Traumatic Hemorrhage Research Articles

REBOA to the Rescue: Successful Endovascular Resuscitation of Methemoglobinemia-Induced Cardiac Arrest

REBOA (Resuscitative Endovascular Balloon Occlusion of the Aorta) is an endovascular occlusion device commonly used to temporize bleeding due to traumatic non-compressible torso hemorrhage. This case report presents the successful utilization of REBOA in the resuscitation of a critically ill trauma patient that presented to the emergency department status post motor vehicle collision, later found to have methemoglobinemia. The REBOA was placed as part of a catch-all trauma workup following cardiac arrest after intubation. The timely placement of the REBOA resulted in a return of spontaneous circulation within 30 seconds of balloon inflation. While it is not a definitive treatment of methemoglobinemia, REBOA allowed us to successfully resuscitate the patient until final diagnosis and treatment of the underlying methemoglobinemia could be made. The patient would go on to regain full neurologic function. We believe that this is the first reported resuscitation of a patient with methemoglobinemia utilizing the REBOA device.

Economic and Humanistic Burden of Moderate and Severe Hemophilia A and B in Spain: Real-World Evidence Insights from the CHESS II Study

Economic and Humanistic Burden of Moderate and Severe Hemophilia A and B in Spain: Real-World Evidence Insights from the CHESS II Study

Paris polyphylla Sm. characterized extract infused ointment accelerates diabetic wound healing in In-vivo model

Ethnopharmacological relevanceThe dried rhizome of Paris polyphylla Sm. is extensively used by traditional healers in India, China, and Vietnam to treat skin inflammation, cut wounds, uterine and traumatic bleeding, and cancer. Aim of the studyThe traditional use of P. polyphylla rhizomes for treating wounds and bleeding has been reported previously. However, the potential of P. polyphylla in the treatment of diabetic wounds has not yet been explored. Our present study focused on the investigation of the wound-healing activity of P. polyphylla infused ointment in streptozotocin (STZ)-induced diabetic rats to validate the traditional claim. Materials and methodsHydroalcoholic extract of the dried rhizomes of P. polyphylla were quantified by validated and optimized HPTLC (High-performance thin layer chromatography) method for Paris saponin VII, Dioscin and Polyphyllin V. The extract was used to prepare P. polyphylla ointments (5 and 10%). P. polyphylla ointment was subjected to physiochemical analysis and skin irritation test. Thirty STZ-induced diabetic adult male Wistar albino rats were divided into five groups (n = 6) and a circular excision wound was created. P. polyphylla ointment, ointment base (OB), and standard (STD) (Povidone Iodine 10%) were administered topically. The wound area of all groups were recorded every six days and compared with that of control. The epithelization period of each group was recorded. On day 18, the histopathological study of skin tissues of all groups was performed using hematoxylin and eosin (H&E) and Mallory's trichrome (MT). ResultsMarker analysis and quantification of phytomolecules in hydroalcoholic extract ofP. Polyphylla were found to be of paris saponin VII (3.28 ± 0.08% w/w), dioscin (1.94 ± 0.12% w/w), and polyphyllin V (1.87 ± 0.84% w/w). A physiochemical study of P. polyphylla ointment showed that the prepared ointment was within an acceptable range and was not irritable to the skin. Daily topical administration of 10% P. polyphylla ointment (PP10) for 18 days completely healed the STZ-induced diabetic wounds. On day 18, the 5% P. polyphylla ointment (PP5) showed 99.1 ± 2.9% wound closure, while that of the standard and control was 78.4 ± 7.3% and 18.5 ± 5.9%, respectively. The epithelialization period of PP10 was 18 days, whereas that of the control was 28 days. Histopathological analysis of the progression of PP10 and PP5 wounds showed a decrease in inflammatory cells, regenerated epithelial layer, keratosis layer, hair follicles, fibroblasts, and collagen. Upon collagen intensity quantification of MT stained sections, an increase in collagen density of PP10 and PP5 treated groups was observed, showing accelerated wound healing potential of P. polyphylla extract in diabetic wounds compared to the standard ointment. ConclusionThis study suggested the potential of P. polyphylla rhizomes derived formulation to treat diabetic wounds, although the plant is traditionally used to treat normal wounds. The results indicate the validation of traditional claim, which has been explored commercially in industrial aspect.

Bleeding and Thrombosis in Patients With Out-of-Hospital Ventricular Tachycardia/Ventricular Fibrillation Arrest Treated With Extracorporeal Cardiopulmonary Resuscitation.

Extracorporeal cardiopulmonary resuscitation improves outcomes after out-of-hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in-hospital mortality. Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out-of-hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96-0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P<0.001) though bleeding was not significantly associated with in-hospital death (aHR, 0.81 [95% CI. 0.55-1.19]). A thrombotic event occurred in 23.5% (47/200) of patients. Venous thromboembolism occurred in 11% (22/200) and arterial thrombi in 15.5% (31/200). Clinical characteristics were comparable between groups. In adjusted analyses, no risk factors for thrombosis were identified. Thrombosis was not associated with in-hospital death (aHR, 0.65 [95% CI, 0.42-1.03]). Bleeding is a frequent complication of extracorporeal cardiopulmonary resuscitation that is associated with decreased fibrinogen levels on admission whereas thrombosis is less common. Neither bleeding nor thrombosis was significantly associated with in-hospital mortality.

Granulocyte- Macrophage Colony-Stimulating Factor Reverses Immunosuppression Acutely Following a Traumatic Brain Injury and Hemorrhage Polytrauma in a Juvenile Male Rat Model.

Traumatic brain injury (TBI) is a common cause of morbidity and mortality in children. We have previously shown that TBI with a concurrent extracranial injury reliably leads to post-injury suppression of the innate and adaptive immune systems. In patients with post-injury immune suppression, if immune function could be preserved, this might represent a therapeutic opportunity. As such, we examined, in an animal injury model, whether systemic administration of granulocyte macrophage colony-stimulating factor (GM-CSF) could reverse post-injury immune suppression and whether treatment was associated with neuroinflammation or functional deficit. Prepubescent male rats were injured using a controlled cortical impact model and then subjected to removal of 25% blood volume (TBI/H). Sham animals underwent surgery without injury induction, and the treatment groups were sham and injured animals treated with either saline vehicle or 50 μg/kg GM-CSF. GM-CSF was administered following injury and then daily until sacrifice at post-injury day (PID) 7. Immune function was measured by assessing tumor necrosis factor-α (TNF-α) levels in whole blood and spleen following ex vivo stimulation with pokeweed mitogen (PWM). Brain samples were assessed by multiplex enzyme-linked immunosorbent assay (ELISA) for cytokine levels and by immunohistochemistry for microglia and astrocyte proliferation. Neuronal cell count was examined using cresyl violet staining. Motor coordination was evaluated using the Rotarod performance test. Treatment with GM-CSF was associated with a significantly increased response to PWM in both whole blood and spleen. GM-CSF in injured animals did not lead to increases in levels of pro-inflammatory cytokines in brain samples but was associated with significant increases in counted astrocytes. Finally, while injured animals treated with saline showed a significant impairment on behavioral testing, injured animals treated with GM-CSF performed similarly to uninjured animals. GM-CSF treatment in animals with combined injury led to increased systemic immune cell response in whole blood and spleen in the acute phase following injury. Improved immune response was not associated with elevated pro-inflammatory cytokine levels in the brain or functional impairment.

Renal Function and Survival are Reduced in a Polytrauma Acute Radiation Injury Rat Model with Extremity Trauma and Hemorrhage

The objective of this study was to evaluate whether the presence of radiation injury (RI) decreases survival in an established model of battlefield trauma and hemorrhage in rats. We hypothesized that the addition of radiation to our established traumatic hemorrhage model would increase mortality. Methods: On day zero (D0), male Sprague Dawley rats (n=6/group) received Buprenorphine SR prior to being anesthetized with isoflurane to perform catheterization of a carotid artery. Twenty-four hours later (day 1 or D1), rats were randomly assigned to 1 of 4 groups: 1- sham (no injury; no radiation); 2- RI only; 3- traumatic hemorrhage alone (ET+HEM); or 4- RI combined with traumatic hemorrhage (RI+ET+HEM). For RI and RI+ET+HEM groups, rats were anesthetized and placed inside a cabinet X-ray irradiator (MultiRad 350, Precision, CT) to receive a single sub-lethal X-ray dose of 5.5 Gy, delivered at 1 Gy/min, to induce acute radiation injury. For ET+HEM and RI+ET+HEM groups, under isoflurane, rat then received a unilateral extremity trauma injury. After 90 minutes, a conscious hemorrhage of 37% of the rat estimated blood volume was withdrawn. Rats were monitored for 14 days following injury or sham procedures and provided Buprenorphine SR as needed for pain. Rats remained un-resuscitated and renal function was assessed in vivo by glomerular filtration rate (GFR). GFR was measured with a probe non-invasively and securely strapped to the belly of the rat for about 2.5h. Samples for GFR were collected on D1, day 3 (D3), and day 15 (D15) (or terminal day) from the injury. Result: Sham rats had 100% survival at D15, while RI and ET+HEM rats both had 50% mortality. RI+ET+HEM rats, however, demonstrated 100% mortality by D15; differences in survival proportions were significant (P=0.005). Sham rats showed no significant decrease in GFR (1.0-1.2 ml/min/100g) from D1 to D15. Rats from RI group showed a slight decrease in GFR from D1 to D3 (1.2 to 0.9 ml/min/100g, respectively) at the D3 of measurement. By D15, GFR was 33% lower than D1 in RI group. ET+HEM group showed significant decline in GFR on D1 and D3. However, RI+ET+HEM group showed the most significant decline in GFR ( i.e., &gt;50% lower than sham group on D1 and D3), with little to no improvement over time. Conclusion: We developed a new rodent model of RI+ET+HEM by combining high dose of X-ray irradiation with traumatic hemorrhage, which allows acute (hours) as well as chronic (days) observation. While RI or ET+HEM alone produced significant mortality, the combination of traumatic hemorrhage with RI increased mortality to 100% before D15. Radiation injury combined with extremity trauma and hemorrhage results in significant impairment of renal function. Extremity trauma and hemorrhage impaired renal function more than radiation injury alone. Disclaimer: The views expressed in this abstract are those of the author(s) and do not reflect the offcial policy or position of the U.S. Army Medical Department, Department of the Army, DoD, or the U.S. Government. Supported by Biomedical Advanced Research and Development Authority (BARDA). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Ketamine Sedation Decreases Survival after Extremity Trauma and Moderate Hemorrhage in Rats

Objective: Traumatic hemorrhage (HEM) is often associated with pain. The use of ketamine (KET) has increased both on the battlefield and in civilian emergency care for analgesia and sedation. We have reported that an analgesic dose of KET does not impact cardiorespiratory responses or survival after HEM (JAP 130: 1583-1593, 2021). In this study, we measured the effects of a larger, sedative, dose of KET on cardiovascular responses and survival to moderate (37% blood volume) HEM combined with extremity trauma (ET), and whether midazolam (MDZ), a drug often given in combination with KET alters these responses. Hypothesis: We hypothesized that either KET (50 mg/kg) or KET+MDZ (5 mg/kg) would compromise cardiovascular responses to HEM and thereby decrease survival. Methods: Male rats were implanted with a telemetry transmitter to measure mean arterial pressure (MAP) and heart rate (HR); buprenorphine SR was used to relieve pain associated with surgical procedures. Following 2 weeks recovery, rats were anesthetized using isoflurane, and a carotid catheter was implanted. The next day, rats were briefly anesthetized using isoflurane to perform ET (fibular fracture + hindlimb soft tissue crush injury) and were allowed to recover 90 min before starting conscious HEM (time = 0-25 min). Rats received either 1) saline vehicle (VEH, n=8); 2) KET (n=8); or 3) KET followed by MDZ (KET+MDZ; n=9) during a 15 min infusion (t = 25-40 min). The study continued for 200 minutes (time = 40-240 min). Data are mean ± SD. Results: There were no differences between groups in MAP or HR at either baseline (t = 0 min) or at end of HEM (t = 25 min). However, during the 20 min after treatment (t = 40-60 min), MAP and HR were significantly lower (P≤0.05) in KET (46 ± 3 mmHg; 220 ± 11 bpm) and KET+MDZ (45 ± 10 mmHg; 212 ± 24 bpm) compared to VEH (68 ± 20 mmHg; 297 ± 37 bpm). During this time, only 3 of 8 rats in the KET group survived HEM, while all rats survived in VEH and KET+MDZ groups. At the end of the study (t = 240 min), survival rate was significantly lower (P=0.003) in KET (37.5%) compared to VEH (87.5%) or KET+MDZ (100%). Similarly, survival time was significantly lower (P=0.004) in KET (115 ± 103 min) compared to VEH (227 ± 37 min) or KET+MDZ (240 ± 0 min). Summary of Results: A sedative dose of KET decreased survival following HEM, but the same dose of KET followed by MDZ was protective. The MDZ effect was not due to improvements in cardiovascular responses to the HEM. Conclusion: Sedation with ketamine alone after trauma and moderate HEM decreased survival. Further studies of the effects of sedation with KET alone or KET+MDZ on respiration and metabolic responses to HEM may provide insight on the overall effect on survival. Congressionally Directed Medical Research Program (CDMRP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Every minute matters: Improving outcomes for penetrating trauma through prehospital advanced resuscitative care.

Prehospital resuscitation with blood products is gaining popularity for patients with traumatic hemorrhage. The MEDEVAC trial demonstrated a survival benefit exclusively among patients who received blood or plasma within 15 minutes of air medical evacuation. In fast-paced urban EMS systems with a high incidence of penetrating trauma, mortality data based on the timing to first blood administration is scarce. We hypothesize a survival benefit in patients with severe hemorrhage when blood is administered within the first 15 minutes of EMS patient contact. This was a retrospective analysis of a prospective database of prehospital blood (PHB) administration between 2021 and 2023 in an urban EMS system facing increasing rates of gun violence. PHB patients were compared to trauma registry controls from an era before prehospital blood utilization (2016-2019). Included were patients with penetrating injury and SBP ≤ 90 mmHg at initial EMS evaluation that received at least one unit of blood product after injury. Excluded were isolated head trauma or prehospital cardiac arrest. Time to initiation of blood administration before and after PHB implementation and in-hospital mortality were the primary variables of interest. A total of 143 patients (PHB = 61, controls = 82) were included for analysis. Median age was 34 years with no difference in demographics. Median scene and transport intervals were longer in the PHB cohort, with a 5-minute increase in total prehospital time. Time to administration of first unit of blood was significantly lower in the PHB vs. control group (8 min vs 27 min; p < 0.01). In-hospital mortality was lower in the PHB vs. control group (7% vs 29%; p < 0.01). When controlling for patient age, NISS, tachycardia on EMS evaluation, and total prehospital time interval, multivariate regression revealed an independent increase in mortality by 11% with each minute delay to blood administration following injury (OR 1.11, 95%CI 1.04-1.19). Compared to patients with penetrating trauma and hypotension who first received blood after hospital arrival, resuscitation with blood products was started 19 minutes earlier after initiation of a PHB program despite a 5-minute increase in prehospital time. A survival for early PHB use was demonstrated, with an 11% mortality increase for each minute delay to blood administration. Interventions such as PHB may improve patient outcomes by helping capture opportunities to improve trauma resuscitation closer to the point of injury. Prospective, Level IV.

Development of an efficient hemostatic material based on cuttlefish ink nanoparticles loaded in cuttlebone biocomposite.

Traumatic hemorrhage is one of the main causes of mortality in civilian and military accidents. This study aimed to evaluate the effectiveness of cuttlefish bone (cuttlebone, CB) and CB loaded with cuttlefish ink (CB-CFI) nanoparticles for hemorrhage control. CB and CB-CFI were prepared and characterized using different methods. The hemostasis behavior of constructed biocomposites was investigated in vitro and in vivo using a rat model. Results showed that CFI nanoparticles (NPs) are uniformly dispersed throughout the CB surface. CB-CFI10 (10 mg CFI in 1.0 g of CB) showed the best blood clotting performance in both in vitro and in vivo tests. In vitro findings revealed that the blood clotting time of CB, CFI, and CB-CFI10 was found to be 275.4 ± 12.4 s, 229.9 ± 19.9 s, and 144.0 ± 17.5 s, respectively. The bleeding time in rat liver injury treated with CB, CFI, and CB-CFI10 was 158.1 ± 9.2 s, 114.0 ± 5.7 s, and 46.8 ± 2.7 s, respectively. CB-CFI10 composite resulted in more reduction of aPTT (11.31 ± 1.51 s) in comparison with CB (17.34 ± 2.12 s) and CFI (16.79 ± 1.46 s) (p < 0.05). Furthermore, CB and CB-CFI10 exhibited excellent hemocompatibility. The CB and CB-CFI did not show any cytotoxicity on human foreskin fibroblast (HFF) cells. The CB-CFI has a negative surface charge and may activate coagulation factors through direct contact with their components, including CaCO3, chitin, and CFI-NPs with blood. Thus, the superior hemostatic potential, low cost, abundant, simple, and time-saving preparation process make CB-CFI a very favorable hemostatic material for traumatic bleeding control in clinical applications.

Research priorities in tranexamic acid after trauma: Secondary analysis of the National Trauma Research Action Plan.

Tranexamic acid (TXA) is an antifibrinolytic drug that is used in traumatic hemorrhage and traumatic brain injury. Although TXA is considered relatively safe and inexpensive and is widely available, data regarding its mechanisms, optimal dosing, and timing, as well as relative risks and benefits for different patient populations, are inconsistent. In this study, we aim to identify and summarize consensus research questions related to TXA across all National Trauma Research Action Plan (NTRAP) Delphi expert panels to identify priorities for future research on TXA in trauma. A secondary analysis was performed using consensus-based research priorities collected by 11 NTRAP topic panels using a Delphi methodology. The database of questions was queried for the keywords "tranexamic" and "TXA." The identified questions were sorted by subject matter and summarized. Seven panels included a total of 73 TXA-related questions. Forty-six questions reached consensus. The most addressed topic was outcomes (discussed in 64% of questions) followed by indications (49%) and specific patient populations (38%). Because of overlap across panels, questions were summarized and sorted by topic resulting in 21 priority research questions. Seventy-three total questions and 46 questions reaching consensus were identified by NTRAP panelists. The key topics identified in these questions should be prioritized in future funded research on TXA in trauma. Prognostic and Epidemiological; Level V.

Multicenter Study Examining Temporal Trends in Traumatic Intracranial Hemorrhage Over Six Years Using Joinpoint Regression.

The aging US population has altered the epidemiology of traumatic injury, but there are few studies examining changing patterns of traumatic intracranial hemorrhage (tICH). We examined temporal changes in incidence, demographics, severity, management, and outcomes of tICH among trauma admissions at six US Level I trauma centers over 6 years (July 1, 2016-June 30, 2022). Patients with tICH (subdural, epidural, subarachnoid, and intracerebral hemorrhage) were identified by 10th revision of the International Statistical Classification of Diseases diagnosis codes. Temporal trends were examined over 12 six-month intervals using joinpoint regression and reported as biannual percent change (BPC); models without joinpoints are described as linear trends over time. There were 67,514 trauma admissions over 6 years and 11,935 (17.7%) patients had a tICH. The proportion of tICH injuries significantly increased 2.6% biannually from July 2016 to July 2019 (BPC = 2.6, p = 0.04), then leveled off through June 2022 (BPC = -0.9, p = 0.19). Similarly, the proportion of geriatric patients (≥65 years old) increased 2.4% biannually from July 2016 to July 2019 (BPC = 2.4, p = 0.001) as did injuries due to falls (BPC = 2.2, p = 0.01). Three of the four most prevalent comorbidities significantly increased: hypertension linearly increased 2.1% biannually, functional dependence increased 25.5% biannually through June 2019, and chronic anticoagulant use increased 19.0% biannually through June 2019 and then 3.1% thereafter. There were no trends in the rates of neurosurgical intervention (BPC = -0.89, p = 0.40), ED Glasgow coma score 3-8 (BPC = -0.4, p = 0.77), or presence of severe extracranial injuries (BPC = -0.7, p = 0.45). In-hospital mortality linearly declined 2.6% biannually (BPC = 2.6, p = 0.05); however, there was a 10.3% biannual linear increase in discharge to hospice care (BPC = 10.3, p < 0.001). These results demonstrate the incidence of tICH admissions is temporally increasing, and the population is growing older with more comorbidities and injuries from falls. Yet, traumatic brain injury severity and neurosurgical management are unchanged. The shift from in-patient death to hospice care suggests an increased need for palliative care services.

Early GFAP and UCH-L1 point-of-care biomarker measurements for the prediction of traumatic brain injury and progression in patients with polytrauma and hemorrhagic shock.

Traumatic brain injury (TBI) and hemorrhage are responsible for the largest proportion of all trauma-related deaths. In polytrauma patients at risk of hemorrhage and TBI, the diagnosis, prognosis, and management of TBI remain poorly characterized. The authors sought to characterize the predictive capabilities of glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase L1 (UCH-L1) measurements in patients with hemorrhagic shock with and without concomitant TBI. The authors performed a secondary analysis on serial blood samples derived from a prospective observational cohort study that focused on comparing early whole-blood and component resuscitation. A convenience sample of patients was used in which samples were collected at three time points and the presence of TBI or no TBI via CT imaging was documented. GFAP and UCH-L1 measurements were performed on plasma samples using the i-STAT Alinity point-of-care platform. Using classification tree recursive partitioning, the authors determined the measurement cut points for each biomarker to maximize the abilities for predicting the diagnosis of TBI, Rotterdam CT imaging scores, and 6-month Glasgow Outcome Scale-Extended (GOSE) scores. Biomarker comparisons demonstrated that GFAP and UCH-L1 measurements were associated with the presence of TBI at all time points. Classification tree analyses demonstrated that a GFAP level > 286 pg/ml for the sample taken upon the patient's arrival had an area under the receiver operating characteristic curve of 0.77 for predicting the presence of TBI. The classification tree results demonstrated that a cut point of 3094 pg/ml for the arrival GFAP measurement was the most predictive for an elevated Rotterdam score on the initial and second CT scans and for TBI progression between scans. No significant associations between any of the most predictive cut points for UCH-L1 and Rotterdam CT scores or TBI progression were found. The predictive capabilities of UCH-L1 were limited by the range allowed by the point-of-care platform. Arrival GFAP cut points remained strong independent predictors after controlling for all potential polytrauma confounders, including injury characteristics, shock severity, and resuscitation. Early measurements of GFAP and UCH-L1 on a point-of-care device are significantly associated with CT-diagnosed TBI in patients with polytrauma and shock. Early elevated GFAP measurements are associated with worse head CT scan Rotterdam scores, TBI progression, and worse GOSE scores, and these associations are independent of other injury attributes, shock severity, and early resuscitation characteristics.

Utilization of point-of-care TEG6S and TEG live manager software in HMC trauma bleeding management: Advancing patient care at the bedside

Utilization of point-of-care TEG6S and TEG live manager software in HMC trauma bleeding management: Advancing patient care at the bedside

The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: A subgroup analysis from the prehospital TXA for TBI trial.

In the prehospital tranexamic acid (TXA) for traumatic brain injury (TBI) trial, TXA administered within 2 hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial ( ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale score < 13) and systolic blood pressure ≥ 90 mm Hg within 2 hours of injury to a 2-g out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-g out-of-hospital TXA bolus/1-g in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) ≤ 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-g TXA bolus group (17%) compared with the other two groups (1-g bolus/1-g infusion 26%, placebo 27%). The estimated adjusted difference between the 2-g bolus and placebo groups was -8·5 percentage points (95% confidence interval [CI], -15.9 to -1.0) and between the 2-g bolus and 1-g bolus/1-g infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). Disability Rating Scale at 6 months was lower in the 2-g TXA bolus group than the 1-g bolus/1-g infusion (estimated difference - 2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. A 2-g out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. Therapeutic/Care Management; Level II.

Total intracranial hemorrhage volume measurement summating all compartments best in traumatic and nontraumatic intracranial bleeding.

The ANNEXA-4 trial measured hemostatic efficacy of andexanet alfa in patients with major bleeding taking factor Xa inhibitors. A proportion of this was traumatic and nontraumatic intracranial bleeding. Different measurements were applied in the trial including volumetrics to assess for intracranial bleeding depending on the compartment involved. We aimed to determine the most reliable way to measure intracranial hemorrhage (ICrH) volume by comparing individual brain compartment and total ICrH volume. Thirty patients were randomly selected from the ANNEXA-4 database to assess measurement of ICrH volume by compartment and in total. Total and compartmental hemorrhage volumes were measured by five readers using Quantomo software. Each reader measured baseline hemorrhage volumes twice separated by 1 week. Twenty-eight different ANNEXA-4 subjects were also randomly selected to assess intra-rater reliability of total ICrH volume measurement change at baseline and 12-h follow up, performed by three readers twice to assess hemostatic efficacy categories used in ANNEXA-4. Compartmental minimal detectable change percentages (MDC%) ranged between 9.72 and 224.13, with the greatest measurement error occurring in patients with a subdural hemorrhage. Total ICrH volume measurements had the lowest MDC%, which ranged between 6.57 and 33.52 depending on the reader. Measurement of total ICrH volumes is more accurate than volume by compartment with less measurement error. Determination of hemostatic efficacy was consistent across readers, and within the same reader, as well as when compared to consensus read. Volumetric analysis of intracranial hemostatic efficacy is feasible and reliable when using total ICrH volumes.

Prospective Outpatient Follow-Up of Early Cognitive Impairment in Patients with Mild Traumatic Brain Injury and Intracranial Hemorrhage.

Mild traumatic brain injury (mTBI) encompasses a spectrum of disability including early cognitive impairment (ECI). The Brain Injury Guidelines suggest that patients with mTBI can be safely discharged from the emergency department. Although half of patients with mTBI with intracranial hemorrhage (ICH) have evidence of ECI, it is unclear what percentage of these patients' ECI persists after discharge. We hypothesize a significant proportion of trauma patients with mTBI and ECI at presentation have persistent ECI at 30-day follow-up. A single-center prospective cohort study including adult trauma patients with ICH or skull fracture and a Glasgow Coma Scale of 13 to 15 on arrival was performed. Participants were screened for ECI using the Rancho Los Amigos Scale (RLA), and ECI was defined as an RLA less than 8. We compared ECI and non-ECI groups for demographics, injury profile, CT imaging (eg Rotterdam CT score) and outcomes with bivariate analysis. Thirty-day follow-up telephone calls were performed to re-evaluate RLA for persistent ECI and concussion symptoms. From 62 patients with ICH or skull fracture and mTBI, 21 (33.9%) had ECI. Patients with ECI had a higher incidence of subarachnoid hemorrhage (85.7% vs 46.3%, p = 0.003) and higher Rotterdam CT score (p = 0.004) compared with those without ECI. On 30-day follow-up, 6 of 21 (26.6%) patients had persistent ECI. In addition, 7 (33.3%) patients had continued concussion symptoms. More than one-third of mTBI patients with ICH had ECI. At 30-day postdischarge follow-up, more than one-fourth of these patients had persistent ECI and 33% had concussion symptoms. This highlights the importance of identifying ECI before discharge as a significant portion may have ongoing difficulties reintegrating into work and society.

Hyperkalaemia in bleeding trauma patients: A potential marker of disease severity – A retrospective cohort study

BackgroundHyperkalaemia is a common electrolyte abnormality seen in critically ill patients. In haemorrhagic shock, it may contribute to cardiac arrest and has been identified as a potential marker for tissue hypoxia. However, the significance of its role in haemorrhagic shock and its contribution to mortality remains unclear. This study aimed to examine the potential underlying pathophysiology and evaluate the incidence and characteristics of patients with hyperkalaemia on hospital arrival in bleeding trauma patients before transfusions and its mortality. MethodsA retrospective cohort study was conducted on adult patients with traumatic bleeding admitted to a European Major Trauma Centre between January 2016 and December 2021. Patients were classified according to their serum potassium levels on arrival, and relevant clinical parameters between non-hyperkalaemic and hyperkalaemic patients were compared. ResultsAmong the 83 patients in this study, 8 (9.6 %) presented with hyperkalaemia on arrival. The median shock index showed a higher tendency in the hyperkalaemic group. Hyperkalaemia was found to be more common among younger patients who sustained penetrating trauma. Mortality rates were higher in the hyperkalaemic group, but the difference was not statistically significant. ConclusionOur results suggest that hyperkalaemia occurs frequently in bleeding trauma patients on hospital arrival pre-transfusions, indicating a more severe illness. Our findings provide insights into the pathophysiology and characteristics of hyperkalaemia in bleeding trauma patients. Further studies are required to investigate the mechanisms by which hyperkalaemia contributes to mortality in haemorrhagic shock patients.

Imaging Findings in Acute Traumatic Brain Injury: a National Institute of Neurological Disorders and Stroke Common Data Element-Based Pictorial Review and Analysis of Over 4000 Admission Brain Computed Tomography Scans from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) Study.

In 2010, the National Institute of Neurological Disorders and Stroke (NINDS) created a set of common data elements (CDEs) to help standardize the assessment and reporting of imaging findings in traumatic brain injury (TBI). However, as opposed to other standardized radiology reporting systems, a visual overview and data to support the proposed standardized lexicon are lacking. We used over 4000 admission computed tomography (CT) scans of patients with TBI from the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study to develop an extensive pictorial overview of the NINDS TBI CDEs, with visual examples and background information on individual pathoanatomical lesion types, up to the level of supplemental and emerging information (e.g., location and estimated volumes). We documented the frequency of lesion occurrence, aiming to quantify the relative importance of different CDEs for characterizing TBI, and performed a critical appraisal of our experience with the intent to inform updating of the CDEs. In addition, we investigated the co-occurrence and clustering of lesion types and the distribution of six CT classification systems. The median age of the 4087 patients in our dataset was 50 years (interquartile range, 29-66; range, 0-96), including 238 patients under 18 years old (5.8%). Traumatic subarachnoid hemorrhage (45.3%), skull fractures (37.4%), contusions (31.3%), and acute subdural hematoma (28.9%) were the most frequently occurring CT findings in acute TBI. The ranking of these lesions was the same in patients with mild TBI (baseline Glasgow Coma Scale [GCS] score 13-15) compared with those with moderate-severe TBI (baseline GCS score 3-12), but the frequency of occurrence was up to three times higher in moderate-severe TBI. In most TBI patients with CT abnormalities, there was co-occurrence and clustering of different lesion types, with significant differences between mild and moderate-severe TBI patients. More specifically, lesion patterns were more complex in moderate-severe TBI patients, with more co-existing lesions and more frequent signs of mass effect. These patients also had higher and more heterogeneous CT score distributions, associated with worse predicted outcomes. The critical appraisal of the NINDS CDEs was highly positive, but revealed that full assessment can be time consuming, that some CDEs had very low frequencies, and identified a few redundancies and ambiguity in some definitions. Whilst primarily developed for research, implementation of CDE templates for use in clinical practice is advocated, but this will require development of an abbreviated version. In conclusion, with this study, we provide an educational resource for clinicians and researchers to help assess, characterize, and report the vast and complex spectrum of imaging findings in patients with TBI. Our data provides a comprehensive overview of the contemporary landscape of TBI imaging pathology in Europe, and the findings can serve as empirical evidence for updating the current NINDS radiologic CDEs to version 3.0.

Isolated Traumatic Subarachnoid Hemorrhage on Head Computed Tomography Scan May Not Be Isolated: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (TRACK-TBI) Study.

Isolated traumatic subarachnoid hemorrhage (tSAH) after traumatic brain injury (TBI) on head computed tomography (CT) scan is often regarded as a "mild" injury, with reduced need for additional workup. However, tSAH is also a predictor of incomplete recovery and unfavorable outcome. This study aimed to evaluate the characteristics of CT-occult intracranial injuries on brain magnetic resonance imaging (MRI) scan in TBI patients with emergency department (ED) arrival Glasgow Coma Scale (GCS) score 13-15 and isolated tSAH on CT. The prospective, 18-center Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (TRACK-TBI; enrollment years 2014-2019) enrolled participants who presented to the ED and received a clinically-indicated head CT within 24 h of TBI. A subset of TRACK-TBI participants underwent venipuncture within 24 h for plasma glial fibrillary acidic protein (GFAP) analysis, and research MRI at 2-weeks post-injury. In the current study, TRACK-TBI participants age ≥17 years with ED arrival GCS 13-15, isolated tSAH on initial head CT, plasma GFAP level, and 2-week MRI data were analyzed. In 57 participants, median age was 46.0 years [quartile 1 to 3 (Q1-Q3): 34-57] and 52.6% were male. At ED disposition, 12.3% were discharged home, 61.4% were admitted to hospital ward, and 26.3% to intensive care unit. MRI identified CT-occult traumatic intracranial lesions in 45.6% (26 of 57 participants; one additional lesion type: 31.6%; 2 additional lesion types: 14.0%); of these 26 participants with CT-occult intracranial lesions, 65.4% had axonal injury, 42.3% had subdural hematoma, and 23.1% had intracerebral contusion. GFAP levels were higher in participants with CT-occult MRI lesions compared with without (median: 630.6 pg/mL, Q1-Q3: [172.4-941.2] vs. 226.4 [105.8-436.1], p = 0.049), and were associated with axonal injury (no: median 226.7 pg/mL [109.6-435.1], yes: 828.6 pg/mL [204.0-1194.3], p = 0.009). Our results indicate that isolated tSAH on head CT is often not the sole intracranial traumatic injury in GCS 13-15 TBI. Forty-six percent of patients in our cohort (26 of 57 participants) had additional CT-occult traumatic lesions on MRI. Plasma GFAP may be an important biomarker for the identification of additional CT-occult injuries, including axonal injury. These findings should be interpreted cautiously given our small sample size and await validation from larger studies.

Association between Lipid-Lowering Drugs and Traumatic Subdural Hemorrhage: A Mendelian Randomization Study.

There are current clinical observations that atorvastatin may promote subdural hematoma resorption. We aimed to assess the causal effects of lipid-lowering agents 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors, Proproteinconvertase subtilisin/kexin type 9 (PCSK9) inhibitors and Niemann-Pick C1-like protein 1 (NPC1L1) inhibitors on traumatic subdural hematomas. We used genetic instruments to proxy lipid-lowering drug exposure, with genetic instruments being genetic variants within or near low-density lipoprotein (LDL cholesterol)-associated drug target genes. These were analyzed by using a two-sample Mendelian randomization (MR) study. A causal relationship was found between HMGCR inhibitors and traumatic subdural hematoma (Inverse variance weighted (β = -0.7593341 (Odds Ratio (OR) = 0.4679779), p = 0.008366947 < 0.05)). However, no causal relationship was found between PCSK9 inhibitors and NPC1L1 inhibitors and traumatic subdural hematoma (PCSK9 inhibitors: Inverse variance weighted (β = 0.23897796 (OR = 1.2699505), p = 0.1126327), NPC1L1 inhibitors: Inverse variance weighted (β = -0.02118558 (OR = 0.9790373), p = 0.9701686)). Sensitivity analysis of the data revealed good stability of the results. This two-sample MR study suggests a potential causal relationship between HMGCR inhibition (atorvastatin) and traumatic subdural hemorrhage.