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Current management of hemorrhagic shock relies on control of surgical bleeding along with resuscitation with packed red blood cells and plasma in a 1-to-1 ratio. Transfusion, however, is not without consequence as red blood cells develop a series of biochemical and physical changes during storage termed "the red blood cell storage lesion." Previous data has suggested that ethanol may stabilize the red blood cell membrane, resulting in improved deformability. We hypothesized that storage of packed red blood cells with ethanol would alter the red blood cell storage lesion.Mice underwent donation and storage of red blood cells with standard storage conditions in AS-3 alone or ethanol at concentrations of 0.07%, 0.14%, and 0.28%. The red blood cell storage lesion parameters of microvesicles, Band-3, free hemoglobin, annexin V, and erythrocyte osmotic fragility were measured and compared. In additional experiments, the mice underwent hemorrhage and resuscitation with stored packed red blood cells to further evaluate the in vivo inflammatory impact.Red blood cells stored with ethanol demonstrated decreased microvesicle accumulation and Band-3 levels. There were no differences in phosphatidylserine or cell-free hemoglobin levels. After hemorrhage and resuscitation with packed red blood cells stored with 0.07% ethanol, mice demonstrated decreased serum levels of interleukin-6, macrophage inflammatory protein-1α, keratinocyte chemokine, and tumor necrosis factor α compared to those mice receiving packed red blood cells stored with additive solution-3.Storage of murine red blood cells with low-dose ethanol results in decreased red blood cell storage lesion severity. Resuscitation with packed red blood cells stored with 0.07% ethanol also resulted in a decreased systemic inflammatory response in a murine model of hemorrhage.

While the pillars of trauma resuscitation are surgical hemostasis and blood product administration, norepinephrine (NE) can be used as an adjunct. The goal of this study was to evaluate the relationship between the maximum dose of NE, timing of NE administration, and mortality in trauma patients.Patients admitted between January 2013 and January 2021 treated with NE were reviewed. Univariate and multivariate logistic regression were used to assess whether maximum NE dose was independently associated with mortality. Optimal dosage rates for NE were determined via Youden Index. Subgroup analyses comparing those who received NE within versus after the first 24 h of admission were conducted.Three hundred fifty-first trauma patients were included, with 217 (62%) surviving. Patients who died received an average maximum dose of 16.7 mcg/min compared to 9.1 mcg/min in survivors (P = 0.0003). Mortality rate increased with dosage (P 0.0001), with doses greater than 20 mcg/min having 79% mortality. Those who received NE within the first 24 h had an inflection point in mortality at 16 mcg/min (Youden = 0.45) (OR 1.06; 95% CI 1.03-1.10). For patients who received NE after the first 24 h, an inflection point in mortality was at 10 mcg/min (Youden = 0.34) (OR 1.09; 95% CI 1.04-1.14).Higher maximum doses of NE were associated with increased mortality. Patients initiated on NE more than 24 h into their admission displayed an inflection point at a lower dose than those initiated later. This suggests that trauma patients initiated on NE after 24 h from injury may have a dire prognosis.

Administration of antifibrinolytic medications, including tranexamic acid (TXA), may reduce head injury-related mortality. The effect of these medications on post-traumatic brain injury (TBI) inflammatory response is unknown. The goal of this study was to investigate the role of available antifibrinolytic medications on both systemic and cerebral inflammation after TBI.An established murine weight drop model was used to induce a moderate TBI. Mice were administered 1, 10, or 100 mg/kg of TXA, 400 mg/kg of aminocaproic acid (Amicar, Hospira, Lake Forest, IL), 100 kIU/kg of aprotonin, or equivalent volume of normal saline (NS) 10 minutes after recovery. Mice were euthanized at 1, 6, or 24 hours. Serum and cerebral tissue were analyzed for neuron-specific enolase and inflammatory cytokines. Hippocampal histology was evaluated at 30 days for phosphorylated tau accumulation.One hour after TBI, mice given TXA displayed decreased cerebral cytokine concentrations of tumor necrosis factor α (TNF-α) and, by 24 hours, displayed decreased concentrations of cerebral TNF-α, interleukin (IL)-6, and monocyte chemoattractant protein 1 compared with TBI-NS. However, serum concentrations of TNF-α and macrophage inflammatory protein 1α (MIP-1α) were significantly elevated from 1 to 24 hours in TBI-TXA groups compared with TBI-NS. The concentration of phosphorylated tau was significantly decreased in a dose-dependent manner in TBI-TXA groups compared with TBI-NS. By contrast, Amicar administration increased cerebral cytokine levels of IL-6 1 hour after TBI, with serum elevations noted in TNF-α, MIP-1α, and monocyte chemoattractant protein 1 at 24 hours compared with TBI-NS. Aprotonin administration increased serum TNF-α, IL-6, and MIP-1α from 1 to 24 hours without differences in cerebral cytokines compared with TBI-NS.Tranexamic acid administration may provide acute neuroinflammatory protection in a dose-dependent manner. Amicar administration may be detrimental after TBI with increased cerebral and systemic inflammatory effects. Aprotonin administration may increase systemic inflammation without significant contributions to neuroinflammation. While no antifibrinolytic medication improved systemic inflammation, these data suggest that TXA may provide the most beneficial inflammatory modulation after TBI.

Massive transfusion with older packed red blood cells is associated with increased morbidity and mortality. As packed red blood cells age, they undergo biochemical and structural changes known as the storage lesion. We developed a novel solution to increase viscosity in stored packed red blood cells. We hypothesized that packed red blood cell storage in this solution would blunt storage lesion formation and mitigate the inflammatory response after resuscitation.Blood was obtained from 8- to 10-week-old C57BL/6 male donor mice or human volunteers and stored as packed red blood cell units for 14 days for mice or 42 days for humans in either standard AS-3 storage solution or EAS-1587, the novel packed red blood cell storage solution. Packed red blood cells were analyzed for microvesicles, cell-free hemoglobin, phosphatidylserine, band-3 protein, glucose utilization, and osmotic fragility. Additional mice underwent hemorrhage and resuscitation with packed red blood cells stored in either AS-3 or EAS-1587. Serum was analyzed for inflammatory markers.Murine packed red blood cells stored in EAS-1587 demonstrated reductions in microvesicle and cell-free hemoglobin accumulation as well as preserved band-3 expression, increase glucose utilization, reductions in phosphatidylserine expression, and susceptibility to osmotic stress. Serum from mice resuscitated with packed red blood cells stored in EAS-1587 demonstrated reduced proinflammatory cytokines. Human packed red blood cells demonstrated a reduction in microvesicle and cell-free hemoglobin as well as an increase in glucose utilization.Storage of packed red blood cells in a novel storage solution mitigated many aspects of the red blood cell storage lesion as well as the inflammatory response to resuscitation after hemorrhage. This modified storage solution may lead to improvement of packed red blood cell storage and reduce harm after massive transfusion.

Chest wall injuries are very common in blunt trauma and development of treatment protocols can significantly improve outcomes. Surgical stabilisation of rib fractures (SSRF) is an adjunct for the most severe chest injuries and can be used as a part of a comprehensive approach to chest injuries care. We hypothesized that implementation of a SSRF programme program would result in improved short-term outcomes.The characteristics of the initial group of SSRF patients (Early-SSRF) were used to identify matching factors. Patients prior to SSRF protocol underwent a propensity score match, followed by screening for operative indications and contraindications. After exclusions, a non-operative (Non-Op) cohort was defined (n=36) resulting in an approximately 1:1 match. An overall operative cohort, inclusive of Early-SSRF and all subsequent operative patients, was defined (All- SSRF). A before-and-after analysis using chi-squared, Students T-tests, and Mann-Whitney U-tests were used to assess significance at the level of 0.05.Early-SSRF (n=22) and All-SSRF (n=45) were compared to Non-Op (n=36). The selection process resulted in well matched groups, and equally well-balanced operative indications between the groups. The Early-SSRF group demonstrated shortened duration of mechanical ventilation and a decreased frequency of being discharged a long-term acute care hospital. The All-SSRF group again demonstrated markedly shorter duration of mechanical ventilation compared to Non-Op (median 6 days vs 16 days, p0.01), more decrease discharge to a long-term acute care hospital (9% vs. 36%, p=0.01), and reduced risk for tracheostomy (8.9% vs. 33.3% respectively, p0.01) CONCLUSION: The introduction of an operative rib fixation to a comprehensive chest wall injury protocol can produce improvements in clinical outcomes that decrease time on the ventilator and tracheostomy rates, and result in more patients being discharged to home. Creation and implementation of a chest wall injury protocol to include SSRF requires a multidisciplinary approach and thoughtful patient selection.

Introduction: The optimal management strategies for patients with polytraumatic injuries that include traumatic brain injury (TBI) are not well defined. Specific interventions including tranexamic acid (TXA), propranolol, and hypertonic saline (HTS) have each demonstrated benefits in patient mortality after TBI, but have not been applied to TBI patients with concomitant hemorrhage. The goals of our study were to determine the inflammatory effects of resuscitation strategy using HTS or shed whole blood (WB) and evaluate the cerebral and systemic inflammatory effects of adjunct treatment with TXA and propranolol after combined TBI + hemorrhagic shock. Methods: Mice underwent TBI via weight drop and were subsequently randomized into six experimental groups: three with HTS resuscitation and three with WB resuscitation. Mice were then subjected to controlled hemorrhagic shock for 1 h to a goal MAP of 25 mmHg. Mice were then treated with an i.p. dose of 4 mg/kg propranolol, 100 mg/kg TXA, or normal saline (NS) as a control. Mice were killed at 1, 6, or 24 h for serum and cerebral biomarker evaluation by multiplex ELISA and serum neuron-specific enolase, a biomarker of cerebral cellular injury. Results: Mice resuscitated with HTS had elevated serum proinflammatory cytokines compared with WB resuscitated groups at 6 and 24 h after injury, with no significant difference in cerebral cytokine levels. Within the TBI/shock + HTS groups, the addition of propranolol or TXA did not significantly alter serum cytokine concentration, but cerebral IL-2, IL-12, and macrophage inflammatory protein-1α (MIP-1α) decreased after propranolol administration. In the TBI/shock + WB cohorts, the addition of both propranolol and TXA increased systemic proinflammatory cytokine levels at 6 and 24 h after injury as demonstrated by serum IL-2, IL-12, MIP-1α, and IL-1β compared with NS control. By contrast, TBI/shock + WB mice demonstrated a significant reduction in cerebral IL-2, IL-12, and MIP-1α in propranolol treated mice 6 h after injury compared with NS group. While serum neuron-specific enolase was significantly increased 1 and 24 h after injury in TBI/shock + HTS + TXA cohorts compared with NS control, it was significantly reduced in the TBI/shock + WB + propranolol mice compared with NS control 24 h after injury. Conclusions: Whole blood resuscitation can reduce the acute postinjury neuroinflammatory response after combined TBI/shock compared with HTS. The addition of either propranolol or TXA may modulate the postinjury systemic and cerebral inflammatory response with more improvements noted after propranolol administration. Multimodal treatment with resuscitation and pharmacologic therapy after TBI and hemorrhagic shock may mitigate the inflammatory response to these injuries to improve recovery.

BACKGROUND: Pulmonary contusions (PCs) have historically been viewed as a serious complicating factor in thoracic injury. Recently, there has been conflicting evidence regarding the influence of PCs on outcomes; however, many studies do not stratify contusions by severity and may miss clinical associations. We sought to identify if contusion severity is associated with worse outcomes. METHODS: A previously published chest wall injury database at an urban Level I trauma center was retrospectively reviewed. All severely injured subjects (defined as Injury Severity Score [ISS] ≥ 15) with moderate to severe thoracic injury (defined as a chest wall Abbreviated Injury Scale [AIS] ≥ 3) who required mechanical ventilation for > 24 h were stratified by contusion severity. Moderate to severe contusions were defined as AIS contusion ≥ 3 and Blunt Pulmonary Contusion 18 (BPC18) score ≥ 3. RESULTS: Over 5 y, 3,836 patients presented with chest wall injuries, of which 1,176 (30.6%) had concomitant contusions. When screened for inclusion criteria, 339 subjects with contusions and 211 subjects without contusions (no-PC) were identified. Of these, 234 had moderate to severe contusions defined by AIS contusion ≥ 3 (PC-A) and 230 had moderate to severe contusions by BPC18 ≥ 3 (PC-B). Compared to no-PC, both PC-A and PC-B groups had significantly lower mortality (17.9% and 17.4%, respectively, vs 28.9%); however, PC-A and PC-B groups had longer durations of mechanical ventilation (6 and 7 d, respectively, vs 5 d), longer ICU length of stay (10 and 10 vs 8 d), and longer overall hospital length of stay (15 and 15 vs 13 d). CONCLUSIONS: In severely injured polytrauma patients, PCs are seen with more severe chest injuries. Furthermore, moderate to severe contusions are associated with longer durations of mechanical ventilation, ICU length of stay, and hospital length of stay. Despite practice pattern changes, contusions appear to contribute significantly to the clinical course of the blunt chest wall injured patients.

Background There is no consensus on what dose of norepinephrine corresponds with futility. The purpose of this study was to investigate the maximum infusion and cumulative doses of norepinephrine associated with survival for patients in medical and surgical intensive care units (MICU and SICU). Materials and Methods A retrospective review was conducted of 661 critically ill patients admitted to a large academic medical center who received norepinephrine. Univariate, multivariate, and area under the curve analyses with optimal cut offs for maximum infusion rate and cumulative dosage were determined by Youden Index. Results The population was 54.9% male, 75.8% white, and 58.7 ± 16.1 y old with 384 (69.8%) admitted to the MICU and 166 (30.2%) admitted to the SICU, including 38 trauma patients. Inflection points in mortality were seen at 18 mcg/min and 17.6 mg. The inflection point was higher in MICU patients at 21 mcg/min and lower in SICU patients at 11 mcg/min. MICU patients also had a higher maximum cumulative dosage of 30.7 mg, compared to 2.7 mg in SICU patients. In trauma patients, norepinephrine infusions up to 5 mcg/min were associated with a 41.7% mortality rate. Conclusion A maximum rate of 18 mcg/min and cumulative dose of 17.6 mg were the inflection points for mortality risk in ICU patients, with SICU patients tolerating lower doses. In trauma patients, even low doses of norepinephrine were associated with higher mortality. These data suggest that MICU, SICU, and trauma patients differ in need for, response to, and outcome from escalating norepinephrine doses.

Over 67,000 individuals died in the United States due to drug overdose in 2018; the majority of these deaths were secondary to opioid ingestion. Our aim was to determine surgeon perceptions on opioid abuse, the adequacy of perioperative and graduate medical education, and the role surgeons may play. We also aimed to investigate any differences in attending and resident surgeon attitudes.Anonymous online survey assessing surgeons' opioid counseling practices, prescribing patterns, and perceptions on opioid abuse, adequacy of education about opioid abuse, and the role physicians play.Two Accreditation Council for Graduate Medical Education accredited general surgery programs at a university-based tertiary hospital and a community hospital in the Midwest.Attending and resident physicians within the Departments of Surgery participated anonymously.Attending surgeons were more likely than residents to discuss posoperative opioids with patients (62% vs. 33%; p0.05), discuss the potential of opioid abuse (31% vs. 6%; p0.05), and check state-specific prescription monitoring programs (15% vs. 0%; p0.05). Surgeons and trainees feel that surgeons have contributed to the opioid epidemic (76% attending vs. 88% resident). Overall, attending and resident surgeons disagree that there is adequate formal education (66% vs. 66%) but adequate informal education (48% vs. 61%) on opioid prescribing. However, when attending physicians were broken down into those who have practiced ≤5 years vs. those with5 years experience, those with ≤5 years experience were more confident in recognizing opioid abuse (61% vs. 34%) and fewer young faculty disagreed that there is adequate formalized education on opioid prescribing (45% vs. 84%).Patient education should be improved upon in the preoperative setting and should be treated as an important component of preoperative discussions. Formalized opioid education should also be undertaken in graduate surgical education to help guide appropriate opioid use by resident and attending physicians.

The goals of sedation in the critically ill surgical patient are to minimize pain, anxiety, and agitation without hindering cardiopulmonary function. One potential benefit of tracheostomy during endotracheal intubation is the reduction of sedation and analgesia; however, there are little data to support this supposition. We hypothesized that patients undergoing tracheostomy would have a rapid reduction in sedation and analgesia following tracheostomy.A retrospective review of tracheostomies performed at a single Level I trauma center from January 2013 to June 2018 was completed. An evaluation of Glasgow Coma Scale, Richmond Agitation-Sedation Scale, and Confusion Assessment Method for the intensive care unit 72 hours pretracheostomy to 72 hours posttracheostomy was performed. The total daily dose of sedation, anxiolytic, and analgesic medications administered were recorded. Mixed-effects models were used to evaluate longitudinal drug does over time (hours).Four hundred sixty-eight patients included for analysis with a mean age of 58.8 ± 18.3 years. There was a significant decrease in propofol and fentanyl utilization from 24 hours pretracheostomy to 24 hours posttracheostomy in both dose and number of patients receiving these continuous intravenous medications. Similarly, total morphine milligram equivalents (MME) use and continuous midazolam significantly decreased from 24 hours pretracheostomy to 24 hours posttracheostomy. By contrast, intermittent enteral quetiapine and methadone administration increased after tracheostomy. Importantly, Richmond Agitation-Sedation Scale, Glasgow Coma Scale, and Confusion Assessment Method scoring were also significantly improved as early as 24 hours posttracheostomy. Total MME use was significantly elevated in patients younger than 65 years and in male patients pretracheostomy compared with female patients. Patients admitted to the medical intensive care unit had significantly higher MME use compared with those in the surgical intensive care unit pretracheostomy.Tracheostomy allows for a rapid and significant reduction in intravenous sedation and analgesia medication utilization. Posttracheostomy sedation can transition to intermittent enteral medications, potentially contributing to the observed improvements in postoperative mental status and agitation.Therapeutic/Care Management; Level III.

The benefit of a balanced resuscitation in low volume transfusions remains unclear This study is aimed at characterizing blood product ratios in this cohort.A retrospective analysis (2017-2019) of the ACS TQIP was performed to identify adult trauma patients who received ≥1 unit of packed red blood cells (pRBCs) 4 and 24 h after admission. Blood products received were used to calculate plasma and platelet ratios.Plasma and platelet ratios were closer to the target 1:1 ratio for ≤4 units pRBCs. Plasma and platelet ratios increased for those receiving ≤10 units pRBCs, demonstrating increasingly unbalanced resuscitation. Transfusion ratios were unbalanced for those receiving ≥5 units pRBC.Transfusion ratios were closer to the desired transfusion ratio for low volume blood product resuscitation. In those receiving ≥5 units pRBC, plasma and platelet ratios were not balanced. The optimal transfusion ratio in low volume trauma resuscitation is unknown.

BackgroundThe majority of critical care air transport (CCAT) flights are regulated, meaning that a theater-validating flight surgeon has confirmed that the patient is medically cleared for flight and that evacuation is appropriate. If the conditions on the ground do not allow for this process, the flight is unregulated. Published data are limited regarding CCAT unregulated missions to include the period of troop drawdown at the end of the Afghanistan conflict. The objective of our study was to characterize the unregulated missions within Afghanistan during troop drawdown and compare them to regulated missions during the same timeframe.Study DesignWe performed a retrospective review of all CCAT medical records of patients transported via CCAT within Afghanistan between January 2017 and December 2019. We abstracted data from the records, including mission characteristics, patient demographics, injury descriptors, preflight military treatment facility procedures, CCAT procedures, in-flight CCAT treatments, in-flight events, and equipment issues. Following descriptive and comparative analysis, a Cochran–Armitage test was performed to evaluate the statistical significance of the trend in categorical data over time. Multivariable regression was used to assess the association between vasopressors and preflight massive transfusions, preflight surgical procedures, injury patterns, and age.ResultsWe reviewed 147 records of patients transported via CCAT: 68 patients were transported in a regulated fashion and 79 on an unregulated flight. The number of patients evacuated increased year-over-year (n = 22 in 2017, n = 57 in 2018, and n = 68 in 2019, P ConclusionDuring the troop drawdown in Afghanistan, the number of unregulated missions increased geometrically because the medical footprint was decreasing. During unregulated missions, CCAT providers used ketamine more frequently, consistent with Tactical Combat Casualty Care guidelines. In addition, TBI was the only predictor of vasopressor use and may reflect an attempt to adhere to unmonitored TBI clinical guidelines. Interoperability between CCAT and AE teams is critical to meet mass casualty needs in unregulated mission environments and highlights a need for joint training. It remains imperative to evaluate changes in mission requirements to inform en route combat casualty care training.

Platelet activation and aggregation are critical to the initiation of hemostasis after trauma with hemorrhage. Platelet dysfunction is a well-recognized phenomenon contributing to trauma-induced coagulopathy. The goal of this study was to evaluate the timing and severity of platelet dysfunction in massively transfused, traumatically injured patients during the first 72 hours after injury and its association with 30-day survival.A retrospective secondary cohort study of platelet count and function was performed using samples from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial. Platelet characteristics were measured at 8 timepoints during the first 72 hours of hospitalization and compared between 30-day survivors and nonsurvivors. Platelet counts were assessed via flow cytometry. Platelet function was analyzed with the use of serial thrombelastography and impedance aggregometry with agonists arachidonic acid, adenosine diphosphate, collagen, thrombin receptor activating peptide, and ristocetin.In total, 680 patients were included for analysis. Platelet counts were significantly lower from baseline to 72 hours after hospital admission with further 1.3 to 2-fold reductions noted in nonsurvivors compared to survivor patients. Platelet aggregation via adenosine diphosphate, arachidonic acid, collagen, thrombin receptor activating peptide, and ristocetin was significantly lower in nonsurvivors at all time points. The nadir of platelet aggregation was 2 to 6 hours after admission with significant improvements in viscoelastic maximum clot formation and agonist-induced aggregation by 12 hours without concomitant improvement in platelet count.Platelet aggregability recovers 12 hours after injury independent of worsening thrombocytopenia. Failure of platelet function to recover portends a poor prognosis.

There is a paucity of data to predict early death or futility after trauma. The objective of this study was to characterize the laboratory values, blood product administration, and hospital disposition for patients with trauma who died within 72 h of admission.All deaths within 72 h of admission over a 5-y period at a level I trauma center were reviewed. Blood transfusion within the first 4 h of arrival and patient disposition from the emergency department to the operating room (OR), surgical intensive care unit, or the neuroscience intensive care unit (NSICU) were analyzed. Kaplan-Meier curves were generated to determine time to death.A total of 622 subjects were identified; 39.5% died in the emergency department, 10.6% went directly to the OR, 13.6% were admitted to the surgical intensive care unit, and 29.7% admitted to the NSICU. Of these subjects, 201 (32.2%) patients received blood within the first 4 h. By 24 h, early blood transfusion was associated with more rapid death for patients who were admitted to the NSICU (80% versus 60% mortality, P = 0.01) but not for patients taken directly to the OR (80% versus 70% mortality, P = 0.2). Admission coagulopathy by international normalized ratio (P 0.01), but not anemia (P = 0.64) or acidosis (P = 0.45), correlated with a shorter time to death. In contrast, laboratory values obtained at 4 h after admission did not correlate with time to death.Our data demonstrate that admission coagulation derangement and need for early blood product transfusion are the two factors most associated with early death after injury, particularly in those patients with traumatic brain injury. These data will help construct future models for futility of continued care in patients with trauma.

Packed red blood cell (pRBC) units administered during resuscitation from hemorrhagic shock are of varied storage ages. We have previously shown that RBC-derived microparticles' impact on thrombogenesis. However, the impact of storage age on pRBC coagulability is unknown. Therefore, we sought to investigate the effect of storage age on innate coagulability and aggregability of stored pRBCs.pRBCs prepared from male C57BL/6J mice were stored in Additive Solution-3 according to our standardized murine blood banking protocols for 14 days. Rotational thromboelastometry (ROTEM) was used to assess the innate coagulation status of fresh and 14-day old pRBCs. Viscoelastic coagulation parameters of clotting time (CT), clot formation time (CFT), alpha angle, and maximum clot firmness (MCF) were analyzed to determine coagulability. Plasma was added to the fresh pRBCs and 15-day old pRBCs to determine if the storage-associated coagulopathy was reversible with plasma. Statistical analyses were conducted with a Student's t-test.Fifteen-day old pRBCs demonstrated a significant reduction in MCF (10.3 vs. 24.4 mm, P-value0.001) and alpha angle (6.0 vs. 27.2 degrees, P-value0.001) as well as significant prolongation of CFT and CT (1126.5 vs. 571.4 s, P-value0.001) compared to fresh pRBCs. FFP addition to 15-day old and fresh pRBCs, demonstrated a significant reduction in MCF and persistent prolongation of CFT. This suggests that pRBCs lost coagulability as they aged and this deficit was not completely corrected by plasma administration.Storage duration may be an important factor in coagulation potential of pRBCs. Transfusion with older pRBCs may contribute to coagulopathy in massively transfused patients.

Introduction Combined burn injury and hemorrhagic shock are a common cause of injury in wounded warfighters. Current protocols for resuscitation for isolated burn injury and isolated hemorrhagic shock are well defined, but the optimal strategy for combined injury is not fully established. Direct peritoneal resuscitation (DPR) has been shown to improve survival in rats after hemorrhagic shock, but its role in a combined burn/hemorrhage injury is unknown. We hypothesized that DPR would improve survival in mice subjected to combined burn injury and hemorrhage. Materials and Methods Male C57/BL6J mice aged 8 weeks were subjected to a 7-second 30% total body surface area scald in a 90°C water bath. Following the scald, mice received DPR with 1.5 mL normal saline or 1.5 mL peritoneal dialysis solution (Delflex). Control mice received no peritoneal solution. Mice underwent a controlled hemorrhage shock via femoral artery cannulation to a systolic blood pressure of 25 mm Hg for 30 minutes. Mice were then resuscitated to a target blood pressure with either lactated Ringer’s (LR) or a 1:1 ratio of packed red blood cells (pRBCs) and fresh frozen plasma (FFP). Mice were observed for 24 hours following injury. Results Median survival time for mice with no DPR was 1.47 hours in combination with intravascular LR resuscitation and 2.08 hours with 1:1 pRBC:FFP. Median survival time significantly improved with the addition of intraperitoneal normal saline or Delflex. Mice that received DPR followed by 1:1 pRBC:FFP required less intravascular volume than mice that received DPR with LR, pRBC:FFP alone, and LR alone. Intraperitoneal Delflex was associated with higher levels of tumor necrosis factor alpha and macrophage inflammatory protein 1 alpha and lower levels of interleukin 10 and intestinal fatty acid binding protein. Intraperitoneal normal saline resulted in less lung injury 1 hour postresuscitation, but increased to similar severity of Delflex at 4 hours. Conclusions After a combined burn injury and hemorrhage, DPR leads to increased survival in mice. Survival was similar with the use of normal saline or Delflex. DPR with normal saline reduced the inflammatory response seen with Delflex and delayed the progression of acute lung injury. DPR may be a valuable strategy in the treatment of patients with combined burn injury and hemorrhage.

BACKGROUND: Recent military and civilian experience suggests that fresh whole blood may be the preferred for treatment of hemorrhagic shock, but its use is limited by its 21-day shelf life. The red blood cell storage lesion and coagulation status of packed red blood cells (pRBCs) salvaged from expired whole blood are unknown. We hypothesized that packed red blood cells can be salvaged from previously stored whole blood. METHODS: Cold stored, low-titer, O-positive, non-leukoreduced, whole blood units were obtained at 21 days of storage. Erythrocytes were separated by centrifugation, resuspended in AS-3, and stored for 21 additional days as salvaged pRBCs. The red blood cell storage lesion parameters of microvesicles, Band-3, free hemoglobin, annexin V, and erythrocyte osmotic fragility were measured and compared to pRBCs prepared at the time of donation and stored in AS-3 for 42 days (standard pRBCs). In additional experiments, murine pRBCs were prepared from expired whole blood units and compared to those stored under standard conditions. Mice underwent hemorrhage and resuscitation with standard and salvaged pRBC units and serum cytokines and free hemoglobin were determined. RESULTS: There were no significant differences in microvesicle formation or cell-free hemoglobin concentration between salvaged and standard pRBCs. There was decreased Band-3 and increased phosphatidylserine in the salvaged units as well as greater osmotic fragility. Salvaged pRBCs maintained consistent clot firmness. After hemorrhage and resuscitation in a murine model, salvaged pRBCs did not demonstrate increased serum cytokine levels. CONCLUSIONS: Salvaged pRBCs from previously stored whole blood accumulate the red blood cell storage lesion in a similar fashion to standard pRBCs and maintain consistent coagulability when reconstituted with plasma. Salvaged pRBCs are not associated with an increased inflammatory response when used for resuscitation in a murine model. Salvaged pRBCs may be a viable product for utilization in the treatment of traumatic hemorrhagic shock. LEVEL OF EVIDENCE: Level II (prospective laboratory study, therapeutic)

Non-compressible torso hemorrhage accounts for a significant portion of preventable trauma deaths. We report here on the development of injectable, targeted supramolecular nanotherapeutics based on peptide amphiphile (PA) molecules that are designed to target tissue factor (TF) and, therefore, selectively localize to sites of injury to slow hemorrhage. Eight TF-targeting sequences were identified, synthesized into PA molecules, co-assembled with non-targeted backbone PA at various weight percentages, and characterized via circular dichroism spectroscopy, transmission electron microscopy, and X-ray scattering. Following intravenous injection in a rat liver hemorrhage model, two of these PA nanofiber co-assemblies exhibited the most specific localization to the site of injury compared to controls (p

Acute lung injury is a major complication of hemorrhagic shock and the required resuscitation with large volumes of crystalloid fluids and blood products. We previously identified a role of macrophage-derived chemokine (CCL22/MDC) pulmonary inflammation following hemorrhage and resuscitation. However, further details regarding the induction of CCL22/MDC and its precise role in pulmonary inflammation after trauma remain unknown. In the current study we used in vitro experiments with a murine alveolar macrophage cell line, as well as an in vivo mouse model of hemorrhage and resuscitation, to identify key regulators in CCL22/MDC production. We show that trauma induces expression of IFNγ, which leads to production of CCL22/MDC through a signaling mechanism involving p38 MAPK, NF-κB, JAK, and STAT-1. IFNγ also activates TNFα production by alveolar macrophages, potentiating CCL22/MDC production via an autocrine mechanism. Neutralization of IFNγ or TNFα with specific antibodies reduced histological signs of pulmonary injury after hemorrhage and reduced inflammatory cell infiltration into the lungs.

Introduction:Acute care research (ACR) is uniquely challenged by the constraints of recruiting participants and conducting research procedures within minutes to hours of an unscheduled critical illness or injury. Existing competencies for clinical research professionals (CRPs) are gaining traction but may have gaps for the acute environment. We sought to expand existing CRP competencies to include the specialized skills needed for ACR settings.Methods:Qualitative data collected from job shadowing, clinical observations, and interviews were analyzed to assess the educational needs of the acute care clinical research workforce. We identified competencies necessary to succeed as an ACR-CRP, and then applied Bloom’s Taxonomy to develop characteristics into learning outcomes that frame both knowledge to be acquired and job performance metrics.Results:There were 28 special interest competencies for ACR-CRPs identified within the eight domains set by the Joint Task Force (JTF) of Clinical Trial Competency. While the eight domains were not prioritized by the JTF, in ACR an emphasis on Communication and Teamwork, Clinical Trials Operations, and Data Management and Informatics was observed. Within each domain, distinct proficiencies and unique personal characteristics essential for success were identified. The competencies suggest that a combination of competency-based training, behavioral-based hiring practices, and continuing professional development will be essential to ACR success.Conclusion:The competencies developed for ACR can serve as a training guide for CRPs to be prepared for the challenges of conducting research within this vulnerable population. Hiring, training, and supporting the development of this workforce are foundational to clinical research in this challenging setting.

Background The aim of this review was to describe emerging therapies that could serve as a prehospital intervention to slow or stop noncompressible torso hemorrhage in the civilian and military settings. Hemorrhage accounts for 90% of potentially survivable military deaths and 30%-40% of trauma deaths. There is a great need to develop novel therapies to slow or stop noncompressible torso hemorrhage at the scene of the injury. Methods A comprehensive literature search was performed using PubMed (1966 to present) for therapies not approved by the Food and Drug Administration for noncompressible torso hemorrhage in the prehospital setting. Therapies were divided into compressive versus intravascular injectable therapies. Ease of administration, skill required to use the therapy, safety profile, stability, shelf-life, mortality benefit, and efficacy were reviewed. Results Multiple potential therapies for noncompressible torso hemorrhage are currently under active investigation. These include (1) tamponade therapies, such as gas insufflation and polyurethane foam injection; (2) freeze-dried blood products and alternatives such as lyophilized platelets; (3) nanoscale injectable therapies such as polyethylene glycol nanospheres, polyethylenimine nanoparticles, SynthoPlate, and tissue factor–targeted nanofibers; and (4) other injectable therapies such as polySTAT and adenosine, lidocaine, and magnesium. Although each of these therapies shows great promise at slowing or stopping hemorrhage in animal models of noncompressible hemorrhage, further research is needed to ensure safety and efficacy in humans. Conclusions Multiple novel therapies are currently under active investigation to slow or stop noncompressible torso hemorrhage in the prehospital setting and show promising results.

Introduction Traumatic brain injury (TBI) has become increasingly prevalent among the injuries sustained in the military. Many wounded warriors require emergency medical evacuation via helicopter and subsequently fixed wing transport. During aeromedical evacuation, both pilots and patients experience whole body vibration due to engine, rotor, and propeller rotation. The impact of posttraumatic vibration and hypoxia exposure characteristic of the aeromedical evacuation environment on TBI is currently unknown. Methods A swine TBI model of controlled cortical impact was utilized. The pigs first underwent TBI or sham injury and were subsequently exposed to vibration or no vibration and hypoxia or normoxia for 2 hours. They were monitored for an additional 4 hours following vibration/hypoxia and blood was drawn at hourly intervals for cytokine and serum biomarker analysis. Continuous physiologic and neurologic monitoring were utilized. Prior to the conclusion of the experiment, the animals underwent brain magnetic resonance imaging. At the end of the study, the brain was extracted for histologic analysis. Results Physiologic parameters except for peripheral capillary oxygen saturation (SpO2) were similar between all groups. The hypoxia groups demonstrated the expected decrease in SpO2 and pO2 during the hypoxic period, and this was sustained throughout the study period. The pH, pCO2 and electrolytes were similar among all groups. Neuron specific enolase was increased over time in the TBI group, however it was similar to the sham TBI group at all time points. There were no differences in IL-1β, IL-6, IL-8, TNFα, GFAP, HIF1α, syndecan-1, or S100β serum levels between groups. The mean ICP during cortical impact in the TBI group was 279.8 ± 56.2 mmHg. However, the postinjury ICP was not different between groups at any subsequent time point. Brain tissue oxygenation and perfusion were similar between all groups. Conclusion In this novel study evaluating the effect of vibration on short-term outcomes following TBI, we demonstrate that the moderate vibration and hypoxia simulating aeromedical evacuation do not impact short term outcomes following TBI.

Introduction During storage, packed red blood cells undergo a series of physical, metabolic, and chemical changes collectively known as the red blood cell storage lesion. One key component of the red blood cell storage lesion is the accumulation of microparticles, which are submicron vesicles shed from erythrocytes as part of the aging process. Previous studies from our laboratory indicate that transfusion of these microparticles leads to lung injury, but the mechanism underlying this process is unknown. In the present study, we hypothesized that microparticles from aged packed red blood cell units induce pulmonary thrombosis. Materials and methods Leukoreduced, platelet-depleted, murine packed red blood cells (pRBCS) were prepared then stored for up to 14 days. Microparticles were isolated from stored units via high-speed centrifugation. Mice were transfused with microparticles. The presence of pulmonary microthrombi was determined with light microscopy, Martius Scarlet Blue, and thrombocyte stains. In additional studies microparticles were labelled with CFSE prior to injection. Murine lung endothelial cells were cultured and P-selectin concentrations determined by ELISA. In subsequent studies, P-selectin was inhibited by PSI-697 injection prior to transfusion. Results We observed an increase in microthrombi formation in lung vasculature in mice receiving microparticles from stored packed red blood cell units as compared with controls. These microthrombi contained platelets, fibrin, and microparticles. Treatment of cultured lung endothelial cells with microparticles led to increased P-selectin in the media. Treatment of mice with a P-selectin inhibitor prior to microparticle infusion decreased microthrombi formation. Conclusions These data suggest that microparticles isolated from aged packed red blood cell units promote the development of pulmonary microthrombi in a murine model of transfusion. This pro-thrombotic event appears to be mediated by P-selectin.

BACKGROUND: Several serum biomarkers have been studied to diagnose incidence and severity of traumatic brain injury (TBI), but a reliable biomarker in TBI has yet to be identified. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) has been proposed as a biomarker in clinical and preclinical studies, largely in the setting of isolated TBI or concussion. The aim of this study was to evaluate the performance of UCH-L1 as a serum biomarker in the setting of polytrauma and TBI. METHODS: Multiple variations of murine TBI and polytrauma models were used to evaluate serum biomarkers. The different models included TBI with and without hemorrhagic shock and resuscitation, isolated extremity vascular ligation, extremity ischemia/reperfusion, and blunt tail injury. Blood was drawn at intervals after injury, and serum levels of neuron-specific enolase, UCH-L1, creatine kinase, and syndecan-1 were evaluated by enzyme-linked immunosorbent assay. RESULTS: UCH-L1 levels were not significantly different between TBI, tail injury, and sham TBI. By contrast, neuron-specific enolase levels were increased in TBI mice compared with tail injury and sham TBI mice. UCH-L1 levels increased regardless of TBI status at 30 min and 4 h after hemorrhagic shock and resuscitation. In mice that underwent femoral artery cannulation followed by hemorrhagic shock/resuscitation, UCH-L1 levels were significantly elevated compared with shock sham mice at 4 h (3158 ± 2168 pg/mL, 4 h shock versus 0 ± 0 pg/mL, 4 h shock sham; P < 0.01) and at 24 h (3253 ± 2954 pg/mL, 24 h shock versus 324 ± 482 pg/mL, 24 h shock sham; P = 0.03). No differences were observed in UCH-L1 levels between the sham shock and the arterial ligation, vein ligation, or extremity ischemia/reperfusion groups at any time point. Similar to UCH-L1, creatine kinase was elevated only after shock compared with sham mice at 4, 24, and 72 h after injury. CONCLUSIONS: Our study demonstrates that UCH-L1 is not a specific marker for TBI but is elevated in models that induce central and peripheral nerve ischemia. Given the increase in UCH-L1 levels observed after hemorrhagic shock, we propose that UCH-L1 may be a useful adjunct in quantifying severity of shock or global ischemia rather than as a specific marker of TBI.

Patients who undergo splenectomy (SPLN) have an estimated 10%-35% risk of venous thromboembolic events; however, the underlying mechanism and strategy for prevention have yet to be identified. The goals of this study were to 1) investigate platelet aggregation after SPLN, 2) examine if aspirin administration could mitigate this effect, and 3) determine if concomitant hemorrhage would affect post-SPLN platelet function and response to aspirin.Murine models of operative SPLN and submandibular bleed (SMB) were utilized. Mice were randomized to eight groups as follows: untouched, SPLN, sham (laparotomy only), SMB, SPLN + SMB, SPLN + aspirin (ASA), SMB + ASA, and SPLN + SMB + ASA. Aspirin (50 mg/kg) was administered on postoperative days (PODs) one and two via oral gavage. Mice were euthanized on POD 3, platelet counts were obtained, and blood samples were analyzed via rotational thromboelastometry and impedance aggregometry with adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists.By POD 3, SPLN mice displayed a significant thrombocytosis compared to untouched, SMB, and sham SPLN mice. Clotting time and clot formation time were significantly decreased in SPLN and SPLN + SMB cohorts compared to untouched and sham controls with elevated mean clot firmness. SPLN mice also displayed a significant increase in ADP- and AA-mediated platelet aggregability compared to untouched controls, SMB, and SPLN + SMB. ASA significantly decreased platelet aggregation via both ADP and AA signaling in SPLN and SPLN + SMB cohorts without affecting viscoelastic coagulation testing.Platelet hyperaggregability after SPLN is mediated by both ADP and AA signaling. Early aspirin administration may prevent increased platelet aggregation exacerbated after polytrauma.

The combined injury of traumatic brain injury and hemorrhagic shock has been shown to worsen coagulopathy and systemic inflammation, thereby increasing posttraumatic morbidity and mortality. Aeromedical evacuation to definitive care may exacerbate postinjury morbidity because of the inherent hypobaric hypoxic environment. We hypothesized that blood product resuscitation may mitigate the adverse physiologic effects of postinjury flight.An established porcine model of controlled cortical injury was used to induce traumatic brain injury. Intracerebral monitors were placed to record intracranial pressure, brain tissue oxygenation, and cerebral perfusion. Each of the 42 pigs was hemorrhaged to a goal mean arterial pressure of 40 ± 5 mm Hg for 1 hour. Pigs were grouped according to resuscitation strategy used-Lactated Ringer's (LR) or shed whole blood (WB)-then placed in an altitude chamber for 2 hours at ground, 8,000 ft, or 22,000 ft, and then observed for 4 hours. Hourly blood samples were analyzed for proinflammatory cytokines and lactate. Internal jugular vein blood flow was monitored continuously for microbubble formation with altitude changes.Cerebral perfusion, tissue oxygenation, and intracranial pressure were unchanged among the six study groups. Venous microbubbles were not observed even with differing altitude or resuscitation strategy. Serum lactate levels from hour 2 of flight to the end of observation were significantly elevated in 22,000 + LR compared with 8,000 + LR and 22,000 + WB. Serum IL-6 levels were significantly elevated in 22,000 + LR compared with 22,000 + WB, 8,000 + LR and ground+LR at hour 1 of observation. Serum tumor necrosis factor-α was significantly elevated at hour 2 of flight in 8,000 + LR versus ground+LR, and in 22,000 + LR vs. 22,000 + WB at hour 1 of observation. Serum IL-1β was significantly elevated hour 1 of flight between 8,000 + LR and ground+LR.Crystalloid resuscitation during aeromedical transport may cause a prolonged lactic acidosis and proinflammatory response that can predispose multiple-injury patients to secondary cellular injury. This physiologic insult may be prevented by using blood product resuscitation strategies.

Purpose of Review With the projected increase in the geriatric patient population, it is of the utmost importance to understand and optimize conditions in the perioperative period to ensure the best surgical outcome. Age-associated changes in respiratory physiology affect the surgical management of geriatric patients. This review focuses on perioperative pulmonary management of elderly individuals. Recent Findings The physiological changes associated with aging include both physical and biochemical alterations that are detrimental to pulmonary function. There is an increased prevalence of chronic lung disease such as COPD and interstitial lung disease which can predispose patients to postoperative pulmonary complications. Additionally, elderly patients, especially those with chronic lung disease, are at risk for frailty. Screening tools have been developed to evaluate risk and aid in the judicious selection of patients for surgical procedures. The concept of “prehabilitation” has been developed to best prepare patients for surgery and may be more influential in the reduction of postoperative pulmonary complications than postoperative rehabilitation. Understanding the age-associated changes in metabolism of drugs has led to dose adjustments in the intraoperative and postoperative periods, reducing respiratory depression and lung protective ventilation and minimally invasive procedures have yielded reductions in postoperative pulmonary complications. Summary The perioperative management of the geriatric population can be divided into three key areas: preoperative risk mitigation, intraoperative considerations, and postoperative management. Preoperative considerations include patient selection and thorough history and physical, along with smoking cessation and prehabilitation in a subset of patients. Operative aspects include careful selection of anesthetic agents, lung protective ventilation, and choice of surgical procedure. Postoperative management should focus on selective use of agents that may contribute to respiratory depression and encouragement of rehabilitation.

Background Although early balanced blood product resuscitation has improved mortality after traumatic injury, many patients still suffer from inflammatory complications. The goal of this study was to identify inflammatory mediators associated with death and multiorgan system failure following severe injury after patients undergo blood product resuscitation. Methods A retrospective secondary analysis of inflammatory markers from the Pragmatic Randomized Optimal Platelet and Plasma Ratios study was performed. Twenty-seven serum biomarkers were measured at 8 time points in the first 72 hours of care and were compared between survivors and nonsurvivors. Biomarkers with significant differences were further analyzed by adjudicated cause of 30-day mortality. Results Biomarkers from 680 patients were analyzed. Seven key inflammatory markers (IL-1ra, IL-6, IL-8, IL-10, eotaxin, IP-10, and MCP-1) were further analyzed. These cytokines were also noted to have the highest hazard ratios of death. Stepwise selection was used for multivariate analysis of survival by time point. MCP-1 at 2 hours, eotaxin and IP-10 at 12 hours, eotaxin at 24 hours, and IP-10 at 72 hours were associated with all-cause mortality. Conclusion Early systemic inflammatory markers are associated with increased risk of mortality after traumatic injury. Future studies should use these biomarkers to prospectively calculate risks of morbidity and causes of mortality for all trauma patients.

While patients undergoing treatment for hematologic malignancies are at risk for a variety of infections, gastrointestinal mucormycosis is a rare and feared complication. Diagnosis requires a high index of suspicion and timely evaluation. Prompt treatment improves patient outcomes.

Background The risk assessment profile (RAP) score has been used to determine patients who would most benefit from lower extremity duplex ultrasound screening (LEDUS). We hypothesized that revising our LEDUS protocol to perform screening ultrasound examinations in patients with an RAP ≥8 within 48 h of admission would reduce the number of LEDUS performed without changing outcomes. Methods A retrospective review was conducted on trauma patients admitted from July 1, 2014, to June 30, 2015, and July 1, 2016, to June 30, 2017. In 2014-2015, patients with an RAP score ≥5 underwent weekly LEDUS examinations starting on hospital day 4. In 2016-2017, the protocol was changed to start screening patients with an RAP score ≥8 by hospital day 2. Both protocols screened with weekly ultrasounds after the first examination. Demographic data, injury characteristics, LEDUS examination findings, chemoprophylaxis type, and venous thromboembolism incidence were collected. Results A total of 602 patients underwent LEDUS examination in 2014-2015, whereas only 412 underwent LEDUS in 2016-2017. No significant difference was seen in the number of patients diagnosed with deep vein thrombosis (DVT) or pulmonary embolism. DVTs were most often identified on the first LEDUS examination in both cohorts. Of patients diagnosed with a DVT on an LEDUS examination, a significantly higher RAP score (12 versus 10), and a shorter time to first duplex (1 versus 3 d), and DVT diagnosis (2 versus 4 d) were observed in the 2016-2017 cohort. In patients diagnosed with a pulmonary embolism, no significant differences were demonstrated between cohorts. Conclusions Refinement of LEDUS protocols can decrease overutilization of hospital resources without compromising trauma patient outcomes.

The operative experience of today's surgery residents is different than years past. Although overall volume remains stable, the composition is changing. As such, trends in open versus laparoscopic surgery for general surgery residents were examined.The Accreditation Council for Graduate Medical Education national operative log reports from 1994 to 2018 were analyzed for the 15 operations recorded as both open and laparoscopic. Operative volume was examined for total major, surgeon chief, and surgeon junior cases.From 1994 to 2018, 26,258 residents graduated with 955.2 ± 31.7 total major cases. The 15 identified operations comprised 38.4% of this volume. During the 25-year study period, laparoscopic volume increased (+9.67 cases per year), whereas open volume decreased (-3.25 cases per year, P.0001 for each). Similar trends were seen for both chief and surgeon junior cases (P.05 for both). For 2 of the 4 core general surgery operations examined (hernia and proctocolectomy), the open approach was still the dominant approach, providing residents an opportunity to perform open surgery in an era of increasing minimally invasive approaches.For select procedures, the frequency of laparoscopy has surpassed open surgery for general surgery residents. These trends raise the concern that when necessary, general surgery graduates may not have adequate experience converting to open.

Aims/objectives The aim of this study was to evaluate the hemostatic consequences of whole blood leukoreduction (LR). Background Whole blood is being used for trauma resuscitation in the military, and an increasing number of civilian trauma centres across the nation. The benefits of LR, such as decreased infectious and transfusion-related complications, are well established, but the effects on hemostatic parameters remain a concern. Methods Twenty-four units of whole blood were assigned to one of the four groups: non-leukoreduced (NLR), leukoreduced at 1 h and a height of 33 in. (LR-1), leukoreduced at 4 h and a height of 33 in. (LR-4(33)), or leukoreduced at 4 h and a height of 28 in. (LR-4(28)). Viscoelastic parameters, platelet aggregation, cell counts, physiological parameters and thrombin potential were evaluated immediately before and after LR, and on days 1, 7, 14 and 21 following LR. Results The viscoelastic parameters and thrombin generation potential were unchanged between the groups. Platelet aggregation was reduced in the LR-1 group compared with NLR after 7 days. The LR-4(28) group also showed a trend of reduced platelet aggregation compared with NLR. Aggregation in LR-4(33) was similar to NLR throughout the storage time. Physiological and electrolyte changes over the whole blood storage period were not affected by LR. Conclusion Our study shows that whole blood can be LR at 4 h after collection and a height of 33 in. while maintaining platelet count and without altering platelet function and hemostatic performance.

PURPOSE OF REVIEW: The first description of non-invasive ventilation use began in the 1920s. Since then, its role in patient care has evolved through increased clinical knowledge and scientific advancements. The utilization of non-invasive ventilation has broadened from initial application in acute in-hospital ICU settings to now include the outpatient settings. This review discusses the history of non-invasive ventilation and its role in acute in-hospital chronic obstructive pulmonary disease (COPD) exacerbations, cardiogenic pulmonary edema, and weaning from mechanical ventilation in the elderly. The elderly population represents a significant portion of patients hospitalized for the aforementioned conditions. These groups often have more limitations related to the use of invasive mechanical ventilation (IMV), therefore, it is essential to understand the impact of non-invasive ventilation on hospital outcomes. RECENT FINDINGS: There is strong clinical evidence supporting the use of non-invasive ventilation in patients with respiratory failure secondary to acute COPD exacerbations and cardiogenic pulmonary edema. When compared to standard medical management of these conditions, there is a consistent and significant reduction in the rate of endotracheal intubation and in-hospital mortality. SUMMARY: The basis of noninvasive ventilation applicability has been determined by significant reduction in mortality and intubation rates. Although survival benefits have been observed, there still remain limitations to the clinical applicability of non-invasive ventilation in certain patient populations and conditions that require further investigation.

BACKGROUNDRates of damage control laparotomy (DCL) vary widely and consensus on appropriate indications does not exist. The purposes of this multicenter quality improvement (QI) project were to decrease the use of DCL and to identify indications where consensus exists.METHODSIn 2016, six US Level I

BACKGROUNDIn patients for whom surgical equipoise exists for damage control laparotomy (DCL) and definitive laparotomy (DEF), the effect of DCL and its associated resource utilization are unknown. We hypothesized that DEF would be associated with fewer abdominal complications and less resource utili

BACKGROUND/AIMS:During sepsis, an unchecked pro-inflammatory response can be detrimental to the host. We investigated the potential protective effect of amitriptyline (AT). METHODS:We used two murine models of sepsis: Cecal ligation and puncture and endotoxemia following LPS challenge. Aural temperatures were taken and cytokines quantified by cytometric bead assay. Lung injury was determined histologically and by protein determination in bronchoalveolar lavage fluid. Cell accumulation in the peritoneum was analyzed by flow cytometry, as well as cytokine production and p38-phosphorylation. Neutrophil chemotaxis was evaluated using an in vitro transwell assay. RESULTS:Our findings demonstrate that AT-treated septic mice have improved survival and are protected from pulmonary edema. Treatment with AT significantly decreased serum levels of KC and monocyte chemoattractant protein-1, as well as the accumulation of neutrophils and monocytes in the peritoneum of septic mice. Peritoneal IL-10 levels in septic mice were increased upon AT treatment. Direct treatment of septic mice with IL-10 recapitulated the effects of AT. Endotoxemic mice also exhibited enhanced IL-10 production upon AT-administration and peritoneal macrophages were identified as the ATinfluenced producers of IL-10. Treatment of these cells with AT in vitro resulted in increased p38-phosphorylation and IL-10 generation, whereas ceramide and p38 inhibition had the opposite effect. CONCLUSION:Altogether, AT treatment improved survival, increased IL-10 levels, and mitigated a pro-inflammatory response during sepsis. We conclude that AT is a promising therapeutic to temper inflammation during septic shock. CA extern

IntroductionWhile damage control surgery and resuscitation techniques have revolutionized the care of injured service members who sustain severe traumatic hemorrhage, the physiologic and inflammatory consequences of hemostatic resuscitation and staged abdominal surgery in the face of early aeromedical evacuation (AE) have not been investigated. We hypothesized that post-injury AE with an open abdomen would have significant physiologic and inflammatory consequences compared to AE with a closed abdomen.Materials and MethodsEvaluation of resuscitation and staged abdominal closure was performed using a murine model of hemorrhagic shock with laparotomy. Mice underwent controlled hemorrhage to a systolic blood pressure of 25 mmHg and received either no resuscitation, blood product resuscitation, or Hextend resuscitation to a systolic blood pressure of either 50 mmHg (partial resuscitation) or 80 mmHg (complete resuscitation). Laparotomies were either closed prior to AE (closed abdomens) or left open during AE (open abdomens) and subsequently closed. AE was simulated with a 1-hour exposure to a hypobaric hypoxic environment at 8,000 feet altitude. Mice were euthanized at 0, 4, or 24 hours following AE. Serum was collected and analyzed for physiologic variables and inflammatory cytokine levels. Samples of lung and small intestine were collected for tissue cytokine and myeloperoxidase analysis as indicators of intestinal inflammation. Survival curves were also performed.ResultsUnresuscitated mice sustained an 85% mortality rate from hemorrhage and laparotomy, limiting the assessment of the effect of simulated AE in these subgroups. Overall survival was similar among all resuscitated groups regardless of the presence of hypobaric hypoxia, type of resuscitation, or abdominal closure status. Simulated AE had no observed effects on acid/base imbalance or the inflammatory response as compared to ground level controls. All mice experienced both metabolic acidosis and an acute inflammatory response after hemorrhage and injury, represented by an initial increase in serum interleukin (IL)-6 levels. Furthermore, mice with open abdomens had an elevated inflammatory response with increased levels of serum IL-10, serum tumor necrosis factor alpha, intestinal IL-6, intestinal IL-10, and pulmonary myeloperoxidase.ConclusionThese results demonstrate the complex interaction of AE and temporary or definitive abdominal closure after post-injury laparotomy. Contrary to our hypothesis, we found that AE in those animals with open abdomens is relatively safe with no difference in mortality compared to those with closed abdomens. However, given the physiologic and inflammatory changes observed in animals with open abdomens, further evaluation is necessary prior to definitive recommendations regarding the safety or downstream effects of exposure to AE prior to definitive abdominal closure.

Background Deep vein thrombosis (DVT) remains a significant cause of morbidity after injury. Lower extremity duplex ultrasound screening (LEDUS) is designed to identify early, asymptomatic DVTs in moderate and high risk patients. We sought to describe when thrombus is detected and identify which trauma patients benefit from LEDUS. Materials and methods A retrospective review was conducted on trauma patients who were moderate or high risk for venous thromboembolism based on risk assessment profile (RAP) scoring. Patients with RAP scores ≥5 underwent LEDUS on hospital Day 4 and then weekly. We defined moderate venous thromboembolism risk as an RAP score of 5-9 and high risk as an RAP score of ≥10. Demographics, injury characteristics, and chemoprophylaxis type and timing were analyzed. Results A total of 579 trauma patients underwent a total of 820 ultrasounds in 1 y. Eighty-eight acute DVTs were identified. There was only one progression of a below- to above-the-knee DVT. Patients with RAP scores ≥10 had significantly higher rates of DVTs compared with patients with lower RAP scores in addition to longer lengths of stay and time to DVT prophylaxis. Moderate- and high-risk patients had similar rates of pulmonary embolism. Two-thirds of all DVTs were diagnosed on the first screening examination. The rate of DVTs in patients with RAP scores 7-9 was 15.4% compared with 6.1% of those with RAP scores of 5-6. Conclusions LEDUS allows for early identification of asymptomatic DVTs. Moderate-risk patients with RAP scores of ≥7 should be considered for LEDUS, given higher rates of DVT.

Background Tranexamic acid (TXA) has been shown to reduce mortality in the treatment of traumatic hemorrhage. This effect seems most profound when given early after injury. We hypothesized that extending a protocol for TXA administration into the prehospital aeromedical setting would improve outcomes while maintaining a similar safety profile to TXA dosed in the emergency department (ED). Materials and methods We identified all trauma patients who received TXA during prehospital aeromedical transport or in the ED at our urban level I trauma center over an 18-mo period. These patients had been selected prospectively for TXA administration using a protocol that selected adult trauma patients with high-risk mechanism and concern for severe hemorrhage to receive TXA. Patient demographics, vital signs, lab values including thromboelastography, blood administration, mortality, and complications were reviewed retrospectively and analyzed. Results One hundred sixteen patients were identified (62 prehospital versus 54 ED). Prehospital TXA patients were more likely to have sustained blunt injury (76% prehospital versus 46% ED, P = 0.002). There were no differences between groups in injury severity score or initial vital signs. There were no differences in complication rates or mortality. Patients receiving TXA had higher rates of venous thromboembolic events (8.1% in prehospital and 18.5% in ED) than the overall trauma population (2.1%, P Conclusions Prehospital administration of TXA during aeromedical transport did not improve survival compared with ED administration. Treatment with TXA was associated with increased risk of venous thromboembolic events. Prehospital TXA protocols should be refined to identify patients with severe hemorrhagic shock or traumatic brain injury.

Whole blood is a powerful resuscitation strategy for trauma patients but has a shorter shelf life than other blood products. The red blood cell storage lesion in whole blood has not previously been investigated beyond the standard storage period. In the present study, we hypothesized that erythrocytes in stored whole blood exhibit similar aspects of the red blood cell storage lesion and that transfusion of extended storage whole blood would not result in a more severe inflammatory response after hemorrhage in a murine model. To test this hypothesis, we stored low-titer, O-positive, whole blood units, and packed red blood cells (pRBCs) for up to 42 days, then determined aspects of the red blood cell storage lesion. Compared with standard storage pRBCs, whole blood demonstrated decreased microvesicle and free hemoglobin at 21 days of storage and no differences in osmotic fragility. At 42 days of storage, rotational thromboelastometry demonstrated that clotting time was decreased, alpha angle was increased, and clot formation time and maximum clot firmness similar in whole blood as compared with pRBCs with the addition of fresh frozen plasma. In a murine model, extended storage whole blood demonstrated decreased microvesicle formation, phosphatidylserine, and cell-free hemoglobin. After hemorrhage and resuscitation, TNF-a, IL-6, and IL-10 were decreased in mice resuscitated with whole blood. Red blood cell survival was similar at 24 h after transfusion. Taken together, these data suggest that red blood cells within whole blood stored for an extended period of time demonstrate similar or reduced accumulation of the red blood cell storage lesion as compared with pRBCs. Further examination of extended-storage whole blood is warranted.

Thrombocytosis and leukocytosis are common after splenectomy. The potential effect of emergency surgery on these postoperative findings is unknown. We hypothesized that emergency splenectomy leads to a more profound and persistent hematologic change as compared to elective splenectomy.A retrospective review was conducted of patients who underwent elective or trauma splenectomy. Records were queried for platelet (PLT) and white blood cell (WBC) count prior to splenectomy, on postoperative days 1-5, and at day 14, 1 month, 3 months, 6 months, and 1 year. Complications, including thromboembolic events, infection, need for repeat operation, and readmission within 30 days of discharge, were recorded.463 patients were identified as being eligible for the study, with 173 patients in the elective cohort and 145 patients in each of the isolated trauma splenectomy and polytrauma cohorts. Both cohorts had peak thrombocytosis at week 2 postoperatively. However, polytrauma patients had a significantly higher peak platelet count (P0.01). The PLT:WBC ratio was lower in both trauma cohorts pre-operatively and postoperative day 1. Trauma splenectomy had a higher PLT:WBC ratio on days 2 and 3 whereas polytrauma had a lower ratio on days 4 and 5. Emergency cases had greater reoperation and infection rates, whereas elective cases were more likely to require readmission. Postoperative thromboembolic events were only higher in the polytrauma cohort.While trauma splenectomy resulted in more profound postoperative leukocytosis and thrombocytosis, there was no correlation with timing of infection or risk of thromboembolic events. These findings suggest that thrombocytosis and leukocytosis may be associated with thrombotic and infectious events but their presence alone does not indicate direct risks of concomitant infection or thrombosis.

Introduction Trauma to the chest wall is one of the most common injuries suffered. Knowing whether there are regular and reproducible changes in frequency or severity of certain injury types may help resource allocation and improve prevention efforts or outcomes; however, no prior studies have evaluated seasonal variation in chest wall injuries (CWIs). We aimed to determine if CWIs vary annually in a consistent distinct temporal variation. Methods Using an established traumatic blunt CWI database at a single urban level 1 trauma center, patients with a moderate-to-severe (chest wall Abbreviated Injury Score (AIS) ≥2) CWI were reviewed. A subpopulation of predominant chest wall injury (pCWI) was defined as those with a chest wall AIS ≥3 and no other anatomic region having a higher AIS. Demographics, injury patterns, mechanisms of injury, and AIS were collected in addition to date of injury over a 4-y period. Data were analyzed using descriptive statistics as well as Poisson time-series regression for periodicity. Seasonal comparison of populations was performed using Student's t-tests and Analysis of Variance (ANOVA) with significance assessed at a level of P Results Over a 4-y period nearly 16,000 patients presented with injury, of which 3042 patients were found to have a blunt CWI. Total CWI patients per year from 2014 to 2017 ranged from 571 to 947. Over this period, August had the highest incidence for patients with any CWI, moderate-to-severe injuries, and pCWI. February had the lowest overall injury incidence as well as lowest moderate-to-severe injury incidence. January had the lowest pCWI incidence. Yearly changes followed a quadratic sinusoid model that predicted a peak between incidence, between June and October, and the low season. A low season was found to be December–April. Comparing low to high seasons of injured patient monthly means revealed significant differences: total injuries (69.94 versus 85.56, P = 0.04), moderate to severe (62.25 versus 78.19, P = 0.06), and pCWI (25.25 versus 34.44, P = 0.01). Analysis of injuries by mechanism revealed a concomitant increase in motorcycle collisions during this period. Conclusions There appears to be a significant seasonal variation in the overall incidence of CWI as well as severe pCWI, with a high-volume injury season in summer months (June–October) and low-volume season in winter (December–April). Motorcycle accidents were the major blunt injury mechanism that changed with this seasonality. These findings may help guide resource utilization and injury prevention.