1.
Tranexamic Acid in Patients Undergoing Noncardiac Surgery
Devereaux PJ, Marcucci M, Painter TW, Conen D, Lomivorotov V, Sessler DI, Chan MTV, Borges FK, Martínez-Zapata MJ, Wang CY, et al
The New England journal of medicine. 2022
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Editor's Choice
Abstract
BACKGROUND Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).
PICO Summary
Population
Patients undergoing non-cardiac surgery (n= 9,535).
Intervention
Tranexamic acid at the start and end of surgery (n= 4,757).
Comparison
Placebo (n= 4,778).
Outcome
The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, non-haemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. A composite bleeding outcome event occurred in 433 patients (9.1%) in the tranexamic acid group and in 561 patients (11.7%) in the placebo group. A composite cardiovascular outcome event occurred in 649 patients (14.2%) in the tranexamic acid group and in 639 patients (13.9%) in the placebo group.
2.
Effect of short-term vs. long-term blood storage on mortality after transfusion
Heddle NM, Cook RJ, Arnold DM, Liu Y, Barty R, Crowther MA, Devereaux PJ, Hirsh J, Warkentin TE, Webert KE, et al
The New England Journal of Medicine. 2016;375((20):):1937-1945
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Free full text
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Full text
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Editor's Choice
Abstract
Background Randomized, controlled trials have suggested that the transfusion of blood after prolonged storage does not increase the risk of adverse outcomes among patients, although most of these trials were restricted to high-risk populations and were not powered to detect small but clinically important differences in mortality. We sought to find out whether the duration of blood storage would have an effect on mortality after transfusion in a general population of hospitalized patients. Methods In this pragmatic, randomized, controlled trial conducted at six hospitals in four countries, we randomly assigned patients who required a red-cell transfusion to receive blood that had been stored for the shortest duration (short-term storage group) or the longest duration (long-term storage group) in a 1:2 ratio. Only patients with type A or O blood were included in the primary analysis, since pilot data suggested that our goal of achieving a difference in the mean duration of blood storage of at least 10 days would not be possible with other blood types. Written informed consent was waived because all the patients received treatment consistent with the current standard of care. The primary outcome was in-hospital mortality, which was estimated by means of a logistic-regression model after adjustment for study center and patient blood type. Results From April 2012 through October 2015, a total of 31,497 patients underwent randomization. Of these patients, 6761 who did not meet all the enrollment criteria were excluded after randomization. The primary analysis included 20,858 patients with type A or O blood. Of these patients, 6936 were assigned to the short-term storage group and 13,922 to the long-term storage group. The mean storage duration was 13.0 days in the short-term storage group and 23.6 days in the long-term storage group. There were 634 deaths (9.1%) in the short-term storage group and 1213 (8.7%) in the long-term storage group (odds ratio, 1.05; 95% confidence interval [CI], 0.95 to 1.16; P=0.34). When the analysis was expanded to include the 24,736 patients with any blood type, the results were similar, with rates of death of 9.1% and 8.8%, respectively (odds ratio, 1.04; 95% CI, 0.95 to 1.14; P=0.38). Additional results were consistent in three prespecified high-risk subgroups (patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer). Conclusions Among patients in a general hospital population, there was no significant difference in the rate of death among those who underwent transfusion with the freshest available blood and those who underwent transfusion according to the standard practice of transfusing the oldest available blood. (Funded by the Canadian Institutes of Health Research and others; INFORM Current Controlled Trials number, ISRCTN08118744 .).
PICO Summary
Population
Adults with type A or type O blood requiring blood transfusion from six centres in Australia, Canada, Israel and USA (n= 20,858).
Intervention
Blood stored for the shortest duration (short-term storage group, n= 6,936).
Comparison
Blood stored for the longest duration (long-term storage group, n= 13,922).
Outcome
The mean storage duration was 13.0 days in the short-term storage group and 23.6 days in the long-term storage group. There were 634 deaths (9.1%) in the short-term storage group and 1213 (8.7%) in the long-term storage group (odds ratio, 1.05; 95% confidence interval [CI], 0.95 to 1.16). When the analysis was expanded to include the 24,736 patients with any blood type, the results were similar, with rates of death of 9.1% and 8.8%, respectively (odds ratio, 1.04; 95% CI, 0.95 to 1.14). Additional results were consistent in three prespecified high-risk subgroups (patients undergoing cardiovascular surgery, those admitted to intensive care, and those with cancer).