Association of Intravenous Tranexamic Acid With Thromboembolic Events and Mortality: A Systematic Review, Meta-analysis, and Meta-regression
JAMA surgery. 2021;:e210884
IMPORTANCE Tranexamic acid (TXA) is an efficient antifibrinolytic agent; however, concerns remain about the potential adverse effects, particularly vascular occlusive events, that may be associated with its use. OBJECTIVE To examine the association between intravenous TXA and total thromboembolic events (TEs) and mortality in patients of all ages and of any medical disciplines. DATA SOURCE Cochrane Central Register of Controlled Trials and MEDLINE were searched for eligible studies investigating intravenous TXA and postinterventional outcome published between 1976 and 2020. STUDY SELECTION Randomized clinical trials comparing intravenous TXA with placebo/no treatment. The electronic database search yielded a total of 782 studies, and 381 were considered for full-text review. Included studies were published in English, German, French, and Spanish. Studies with only oral or topical tranexamic administration were excluded. DATA EXTRACTION AND SYNTHESIS Meta-analysis, subgroup and sensitivity analysis, and meta-regression were performed. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. MAIN OUTCOMES AND MEASURES Vascular occlusive events and mortality. RESULTS A total of 216 eligible trials including 125 550 patients were analyzed. Total TEs were found in 1020 (2.1%) in the group receiving TXA and 900 (2.0%) in the control group. This study found no association between TXA and risk for total TEs (risk difference = 0.001; 95% CI, -0.001 to 0.002; P = .49) for venous thrombosis, pulmonary embolism, venous TEs, myocardial infarction or ischemia, and cerebral infarction or ischemia. Sensitivity analysis using the risk ratio as an effect measure with (risk ratio = 1.02; 95% CI, 0.94-1.11; P = .56) and without (risk ratio = 1.03; 95% CI, 0.95-1.12; P = .52) studies with double-zero events revealed robust effect size estimates. Sensitivity analysis with studies judged at low risk for selection bias showed similar results. Administration of TXA was associated with a significant reduction in overall mortality and bleeding mortality but not with nonbleeding mortality. In addition, an increased risk for vascular occlusive events was not found in studies including patients with a history of thromboembolism. Comparison of studies with sample sizes of less than or equal to 99 (risk difference = 0.004; 95% CI, -0.006 to 0.014; P = .40), 100 to 999 (risk difference = 0.004; 95% CI, -0.003 to 0.011; P = .26), and greater than or equal to 1000 (risk difference = -0.001; 95% CI, -0.003 to 0.001; P = .44) showed no association between TXA and incidence of total TEs. Meta-regression of 143 intervention groups showed no association between TXA dosing and risk for venous TEs (risk difference, -0.005; 95% CI, -0.021 to 0.011; P = .53). CONCLUSIONS AND RELEVANCE Findings from this systematic review and meta-analysis of 216 studies suggested that intravenous TXA, irrespective of dosing, is not associated with increased risk of any TE. These results help clarify the incidence of adverse events associated with administration of intravenous TXA and suggest that TXA is safe for use with undetermined utility for patients receiving neurological care.
Patients of all ages and of any medical disciplines (216 studies, n= 125,550).
Intravenous tranexamic acid (TXA).
Total thromboembolic events (TEs) were found in 1020 (2.1%) in the group receiving TXA and 900 (2.0%) in the control group. No association was found between TXA and risk for total TEs for venous thrombosis, pulmonary embolism, venous TEs, myocardial infarction or ischemia, and cerebral infarction or ischemia. Administration of TXA was associated with a significant reduction in overall mortality and bleeding mortality but not with non-bleeding mortality. An increased risk for vascular occlusive events was not found in studies including patients with a history of thromboembolism. Comparison of studies with sample sizes ranging between less than or equal to 99 and greater than or equal to 1000 showed no association between TXA and incidence of total TEs. Meta-regression of 143 intervention groups showed no association between TXA dosing and risk for venous TEs.
Comparison of common perioperative blood loss estimation techniques: a systematic review and meta-analysis
Journal of clinical monitoring and computing. 2020
Estimating intraoperative blood loss is one of the daily challenges for clinicians. Despite the knowledge of the inaccuracy of visual estimation by anaesthetists and surgeons, this is still the mainstay to estimate surgical blood loss. This review aims at highlighting the strengths and weaknesses of currently used measurement methods. A systematic review of studies on estimation of blood loss was carried out. Studies were included investigating the accuracy of techniques for quantifying blood loss in vivo and in vitro. We excluded nonhuman trials and studies using only monitoring parameters to estimate blood loss. A meta-analysis was performed to evaluate systematic measurement errors of the different methods. Only studies that were compared with a validated reference e.g. Haemoglobin extraction assay were included. 90 studies met the inclusion criteria for systematic review and were analyzed. Six studies were included in the meta-analysis, as only these were conducted with a validated reference. The mixed effect meta-analysis showed the highest correlation to the reference for colorimetric methods (0.93 95% CI 0.91-0.96), followed by gravimetric (0.77 95% CI 0.61-0.93) and finally visual methods (0.61 95% CI 0.40-0.82). The bias for estimated blood loss (ml) was lowest for colorimetric methods (57.59 95% CI 23.88-91.3) compared to the reference, followed by gravimetric (326.36 95% CI 201.65-450.86) and visual methods (456.51 95% CI 395.19-517.83). Of the many studies included, only a few were compared with a validated reference. The majority of the studies chose known imprecise procedures as the method of comparison. Colorimetric methods offer the highest degree of accuracy in blood loss estimation. Systems that use colorimetric techniques have a significant advantage in the real-time assessment of blood loss.
Adult surgery and obstetric patients (90 in vitro and in vivo studies).
Visual blood loss estimation methods.
Several methods including: gravimetric and colorimetric methods.
The mixed effect meta-analysis showed the highest correlation to the reference for colorimetric methods (0.93), followed by gravimetric (0.77) and finally visual methods (0.61). The bias for estimated blood loss (ml) was lowest for colorimetric methods (57.59) compared to the reference, followed by gravimetric (326.36) and visual methods (456.51). Colorimetric methods offer the highest degree of accuracy in blood loss estimation.
Multimodal Patient Blood Management Program Based on a Three-pillar Strategy: A Systematic Review and Meta-analysis
Annals of Surgery. 2018
OBJECTIVES To determine whether a multidisciplinary, multimodal Patient Blood Management (PBM) program for patients undergoing surgery is effective in reducing perioperative complication rate, and thereby is effective in improving clinical outcome. BACKGROUND PBM is a medical concept with the focus on a comprehensive anemia management, to minimize iatrogenic (unnecessary) blood loss, and to harness and optimize patient-specific physiological tolerance of anemia. METHODS A systematic review and meta-analysis was performed. Eligible studies had to address each of the 3 PBM pillars with at least 1 measure per pillar, for example, preoperative anemia management plus cell salvage plus rational transfusion strategy. The study protocol has been registered with PROSPERO (CRD42017079217). RESULTS Seventeen studies comprising 235,779 surgical patients were included in this meta-analysis (100,886 pre-PBM group and 134,893 PBM group). Implementation of PBM significantly reduced transfusion rates by 39% [risk ratio (RR) 0.61, 95% confidence interval (CI) 0.55-0.68, P < 0.00001], 0.43 red blood cell units per patient (mean difference -0.43, 95% CI -0.54 to -0.31, P < 0.00001), hospital length of stay (mean difference -0.45, 95% CI -0.65 to -0.25, P < 0,00001), total number of complications (RR 0.80, 95% CI 0.74-0.88, P <0.00001), and mortality rate (RR 0.89, 95% CI 0.80-0.98, P = 0.02). CONCLUSIONS Overall, a comprehensive PBM program addressing all 3 PBM pillars is associated with reduced transfusion need of red blood cell units, lower complication and mortality rate, and thereby improving clinical outcome. Thus, this first meta-analysis investigating a multimodal approach should motivate all executives and health care providers to support further PBM activities.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.
Washed cell salvage in surgical patients: a review and meta-analysis of prospective randomized trials under PRISMA
BACKGROUND Cell salvage is commonly used as part of a blood conservation strategy. However concerns among clinicians exist about the efficacy of transfusion of washed cell salvage. METHODS We performed a meta-analysis of randomized controlled trials in which patients, scheduled for all types of surgery, were randomized to washed cell salvage or to a control group with no cell salvage. Data were independently extracted, risk ratio (RR), and weighted mean differences (WMD) with 95% confidence intervals (CIs) were calculated. Data were pooled using a random effects model. The primary endpoint was the number of patients exposed to allogeneic red blood cell (RBC) transfusion. RESULTS Out of 1140 search results, a total of 47 trials were included. Overall, the use of washed cell salvage reduced the rate of exposure to allogeneic RBC transfusion by a relative 39% (RR = 0.61; 95% CI 0.57 to 0.65; P < 0.001), resulting in an average saving of 0.20 units of allogeneic RBC per patient (weighted mean differences [WMD] = -0.20; 95% CI -0.22 to -0.18; P < 0.001), reduced risk of infection by 28% (RR = 0.72; 95% CI 0.54 to 0.97; P = 0.03), reduced length of hospital stay by 2.31 days (WMD = -2.31; 95% CI -2.50 to -2.11; P < 0.001), but did not significantly affect risk of mortality (RR = 0.92; 95% CI 0.63 to 1.34; P = 0.66). No statistical difference could be observed in the number of patients exposed to re-operation, plasma, platelets, or rate of myocardial infarction and stroke. CONCLUSIONS Washed cell salvage is efficacious in reducing the need for allogeneic RBC transfusion and risk of infection in surgery.
Aprotinin may increase mortality in low and intermediate risk but not in high risk cardiac surgical patients compared to tranexamic acid and -aminocaproic acid - a meta-analysis of randomised and observational trials of over 30.000 patients
PLoS ONE. 2013;8((3):):e58009.
BACKGROUND To compare the effect of aprotinin with the effect of lysine analogues (tranexamic acid and -aminocaproic acid) on early mortality in three subgroups of patients: low, intermediate and high risk of cardiac surgery. METHODS AND FINDINGS We performed a meta-analysis of randomised controlled trials and observational with the following data sources: Medline, Cochrane Library, and reference lists of identified articles. The primary outcome measure was early (in-hospital/30-day) mortality. The secondary outcome measures were any transfusion of packed red blood cells within 24 hours after surgery, any re-operation for bleeding or massive bleeding, and acute renal dysfunction or failure within the selected cited publications, respectively. Out of 328 search results, 31 studies (15 trials and 16 observational studies) included 33,501 patients. Early mortality was significantly increased after aprotinin vs. lysine analogues with a pooled risk ratio (95% CI) of 1.58 (1.13-2.21), p<0.001 in the low (n=14,297) and in the intermediate risk subgroup (1.42 (1.09-1.84), p<0.001; n=14,427), respectively. Contrarily, in the subgroup of high risk patients (n=4,777), the risk for mortality did not differ significantly between aprotinin and lysine analogues (1.03 (0.67-1.58), p=0.90). CONCLUSION Aprotinin may be associated with an increased risk of mortality in low and intermediate risk cardiac surgery, but presumably may has no effect on early mortality in a subgroup of high risk cardiac surgery compared to lysine analogues. Thus, decisions to re-license aprotinin in lower risk patients should critically be debated. In contrast, aprotinin might probably be beneficial in high risk cardiac surgery as it reduces risk of transfusion and bleeding complications.
Point-of-care testing: a prospective, randomized clinical trial of efficacy in coagulopathic cardiac surgery patients
INTRODUCTION The current investigation aimed to study the efficacy of hemostatic therapy guided either by conventional coagulation analyses or point-of-care (POC) testing in coagulopathic cardiac surgery patients. METHODS Patients undergoing complex cardiac surgery were assessed for eligibility. Those patients in whom diffuse bleeding was diagnosed after heparin reversal or increased blood loss during the first 24 postoperative hours were enrolled and randomized to the conventional or POC group. Thromboelastometry and whole blood impedance aggregometry have been performed in the POC group. The primary outcome variable was the number of transfused units of packed erythrocytes during the first 24 h after inclusion. Secondary outcome variables included postoperative blood loss, use and costs of hemostatic therapy, and clinical outcome parameters. Sample size analysis revealed a sample size of at least 100 patients per group. RESULTS There were 152 patients who were screened for eligibility and 100 patients were enrolled in the study. After randomization of 50 patients to each group, a planned interim analysis revealed a significant difference in erythrocyte transfusion rate in the conventional compared with the POC group [5 (4;9) versus 3 (2;6) units [median (25 and 75 percentile)], P<0.001]. The study was terminated early. The secondary outcome parameters of fresh frozen plasma and platelet transfusion rates, postoperative mechanical ventilation time, length of intensive care unit stay, composite adverse events rate, costs of hemostatic therapy, and 6-month mortality were lower in the POC group. CONCLUSIONS Hemostatic therapy based on POC testing reduced patient exposure to allogenic blood products and provided significant benefits with respect to clinical outcomes.