Impact of Tranexamic Acid on Traumatic Hemorrhage Outcomes in Emergency Medicine: A Systematic Review and...

Hemorrhage is the predominant cause of death among trauma patients. Therefore, pharmacological treatments such as tranexamic acid (TXA) have been explored to supplement the conventional measures of controlling bleeding in this population. TXA has been found beneficial among patients undergoing elective surgery. However, its use to mitigate bleeding among trauma patients in different settings remains controversial. Therefore, we carried out this study to examine the efficacy of prehospital and in-hospital TXA among trauma patients in military and civilian settings. PubMed, MEDLINE, Cochrane Center Register of Controlled Trials (CENTRAL), ProQuest, and Google Scholar databases were searched for observational and randomized controlled trials (RCTs) related to our topic. Two authors independently abstracted the data required for review and analysis and recorded them in a standardized table. When possible, meta-analysis was performed using the Review Manager software (RevMan 5.4.1, The Cochrane Collaboration, London, UK). Of the 5383 articles obtained from the database search, only 22 met our inclusion criteria. Data pooled from five of these studies showed that prehospital TXA had a non-significant decrease in mortality (OR: 0.91; 95% CI: 0.71 - 1.17; p = 0.45; I² = 0) and no significant increase in thromboembolic events (OR: 2.96; 95% CI: 0.66 - 13.20; p = 0.16). However, prehospital TXA was associated with a significantly lower amount of blood transfusion (MD: -1.36; 95% CI: -5.36 to -2.16; p <0.00001). The pooled analysis also showed that TXA administered in hospitals is associated with significantly lower all-cause mortality (OR: 0.86; 95% CI: 0.76 - 0.98; p = 0.02) and mortality due to hemorrhage (OR: 0.84; 95% CI: 0.74 - 0.95; p = 0.005). However, in military settings, it was associated with increased incidences of thromboembolic events (OR: 3.22; 95% CI: 1.37 - 7.57; p = 0.007). Additionally, the pooled analysis has shown that a second dose of TXA has no mortality benefit (OR: 0.96; 95% CI: 0.21 - 4.41; p = 0.96 and OR: 1.51; 95% CI: 0.62 - 3.66; p = 0.36, for 24-hour and 28-day mortality, respectively) even though it does not increase incidences of thromboembolic complications (OR: 2.28; 95% CI: 0.48 - 10.81; p = 0.30). On the other hand, pooled analysis of TXA effects in patients undergoing massive transfusion has shown a trend of significantly lower mortality. However, it was associated with an increased risk of thromboembolic complications. Prehospital TXA appears to have a non-significant reduction in mortality. However, we believe that additional RCTs might result in a significant difference. On the other hand, TXA administered in hospitals appears to reduce mortality in trauma patients with hemorrhage. However, we could not determine who was more likely to benefit from the treatment between civilians and the military. Moreover, we found that a second dose of TXA has no benefit among trauma patients; therefore, we suggest that clinicians withhold subsequent doses unless hyperfibrinolysis is observed. Lastly, TXA is beneficial for patients undergoing massive transfusion; therefore, we suggest that TXA be administered as early as possible in these patients.