, subspecialty exposure, procedural skill experience, and approaches to airway management. Methods Data for this single center, retrospective cohort study came from an Institutional Review Board approved repository for clinical data. Date ranges were divided into the following phases in 2020: Pre-Pandemic (PP), Early Pandemic (EP), Recovery 1 (R1), and Recovery 2 (R2). All periods were compared to the same period from 2019 for case volume, anesthesia provider type, trainee exposure to Accreditation Council for Graduate Medical Education (ACGME) index case categories, airway technique, and patient variables. Results 15,087 cases were identified, with 5,598 (37.6%) in the PP phase, 1,570 (10.5%) in the EP phase, 1,451 (9.7%) in the R1 phase, and 6,269 (42.1%) in the R2 phase. There was a significant reduction in case volume during the EP phase compared to the corresponding period in 2019 (-55.3%; P < .001) that improved but did not return to baseline by the R2 phase (-17.6%; P < .001). ACGME required minimum cases were reduced during the EP phase compared to 2019 data for pediatric cases (age < 12 y, -72.1%; P < .001 and age < 3 y, -53.5%; P < .006) and cardiopulmonary bypass cases (52.3%, P < .003). Surgical subspecialty case volumes were significantly reduced in the EP phase except for transplant surgery. By the R2 phase, all subspecialty volumes had recovered except for plastic surgery (14.9 vs. 10.5 cases/week; P < .006) and surgical endoscopy (59.2 vs. 40 cases/week; P < .001). Use of video laryngoscopy (VL) and rapid sequence induction and intubation (RSII) also increased from the PP to the EP phase (24.6 vs. 79.6%; P < .001 and 10.3 vs. 52.3%; P < .001, respectively) and remained elevated into the R2 phase (35.2%; P < 0.001 and 23.1%; P < .001, respectively). Conclusions The COVID-19 pandemic produced significant changes in surgical case exposure for a relatively short period. The impact was short-lived, with sufficient remaining time to meet the annual ACGME program minimum case requirements and procedural experiences. The longer-term impact may be a shift towards the increased use of VL and RSII, which became more prevalent during the early phase of the pandemic.

Dutton, Richard P. MD, MBA, FASA*; Grissom, Thomas E. MD, MSIS, FASA, FCCM†; Herbstreit, Frank PD, Dr med.‡,§; Pivalizza, Evan G. MBChB, FFASA‖ Author Information

See Article, p 21 Early hemorrhage remains a leading cause of death in trauma patients despite current guidelines for trauma resuscitation focused on rapid control of bleeding and management of shock. When combining early deaths from exsanguinating hemorrhage and later deaths from multiple organ dysfunction, half of trauma patients who present with major bleeding will die.1,2 Damage control resuscitation (DCR) focuses on rapid bleeding control while minimizing surgical trauma and has become the international standard of care in trauma patients. Hemostatic concepts of DCR focus on appropriate volume restoration and prevention and treatment of coagulation disorders.3 This is commonly accomplished with thawed plasma, packed red blood cells (PRBCs), and platelets in a fixed ratio according to institutional or guideline-based massive transfusion protocols. However, with the increasing availability of point-of-care viscoelastic hemostatic assays (VHAs) and fractionated blood products, a targeted approach to hemostatic resuscitation could potentially replace fixed-ratio algorithms and offer individualized, tailored care. In this issue of Anesthesia & Analgesia, Blaine and Dudaryk4 elegantly discuss both approaches in a pro-con format, with a robust review of the current literature, presenting clinical and logistical considerations for potential benefits and limitations of VHA-guided hemostatic resuscitation.4 In the pro presentation, the utility of VHAs to better follow the dynamic process of trauma-related coagulopathy than standard laboratory measures is well supported. Time to initial results, while suggested as a limitation, is more rapid than plasma-based assays and continued innovation with tissue-factor activated VHA analysis and confirmation of accuracy of early clot-strengthening indices at 5 or 10 minutes, supports the clinical utility of VHAs with rapidly available data.5 In the con discussion, the absence of trauma-specific “control” values, decreased sensitivity to small variations in fibrinolysis compared to laboratory-based assays and the limitation of VHAs to routinely detect individual effects of anticoagulant or antiplatelet agents is recognized, which may complicate the hemorrhagic presentation of an elderly trauma patient with cardiac or other comorbidities. Newer iterations of commonly used VHA devices may facilitate detection of such agents but may require use of a separate cartridge. Meta-analyses of VHA use in cardiac surgery6 and liver transplantation7 suggest a positive effect on decreased blood product use. Unfortunately, as discussed in the pro-con, the available trauma literature does not yet support aggregated conclusions. Not surprisingly, the inability to document a mortality benefit is a current limitation although further analysis of the Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (iTACTIC) data may be helpful.8 Finally, the authors succinctly summarize these knowledge deficits and the need for additional robust, prospective data to further inform practice. There are several additional considerations to this debate: As trauma resuscitation accelerates in the prehospital phase with use of plasma or tranexamic acid in the air or ground ambulance,9 early availability of VHA data will be important, similar to point-of-care testing in mobile stroke units to target appropriate therapy. With VHA devices becoming increasingly portable and less sensitive to environmental artifact, their use in other settings will likely increase.10 Similarly, the physiologic appeal and initial reassuring safety profile of early whole blood resuscitation in traumatic hemorrhage has led to increased civilian use.11 This too is an area for investigation of VHA use and possible guidance Given this current equipoise and international enthusiasm for VHA use, a move toward a hybrid approach with initial ratio-based resuscitation followed by a more targeted approach as VHA data becomes available may be a reasonable compromise until further data are obtained. At one of this author’s institutions, VHA analysis on arrival to the emergency department has completely replaced standardized laboratory tests and convenient cartridge-based results are available in the operating room. Trauma surgeons and anesthesiologists typically have technician support to obtain samples and are comfortable using VHA to guide hemostatic decisions. This can be readily accomplished with the caveat that clinical conditions dictate management allied with VHA results, rather than reflex intervention to achieve a specific index or value potentially contributing to excess product or factor administration such as was noted in the iTACTIC trial.8 We commend Blaine and Dudaryk4 for a timely, thorough pro-con presentation of use of VHA in trauma hemorrhage. While we cannot adjudicate a “winner” in this format, the discussion of benefits and limitations is useful for both the occasional and seasoned trauma anesthesiologist. We look forward to continued prospective studies of VHA in trauma resuscitation and productive discussions in the new pro-con format in the journal. DISCLOSURES Name: Frank Herbstreit, Dr.Med. Contribution: This author helped write the manuscript and read and approved the final version. Name: Thomas E. Grissom, MD, FASA, FCCM. Contribution: This author helped write the manuscript and read and approved the final version. Name: Evan G. Pivalizza, MBChB, FFASA. Contribution: This author helped write the manuscript and read and approved the final version. This manuscript was handled by: Richard P. Dutton, MD.

Traumatic brain injury (TBI) has been associated with the development of indirect acute respiratory distress syndrome (ARDS). However, the causative relationship between TBI and lung injury remains unclear. To explore potential mechanisms linking TBI with the development of ARDS, we characterized the effects of serum factors released following TBI and hemorrhagic shock (HS) in a rat model on the pulmonary endothelial cell (EC) barrier dysfunction, a key feature of ARDS. We found that serum samples from animals exposed to both controlled cortical impact (CCI) and HS, but not from sham-operated rats induced significant barrier dysfunction in human pulmonary artery EC monolayers at 2 days post injury. Thrombin inhibitor and thrombin receptor antagonist attenuated the acute phase of the serum-induced trans-endothelial resistance (TER) decline caused by CCI-HS serum, but not in later time points. However, both the early and late phases of CCI-HS-induced EC permeability were inhibited by heparin. The barrier disruptive effects of CCI-HS serum were also prevented by serum preincubation with heparin-sepharose. Pulmonary EC treated for 3 h with serum from CCI-HS rats demonstrated a significant decline in expression of EC junctional protein, VE-Cadherin, and disassembly of peripheral EC adherens junction complexes monitored by immunostaining with VE-cadherin antibody. These results suggest that exposure to CCI-HS causes early and late-phase barrier disruptive effects in vascular endothelium. While thrombin-PAR1 signaling has been identified as a mechanism of acute EC permeability increase by CCI-HS serum, the factor(s) defining long-term EC barrier disruption in CCI-HS model remains to be determined.

BACKGROUND Tranexamic acid (TXA) administration is recommended in severely injured trauma patients. We examined TXA administration, admission fibrinolysis phenotypes, and clinical outcomes following traumatic injury and hypothesized that TXA was associated with increased multiple organ failure (MOF). METHODS Two-year, single-center, retrospective investigation. Inclusion criteria were age ≥ 18 years, Injury Severity Score (ISS) >16, admitted from scene of injury, thromboelastography within 30 min of arrival. Fibrinolysis was evaluated by lysis at 30 min (LY30) and fibrinolysis phenotypes were defined as: Shutdown: LY30 ≤ 0.8%, Physiologic: LY30 0.81-2.9%, Hyperfibrinolysis: LY30 ≥ 3.0%. Primary outcomes were 28-day mortality and MOF. The association of TXA with mortality and MOF was assessed among the entire study population and in each of the fibrinolysis phenotypes. RESULTS Four hundred twenty patients: 144/420 Shutdown (34.2%), 96/420 Physiologic (22.9%), and 180/410 Hyperfibrinolysis (42.9%). There was no difference in 28-day mortality by TXA administration among the entire study population (P = 0.52). However, there was a significant increase in MOF in patients who received TXA (11/46, 23.9% vs 16/374, 4.3%; P < 0.001). TXA was associated MOF (OR: 3.2, 95% CI 1.2-8.9), after adjusting for confounding variables. There was no difference in MOF in patients who received TXA in the Physiologic (1/5, 20.0% vs 7/91, 7.7%; P = 0.33) group. There was a significant increase in MOF among patients who received TXA in the Shutdown (3/11, 27.3% vs 5/133, 3.8%; P = 0.001) and Hyperfibrinolysis (7/30, 23.3% vs 5/150, 3.3%; P = 0.001) groups. CONCLUSIONS Administration of TXA following traumatic injury was associated with MOF in the fibrinolysis shutdown and hyperfibrinolysis phenotypes and warrants continued evaluation.

Anesthesiologists will continue to be recognized as airway experts and other specialties will need ongoing access to the clinical volume available in the OR setting when looking for opportunities to meet their residents' and fellows' airway management training needs. At the same time, critical care, EM, and other physicians have acquired an ever-expanding array of skills and experience managing the airways of critically ill and injured patients. When considering the needs of nonanesthesiologist trainees coming to our domain, it is essential to recognize the differences inherent in practicing outside of the OR and to incorporate those aspects of airway management considerations into training paradigms. This should be viewed as an opportunity to work toward a more universal approach to training and airway management in our individual institutions incorporating a multidisciplinary approach to education and clinical activities.

See Article, p 326 The global coronavirus pandemic has affected every aspect of modern life, including health care, yet few specialties are so directly affected as trauma anesthesiology. Quieter city streets with less vehicular traffic have reduced the volume of trauma cases, but injured patients now pose a unique new challenge: the risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2).1 The need for infection control measures, superimposed on the need for rapid treatment, has forced the development of new protocols. This issue of Anesthesia & Analgesia includes an article by Gong et al2 from Wuhan, China, describing their experience caring for trauma patients during the initial coronavirus disease 2019 (COVID-19) surge in Wuhan, China. The key recommendations of Gong et al2 include the following: Screening and testing every patient on admission for coronavirus infection Rigorous adherence to the use of personal protective equipment (PPE) for medical care of emergency surgery patients, regardless of screening status Collection of bronchoalveolar lavage (BAL) specimens at the time of intubation in patients with uncertain status Use of computed tomography (CT) scan, a common diagnostic tool in trauma patients, to additionally diagnose COVID-19 Use of negative pressure operating rooms for emergency cases Preoperative review of medications, noting the potential anesthetic interactions of chloroquine or hydroxychloroquine (dysrhythmia) and lopinavir–ritonavir (increased placental transfer of bupivacaine) Consideration of the potential for coagulation disorders in COVID-19 patients For general anesthesia, rapid sequence intubation with minimal bag-valve-mask ventilation Damage control principles for surgery in severely injured patients, minimizing organ manipulation and surgical duration Lung-protective ventilation and goal-directed fluid therapy, with individualized resuscitation aimed at restoring and maintaining euvolemia Extubation in the operating room, with transport directly to a dedicated COVID unit if possible Measurement of d-dimer to assess ongoing systemic inflammation, with aggressive use of thromboprophylaxis once bleeding risk has dissipated Routine use of multimodal analgesia and postoperative nausea and vomiting (PONV) prophylaxis Limited family visitation with appropriate social distancing While much of this information will seem routine for experienced trauma anesthesiologists, the integration of COVID-19–specific recommendations for avoiding viral spread makes this article an important read. The need for trauma and emergency surgery is not going away, but the additional need for preserving the health and safety of the anesthesia workforce―not to mention other patients in the hospital―makes the tactical advice in this article a useful guide for any hospital anesthesia department and staff. Not addressed by Gong et al,2 but very much on the minds of those confronting a local surge in COVID-19 patients, are the difficult ethical questions posed by the disease: protection of health care workers versus rapid treatment of critical trauma patients; rationed use of blood products; and tough decisions about surgical timing and resource allocation. During the COVID-19 pandemic, there has been a focus on protecting perioperative health care providers to sustain their ability to care for both nonelective and COVID-19 patient populations. For many hospital systems, this has been a challenge with shortages of PPE, changes in patient flow, and altered staffing requirements. For regions with a high incidence of COVID-19, Gong et al2 have suggested that the standard PPE approach should include implementation of high-level precautions (level 3) for all trauma and acute care surgical patients, including the use of negative pressure receiving and operating rooms where available. Given the need for universal precautions in all trauma admissions, this adds the requirement for an N95 respirator or powered air-purifying respirator system for all clinicians in close patient proximity. Additional gowning might be needed as well, depending on available supplies. While the approach does not appear to add a large burden for trauma admission preparation, the shortage of PPE, limited access to true negative pressure capability, and need to emergently move patients from the receiving location or emergency department to the operating room can challenge our usual expectations for trauma care. When time from the field to admission is adequate, there should be little trouble preparing for the patient’s arrival. In the urban setting, however, this time interval can be extremely short. In the face of sometimes chaotic early evaluation and treatment period, the maintenance of strict level 3 precautions becomes extremely challenging. Medical professionals supporting trauma need to balance rapid interventions, including intubation, manual ventilation, chest tube placement, and other invasive procedures, against the risk of exposure. This applies not only to anesthesiologists but also all medical professionals providing care for the trauma patient.3,4 The need to preserve our highly skilled workforce must be emphasized even in settings where time to interventions is critical. We are seeing other challenges related to trauma management that might influence our actions. One of the major concerns is a decrease in blood product availability. While the risk of transmission of the SARS-CoV-2 remains theoretical, donor centers are excluding symptomatic individuals or potential donors with known or potential close contact with a person with COVID-19.5 Current recommendations are that these individuals should refrain from donating until at least 28 days after resolution of symptoms or last contact, respectively. The real threat, however, is not from the virus itself, but from the impact of social distancing on blood collection, as donor centers might be closed, and prospective donors might choose to remain home.6 Many institutions have implemented blood conservation programs affecting blood availability, transfusion triggers, and massive transfusion events. In specific cases, this might require a discussion among the care team regarding the utility of ongoing resuscitative efforts due to concerns about diverting resources that might benefit other patients. Gong et al2 acknowledge that increased attention to blood conservation practices might be necessary to minimize difficult decisions. In the face of a potentially lethal and highly contagious disease and international shortages of equipment and medications, anesthesiologists have led their hospitals in adopting new standards for PPE and have pioneered mechanisms for recycling and reusing needed equipment. As innovators, we have developed novel solutions for infection control and workforce safety, ranging from homemade respirator systems, to the intubating teams used in Wuhan, to “intubation boxes” to limit viral spread in the operating room. In our capacity as intensivists, anesthesiologists have helped open thousands of new intensive care unit (ICU) beds around the world and have equipped them with repurposed anesthesia machines, invasive monitoring, and expert clinician coverage. Anesthesiologists in less busy facilities have welcomed transfers from hard-hit areas or travelled themselves to provide additional coverage where desperately needed. In the face of a global crisis, an unexpectedly high number of patients, and shortages in personnel and equipment, anesthesiologists and intensivists have initiated interprofessional collaborations to optimize patient care. Through mostly informal contacts, knowledge has been transferred from countries that were heavily impacted early to enable better care in areas affected later by the pandemic. We have developed collaborations that will reach far into the future. Trauma anesthesiology is already one of the most collaborative specialties in medicine, spanning from prehospital to the operating room to intensive care, and connecting with multiple surgical and medical subspecialties. Even more than local connections, though, the trauma care community has always been closely connected across systems, nations, and the entire world. Our outcome research has benefitted from multi-institutional registries and from the ability to share knowledge rapidly through scientific and practice communities. Early in the crisis, the Trauma Anesthesiology Society, working with DocMatter, created an open discussion forum with >30,000 users (https://www.docmatter.com/dm/app/profile/specialty/?id=11110). Anesthesiologists around the world are in regular communication with colleagues in hard-hit areas—including Wuhan, Milan, and New York City—and are sharing the lessons learned with their professional colleagues and hospital administrators. A novel disease requires novel therapies. Anesthesiologists worldwide are collaborating with intensivists and infectious disease specialists to expedite clinical trials of promising prophylactic and therapeutic agents. These efforts are likely to lead to therapies that can effectively counter the disease and limit its spread, with a future cascade of benefit to medical knowledge and the treatment of other viral conditions. Even the risk to health care workers is being assessed, for example, the IntubateCOVID project organized by researchers at the University of Pennsylvania is designed to gather real-world experience from anesthesiologists called to care for patients with COVID-19 (www.intubatecovid.org). We urge every practicing anesthesiologist to participate. While COVID-19 has changed the world as we know it, the ability of trauma anesthesiologists to adjust to chaotic circumstances, novel patient injuries, and changing environmental conditions will stand us in good stead. Like the US Marines, we have improvised, we have adapted, and we will overcome! DISCLOSURES Name: Richard P. Dutton, MD, MBA. Contribution: This author helped review the primary paper and conceive, draft, and edit this commentary. Name: Thomas E. Grissom, MD, FCCM. Contribution: This author helped review the primary paper and conceive, draft, and edit this commentary. Name: Frank Herbstreit, Dr Med. Contribution: This author helped review the primary paper and conceive, draft, and edit this commentary. This manuscript was handled by: Thomas R. Vetter, MD, MPH.

Fibrinolysis is a physiologic element of hemostasis that works to regulate clot formation through enzymatic breakdown of fibrin blood clots. Like the coagulation cascade, fibrinolysis is closely controlled by a series of cofactors, inhibitors, and receptors. In the perioperative period, tissue injury associated with trauma or surgery, blood contact with large nonendothelial surfaces such as cardiopulmonary bypass circuits, or ischemia and reperfusion may produce excessive fibrinolysis, contributing to worsened coagulopathy or bleeding.

644 www.anesthesia-analgesia.org September 2019 • Volume 129 • Number 3 DOI: 10.1213/ANE.0000000000004320 GLOSSARY CRASH-2 = Clinical Randomization of an Antifibrinolytic in Severe Hemorrhage; PATCH-Trauma = Pre-hospital Anti-Fibrinolytics for Traumatic Coagulopathy & Haemorrhage; PROPPR = Pragmatic, Randomized Optimal Platelet and Plasma Ratios; STAAMP = Study of Tranexamic Acid during Aeromedical Prehospital Transport; TAMPITI = Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury; TXA = tranexamic acid; VHA = viscoelastic hemostatic assays

In the setting of major trauma, musculoskeletal injuries are the most common indication for surgery in the severely injured polytrauma patient [1–3]. The current consensus statement for polytrauma defines it as an abbreviated injury score (AIS) ≥3 points in at least 2 body regions with a least 1 pathologic value (systolic blood pressure ≤90 mm Hg, Glasgow Coma scale ≤8, base deficit ≥6, partial thromboplastin time ≥40 s, or age ≥70) with the presence of concomitant limb and pelvic fractures counting as a single body region [4].

Anesthesiologists managing traumatically injured patients are seeing an increased incidence of patients on direct oral anticoagulants (DOACs). Management of these patients requires an understanding of the pharmacology and pharmacodynamics of these agents in the perioperative setting. With limited reversal options, what are the best options for managing these often complex patients?