RESUMEN
Importance: Blood transfusions are commonly administered to patients with acute brain injury. The optimal hemoglobin transfusion threshold is uncertain in this patient population. Objective: To assess the impact on neurological outcome of 2 different hemoglobin thresholds to guide red blood cell transfusions in patients with acute brain injury. Design, Setting, and Participants: Multicenter, phase 3, parallel-group, investigator-initiated, pragmatic, open-label randomized clinical trial conducted in 72 intensive care units across 22 countries. Eligible patients had traumatic brain injury, aneurysmal subarachnoid hemorrhage, or intracerebral hemorrhage; hemoglobin values below 9 g/dL within the first 10 days after injury; and an expected intensive care unit stay of at least 72 hours. Enrollment occurred between September 1, 2017, and December 31, 2022. The last day of follow-up was June 30, 2023. Interventions: Eight hundred fifty patients were randomly assigned to undergo a liberal (transfusion triggered by hemoglobin <9 g/dL; n = 408) or a restrictive (transfusion triggered by hemoglobin <7 g/dL; n = 442) transfusion strategy over a 28-day period. Main Outcomes and Measures: The primary outcome was occurrence of an unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score between 1 and 5, at 180 days following randomization. There were 14 prespecified serious adverse events, including occurrence of cerebral ischemia after randomization. Results: Among 820 patients who completed the trial (mean age, 51 years; 376 [45.9%] women), 806 had available data on the primary outcome, 393 in the liberal strategy group and 413 in the restrictive strategy group. The liberal strategy group received a median of 2 (IQR, 1-3) units of blood, and the restrictive strategy group received a median of 0 (IQR, 0-1) units of blood, with an absolute mean difference of 1.0 unit (95% CI, 0.87-1.12 units). At 180 days after randomization, 246 patients (62.6%) in the liberal strategy group had an unfavorable neurological outcome compared with 300 patients (72.6%) in the restrictive strategy group (absolute difference, -10.0% [95% CI, -16.5% to -3.6%]; adjusted relative risk, 0.86 [95% CI, 0.79-0.94]; P = .002). The effect of the transfusion thresholds on neurological outcome at 180 days was consistent across prespecified subgroups. In the liberal strategy group, 35 (8.8%) of 397 patients had at least 1 cerebral ischemic event compared with 57 (13.5%) of 423 in the restrictive strategy group (relative risk, 0.65 [95% CI, 0.44-0.97]). Conclusions and Relevance: Patients with acute brain injury and anemia randomized to a liberal transfusion strategy were less likely to have an unfavorable neurological outcome than those randomized to a restrictive strategy. Trial Registration: ClinicalTrials.gov Identifier: NCT02968654.
RESUMEN
BACKGROUND: Rebleeding from a ruptured aneurysm increases the risk of unfavorable outcomes after subarachnoid hemorrhage (SAH) and is prevented by early aneurysm occlusion. The role of antifibrinolytics before aneurysm obliteration remains controversial. We investigated the effects of tranexamic acid on long-term functional outcomes of patients with aneurysmal SAH (aSAH). METHODS: This was a single-center, prospective, observational study conducted in a high-volume tertiary hospital in a middle-income country from December 2016 to February 2020. We included all consecutive patients with aSAH who either received or did not receive tranexamic acid (TXA) treatment. Multivariate logistic regression analysis using propensity score was used to evaluate the association of TXA use with long-term functional outcomes, measured by the modified Rankin Scale (mRS) at 6 months. RESULTS: A total of 230 patients with aSAH were analyzed. The median (interquartile range) age was 55 (46-63) years, 72% were women, 75% presented with good clinical grade (World Federation of Neurological Surgeons grade 1-3), and 83% had a Fisher scale of 3 or 4. Around 80% of patients were admitted up to 72 h from ictus. The aneurysm occlusion method was surgical clipping in 80% of the patients. A total of 129 patients (56%) received TXA. In multivariable logistic regression using inverse probability treatment weighting, the long-term rate of unfavorable outcomes (modified Rankin scale 4-6) was the same in the TXA and non-TXA groups (61 [48%] in TXA group vs. 33 [33%] in non-TXA group; odds ratio [OR] 1.39, 95% confidence interval [CI] 0.67-2.92; p = 0.377). The TXA group had higher in-hospital mortality (33 vs. 11% in non-TXA group; OR 4.13, 95% CI 1.55-12.53, p = 0.007). There were no differences between the groups concerning intensive care unit length of stay (16 ± 11.22 days in TXA group vs. 14 ± 9.24 days in non-TXA group; p = 0.2) or hospital (23 ± 13.35 days in TXA group vs. 22 ± 13.36 days in non-TXA group; p = 0.9). There was no difference in the rates of rebleeding (7.8% in TXA group vs. 8.9% in non-TXA group; p = 0.31) or delayed cerebral ischemia (27% in TXA group vs. 19% in non-TXA group; p = 0.14). For the propensity-matched analysis, 128 individuals were selected (64 in TXA group and 64 in non-TXA group), and the rates of unfavorable outcomes at 6 months were also similar between groups (45% in TXA group and 36% in non-TXA group; OR 1.22, 95% CI 0.51-2.89; p = 0.655). CONCLUSIONS: Our findings in a cohort with delayed aneurysm treatment reinforce previous data that TXA use before aneurysm occlusion does not improve functional outcomes in aSAH.