1. Prehospital tranexamic acid is associated with a survival benefit without an increase in complications: Results of two harmonized randomized clinical trials. Mazzei M, Donohue JK, Schreiber M, et al. J Trauma Acute Care Surg. 2024;97:697–702.
2. Every minute matters: Improving outcomes for penetrating trauma through prehospital advanced resuscitative care. Duchesne J, McLafferty BJ, Broome JM, et al. J Trauma Acute Care Surg. 2024;97:710–715.
3. A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest. Couper K, Ji C, Deakin CD, et al. New Engl J Med. 2024 Published on-line at: https://www.nejm.org/doi/full/10.1056/NEJMoa2407780
4. Pediatric trauma population spine immobilization during resuscitation: A call for improved guidelines. Breeding T, Nasef H, Amin Q, Smith C, Elkbuli A. Amer J Emerg Med 2024;76:150-154.
International Prehospital Medicine Institute Literature Review, November 2024
1. Prehospital tranexamic acid is associated with a survival benefit without an increase in complications: Results of two harmonized randomized clinical trials. Mazzei M, Donohue JK, Schreiber M, et al. J Trauma Acute Care Surg. 2024;97:697–702.
Prehospital trauma resuscitation practices have continued to evolve and improve over the past decade. One of the most adopted practices has been the administration of prehospital tranexamic acid (TXA) to patients with known or suspected severe hemorrhage. TXA is classified as an anti-fibrinolytic drug, meaning it is meant to slow the breakdown of clot formation. Multiple trials, both in-hospital and prehospital, show conflicting results as to whether TXA administration improves survival after injury.
This study combined data from two previously published studies on prehospital TXA use – the Study of Tranexamic Acid during Air Medical Prehospital Transport (STAAMP) and the Prehospital Tranexamic Acid Use for Traumatic Brain Injury (ROC-TXA) trials. Both studies were multicenter, double-blind, randomized, placebo-controlled trials.
The STAAMP trial included patients with either hypotension (SBP < 90 mmHg) or tachycardia (heart rate > 110 beats per minute) treated within two hours of injury. They were administered either a TXA 1g bolus over 10 minutes while en route to the hospital or placebo. Once in the hospital, patients received either no additional TXA (1g total), an additional 1g via an 8-hour infusion (2g total), or an additional 1g bolus followed by an additional 1g infusion over 8 hours (3g total).
The ROC-TXA trial studied patients with suspected head injury with an initial Glasgow Coma Scale (GCS) score < 13, with at least one reactive pupil and SBP > 90 mmHg. Eligible patients were administered either 1g of prehospital TXA plus 1g TXA infusion over 8 hours after trauma center arrival, 2g of prehospital TXA, or placebo.
Data from both trials were harmonized. Overlapping variables included time of death, 24-hour transfusion requirements, and adverse events. The authors hypothesized that prehospital TXA administration is associated with a survival benefit and reduced transfusion requirement.
A total of 1,744 patients were combined to be included in the study. The overall mortality was 11.2% of the cohort with a median injury severity score (ISS) of 16. A total of 903 patients came from the STAAMP trial and 841 from the ROC-TXA trial. After adjusting for all clinically and statistically significant covariates, TXA was independently associated with a lower risk of 28-day mortality. The dosage of TXA also mattered. A 22% lower risk of mortality was noted for every gram of prehospital TXA administered. The patients who received prehospital TXA also had a lower 24-hour red blood cell transfusion requirement compared to placebo. Prehospital TXA administration was not associated with higher rates of adverse outcomes, including venous thromboembolism, stroke, or seizures. Additionally, there was no association between prehospital TXA dose and rate of thromboembolic events.
This study has limitations. This is a secondary analysis of pooled data from two separate studies, which had different injury patterns. Each study had different inclusion criteria, randomization allocation, and prehospital TXA dosing regiments. Results may not be applicable across all patient populations. The study analysis was quite complicated and beyond the scope of discussion in this article. While that alone is not a limitation, many other studies have come to different conclusions regarding the efficacy of prehospital TXA use.
This complicated study combines data from two prior studies to conclude that prehospital TXA improves mortality in trauma patients. It also demonstrates that the benefit is dose-dependent, with an increased benefit noted among those who received a higher dose of TXA. It is a good addition to the bodies of literature both supporting and refuting the benefits of TXA for prehospital trauma.
2. Every minute matters: Improving outcomes for penetrating trauma through prehospital advanced resuscitative care. Duchesne J, McLafferty BJ, Broome JM, et al. J Trauma Acute Care Surg. 2024;97:710–715.
The prehospital administration of blood and blood products for trauma resuscitation is being implemented in increasing numbers of EMS agencies. The authors of this study sought to show if there is a survival benefit in patients with severe hemorrhage after trauma when blood is administered within the first 15 minutes of EMS patient contact using an Advanced Resuscitative Care (ARC) bundle comprised of 2 units of packed red blood cells, calcium and tranexamic acid (TXA).
A retrospective analysis was conducted of a prospectively collected database of prehospital blood (PHB) administration in an urban EMS system between October 2021 and January 2023. PHB patients were compared to patient data collected from the trauma registry between 2016 and 2019 before prehospital blood administration protocols were in place.
Inclusion criteria were penetrating injury patients with a SBP ≤70 or SBP ≤ 90mmHg with HR ≥ 110 on initial EMS evaluation that received at least 1 unit of blood. A total of 143 patients were included in their analysis: 61that received prehospital blood products and 82 in the control group.
A 4.5 minute increase in total prehospital time was documented in the patients that received blood products. Of note, the group that did receive prehospital blood products recorded a reduction in time of administration of the first unit of blood from 27 minutes in the control group who received blood in the hospital to 8 minutes. In-hospital mortality in the group that received prehospital blood products was reduced to 7% from 29%. Multivariate analysis revealed that mortality increased 11% for each additional minute of delay to receiving blood.
Among limitations of this study, the small number pf patients, missing data, the potential of selection bias were the most notable. They also noted that as familiarity of the ARC bundle protocols, TXA use increased towards the end of the period studied. Since an ARC Bundle protocol (Calcium, TXA and packed red blood cells) was used, they were not able to isolate the independent effects of the three elements of the ARC. One curious finding was that the distance from the scene to the hospital was similar in both groups of patients (3.9 vs 3.8 miles) however the transport time form scene departure to arrival at the hospital was 2.5 minutes greater in the PHB group.
Despite the additional 5 minutes of total prehospital time when blood products were administered in the field, the PHB group had their trauma resuscitation initiated 19 minutes sooner than did the control group that did not receive prehospital blood products. Mortality increased by 11% with each additional minute of delay in starting blood products. Prehospital blood product administration initiated trauma resuscitation closer to the point of injury and significantly improved mortality in this retrospective review.
3. A Randomized Trial of Drug Route in Out-of-Hospital Cardiac Arrest. Couper K, Ji C, Deakin CD, et al. New Engl J Med. 2024 Published on-line at: https://www.nejm.org/doi/full/10.1056/NEJMoa2407780
Over the years of managing prehospital cardiac arrest, many routes of medication administration have been commonly used including intravenous (IV), intraosseous (IO), endotracheal, and central lines. All of these approaches have one goal: to administer the medications commonly used in patients experiencing cardiac arrest in the quickest, most efficient fashion. Consideration also needs to be given to not just the speed of the procedure but also the efficiency of the medication reaching the target organ.
The authors of this multi-center randomized study involved 11 EMS systems in the United Kingdom with data gathered from November 2021 through July 2024. Adult patients in cardiac arrest over the age of 18 years were randomized equally into two cohorts, one receiving IV (3042 patients) and the second receiving IO (3040 patients) as the first intervention for medication access. The only exclusion criteria was known or obvious pregnancy. The primary target outcome for the study was survival at 30 days post-arrest.
At 30 days, 4.5% of patients in the intraosseous group and 5.1% in the intravenous group were alive, with no significant difference between the groups. Among those who survived to hospital discharge, favorable neurologic outcomes were observed in 2.7% of the intraosseous group and 2.8% of the intravenous group. Both groups had similar time to drug administration, time on the scene, and time of arrival to the hospital, however the IV group had a slightly better return of spontaneous circulation 39.1% vs 36%.
The authors note limitations including the termination of the study prior to reaching the desired enrolment numbers. This was primarily due to lower-than-expected patient contacts during the study period which left the trial underpowered to detect a 1% difference in outcome. The nature of the study obviously did not lend itself to being a blinded study. Also, they did not collect data on the quality of the resuscitation efforts between providers.
This study demonstrated that neither the IV nor the IO routes of first placement resulted in a significant difference on patients’ outcomes after prehospital cardiac arrest.
4. Pediatric trauma population spine immobilization during resuscitation: A call for improved guidelines. Breeding T, Nasef H, Amin Q, Smith C, Elkbuli A. Amer J Emerg Med 2024;76:150-154.
This study looked at current practices regarding spinal immobilization in pediatric trauma patients in an effort to determine the effectiveness and impact on these patients. They hoped that their finding could guide researchers toward improved evidence-based guidelines.
The authors performed a comprehensive literature review using the resources in Google search scholar, Cochrane, PreQuest, Embase, and PubMed. They identified 9,760 articles. After filtering for duplicates and applying the inclusion and exclusion criteria, they ended up with 6 studies divided into two groups. There were 2 studies in the first group that addressed the impact of cervical spine immobilization on clinical outcomes. The second group included 4 studies that looked at the “efficacy and reliability of pediatric spinal immobilization based on the maintenance of a neutral spine and consistency in spinal immobilization practices”. The quality of the evidence was judged to be moderate in three papers, low in two, and very low in one.
In looking at the two studies focused on the impact of practices on clinical outcomes, they found that “immobilized children were 8 times more likely to undergo spinal imaging, 4 times more likely to be admitted” to a hospital floor bed and 5 times more likely to be admitted to the ICU or sent to the operating room when compared to patients that were not immobilized. There was no difference in the length of stay. When looking at the “impact of a selective prehospital pediatric spinal protection protocol on the frequency of spinal imaging” and disposition, they found a decrease in hospital admission rates and no difference in the percentage of patients undergoing radiographic imaging.
Of the 4 studies they reviewed that looked at efficacy and reliability, 2 looked at the effectiveness in achieving a neutral spine position. While only 1 of the 22 patients was identified by physicians and paramedics as being in a non-neutral position, none of the patients consistently achieved neutral positioning when evaluated with X-Rays.
In the two studies that looked at consistency in spinal immobilization, they found that older children were more likely to be immobilized and that when children under the age of two were immobilized the immobilization techniques were significantly different than used on children between the ages of 8 and 15. Only 6 (38%) of the children under the age of 2 were immobilized while 49 or (63%) of the children aged 2 to 7 and 175 (79%) among children aged 8 to 15. They also saw a decrease in application of full spinal immobilization when performing tasks such as administering supplemental oxygen or cervical collar application.
The authors cited the diversity in the use of spinal immobilization techniques as an important limitation of the review. They stated that “many studies did not specify the implementation of a specific immobilization technique or EMS agency-specific protocols based on age or patient population”. In addition the diversity of the types of traumatic injuries including some patients that had severe traumatic injuries including injuries to the spine while others did not.” They also recognized that the small number of patients in the studies was limiting and more robust patient sample studies were needed.
This literature review noted that immobilized children had more X-rays (mirroring adult studies) and were admitted to the hospital more often than children who were not immobilized. They also noted more ICU admissions and higher mean pain scores when compared to non-immobilized patients. Further, they noted that spinal immobilization practices were not consistent in their ability to maintain immobilization during resuscitation. No techniques reliably achieved neutral alignment of the spine in children. The authors closed by saying that these findings suggest that “current immobilization practices for pediatric patients are unreliable and may result in worse clinical outcomes”. They go on to say that current guidelines lack strong evidence and clearly “further research is needed to investigate the impact of individual immobilization techniques on varying pediatric age groups and the scenarios where they would be most appropriate” and to develop the evidence for future protocols and guidelines.
