Prolonged hourly neurological examinations are associated with increased delirium and no discernible benefit in mild/moderate geriatric traumatic brain injury.

BACKGROUND: Serial neurological examinations (NEs) are routinely recommended in the intensive care unit (ICU) within the first 24 hours following a traumatic brain injury (TBI). There are currently no widely accepted guidelines for the frequency of NEs. Disruptions to the sleep-wake cycles increase the delirium rate. We aimed to evaluate whether there is a correlation between prolonged hourly (Q1)-NE and development of delirium and to determine if this practice reduces the likelihood of missing the detection of a process requiring emergent intervention. METHODS: A retrospective analysis of patients with mild/moderate TBI, admitted to the ICU with serial NEs, was performed. Cohorts were stratified by the duration of exposure to Q1-NE, into prolonged (≥24 hours) and nonprolonged (<24 hours). Our primary outcomes of interest were delirium, evaluated using the Confusion Assessment Method; radiological progression from baseline images; neurological deterioration (focal neurological deficit, abnormal pupillary examination, or Glasgow Coma Scale score decrease >2); and neurosurgical procedures. RESULTS: A total of 522 patients were included. No significant differences were found in demographics. Patients in the prolonged Q1-NE group (26.1%) had higher Injury Severity Score with similar head Abbreviated Injury Score, significantly higher delirium rate (59% vs. 35%, p < 0.001), and a longer hospital/ICU length of stay when compared with the nonprolonged Q1-NE group. No neurosurgical interventions were found to be performed emergently as a result of findings on NEs. Multivariate analysis demonstrated that prolonged Q1-NE was the only independent risk factor associated with a 2.5-fold increase in delirium rate. The number needed to harm for prolonged Q1-NE was 4. CONCLUSION: Geriatric patients with mild/moderate TBI exposed to Q1-NE for periods longer than 24 hours had nearly a threefold increase in ICU delirium rate. One of five patients exposed to prolonged Q1-NE is harmed by the development of delirium. No patients were found to directly benefit as a result of more frequent NEs. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Dose-Dependent Tranexamic Acid Blunting of Penumbral Leukocyte Mobilization and Blood-Brain Barrier Permeability Following Traumatic Brain Injury: An In Vivo Murine Study.

BACKGROUND: Early posttraumatic brain injury (TBI) tranexamic acid (TXA) may reduce blood-brain barrier (BBB) permeability, but it is unclear if this effect is fixed regardless of dose. We hypothesized that post-TBI TXA demonstrates a dose-dependent reduction of in vivo penumbral leukocyte mobilization, BBB microvascular permeability, and enhancement of neuroclinical recovery. METHODS: CD1 male mice (n = 40) were randomly assigned to TBI by controlled cortical impact (injury [I]) or sham TBI (S), followed by intravenous bolus of either saline (placebo [P]) or TXA (15, 30, or 60 mg/kg). At 48 h, in vivo pial intravital microscopy visualized live penumbral BBB microvascular leukocytes and albumin leakage. Neuroclinical recovery was assessed by Garcia Neurological Test scores and animal weight changes at 24 h and 48 h after injury. RESULTS: I + TXA60 reduced live penumbral leukocyte rolling compared with I + P (p < 0.001) and both lower TXA doses (p = 0.017 vs. I + TXA15, p = 0.012 vs. I + TXA30). Leukocyte adhesion was infrequent and similar across groups. Only I + TXA60 significantly reduced BBB permeability compared with that in the I + P (p = 0.004) group. All TXA doses improved Garcia Test scores relative to I + P at both 24 h and 48 h (p < 0.001 vs. I + P for all at both time points). Mean 24-h body weight loss was greatest in the I + P (- 8.7 ± 1.3%) group and lowest in the I + TXA15 (- 4.4 ± 1.0%, p = 0.051 vs. I + P) group. CONCLUSIONS: Only higher TXA dosing definitively abrogates penumbral leukocyte mobilization, preserving BBB integrity post TBI. Some neuroclinical recovery is observed, even with lower TXA dosing. Better outcomes with higher dose TXA after TBI may occur secondary to blunting of leukocyte-mediated penumbral cerebrovascular inflammation.

Inadequate prophylaxis in patients with trauma: anti-Xa-guided enoxaparin dosing management in critically ill patients with trauma.

Venous thromboembolism (VTE) causes significant morbidity in patients with trauma despite advances in pharmacologic therapy. Prior literature suggests standard enoxaparin dosing may not achieve target prophylactic anti-Xa levels. We hypothesize that a new weight-based enoxaparin protocol with anti-Xa monitoring for dose titration in critically injured patients is safe and easily implemented. Methods: This prospective observational study included patients with trauma admitted to the trauma intensive care unit (ICU) from January 2021 to September 2022. Enoxaparin dosing was adjusted based on anti-Xa levels as standard of care via a performance improvement initiative. The primary outcome was the proportion of subtarget anti-Xa levels (<0.2 IU/mL) on 30 mg two times per day dosing of enoxaparin. Secondary outcomes included the dosing modifications to attain goal anti-Xa levels, VTE and bleeding events, and hospital and ICU lengths of stay. Results: A total of 282 consecutive patients were included. Baseline demographics revealed a median age of 36 (26-55) years, and 44.7% with penetrating injuries. Of these, 119 (42.7%) achieved a target anti-Xa level on a starting dose of 30 mg two times per day. Dose modifications for subtarget anti-Xa levels were required in 163 patients (57.8%). Of those, 120 underwent at least one dose modification, which resulted in 78 patients (47.8%) who achieved a target level prior to hospital discharge on a higher dose of enoxaparin. Overall, only 69.1% of patients achieved goal anti-Xa level prior to hospital discharge. VTE occurred in 25 patients (8.8%) and major bleeding in 3 (1.1%) patients. Conclusion: A majority of critically injured patients do not meet target anti-Xa levels with 30 mg two times per day enoxaparin dosing. This study highlights the need for anti-Xa-based dose modification and efficacy of a pharmacy-driven protocol. Further optimization is warranted to mitigate VTE events. Level of evidence: Therapeutic/care management, level III.

Brief report on the development of hemorrhagic pericardial effusion after thoracic surgery for traumatic injuries.

Introduction: Hemorrhagic pericardial effusion (HPE) is a rare but life-threatening diagnosis that may occur after thoracic trauma. Previous reports have concentrated on delayed HPE in those who did not require initial surgical intervention for their traumatic injuries. In this report, we identify and characterize the phenomenon of HPE after emergent thoracic surgery for trauma. Methods: This is a retrospective review of patients who required emergent thoracic surgery for trauma at a level 1 trauma center from 2017 to 2021. Using the institutional trauma database, demographics, injury characteristics, and outcomes were compared between patients with HPE and those without HPE after thoracic surgery for trauma. Results: Ninety-one patients were identified who underwent emergent thoracic surgery for trauma. Most were young men who sustained a penetrating thoracic injury. Seven patients (7.7%) went on to develop HPE. Patients who developed HPE were younger (18 vs. 32 years, p=0.034), required bilateral anterolateral thoracotomy (85% vs. 7%, p<0.001), and were more likely to have pulmonary injuries (100% vs. 52.4%, p<0.001). Five patients with HPE survived to hospital discharge. The two patients with HPE who died were both coagulopathic and had HPE diagnosed within 4 days of injury. The median time to HPE diagnosis in survivors was 24 days with four of five HPE survivors on therapeutic anticoagulation at the time of diagnosis. Conclusions: HPE may occur after emergent thoracic surgery for trauma. Those at highest risk of HPE include younger patients with bilateral thoracotomy incisions and pulmonary injuries. Early HPE, clinical signs of tamponade, and/or coagulopathy in patients with HPE portend a worse prognosis. Surgeons and trauma team members caring for patients after emergent thoracic exploration for trauma should be aware of this potentially devastating complication and should consider postoperative echocardiography in high-risk patients.

Rethinking protocolized completion angiography following extremity vascular trauma: A prospective observational multicenter trial.

BACKGROUND: Completion angiography (CA) is commonly used following repair of extremity vascular injury and is recommended by the Eastern Association for the Surgery of Trauma practice management guidelines for extremity trauma. However, it remains unclear which patients benefit from CA because only level 3 evidence exists. METHODS: This prospective observational multicenter (18LI, 2LII) analysis included patients 15 years or older with extremity vascular injuries requiring operative management. Clinical variables and outcomes were analyzed with respect to with our primary study endpoint, which is need for secondary vascular intervention. RESULTS: Of 438 patients, 296 patients required arterial repair, and 90 patients (30.4%) underwent CA following arterial repair. Institutional protocol (70.9%) was cited as the most common reason to perform CA compared with concern for inadequate repair (29.1%). No patients required a redo extremity vascular surgery if a CA was performed per institutional protocol; however, 26.7% required redo vascular surgery if the CA was performed because of a concern for inadequate repair. No differences were observed in hospital mortality, length of stay, extremity ischemia, or need for amputation between those who did and did not undergo CA. CONCLUSION: Completion angiogram following major extremity injury should be considered in a case-by-case basis. Limiting completion angiograms to those patients with concern for an inadequate vascular repair may limit unnecessary surgery and morbidity. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Early posttraumatic brain injury tranexamic acid prevents blood-brain barrier hyperpermeability and improves surrogates of neuroclinical recovery.

BACKGROUND: Tranexamic acid (TXA) given early, but not late, after traumatic brain injury (TBI) appears to improve survival. This may be partly related to TXA-driven profibrinolysis and increased leukocyte (LEU)-mediated inflammation when administered late post-injury. We hypothesized that early TXA (1 hour post-TBI), blunts penumbral, blood-brain barrier (BBB) leukocyte-endothelial cell (LEU-EC) interactions and microvascular permeability, in vivo when compared with late administration (24 hours post-TBI). METHODS: CD1 male mice (n = 35) were randomized to severe TBI (injury by controlled cortical impact; injury: velocity, 6 m/s; depth, 1 mm; diameter, 3 mm) or sham craniotomy followed by intravenous saline (placebo) at 1 hour, or TXA (30 mg/kg) at 1 hour or 24 hours. At 48 hours, in vivo pial intravital microscopy visualized live penumbral LEU-EC interactions and BBB microvascular fluorescent albumin leakage. Neuroclinical recovery was assessed by the Garcia Neurological Test (motor, sensory, reflex, and balance assessments) and body weight loss recovery at 1 and 2 days after injury. Analysis of variance with Bonferroni correction assessed intergroup differences ( p < 0.05). RESULTS: One-hour, but not 24-hour, TXA improved Garcia Neurological Test performance on day 1 post-TBI compared with placebo. Both 1 hour and 24 hours TXA similarly improved day 1 weight loss recovery, but only 1 hour TXA significantly improved weight loss recovery on day 2 compared with placebo ( p = 0.04). No intergroup differences were found in LEU rolling or adhesion between injured animal groups. Compared with untreated injured animals, only TXA at 1 hour reduced BBB permeability. CONCLUSION: Only early post-TBI TXA consistently improves murine neurological recovery. Tranexamic acid preserves BBB integrity but only when administered early. This effect appears independent of LEU-EC interactions and demonstrates a time-sensitive effect that supports only early TXA administration.

Neurotrauma.

PURPOSE OF REVIEW: This review will highlight the latest research relevant to the clinical care of traumatic brain injury (TBI) patients over the last 2 years while underscoring the implications of these advances in the understanding of diagnosis, treatment, and prognosis of TBI. RECENT FINDINGS: Brain tissue oxygenation monitoring can identify hypoperfusion as an adjunct to intracerebral pressure monitoring. Multiple biomarker assays are now available to help clinicians screen for mild TBI and biomarker elevations correlate with the size of intracranial injury. Beta-blocker exposure following TBI has demonstrated a survival benefit in those with TBI though the mechanism for this remains unknown. The optimal timing for venous thromboembolism prophylaxis for TBI patients is still uncertain. SUMMARY: The current characterization of TBI as mild, moderate, or severe fails to capture the complexity of the disease process and helps little with prognostication. Molecular biomarkers and invasive monitoring devices including brain tissue oxygenation and measures of cerebral autoregulation are being utilized more commonly and can help guide therapy. Extracranial complications following TBI are common and include infection, respiratory failure, coagulopathy, hypercoagulability, and paroxysmal sympathetic hyperactivity.

"Early results after initiation of a rib fixation programme: A propensity score matched analysis".

INTRODUCTION: 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. MATERIALS AND METHODS: 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. RESULTS: 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, p < 0.01), 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, p<0.01) 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.

Attending and Resident Surgeon Perspectives and Prescribing Practices of Pain Medication During the Opioid Epidemic.

OBJECTIVE: 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. DESIGN: 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. SETTING: Two Accreditation Council for Graduate Medical Education accredited general surgery programs at a university-based tertiary hospital and a community hospital in the Midwest. PARTICIPANTS: Attending and resident physicians within the Departments of Surgery participated anonymously. RESULTS: Attending surgeons were more likely than residents to discuss posoperative opioids with patients (62% vs. 33%; p < 0.05), discuss the potential of opioid abuse (31% vs. 6%; p < 0.05), and check state-specific prescription monitoring programs (15% vs. 0%; p < 0.05). 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 with >5 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%). CONCLUSION AND RELEVANCE: 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 Role of Acid Sphingomyelinase Inhibition in Repetitive Mild Traumatic Brain Injury.

BACKGROUND: Chronic traumatic encephalopathy is a consequence of repetitive mild traumatic brain injury (rmTBI). These injuries can result in psychiatric disorders that are treated with amitriptyline. Amitriptyline improves neuronal regeneration in major depression via inhibition of acid sphingomyelinase. We hypothesized that acid sphingomyelinase inhibition would preserve neuronal regeneration and decrease depressive symptoms following rmTBI in a murine model. METHODS: A murine model of rmTBI was established using a weight-drop method. Mice were subjected to mTBI every other day for 7 d. Mice received amitriptyline injection 2 h prior to each mTBI. After the final mTBI, mice underwent behavioral studies or biochemical analysis. Hippocampi were analyzed for markers of neurogenesis and phosphorylated tau aggregation. RESULTS: Mice that underwent rmTBI showed increased hippocampal phosphorylated tau aggregation 1 mo following rmTBI as well as decreased neuronal regeneration by bromodeoxyuridine uptake and doublecortin immunohistochemistry. Mice with either genetic deficiency or pharmacologic inhibition of acid sphingomyelinase demonstrated improved neuronal regeneration and decreased phosphorylated tau aggregation compared to untreated rmTBI mice. Behavioral testing showed rmTBI mice spent significantly more time in the dark and waiting to initiate feeding compared to sham mice. These behaviors were partially prevented by the inhibition of acid sphingomyelinase. CONCLUSIONS: We established a murine model of rmTBI that leads to tauopathy, depression, and impaired hippocampal neurogenesis. Inhibition of acid sphingomyelinase prevented the harmful neurologic and behavioral effects of rmTBI. These findings highlight an important opportunity to improve recovery or prevent neuropsychiatric decline in patients at risk for chronic traumatic encephalopathy.

Intrathoracic Pressure Regulator Performance in the Setting of Hemorrhage and Acute Lung Injury.

INTRODUCTION: Intrathoracic pressure regulation (ITPR) can be utilized to enhance venous return and cardiac preload by inducing negative end expiratory pressure in mechanically ventilated patients. Previous preclinical studies have shown increased mean arterial pressure (MAP) and decreased intracranial pressure (ICP) with use of an ITPR device. The aim of this study was to evaluate the hemodynamic and respiratory effects of ITPR in a porcine polytrauma model of hemorrhagic shock and acute lung injury (ALI). METHODS: Swine were anesthetized and underwent a combination of sham, hemorrhage, and/or lung injury. The experimental groups included: no injury with and without ITPR (ITPR, Sham), hemorrhage with and without ITPR (ITPR/Hem, Hem), and hemorrhage and ALI with and without ITPR (ITPR/Hem/ALI, Hem/ALI). The ITPR device was initiated at a setting of -3 cmH2O and incrementally decreased by 3 cmH2O after 30 minutes on each setting, with 15 minutes allowed for recovery between settings, to a nadir of -12 cmH2O. Histopathological analysis of the lungs was scored by blinded, independent reviewers. Of note, all animals were chemically paralyzed for the experiments to suppress gasping at ITPR pressures below -6 cmH2O. RESULTS: Adequate shock was induced in the hemorrhage model, with the MAP being decreased in the Hem and ITPR/Hem group compared with Sham and ITPR/Sham, respectively, at all time points (Hem 54.2 ± 6.5 mmHg vs. 88.0 ± 13.9 mmHg, p < 0.01, -12 cmH2O; ITPR/Hem 59.5 ± 14.4 mmHg vs. 86.7 ± 12.1 mmHg, p < 0.01, -12 cmH2O). In addition, the PaO2/FIO2 ratio was appropriately decreased in Hem/ALI compared with Sham and Hem groups (231.6 ± 152.5 vs. 502.0 ± 24.6 (Sham) p < 0.05 vs. 463.6 ± 10.2, (Hem) p < 0.01, -12 cmH2O). Heart rate was consistently higher in the ITPR/Hem/ALI group compared with the Hem/ALI group (255 ± 26 bpm vs. 150.6 ± 62.3 bpm, -12 cmH2O) and higher in the ITPR/Hem group compared with Hem. Respiratory rate (adjusted to maintain pH) was also higher in the ITPR/Hem/ALI group compared with Hem/ALI at -9 and - 12 cmH2O (32.8 ± 3.0 breaths per minute (bpm) vs. 26.8 ± 3.6 bpm, -12 cmH2O) and higher in the ITPR/Hem group compared with Hem at -6, -9, and - 12 cmH2O. Lung compliance and end expiratory lung volume (EELV) were both consistently decreased in all three ITPR groups compared with their controls. Histopathologic severity of lung injury was worse in the ITPR and ALI groups compared with their respective injured controls or Sham. CONCLUSION: In this swine polytrauma model, we demonstrated successful establishment of hemorrhage and combined hemorrhage/ALI models. While ITPR did not demonstrate a benefit for MAP or ICP, our data demonstrate that the ITPR device induced tachycardia with associated increase in cardiac output, as well as tachypnea with decreased lung compliance, EELV, PaO2/FIO2 ratio, and worse histopathologic lung injury. Therefore, implementation of the ITPR device in the setting of polytrauma may compromise pulmonary function without significant hemodynamic improvement.

Death by Decade: Establishing a Transfusion Ceiling for Futility in Massive Transfusion.

BACKGROUND: Age and massive transfusion are predictors of mortality after trauma. We hypothesized that increasing age and high-volume transfusion would result in progressively elevated mortality rates and that a transfusion "ceiling" would define futility. METHODS: The Trauma Quality Improvement Program (TQIP) database was queried for 2013-2016 records and our level I trauma registry was reviewed from 2013 to 2018. Demographic, mortality, and blood transfusion data were collected. Patients were grouped by decade of life and by packed red blood cell (pRBC) transfusion requirement (zero units, 1-3 units, or ≥4 units) within 4 h of admission. RESULTS: TQIP analysis demonstrated an in-hospital mortality risk that increased linearly with age, to an odds ratio of 10.1 in ≥80 y old (P < 0.01). Mortality rates were significantly higher in older adults (P < 0.01) and those with more pRBCs transfused. In massively transfused patients, the transfusion "ceiling" was dependent on age. Owing to the lack granularity in the TQIP database, 230 patients from our institution who received ≥4 units of pRBCs within 4 h of admission were reviewed. On arrival, younger patients had significantly higher heart rates and more severe derangements in lactate levels, base deficits, and pH compared with older patients. There were no differences among age groups in injury severity score, systolic blood pressure, or mortality. CONCLUSIONS: In massively transfused patients, mortality increased with age. However, a significant proportion of older adults were successfully resuscitated. Therefore, age alone should not be considered a contraindication to high-volume transfusion. Traditional physiologic and laboratory criteria indicative of hemorrhagic shock may have reduced reliability with increasing age, and thus providers must have a heightened suspicion for hemorrhage in the elderly. Early transfusion requirements can be combined with age to establish prognosis to define futility to help counsel families regarding mortality after traumatic injury.

Acid Sphingomyelinase Inhibition Mitigates Histopathological and Behavioral Changes in a Murine Model of Traumatic Brain Injury.

Traumatic brain injury (TBI) can lead to the development of chronic traumatic encephalopathy as a result of neuronal phosphorylated tau (p-tau) protein aggregation and neuroinflammation. Acid sphingomyelinase (Asm) may also contribute to post-TBI neurodegenerative disorders. We hypothesized that Asm inhibition would ameliorate p-tau aggregation, neuroinflammation, and behavioral changes after TBI in a murine model. TBI was generated using a weight-drop method. Asm inhibition in wild-type mice was achieved with a single injection of amitriptyline 1 h after TBI. Genetic Asm ablation was achieved using Asm-deficient mice (Asm-/-). Thirty days after TBI, mice underwent behavioral testing with the forced swim test for symptoms of depression or were euthanized for neurohistological analysis. Neuroinflammation was quantified using the microglial markers, ionized calcium-binding adaptor molecule 1 and transmembrane protein 119. Compared to sham mice, TBI mice demonstrated increased hippocampal p-tau. Mice that received amitriptyline after TBI demonstrated decreased p-tau compared to mice that received a saline control. Further, post-TBI Asm-/- mice demonstrated lower levels of p-tau compared to wild-type mice. Though a decrease in neuroinflammation was observed at 1 month post-TBI, no change was demonstrated with mice treated with amitriptyline. Similarly, TBI mice were more likely to show depression compared to mice that received amitriptyline after TBI. Utilizing a weight-drop method to induce moderate TBI, we have shown that genetic deficiency or pharmacological inhibition of Asm prevented hippocampal p-tau aggregation 1 month after injury as well as decreased symptoms of depression. These findings highlight an opportunity to potentially reduce the long-term consequences of TBI.

Oxygenation extremes after traumatic brain injury transiently affect coagulation.

INTRODUCTION: Trauma patients may become hypoxic or iatrogenically hyperoxic in the early post-injury period. While both extremes of oxygenation may be harmful following injury, the mechanism has yet to be elucidated. We hypothesized that hypoxia or hyperoxia would induce changes in coagulation, creating a secondary insult exacerbating the primary injury. MATERIALS AND METHODS: Mice underwent traumatic brain injury (TBI) or sham and were subsequently exposed to room air or brief hypoxia (15% FiO2) then sacrificed at intervals. Another cohort of uninjured mice underwent more prolonged hypoxia (10% FiO2) or hyperoxia (60% FiO2). Platelet function was evaluated by ADP- or ASPi-induced impedance aggregometry and viscoelastic coagulation parameters were assessed with rotational thromboelastometry. RESULTS: In uninjured mice, ADP-induced platelet aggregation was acutely increased after prolonged hypoxia, but this difference did not persist at 6 h. Hypoxic and hyperoxic TBI mice had increased ADP induced platelet aggregation at 1 h compared to the normoxia group. TBI mice demonstrated an early increased platelet aggregation after hypoxia or hyperoxia. Viscoelastic coagulation parameters were similar between hypoxic, hyperoxic and room air groups at 1 h and 6 h. However, ROTEM clotting time and clot formation time were prolonged and maximal clot firmness were lower in sham TBI/hypoxia mice at 24 h. CONCLUSION: Post-TBI hypoxia and hyperoxia resulted in transiently increased platelet aggregation in response to ADP, without lasting effecting on platelet function or coagulation. Hypoxia also induced delayed hypocoagulability after platelet aggregation normalized. Brief changes in oxygenation may temporally affect coagulation and platelet aggregation, which could contribute to physiologic secondary injury after trauma.

UCH-L1 is a Poor Serum Biomarker of Murine Traumatic Brain Injury After Polytrauma.

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.

Optimizing Lower Extremity Duplex Ultrasound Screening After Traumatic Injury.

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.