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.
Health economics of Patient Blood Management: a cost-benefit analysis based on a meta-analysis
Vox sanguinis. 2019
BACKGROUND AND OBJECTIVES Patient Blood Management (PBM) is the timely application of evidence-based medical and surgical concepts designed to improve haemoglobin concentration, optimize haemostasis and minimize blood loss in an effort to improve patient outcomes. The focus of this cost-benefit analysis is to analyse the economic benefit of widespread implementation of a multimodal PBM programme. MATERIALS AND METHODS Based on a recent meta-analysis including 17 studies (>235 000 patients) comparing PBM with control care and data from the University Hospital Frankfurt, a cost-benefit analysis was performed. Outcome data were red blood cell (RBC) transfusion rate, number of transfused RBC units, and length of hospital stay (LOS). Costs were considered for the following three PBM interventions as examples: anaemia management including therapy of iron deficiency, use of cell salvage and tranexamic acid. For sensitivity analysis, a Monte Carlo simulation was performed. RESULTS Iron supplementation was applied in 3.1%, cell salvage in 65% and tranexamic acid in 89% of the PBM patients. In total, applying these three PBM interventions costs euro129.04 per patient. However, PBM was associated with a reduction in transfusion rate, transfused RBC units per patient, and LOS which yielded to mean savings of euro150.64 per patient. Thus, the overall benefit of PBM implementation was euro21.60 per patient. In the Monte Carlo simulation, the cost savings on the outcome side exceeded the PBM costs in approximately 2/3 of all repetitions and the total benefit was euro1 878 000 in 100.000 simulated patients. CONCLUSION Resources to implement a multimodal PBM concept optimizing patient care and safety can be cost-effectively.
A model-based cost-effectiveness analysis of patient blood management
Blood Transfusion = Trasfusione Del Sangue. 2018;:1-17.
BACKGROUND Patient blood management (PBM) is a multidisciplinary concept focused on the management of anaemia, minimisation of iatrogenic blood loss and rational use of allogeneic blood products. The aims of this study were: (i) to analyse post-operative outcome in patients with liberal vs restrictive exposure to allogeneic blood products and (ii) to evaluate the cost-effectiveness of PBM in patients undergoing surgery. MATERIALS AND METHODS A systematic literature review and meta-analysis were performed to compare post-operative complications in predominantly non-transfused patients (restrictive transfusion group) and patients who received one to three units of red blood cells (liberal transfusion group). Outcome measures included sepsis with/without pneumonia, acute renal failure, acute myocardial infarction and acute stroke. In a second step, a health economic model was developed to calculate cost-effectiveness of PBM (PBM-arm vs control-arm) for simulated cohorts of 10,000 cardiac and non-cardiac surgical patients based on the results of the meta-analysis and costs. RESULTS Out of 478 search results, 22 studies were analysed in the meta-analysis. The pooled relative risk of any complication in the restrictive transfusion group was 0.43 for non-cardiac and 0.34 for cardiac surgical patients. In the simulation model, PBM was related to reduced complications (1,768 vs 1,245) and complication-related deaths (411 vs 304) compared to standard care. PBM-related costs of therapy exceeded costs of the control arm by euro 150 per patient. However, total costs, including hospitalisation, were higher in the control-arm for both non-cardiac (euro 2,885.11) and cardiac surgery patients (euro 1,760.69). The incremental cost-effectiveness ratio including hospitalisation showed savings of euro 30,458 (non-cardiac and cardiac surgery patients) for preventing one complication and euro 128,023 (non-cardiac and cardiac surgery patients) for prevention of one complication-related death in the PBM-arm. DISCUSSION Our results indicate that PBM may be associated with fewer adverse clinical outcomes compared to control management and may, thereby, be cost-effective.
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.