Prehospital synergy: Tranexamic acid and blood transfusion in patients at risk for hemorrhage
Deeb AP, Hoteit L, Li S, Guyette FX, Eastridge BJ, Nirula R, Vercruysse GA, O'Keeffe T, Joseph B, Neal MD, et al
The journal of trauma and acute care surgery. 2022
BACKGROUND Growing evidence supports improved survival with prehospital blood products. Recent trials show a benefit of prehospital tranexamic acid (TXA) administration in select subgroups. Our objective was to determine if receiving prehospital packed red blood cells (pRBC) in addition to TXA improved survival in injured patients at risk of hemorrhage. METHODS We performed a secondary analysis of all scene patients from the STAAMP trial. Patients were randomized to prehospital TXA or placebo. Some participating EMS services utilized pRBC. Four resuscitation groups resulted: TXA, pRBC, pRBC+TXA, and neither. Our primary outcome was 30-day mortality and secondary outcome was 24-hour mortality. Cox regression tested the association between resuscitation group and mortality while adjusting for confounders. RESULTS A total of 763 patients were included. Patients receiving prehospital blood had higher injury severity scores in the pRBC (22 [10, 34]) and pRBC+TXA (22 [17, 36]) groups than the TXA (12 [5, 21]) and neither (10 [4, 20]) groups (p < 0.01). Mortality at 30 days was greatest in the pRBC+TXA and pRBC groups at 18.2% and 28.6% compared to the TXA only and neither groups at 6.6% and 7.4% respectively. Resuscitation with pRBC+TXA was associated with a 35% reduction in relative hazards of 30-day mortality compared to neither (HR 0.65; 95%CI 0.45-0.94, p = 0.02). No survival benefit was observed in 24-hour mortality for pRBC+TXA, but pRBC alone was associated with a 61% reduction in relative hazards of 24 h mortality compared to neither (HR 0.39; 95%CI 0.17-0.88, p = 0.02). CONCLUSIONS For injured patients at risk of hemorrhage, prehospital pRBC+TXA is associated with reduced 30-day mortality. Use of pRBC transfusion alone was associated with a reduction in early mortality. Potential synergy appeared only in longer term mortality and further work to investigate mechanisms of this therapeutic benefit is needed to optimize the prehospital resuscitation of trauma patients. LEVEL OF EVIDENCE Therapeutic, Level III.
Early Prehospital Tranexamic Acid Following Injury is Associated with a 30-day Survival Benefit: A Secondary Analysis of a Randomized Clinical Trial
Li SR, Guyette F, Brown J, Zenati M, Reitz KM, Eastridge B, Nirula R, Vercruysse GA, O'Keeffe T, Joseph B, et al
Annals of surgery. 2021
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OBJECTIVE We sought to characterize the timing of administration of prehospital Tranexamic Acid (TXA) and associated outcome benefits. BACKGROUND TXA has been shown to be safe in the prehospital setting post-injury. METHODS We performed a secondary analysis of a recent prehospital randomized TXA clinical trial in injured patients. Those who received prehospital TXA within 1hr (EARLY) from time of injury were compared to those who received prehospital TXA beyond 1hr (DELAYED). We included patients with a shock index of > 0.9. Primary outcome was 30-day mortality. Kaplan-Meier and Cox Hazard regression were utilized to characterize mortality relationships. RESULTS EARLY and DELAYED patients had similar demographics, injury characteristics and shock severity but DELAYED patients had greater prehospital resuscitation requirements and longer prehospital times. Stratified Kaplan-Meier analysis demonstrated significant separation for EARLY patients (N =238, log-rank chi-square test, 4.99; P = .03) with no separation for DELAYED patients (N=238, log-rank chi-square test, 0.04; P = .83). Stratified Cox Hazard regression verified, after controlling for confounders, that EARLY TXA was associated with a 65% lower independent hazard for 30-day mortality (HR 0.35, 95%CI 0.19-0.65, P = .001) with no independent survival benefit found in DELAYED patients (HR 1.00, 95%CI 0.63-1.59, P = .999). EARLY TXA patients had lower incidence of multiple organ failure and 6-hour and 24-hour transfusion requirements compared to placebo. CONCLUSIONS Administration of prehospital TXA within 1 hour from injury in patients at risk of hemorrhage is associated with 30-day survival benefit, lower incidence of multiple organ failure, and lower transfusion requirements.
Tranexamic Acid During Prehospital Transport in Patients at Risk for Hemorrhage After Injury: A Double-blind, Placebo-Controlled, Randomized Clinical Trial
Injured patients (n= 476).
Prehospital tranexamic acid (TXA) within 1 hour from time of injury (Early group, n= 238).
Prehospital TXA beyond 1 hour (Delayed group, n= 238).
Patients from both groups had similar demographics, injury characteristics and shock severity but those in the delayed group had greater prehospital resuscitation requirements and longer prehospital times. Stratified Kaplan-Meier analysis demonstrated significant separation for those in the early group (log-rank chi-square test, 4.99) with no separation for patients in the delayed group (log-rank chi-square test, 0.04). Stratified Cox Hazard regression verified, after controlling for confounders, that early TXA was associated with a 65% lower independent hazard for 30-day mortality (HR 0.35) with no independent survival benefit found in delayed patients (HR 1.00). Early TXA patients had lower incidence of multiple organ failure and 6-hour and 24-hour transfusion requirements.
Guyette FX, Brown JB, Zenati MS, Early-Young BJ, Adams PW, Eastridge BJ, Nirula R, Vercruysse GA, O'Keeffe T, Joseph B, et al
JAMA surgery. 2020
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IMPORTANCE In-hospital administration of tranexamic acid after injury improves outcomes in patients at risk for hemorrhage. Data demonstrating the benefit and safety of the pragmatic use of tranexamic acid in the prehospital phase of care are lacking for these patients. OBJECTIVE To assess the effectiveness and safety of tranexamic acid administered before hospitalization compared with placebo in injured patients at risk for hemorrhage. DESIGN, SETTING, AND PARTICIPANTS This pragmatic, phase 3, multicenter, double-blind, placebo-controlled, superiority randomized clinical trial included injured patients with prehospital hypotension (systolic blood pressure ≤90 mm Hg) or tachycardia (heart rate ≥110/min) before arrival at 1 of 4 US level 1 trauma centers, within an estimated 2 hours of injury, from May 1, 2015, through October 31, 2019. INTERVENTIONS Patients received 1 g of tranexamic acid before hospitalization (447 patients) or placebo (456 patients) infused for 10 minutes in 100 mL of saline. The randomization scheme used prehospital and in-hospital phase assignments, and patients administered tranexamic acid were allocated to abbreviated, standard, and repeat bolus dosing regimens on trauma center arrival. MAIN OUTCOMES AND MEASURES The primary outcome was 30-day all-cause mortality. RESULTS In all, 927 patients (mean [SD] age, 42  years; 686 [74.0%] male) were eligible for prehospital enrollment (460 randomized to tranexamic acid intervention; 467 to placebo intervention). After exclusions, the intention-to-treat study cohort comprised 903 patients: 447 in the tranexamic acid arm and 456 in the placebo arm. Mortality at 30 days was 8.1% in patients receiving tranexamic acid compared with 9.9% in patients receiving placebo (difference, -1.8%; 95% CI, -5.6% to 1.9%; P = .17). Results of Cox proportional hazards regression analysis, accounting for site, verified that randomization to tranexamic acid was not associated with a significant reduction in 30-day mortality (hazard ratio, 0.81; 95% CI, 0.59-1.11, P = .18). Prespecified dosing regimens and post-hoc subgroup analyses found that prehospital tranexamic acid were associated with significantly lower 30-day mortality. When comparing tranexamic acid effect stratified by time to treatment and qualifying shock severity in a post hoc comparison, 30-day mortality was lower when tranexamic acid was administered within 1 hour of injury (4.6% vs 7.6%; difference, -3.0%; 95% CI, -5.7% to -0.3%; P < .002). Patients with severe shock (systolic blood pressure ≤70 mm Hg) who received tranexamic acid demonstrated lower 30-day mortality compared with placebo (18.5% vs 35.5%; difference, -17%; 95% CI, -25.8% to -8.1%; P < .003). CONCLUSIONS AND RELEVANCE In injured patients at risk for hemorrhage, tranexamic acid administered before hospitalization did not result in significantly lower 30-day mortality. The prehospital administration of tranexamic acid after injury did not result in a higher incidence of thrombotic complications or adverse events. Tranexamic acid given to injured patients at risk for hemorrhage in the prehospital setting is safe and associated with survival benefit in specific subgroups of patients. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02086500.
The effects of leukoreduced blood transfusion on infection risk following injury: a randomized controlled trial
Nathens AB, Nester TA, Rubenfeld GD, Nirula R, Gernsheimer TB
Shock (Augusta, Ga.). 2006;26((4):):342-7.
Allogeneic blood transfusions in surgical patients have been associated with an increased risk of infectious complications and organ dysfunction. Residual leukocytes contaminating units of packed red blood cells have been incriminated through the induction of anergy and/or a potentiated inflammatory response, leading to the possibility that leukoreduced red blood cell transfusion might mitigate these effects. We set out to evaluate the effect of leukoreduced red cell transfusion on the risk of infections complications in patients requiring transfusion following injury. We conducted a single-center, double-blinded randomized controlled trial of leukoreduced versus standard, nonleukoreduced red blood cell transfusions in injured patients receiving transfusion within 24 hrs of injury. The primary endpoint was infectious complications within 28 days of randomization. Secondary end points were multiple organ failure, length of stay, febrile episodes, and mortality. Two hundred sixty eight subjects were eligible for analysis. Rates of infectious complications were similar in subjects receiving leukoreduced transfusions (30%) or standard transfusions (36%) ([RR], 0. 84 [0. 55-1. 3]) and there was no statistically significant effect of leukoreduced blood transfusion on mortality [RR, 1. 20 (0. 74-1. 9)], febrile episodes [RR, 1. 01 (0. 89-1. 2)], or organ dysfunction scores (5. 9 vs. 6. 6; P=0. 29). Thus, pre-storage leukoreduction of allogeneic red blood cells had a small, but non-significant effect on the rate of infectious complication in this high-risk population requiring transfusion. There was no effect on the rates of febrile episodes, mortality, length of stay, or severity of organ dysfunction.