Methodological Rigor in Pre-Hospital Studies

Date: July 1, 2023 Reference: PATCH-Trauma Investigators and ANZICS Clinical Trial Group. Prehospital Tranexamic Acid for Severe Trauma. NEJM 2023. Guest Skeptic: Dr. Salim Rezaie is a community emergency physician in San Antonio, TX.  He is the Creator and founder of REBEL EM, a free, critical appraisal blog that tries to cut down knowledge translation gaps of research to bedside clinical practice (https://rebelem.com). Case: A 48-year-old man involved in a motor vehicle collision (MVC) is being evaluated by paramedics. He was entrapped in his vehicle for over one hour, had an initial blood pressure of 78/46 mmHg, and appeared to have a seat belt sign with deformities to bilateral lower extremities.  His Glasgow Coma Scale (GCS) score is 13 with obvious head trauma as well.  Emergency Medical Services (EMS) calls in ahead of time to warn the facility that they are 20 minutes out, to give report about the patient, and ask whether they should give tranexamic acid (TXA) pre-hospital. Background: We have looked at the use of TXA many times on the SGEM. Most of the times the RCTs we critically appraised did not demonstrate superiority for their primary outcome. This has included: Post-Partum Hemorrhage (WOMAN): SGEM#214 Gastrointestinal Bleeding (HALT-IT): SGEM#301 Intracranial hemorrhage (TICH-2 and ULTRA): SGEM#236 and SGEM#322) Isolated Traumatic Brain Injury (CRASH-3): SGEM#270 Pre-Hospital TBI: SGEM#305 Epistaxis (NoPAC): SGEM#321 There is some evidence of efficacy for TXA in epistaxis (SGEM#55, SGEM#210, and SGEM#395). There is also the CRASH-2 trial from 2010 which was reviewed with our good friend Dr. Anand Swaminathan (SGEM#80). That classic practice changing paper showed a 1.5% absolute decrease in death in trauma patients receiving TXA vs placebo (NNT = 66). Despite these results, many clinicians remained skeptical of the benefit of TXA in trauma patients.  One of the major criticisms of the CRASH-2 trial was it was performed in under-resourced trauma systems and therefore may not be generalizable to care in advanced trauma systems. Clinical Question: In advanced trauma systems, does the prehospital use of TXA increase the rate of survival with a favorable functional outcome in patients at risk for trauma-induced coagulopathy? Reference: PATCH-Trauma Investigators and ANZICS Clinical Trial Group. Prehospital Tranexamic Acid for Severe Trauma. NEJM 2023. Population: Adults (>18 years of age) with suspected severe traumatic injuries at risk for trauma induced coagulopathy (Assessed using the Coagulopathy of Severe Trauma [COAST] score) that could receive TXA within three hours of injury. Coagulopathy of Severe Trauma (COAST Score) Intervention: TXA 1g intravenous (IV) bolus over 10 minutes followed by 1g over 8 hours Comparison: 9% saline (same volume as TXA) administered as bolus and infusion over 8 hours Outcome: Primary Outcome: Survival with a favorable functional outcome at six months assessed using the Glasgow Outcome Scale – Extended (GOS-E) Secondary Outcomes: Death within 24 hours, 28 days, and 6 months after injury Safety: Risk of thromboembolic phenomenon (deep vein thrombosis, pulmonary embolism, myocardial infarction, or stroke) Glasgow Outcome Scale – Extended (GOS-E) Type of Study: International, randomized, double-blind, placebo-controlled trial Authors’ Conclusions: “Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo.” Quality Checklist for Randomized Clinical Trials: The study population included or focused on those in the emergency department. No The patients were adequately randomized. Yes