Diagnostic Performance of GFAP, UCH-L1, and MAP-2 Within 30 and 60 Minutes of Traumatic Brain Injury.

Importance: Data on the performance of traumatic brain injury (TBI) biomarkers within minutes of injury are lacking. Objectives: To examine the performance of glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), and microtubule-associated protein 2 (MAP-2) within 30 and 60 minutes of TBI in identifying intracranial lesions on computed tomography (CT) scan, need for neurosurgical intervention (NSI), and clinically important early outcomes (CIEO). Design, Setting, and Participants: This cohort study is a biomarker analysis of a multicenter prehospital TBI cohort from the Prehospital Tranexamic Acid Use for TBI clinical trial conducted across 20 centers and 39 emergency medical systems in North America from May 2015 to March 2017. Prehospital hemodynamically stable adult patients with traumatic injury and suspected moderate to severe TBI were included. Blood samples were measured for GFAP, UCH-L1, and MAP-2. Data were analyzed from December 1, 2023, to March 15, 2024. Main Outcomes and Measures: The presence of CT lesions, diffuse injury severity on CT, NSI within 24 hours of injury, and CIEO (composite outcome including early death, neurosurgery, or prolonged mechanical ventilation ≥7 days) within 7 days of injury. Results: Of 966 patients enrolled, 804 patients (mean [SD] age, 41 [19] years; 418 [74.2%] male) had blood samples, including 563 within 60 minutes and 375 within 30 minutes of injury. Among patients with blood drawn within 30 minutes of injury, 212 patients (56.5%) had CT lesions, 61 patients (16.3%) had NSI, and 112 patients (30.0%) had CIEO. Among those with blood drawn within 60 minutes, 316 patients (56.1%) had CT lesions, 95 patients (16.9%) had NSI, and 172 patients (30.6%) had CIEO. All biomarkers showed significant elevations with worsening diffuse injury on CT within 30 and 60 minutes of injury. Among blood samples taken within 30 minutes, GFAP had the highest area under the receiver operating characteristic curve (AUC) to detect CT lesions, at 0.88 (95% CI, 0.85-0.92), followed by MAP-2 (AUC, 0.78; 95% CI, 0.73-0.83) and UCH-L1 (AUC, 0.75; 95% CI, 0.70-0.80). Among blood samples taken within 60 minutes, AUCs for CT lesions were 0.89 (95% CI, 0.86-0.92) for GFAP, 0.76 (95% CI, 0.72-0.80) for MAP-2, and 0.73 (95% CI, 0.69-0.77) for UCH-L1. Among blood samples taken within 30 minutes, AUCs for NSI were 0.78 (95% CI, 0.72-0.84) for GFAP, 0.75 (95% CI, 0.68-0.81) for MAP-2, and 0.69 (95% CI, 0.63-0.75) for UCH-L1; and for CIEO, AUCs were 0.89 (95% CI, 0.85-0.93) for GFAP, 0.83 (95% CI, 0.78-0.87) for MAP-2, and 0.77 (95% CI, 0.72-0.82) for UCH-L1. Combining the biomarkers was no better than GFAP alone for all outcomes. At GFAP of 30 pg/mL within 30 minutes, sensitivity for CT lesions was 98.1% (95% CI, 94.9%-99.4%) and specificity was 34.4% (95% CI, 27.2%-42.2%). GFAP levels greater than 6200 pg/mL were associated with high risk of NSI and CIEO. Conclusions and Relevance: In this cohort study of prehospital patients with TBI, GFAP, UCH-L1, and MAP-2 measured within 30 and 60 minutes of injury were significantly associated with traumatic intracranial lesions and diffuse injury severity on CT scan, 24-hour NSI, and 7-day CIEO. GFAP was the strongest independent marker associated with all outcomes. This study sets a precedent for the early utility of GFAP in the first 30 minutes from injury in future clinical and research endeavors.

Are Data Driving Our Ambulances? Liberal Use of Tranexamic Acid in the Prehospital Setting.

BACKGROUND: Current data on tranexamic acid (TXA) supports early administration for severe hemorrhagic shock. Administration by EMS has been facilitated by developing protocols and standing orders informed by these data. In this study, patterns of TXA use by EMS agencies serving a large level 1 trauma center were examined. We hypothesized that current widespread TXA use often includes administration outside of data-driven indications. METHODS: The trauma registry at a level 1 trauma center was queried for patients who received TXA. To determine the practice patterns and appropriateness of administration of TXA, patients' physiologic state in the prehospital environment based on EMS records, physiologic state on arrival to hospital, and interventions performed in both settings were examined. Over 20 separately managed EMS systems that administer TXA transport patients to this trauma center, allowing for a broad survey of practices. RESULTS: From 2016 to 2021 1089 patients received TXA, 406 (37.3%) having treatment initiated by EMS services. Of these, the average prehospital systolic blood pressure (SBP) was 108.2 mmHg and initial ED SBP was 107.8 mmHg. Only 58.4% of these patients received blood transfusion after arrival to this trauma center. Compliance with standard indications was low with only 14.6% of administrations meeting any data-driven SBP indication. Similar levels of compliance were seen across high volume EMS services. DISCUSSION: Tranexamic acid use has become common in trauma and has been adopted by many EMS systems. These results indicate TXA in the prehospital setting is over-used as administration is not being limited to indications that have shown benefit in prior data.

The effects of timing of prehospital tranexamic acid on outcomes after traumatic brain injury: Subanalysis of a randomized controlled trial.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic that has shown some promise in improving outcomes in traumatic brain injury (TBI), but only when given early after injury. We examined the association between timing of prehospital TXA administration and outcomes in patients with moderate to severe TBI. METHODS: Patients enrolled in the multi-institutional, double-blind randomized prehospital TXA for TBI trial with blunt or penetrating injury and suspected TBI (Glasgow Coma Scale score ≤ 12, SBP ≥90) who received either a 2-g TXA bolus or a 1-g bolus plus 1 g 8 hour infusion within 2 hours of injury were analyzed. Outcomes were compared between early administration (<45 minutes from injury) and late administration ≥45 minutes from injury) using a χ 2 , Fischer's exact test, t test, or Mann-Whitney U test as indicated. Logistic regression examined time to drug as an independent variable. A p value less than 0.05 was considered significant. RESULTS: Six hundred forty-nine patients met inclusion criteria (354 early and 259 late). Twenty-eight-day and 6-month mortalities, 6-month Glasgow Outcome Scale-Extended, and disability rating scale scores were not different between early and late administration. Late administration was associated with higher rates of deep venous thrombosis (0.8 vs. 3.4%, p = 0.02), cerebral vasospasm (0% vs. 2%, p = 0.01), as well as prolonged EMS transport and need for a prehospital airway ( p < 0.01). CONCLUSION: In patients with moderate or severe TBI who received TXA within 2 hours of injury, no mortality benefit was observed in those who received treatment within 45 minutes of injury, although lower rates of select complications were seen. These results support protocols that recommend TXA administration within 45 minutes of injury for patients with suspected TBI. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.

Prehospital resuscitation.

Traumatic injury is the leading cause of death in young people in the USA. Our knowledge of prehospital resuscitation is constantly evolving and is often informed by research based on military experience. A move toward balanced blood product resuscitation and away from excessive crystalloid use has led to improvements in outcomes for trauma patients. This has been facilitated by new technologies allowing more front-line use of blood products as well as use of tranexamic acid in the prehospital setting. In this article, we review current practices in prehospital resuscitation and the studies that have informed these practices.