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Platelet Transfusion in Cardiac Surgery: A Systematic Review and Meta-Analysis
Yanagawa B, Ribeiro R, Lee J, Mazer CD, Cheng D, Martin J, Verma S, Friedrich JO
Ann Thorac Surg. 2020
Abstract
BACKGROUND Blood transfusion is a well-established independent risk factor for mortality in patients undergoing cardiac surgery but the impact of platelet transfusion is less clear. We performed a systematic review and meta-analysis of observational studies comparing outcomes of patients who received platelet transfusion following cardiac surgery. METHODS We searched MEDLINE and EMBASE databases to January 2019 for studies comparing peri-operative outcomes in patients undergoing cardiac surgery with and without platelet transfusion. RESULTS There were 9 observational studies reporting on 101,511 patients: 12% with and 88% without platelet transfusion. In unmatched/unadjusted studies, patients who received platelet transfusion were older with greater incidence of renal, peripheral and cerebrovascular disease, myocardial infarction, left ventricular dysfunction, and anemia. They were more likely to have non-elective, combined surgery; pre-operative hemodynamic instability and endocarditis; and more likely to be on clopidogrel preoperatively. Perioperative complications were significantly increased without adjusting for these baseline differences. After pooling only matched/adjusted data, differences were not found in patients who did vs did not receive platelets for operative mortality (risk ratio [RR] 1.26, 95%CI:0.69-2.32, p=0.46, 5 studies), stroke (RR 0.94, 95%CI:0.62-1.45, p=0.79, 5 studies), myocardial infarction (RR1.29, 95%CI:0.95-1.77, p=0.11, 3 studies), reoperation for bleeding (RR1.20, 95%CI:0.46-3.18, p=0.71, 3 studies), infection (RR1.02, 95%CI:0.86-1.20, p=0.85, 6 studies), and peri-operative dialysis (RR0.91, 95%CI:0.63-1.32, p=0.62, 3 studies). CONCLUSIONS After accounting for baseline differences, platelet transfusion was not linked with perioperative complications in cardiac surgery patients. Given the small number of observational studies, these findings should be considered hypothesis generating.
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Efficacy and safety of erythropoietin and iron therapy to reduce red blood cell transfusion in surgical patients: a systematic review and meta-analysis
Kei T, Mistry N, Curley G, Pavenski K, Shehata N, Tanzini RM, Gauthier MF, Thorpe K, Schweizer TA, Ward S, et al
Canadian journal of anaesthesia = Journal canadien d'anesthesie. 2019
Abstract
PURPOSE Iron restricted anemia is prevalent in surgical patients and is associated with an increased risk of allogeneic red blood cell (RBC) transfusion and adverse events. Treatment of anemia includes oral and intravenous iron and erythropoiesis stimulating agents (ESAs). More recent studies have focused on the use of intravenous iron as the primary approach to treating anemia. Nevertheless, the optimal treatment strategy for anemia remains to be established. Our primary objective was to evaluate the efficacy and safety of ESA and iron therapy relative to iron therapy alone in reducing RBC transfusion in surgical patients. SOURCE We searched the Cochrane Library, MEDLINE, EMBASE, and ClinicalTrials.gov from inception to May 2018. We included randomized-controlled trials in which adult surgical patients received an ESA and iron, vs iron alone, prior to cardiac and non-cardiac surgery. Our primary outcome was RBC transfusion rate. Secondary outcomes included hemoglobin concentration (post-treatment and postoperatively), number of RBC units transfused, mortality, stroke, myocardial infarction (MI), renal dysfunction, pulmonary embolism (PE), and deep vein thrombosis (DVT). PRINCIPAL FINDINGS In total, 25 studies (4,719 participants) were included. Erythropoiesis stimulating agents and iron therapy reduced RBC transfusion relative to iron therapy (relative risk [RR] 0.57; 95% confidence interval [CI], 0.46 to 0.71) without any change in mortality (RR 1.31; 95% CI, 0.80 to 2.16), stroke (RR 1.91; 95% CI, 0.63 to 5.76), MI (RR 1.12; 95% CI, 0.50 to 2.50), renal dysfunction (RR 0.96; 95% CI, 0.72 to 1.26), PE (RR 0.92; 95% CI, 0.15 to 5.83), or DVT (RR 1.48; 95% CI, 0.95 to 2.31). CONCLUSION Administration of ESA and iron therapy reduced the risk for RBC transfusion compared with iron therapy alone in patients undergoing cardiac and non-cardiac surgery. Nevertheless, publication bias and heterogeneity reduces the confidence of the finding. Although the analysis was probably under-powered for some outcomes, no difference in the incidence of serious adverse events was observed with ESA and iron compared with iron alone. Further large prospective trials are required to confirm these findings.
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Restrictive compared with liberal red cell transfusion strategies in cardiac surgery: a meta-analysis
Shehata N, Mistry N, da Costa BR, Pereira TV, Whitlock R, Curley GF, Scott DA, Hare GMT, Juni P, Mazer CD
European Heart Journal. 2018
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Abstract
Aims: To determine whether a restrictive strategy of red blood cell (RBC) transfusion at lower haemoglobin concentrations is inferior to a liberal strategy of RBC transfusion at higher haemoglobin concentrations in patients undergoing cardiac surgery. Methods and results: We conducted a systematic review, meta-analysis, and trial sequential analysis of randomized controlled trials of the effect of restrictive and liberal RBC transfusion strategies on mortality within 30 days of surgery as the primary outcome. Secondary outcomes were those potentially resulting from anaemia-induced tissue hypoxia and transfusion outcomes. We searched the electronic databases MEDLINE, EMBASE, and the Cochrane Library until 17 November 2017. Thirteen trials were included. The risk ratio (RR) of mortality derived from 4545 patients assigned to a restrictive strategy when compared with 4547 transfused according to a liberal strategy was 0.96 [95% confidence interval (CI) 0.76-1.21, I2 = 0]. A restrictive strategy did not have a statistically significant effect on the risk of myocardial infarction (RR 1.01, 95% CI 0.81-1.26; I2=0), stroke (RR 0.93, 95% CI 0.68-1.27, I2 = 0), renal failure (RR 0.96, 95% CI 0.76-1.20, I2 = 0), or infection (RR 1.12, 95% CI 0.98-1.29, I2 = 0). Subgroup analysis of adult and paediatric trials did not show a significant interaction. At approximately 70% of the critical information size, the meta-analysis of mortality crossed the futility boundary for inferiority of the restrictive strategy. Conclusion: The current evidence does not support the notion that restrictive RBC transfusion strategies are inferior to liberal RBC strategies in patients undergoing cardiac surgery.
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Efficacy and Safety of Erythropoietin and Iron Therapy to Reduce Red Blood Cell Transfusion in Surgical Patients: A Systematic Review and Meta-Analysis
Kei T, Curley G, Pavenski K, Ward S, Shehata N, Tanzini R, Gauthier M-F, Mistry N, Mazer CD, Hare G
Transfusion. 2017;57((53)):114A.. cp-124
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Transfusion triggers for guiding RBC transfusion for cardiovascular surgery: a systematic review and meta-analysis
Curley GF, Shehata N, Mazer CD, Hare GM, Friedrich JO
Critical Care Medicine. 2014;42((12):):2611–2624.
Abstract
OBJECTIVE Restrictive red cell transfusion is recommended to minimize risk associated with exposure to allogeneic blood. However, perioperative anemia is an independent risk factor for adverse outcomes after cardiovascular surgery. The purpose of this systematic review and meta-analysis is to determine whether perioperative restrictive transfusion thresholds are associated with inferior clinical outcomes in randomized trials of cardiovascular surgery patients. DATA SOURCES The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE from inception to October 2013; reference lists of published guidelines, reviews, and associated articles, as well as conference proceedings. No language restrictions were applied. STUDY SELECTION We included controlled trials in which adult patients undergoing cardiac or vascular surgery were randomized to different transfusion thresholds, described as a hemoglobin or hematocrit level below which RBCs were transfused. DATA EXTRACTION Two authors independently extracted data from included trials. We pooled risk ratios of dichotomous outcomes and mean differences of continuous outcomes across trials using random-effects models. DATA SYNTHESIS Seven studies (enrolling 1,262 participants) met inclusion criteria with restrictive and liberal transfusion thresholds most commonly differing by a hemoglobin of 1 g/dL or hematocrit of 6-7%, resulting in decreased transfusions by 0.71 units of RBCs (95% CI, 0.31-1.09, p = 0.0002) without an associated change in adverse events: mortality (risk ratio, 1.12; 95% CI, 0.65-1.95; p = 0.60), myocardial infarction (risk ratio, 0.94; 95% CI, 0.30-2.99; p = 0.92), stroke (risk ratio, 1.15; 95% CI, 0.57-2.32; p = 0.70), acute renal failure (risk ratio, 0.98; 95% CI, 0.64-1.49; p = 0.91), infections (risk ratio, 1.23; 95% CI, 0.85-1.78; p = 0.27), or length of stay. There was no between-trial heterogeneity for any pooled analysis. Including four pediatric trials (456 participants) and 10 trials utilizing only intraoperative acute normovolemic hemodilution (872 participants) did not substantially change the results except that unlike the transfusion threshold trials, the hemodilution trials did not reduce the proportion of patients transfused (interaction p = 0.01). CONCLUSIONS Further randomized controlled trials are necessary to determine the optimal transfusion strategy for patients undergoing cardiovascular surgery.
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Risks of harms using antifibrinolytics in cardiac surgery: systematic review and network meta-analysis of randomised and observational studies
Hutton B, Joseph L, Fergusson D, Mazer CD, Shapiro S, Tinmouth A
Bmj.. 2012;345:e5798.
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Abstract
OBJECTIVE To estimate the relative risks of death, myocardial infarction, stroke, and renal failure or dysfunction between antifibrinolytics and no treatment following the suspension of aprotinin from the market in 2008 for safety reasons and its recent reintroduction in Europe and Canada. DESIGN Systematic review and network meta-analysis. DATA SOURCES A Cochrane review of antifibrinolytic treatments was chosen as the starting point for this systematic review. Medline, Embase, and the Cochrane register of trials were searched with no date restrictions for observational evidence. STUDY SELECTION Propensity matched or adjusted observational studies with two or more of the interventions of interest (aprotinin, tranexamic acid, epsilon-aminocaproic acid, and no treatment) that were carried out in patients undergoing cardiac surgery. DATA ANALYSIS Network meta-analysis was used to compare treatments, and odds ratios with 95% credible intervals were estimated. Meta-analyses were carried out for randomised controlled trials alone and for randomised controlled trials with observational studies. RESULTS 106 randomised controlled trials and 11 observational studies (43 270 patients) were included. Based on the results from analysis of randomised controlled trials, tranexamic acid was associated on average with a reduced risk of death compared with aprotinin (odds ratio 0.64, 95% credible interval 0.41 to 0.99). When observational data were incorporated, comparisons showed an increased risk of mortality with aprotinin on average relative to tranexamic acid (odds ratio 0.71, 95% credible interval 0.50 to 0.98) and epsilon-aminocaproic acid (0.60, 0.43 to 0.87), and an increased risk of renal failure or dysfunction on average relative to all comparators: odds ratio 0.66 (95% credible interval 0.45 to 0.88) compared with no treatment, 0.66 (0.48 to 0.91) versus tranexamic acid, and 0.65 (0.45 to 0.88) versus epsilon-aminocaproic acid. CONCLUSION Although meta-analyses of randomised controlled trials were largely inconclusive, inclusion of observational data suggest concerns remain about the safety of aprotinin. Tranexamic and epsilon-aminocaproic acid are effective alternatives that may be safer for patients.
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Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline
Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Ferraris VA, Ferraris SP, Saha SP, Hessel EA 2nd, Haan CK, Royston BD, Bridges CR, Higgins RS, Despotis G, et al
Annals of Thoracic Surgery. 2007;83((5 Suppl):):S27-86.
Abstract
BACKGROUND A minority of patients having cardiac procedures (15% to 20%) consume more than 80% of the blood products transfused at operation. Blood must be viewed as a scarce resource that carries risks and benefits. A careful review of available evidence can provide guidelines to allocate this valuable resource and improve patient outcomes. METHODS We reviewed all available published evidence related to blood conservation during cardiac operations, including randomized controlled trials, published observational information, and case reports. Conventional methods identified the level of evidence available for each of the blood conservation interventions. After considering the level of evidence, recommendations were made regarding each intervention using the American Heart Association/American College of Cardiology classification scheme. RESULTS Review of published reports identified a high-risk profile associated with increased postoperative blood transfusion. Six variables stand out as important indicators of risk: (1) advanced age, (2) low preoperative red blood cell volume (preoperative anemia or small body size), (3) preoperative antiplatelet or antithrombotic drugs, (4) reoperative or complex procedures, (5) emergency operations, and (6) noncardiac patient comorbidities. Careful review revealed preoperative and perioperative interventions that are likely to reduce bleeding and postoperative blood transfusion. Preoperative interventions that are likely to reduce blood transfusion include identification of high-risk patients who should receive all available preoperative and perioperative blood conservation interventions and limitation of antithrombotic drugs. Perioperative blood conservation interventions include use of antifibrinolytic drugs, selective use of off-pump coronary artery bypass graft surgery, routine use of a cell-saving device, and implementation of appropriate transfusion indications. An important intervention is application of a multimodality blood conservation program that is institution based, accepted by all health care providers, and that involves well thought out transfusion algorithms to guide transfusion decisions. CONCLUSIONS Based on available evidence, institution-specific protocols should screen for high-risk patients, as blood conservation interventions are likely to be most productive for this high-risk subset. Available evidence-based blood conservation techniques include (1) drugs that increase preoperative blood volume (eg, erythropoietin) or decrease postoperative bleeding (eg, antifibrinolytics), (2) devices that conserve blood (eg, intraoperative blood salvage and blood sparing interventions), (3) interventions that protect the patient's own blood from the stress of operation (eg, autologous predonation and normovolemic hemodilution), (4) consensus, institution-specific blood transfusion algorithms supplemented with point-of-care testing, and most importantly, (5) a multimodality approach to blood conservation combining all of the above.