Page 141 - JSOM Spring 2023

participants (N = 1280) included out-of-hospital patients with TBI an estimated 2 hours of injury, from May 1, 2015, through Oc-
aged 15 years or older with Glasgow Coma Scale score of 12 or tober 31, 2019. Interventions: Patients received 1g of tranexamic
less and systolic blood pressure of 90mmHg or higher. Interven- acid before hospitalization (447 patients) or placebo (456 patients)
tions: Three interventions were evaluated, with treatment initiated infused for 10 minutes in 100mL of saline. The randomization
within 2 hours of TBI: out-of-hospital tranexamic acid (1g) bo- scheme used prehospital and in-hospital phase assignments, and
lus and in-hospital tranexamic acid (1g) 8-hour infusion (bolus patients administered tranexamic acid were allocated to abbre-
maintenance group; n = 312), out-of-hospital tranexamic acid viated, standard, and repeat bolus dosing regimens on trauma
(2g) bolus and in-hospital placebo 8-hour infusion (bolus only center arrival. Main outcomes and measures: The primary out-
group; n = 345), and out-of-hospital placebo bolus and in- hospital come was 30-day all-cause mortality. Results: In all, 927 patients
placebo 8-hour infusion (placebo group; n = 309). Main out- (mean [SD] age, 42 [18] years; 686 [74.0%] male) were eligible
comes and measures: The primary outcome was favorable neu- for prehospital enrollment (460 randomized to tranexamic acid
rologic function at 6 months (Glasgow Outcome Scale-Extended intervention; 467 to placebo intervention). After exclusions, the
score >4 [moderate disability or good recovery]) in the combined intention-to-treat study cohort comprised 903 patients: 447 in the
tranexamic acid group vs the placebo group. Asymmetric signif- tranexamic acid arm and 456 in the placebo arm. Mortality at 30
icance thresholds were set at 0.1 for benefit and 0.025 for harm. days was 8.1% in patients receiving tranexamic acid compared
There were 18 secondary end points, of which 5 are reported in with 9.9% in patients receiving placebo (difference, –1.8%; 95%
this article: 28-day mortality, 6-month Disability Rating Scale CI, –5.6% to 1.9%; p = .17). Results of Cox proportional hazards
score (range, 0 [no disability] to 30 [death]), progression of intra- regression analysis, accounting for site, verified that randomization
cranial hemorrhage, incidence of seizures, and incidence of throm- to tranexamic acid was not associated with a significant reduc-
boembolic events. Results: Among 1063 participants, a study drug tion in 30-day mortality (hazard ratio, 0.81; 95% CI, 0.59–1.11,
was not administered to 96 randomized participants and 1 par- p = .18). Prespecified dosing regimens and post hoc subgroup anal-
ticipantwas excluded, resulting in 966 participants in the analysis yses found that prehospital tranexamic acid were associated with
population (mean age, 42 years; 255 [74%] male participants; significantly lower 30-day mortality. When comparing tranexamic
mean Glasgow Coma Scale score, 8). Of these participants, 819 acid effect stratified by time to treatment and qualifying shock se-
(84.8%) were available for primary outcome analysis at 6-month verity in a post hoc comparison, 30-day mortality was lower when
followup. The primary outcome occurred in 65% of patients in tranexamic acid was administered within 1 hour of injury (4.6%
the tranexamic acid groups vs 62% in the placebo group (differ- vs 7.6%; difference, −3.0%; 95% CI, −5.7% to −0.3%; p < .002).
ence, 3.5%; [90% 1-sided confidence limit for benefit, −0.9%]; Patients with severe shock (systolic blood pressure ≤70mmHg)
p = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; who received tranexamic acid demonstrated lower 30-day mortal-
p = .84). There was no statistically significant difference in 28- ity compared with placebo (18.5% vs 35.5%; difference, −17%;
day mortality between the tranexamic acid groups vs the pla- 95% CI, −25.8% to −8.1%; p < .003). Conclusions and relevance:
cebo group (14% vs 17%; difference, −2.9% [95% CI, −7.9% to In injured patients at risk for hemorrhage, tranexamic acid admin-
2.1%]; p = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; istered before hospitalization did not result in significantly lower
difference, −0.9 [95% CI, −2.5 to 0.7]; p = .29), or progression of 30-day mortality. The prehospital administration of tranexamic
intracranial hemorrhage (16% vs 20%; difference, −5.4% [95% acid after injury did not result in a higher incidence of thrombotic
CI, −12.8% to 2.1%]; p = .16). Conclusions and relevance: Among complications or adverse events. Tranexamic acid given to injured
patients with moderate to severe TBI, out-of-hospital tranexamic patients at risk for hemorrhage in the prehospital setting is safe and
acid administration within 2 hours of injury compared with pla- associated with survival benefit in specific subgroups of patients.
cebo did not significantly improve 6-month neurologic outcome
as measured by the Glasgow Outcome Scale-Extended. Efficacy and safety of tranexamic acid administration in
traumatic brain injury patients: a systematic review and
Tranexamic acid during prehospital transport in patients meta-analysis
at risk for hemorrhage after injury: a double-blind, Shoji Yokobori, Tomoaki Yatabe, Yutaka Kondo, Kosaku Kinoshita,
placebo-controlled, randomized clinical trial the Japan Resuscitation Council (JRC) Neuroresuscitation Task
Francis X Guyette, MD, MPH; Joshua B Brown, MD, MSc; Mazen Force and the Guidelines Editorial Committee
S Zenati, MD, PhD; Barbara J Early-Young, BSN; Peter W Adams, J Intensive Care. 2020;8:46.
BS; Brian J Eastridge, MD; Raminder Nirula, MD, MPH; Gary A
Vercruysse, MD; Terence O’Keeffe, MD; Bellal Joseph, MD; Louis Background: The exacerbation of intracranial bleeding is critical
H Alarcon, MD; Clifton W Callaway, MD, PhD; Brian S Zucker- in traumatic brain injury (TBI) patients. Tranexamic acid (TXA)
braun, MD; Matthew D Neal, MD; Raquel M Forsythe, MD; Mat- has been used to improve outcomes in TBI patients. However,
thew R Rosengart, MD, MPH; Timothy R Billiar, MD; Donald M the effectiveness of TXA treatment remains unclear. This study
Yealy, MD; Andrew B Peitzman, MD; Jason L Sperry, MD, MPH; aimed to assess the effect of administration of TXA on clinical
and the STAAMP Study Group outcomes in patients with TBI by systematically reviewing the lit-
erature and synthesizing evidence of randomized controlled trials
JAMA Surg. 2020;156(1):11–20.
(RCTs). Methods: MEDLINE, the Cochrane Central Register of
Importance: In-hospital administration of tranexamic acid after Controlled Trials, and Igaku Chuo Zasshi (ICHUSHI) Web were
injury improves outcomes in patients at risk for hemorrhage. searched. Selection criteria included randomized controlled trials
Data demonstrating the benefit and safety of the pragmatic use with clinical outcomes of adult TBI patients administered TXA
of tranexamic acid in the prehospital phase of care are lacking or placebo within 24 hr after admission. Two investigators inde-
for these patients. Objective: To assess the effectiveness and safety pendently screened citations and conducted data extraction. The
of tranexamic acid administered before hospitalization compared primary “critical” outcome was all-cause mortality. The secondary
with placebo in injured patients at risk for hemorrhage. Design, “important” outcomes were good neurological outcome rates, en-
setting, and participants: This pragmatic, phase 3, multicenter, largement of bleeding, incidence of ischemia, and hemorrhagic in-
double-blind, placebo-controlled, superiority randomized clini- tracranial complications. Random effect estimators with weights
cal trial included injured patients with prehospital hypotension calculated by the inverse variance method were used to report risk
(systolic blood pressure ≤90mmHg) or tachycardia (heart rate ratios (RRs). Results: A total of 640 records were screened. Seven
≥110/min) before arrival at 1 of 4 US level 1 trauma centers, within studies were included for quantitative analysis. Of 10,044 patients

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