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.
Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial
Marcucci M, Duceppe E, Le Manach Y, Kearon C, Eikelboom JW, Pohl K, Vincent J, Darvish-Kazem S, Srinathan SK, Neary JDD, et al
Pilot Feasibility Stud. 2020;6:104
Abstract
BACKGROUND Surgical bleeding is associated with postoperative cardiovascular complications. The efficacy and safety of tranexamic acid (TXA) in noncardiac surgery are still uncertain. Statins may prevent perioperative cardiovascular complications. We conducted a pilot to assess the feasibility of a perioperative trial of TXA and rosuvastatin. METHODS Using a factorial design, we randomized patients at cardiovascular risk undergoing noncardiac surgery to intravenous TXA (1 g at the start and end of surgery) or placebo, and oral rosuvastatin (40 mg before and 20 mg daily for 30 days after surgery) or placebo. Feasibility outcomes included recruitment rates, follow-up, and compliance to interventions. Clinical outcomes were secondarily explored. RESULTS After 3 months, we changed the design to a partial factorial due to the difficult recruitment of statin-naive patients. Over 6 months, 100 patients were randomized in the TXA trial (49 TXA, 51 placebo), 34 in the rosuvastatin trial (18 rosuvastatin, 16 placebo). Ninety-two percent (95% CI 80-98) of TXA and 86% (95% CI 74-94) of TXA-placebo patients received the 2 study doses. Thirty-three percent (95% CI 13-59) of rosuvastatin patients and 37% (95% CI 15-65) of rosuvastatin-placebo patients discontinued the study drug. A major cardiovascular complication occurred at 30 days in 1 TXA and 6 TXA-placebo patients, and 1 rosuvastatin and no rosuvastatin-placebo patients. CONCLUSIONS Our pilot study supports the feasibility of a perioperative TXA trial in noncardiac surgery. Feasibility of a perioperative rosuvastatin trial is uncertain because of a high prevalence of statin use in the target population and concerns about compliance. TRIAL REGISTRATION ClinicalTrials.govNCT02546648.
3.
The effects of mild perioperative hypothermia on blood loss and transfusion requirement
Rajagopalan S, Mascha E, Na J, Sessler DI
Anesthesiology. 2008;108((1):):71-7.
Abstract
BACKGROUND Anesthetic-induced hypothermia is known to reduce platelet function and impair enzymes of the coagulation cascade. The objective of this meta-analysis and systematic review was to evaluate the hypothesis that mild perioperative hypothermia increases surgical blood loss and transfusion requirement. METHODS The authors conducted a systematic search of published randomized trials that compared blood loss and/or transfusion requirements in normothermic and mildly hypothermic (34-36 degrees C) surgical patients. Results are expressed as a ratio of the means or relative risks and 95% confidence intervals (CI); P < 0.05 was considered statistically significant. RESULTS Fourteen studies were included in analysis of blood loss, and 10 in the transfusion analysis. The median (quartiles) temperature difference between the normothermic and hypothermic patients among studies was 0.85 degrees C (0.60 degrees C versus 1.1 degrees C). The ratio of geometric means of total blood loss in the normothermic and hypothermic patients was 0.84 (0.74 versus 0.96), P = 0.009. Normothermia also reduced transfusion requirement, with an overall estimated relative risk of 0.78 (95% CI 0.63, 0.97), P = 0.027. CONCLUSION Even mild hypothermia (<1 degree C) significantly increases blood loss by approximately 16% (4-26%) and increases the relative risk for transfusion by approximately 22% (3-37%). Maintaining perioperative normothermia reduces blood loss and transfusion requirement by clinically important amounts.
4.
Mild hypothermia increases blood loss and transfusion requirements during total hip arthroplasty
Schmied H, Kurz A, Sessler DI, Kozek S, Reiter A
Lancet. 1996;347((8997):):289-92.
Abstract
BACKGROUND In-vitro studies indicate that platelet function and the coagulation cascade are impaired by hypothermia. However, the extent to which perioperative hypothermia influences bleeding during surgery remains unknown. Accordingly, we tested the hypothesis that mild hypothermia increases blood loss and allogeneic transfusion requirements during hip arthroplasty. METHODS Blood loss and transfusion requirements were evaluated in 60 patients undergoing primary, unilateral total hip arthroplasties who were randomly assigned to normothermia (final intraoperative core temperature 36.6 [0.4] degrees C) or mild hypothermia (35.0 [0.5] degrees C). Crystalloid, colloid, scavenged red cells, and allogeneic blood were administered by strict protocol. FINDINGS Intra- and postoperative blood loss was significantly greater in the hypothermic patients: 2.2 (0.5) L vs 1.7 (0.3) L, p < 0.001). Eight units of allogeneic packed red cells were required in seven of the 30 hypothermic patients, whereas only one normothermic patient required a unit of allogeneic blood (p < 0.05 for administered volume). A typical decrease in core temperature in patients undergoing hip arthroplasty will thus augment blood loss by approximately 500 mL. INTERPRETATION The maintenance of intraoperative normothermia reduces blood loss and allogeneic blood requirements in patients undergoing total hip arthroplasty.