Abstract

PURPOSE Blood transfusions are frequently administered in cardiac surgery. Despite a large number of published studies comparing a "restrictive" strategy with a "liberal" strategy, no clear consensus has emerged to guide blood transfusion practice in cardiac surgery patients. The purpose of this study was to identify, critically appraise, and summarize the evidence on the overall effect of restrictive transfusion strategies compared with liberal transfusion strategies on mortality, other clinical outcomes, and transfusion-related outcomes in adult patients undergoing cardiac surgery. SOURCE We searched MEDLINE (OvidSP), EMBASE (OvidSP) and Cochrane CENTRAL (Wiley) from inception to 1 December 2017 and queried clinical trial registries and conference proceedings for randomized-controlled trials of liberal vs restrictive transfusion strategies in cardiac surgery. PRINCIPAL FINDINGS From 7,908 citations, we included ten trials (9,101 patients) and eight companion publications. Overall, we found no significant difference in mortality between restrictive and liberal transfusion strategies (risk ratio [RR], 1.08; 95% confidence interval [CI], 0.76 to 1.54; I(2) = 33%; seven trials; 8,661 patients). The use of a restrictive transfusion strategy did not appear to adversely impact any of the secondary clinical outcomes. As expected, the proportion of patients who received red blood cells (RBCs) in the restrictive group was significantly lower than in the liberal group (RR, 0.68; 95% CI, 0.64 to 0.73; I(2) = 56%; 5 trials; 8,534 patients). Among transfused patients, a restrictive transfusion strategy was associated with fewer transfused RBC units per patient than a liberal transfusion strategy. CONCLUSIONS In adult patients undergoing cardiac surgery, a restrictive transfusion strategy reduces RBC transfusion without impacting mortality rate or the incidence of other perioperative complications. Nevertheless, further large trials in subgroups of patients, potentially of differing age, are needed to establish firm evidence to guide transfusion in cardiac surgery. TRIAL REGISTRATION PROSPERO (CRD42017071440); registered 20 April, 2018.

Abstract

PURPOSE Thromboelastography and rotational thromboelastometry are point-of-care (POC) viscoelastic tests used to help guide blood product administration. It is unclear whether these tests improve clinical or transfusion-related outcomes. The objective of this study was to appraise data from randomized trials evaluating the benefit of POC testing in cardiac surgery patients. Primary outcomes were the proportion of patients transfused with blood products and all-cause mortality. SOURCE Medline (Ovid), EMBASE (Ovid), CENTRAL (the Cochrane Library-Wiley), Web of Science, Biosis, Scopus, and CINAHL databases, as well as clinical trial registries and conference proceedings were queried from inception to February 2018. PRINCIPAL FINDINGS We identified 1,917 records, 11 of which were included in our analysis (8,294 patients). Point-of-care testing was not associated with a difference in the proportion of patients transfused with any blood product (risk ratio [RR], 0.90; 95% confidence interval [CI], 0.79 to 1.02; I(2) = 51%; four trials, 7,623 patients), or all-cause mortality (RR, 0.73; 95% CI, 0.47 to 1.13; I(2) = 5%; six trials, 7,931 patients). Nevertheless, POC testing was weakly associated with a decrease in the proportion of patients receiving red blood cells (RBC) (RR, 0.91; 95% CI, 0.85 to 0.96; I(2) = 0%; seven trials, 8,029 patients), and heterogeneous reductions in frozen plasma (FP) (RR, 0.58; 95% CI, 0.34 to 0.99; I(2) = 87%; six trials, 7,989 patients) and platelets (RR, 0.66; 95% CI, 0.49 to 0.90; I(2) = 65%; seven trials, 8,029 patients). Meta-analysis of the number of units of RBCs and FP was not possible due to heterogeneity in reporting, however POC testing significantly reduced the units of platelets transfused (standard mean difference, -0.09; 95% CI, -0.18 to 0.00; four trials, 7,643 patients). CONCLUSION Our review indicates that in cardiac surgery patients, POC viscoelastic hemostatic testing is not associated with a reduction in the proportion of patients receiving any blood product or all-cause mortality. However, viscoelastic testing is weakly associated with a reduction in proportion of patients transfused with specific blood products. Presently, the benefits associated with viscoelastic testing in cardiac surgery patients are insufficiently robust to recommend routine implementation of this technology. TRIAL REGISTRATION PROSPERO (CRD4201706577). Registered 11 May 2017.

Abstract

Background We reported previously that, in patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive transfusion strategy was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or 28 days after surgery, whichever came first. We now report the clinical outcomes at 6 months after surgery. Methods We randomly assigned 5243 adults undergoing cardiac surgery to a restrictive red-cell transfusion strategy (transfusion if the hemoglobin concentration was <7.5 g per deciliter intraoperatively or postoperatively) or a liberal red-cell transfusion strategy (transfusion if the hemoglobin concentration was <9.5 g per deciliter intraoperatively or postoperatively when the patient was in the intensive care unit [ICU] or was <8.5 g per deciliter when the patient was in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis occurring within 6 months after the initial surgery. An expanded secondary composite outcome included all the components of the primary outcome as well as emergency department visit, hospital readmission, or coronary revascularization occurring within 6 months after the index surgery. The secondary outcomes included the individual components of the two composite outcomes. Results At 6 months after surgery, the primary composite outcome had occurred in 402 of 2317 patients (17.4%) in the restrictive-threshold group and in 402 of 2347 patients (17.1%) in the liberal-threshold group (absolute risk difference before rounding, 0.22 percentage points; 95% confidence interval [CI], -1.95 to 2.39; odds ratio, 1.02; 95% CI, 0.87 to 1.18; P=0.006 for noninferiority). Mortality was 6.2% in the restrictive-threshold group and 6.4% in the liberal-threshold group (odds ratio, 0.95; 95% CI, 0.75 to 1.21). There were no significant between-group differences in the secondary outcomes. Conclusions In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy for red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis at 6 months after surgery. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Abstract

OBJECTIVES To determine if a restrictive transfusion threshold is noninferior to a higher threshold as measured by a composite outcome of mortality and serious morbidity. DESIGN Transfusion Requirements in Cardiac Surgery (TRICS) III was a multicenter, international, open-label randomized controlled trial of two commonly used transfusion strategies in patients having cardiac surgery using a noninferiority trial design (ClinicalTrials.gov number, NCT02042898). SETTING Eligible patients were randomized prior to surgery in a 1:1 ratio. PARTICIPANTS Potential participants were 18 years or older undergoing planned cardiac surgery using cardiopulmonary bypass (CPB) with a preoperative European System for Cardiac Operative Risk Evaluation (EuroSCORE I) of 6 or more. INTERVENTIONS Five thousand patients; those allocated to a restrictive transfusion group received a red blood cell (RBC) transfusion if the hemoglobin concentration (Hb) was less than 7.5 g/dL intraoperatively and/or postoperatively. Patients allocated to a liberal transfusion strategy received RBC transfusion if the Hb was less than 9.5 g/dL intraoperatively or postoperatively in the intensive care unit or less than 8.5 g/dL on the ward. MEASUREMENTS AND MAIN RESULTS The primary outcome was a composite of all-cause mortality, myocardial infarction, stroke, or new onset renal dysfunction requiring dialysis at hospital discharge or day 28, whichever comes first. The primary outcome was analyzed as a per-protocol analysis. The trial monitored adherence closely as adherence to the transfusion triggers is important in ensuring that measured outcomes reflect the transfusion strategy. CONCLUSION By randomizing prior to surgery, the TRICS III trial captured the most acute reduction in hemoglobin during cardiopulmonary bypass.

Abstract

Background The effect of a restrictive versus liberal red-cell transfusion strategy on clinical outcomes in patients undergoing cardiac surgery remains unclear. Methods In this multicenter, open-label, noninferiority trial, we randomly assigned 5243 adults undergoing cardiac surgery who had a European System for Cardiac Operative Risk Evaluation (EuroSCORE) I of 6 or more (on a scale from 0 to 47, with higher scores indicating a higher risk of death after cardiac surgery) to a restrictive red-cell transfusion threshold (transfuse if hemoglobin level was <7.5 g per deciliter, starting from induction of anesthesia) or a liberal red-cell transfusion threshold (transfuse if hemoglobin level was <9.5 g per deciliter in the operating room or intensive care unit [ICU] or was <8.5 g per deciliter in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or by day 28, whichever came first. Secondary outcomes included red-cell transfusion and other clinical outcomes. Results The primary outcome occurred in 11.4% of the patients in the restrictive-threshold group, as compared with 12.5% of those in the liberal-threshold group (absolute risk difference, -1.11 percentage points; 95% confidence interval [CI], -2.93 to 0.72; odds ratio, 0.90; 95% CI, 0.76 to 1.07; P<0.001 for noninferiority). Mortality was 3.0% in the restrictive-threshold group and 3.6% in the liberal-threshold group (odds ratio, 0.85; 95% CI, 0.62 to 1.16). Red-cell transfusion occurred in 52.3% of the patients in the restrictive-threshold group, as compared with 72.6% of those in the liberal-threshold group (odds ratio, 0.41; 95% CI, 0.37 to 0.47). There were no significant between-group differences with regard to the other secondary outcomes. Conclusions In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy regarding red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis, with less blood transfused. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Abstract

BACKGROUND -Cardiac surgery is frequently complicated by coagulopathic bleeding that is difficult to optimally manage using standard hemostatic testing. We hypothesized that point-of-care hemostatic testing within the context of an integrated transfusion algorithm would improve the management of coagulopathy in cardiac surgery and thereby reduce blood transfusions. METHODS -We conducted a pragmatic multi-centered stepped-wedge cluster randomized controlled trial of a POC-based transfusion algorithm in consecutive patients undergoing cardiac surgery with cardiopulmonary bypass at 12 hospitals from Oct 6, 2014 to May 1, 2015. Following a 1-month data collection at all participating hospitals, a transfusion algorithm incorporating point-of-care hemostatic testing was sequentially implemented at 2 hospitals at a time in 1-month intervals, with the implementation order randomly assigned. No other aspects of care were modified. The primary outcome was red cell transfusion from surgery to postoperative day seven. Other outcomes included transfusion of other blood products, major bleeding, and major complications. The analysis adjusted for secular time-trends, within-hospital clustering, and patient-level risk factors. All outcomes and analyses were pre-specified before study initiation. RESULTS -Among the 7402 patients studied, 3555 underwent surgery during the control phase and 3847 during the intervention phase. Overall, 3329 (45.0%) received red cells, 1863 (25.2%) received platelets, 1645 (22.2%) received plasma, and 394 (5.3%) received cryoprecipitate. Major bleeding occurred in 1773 (24.1%) patients and major complications occurred in 740 (10.2%) patients. The trial intervention reduced rates of red cell transfusion (adjusted relative risk [RR], 0.91; 95% CI, 0.85 to 0.98; P = 0.02; Number needed to treat [NNT] 24.7), platelet transfusion (RR, 0.77; 95% CI, 0.68 to 0.87; P < 0.001; NNT 16.7), and major bleeding (RR, 0.83; 95% CI, 0.72 to 0.94; P = 0.004; NNT 22.6), but had no effect on other blood product transfusions or major complications. CONCLUSIONS -Implementation of point-of-care hemostatic testing within the context of an integrated transfusion algorithm reduces red cell transfusions, platelet transfusions, and major bleeding following cardiac surgery. Our findings support the broader adoption of point-of-care hemostatic testing into clinical practice. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02200419.

Abstract

OBJECTIVE Ecallantide is a recombinant peptide in the same class as aprotinin that inhibits plasma kallikrein, a major component of the contact coagulation and inflammatory cascades. Therefore, ecallantide was expected to reduce blood loss associated with cardiac surgery requiring cardiopulmonary bypass. METHODS This prospective multinational, randomized, double-blind trial enrolled patients undergoing cardiac surgery using cardiopulmonary bypass for procedures associated with a high risk of bleeding. Patients were randomly assigned to ecallantide (n = 109) or tranexamic acid (high dose, n = 24; low dose, n = 85). Efficacy was assessed from the volume of packed red blood cells administered within the first 12 hours after surgery. RESULTS The study was terminated early after the independent data safety and monitoring board observed a statistically significantly higher 30-day mortality in the ecallantide group (12%) than in the tranexamic acid groups (4%, P = .041). Patients receiving ecallantide received more packed red blood cells within 12 hours of surgery than tranexamic acid-treated patients: median = 900 mL (95% confidence interval, 600-1070) versus 300 mL (95% confidence interval, 0-523) (P < .001). Similar differences were seen at 24 hours and at discharge. Patients treated with the higher tranexamic acid dose received less packed red blood cells, 0 mL (95% confidence interval, 280-600), than the group treated with the lower dose, 400 mL (95% confidence interval, 0-400) (P = .008). No deaths occurred in the higher dose tranexamic acid group. CONCLUSIONS Ecallantide was less effective at reducing perioperative blood loss than tranexamic acid. High-dose tranexamic acid was more effective than the low dose in reducing blood loss. Copyright 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.