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
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.
Impact of Goal-Directed Therapy on Delayed Ischemia After Aneurysmal Subarachnoid Hemorrhage: Randomized Controlled Trial
Anetsberger A, Gempt J, Blobner M, Ringel F, Bogdanski R, Heim M, Schneider G, Meyer B, Schmid S, Ryang YM, et al
BACKGROUND AND PURPOSE Delayed cerebral ischemia (DCI) is the most important cause for a poor clinical outcome after a subarachnoid hemorrhage. The aim of this study was to assess whether goal-directed hemodynamic therapy (GDHT), as compared to standard clinical care, reduces the rate of DCI after subarachnoid hemorrhage. METHODS We conducted a prospective randomized controlled trial. Patients >18 years of age with an aneurysmal subarachnoid hemorrhage were enrolled and randomly assigned to standard therapy or GDHT. Advanced hemodynamic monitoring and predefined GDHT algorithms were applied in the GDHT group. The primary end point was the occurrence of DCI. Functional outcome was assessed using the Glasgow Outcome Scale (GOS) 3 months after discharge. RESULTS In total, 108 patients were randomized to the control (n=54) or GDHT group (n=54). The primary outcome (DCI) occurred in 13% of the GDHT group and in 32% of the control group patients (odds ratio, 0.324 [95% CI, 0.11-0.86]; P=0.021). Even after adjustment for confounding parameters, GDHT was found to be superior to standard therapy (hazard ratio, 2.84 [95% CI, 1.18-6.86]; P=0.02). The GOS was assessed 3 months after discharge in 107 patients; it showed more patients with a low disability (GOS 5, minor or no deficits) than patients with higher deficits (GOS 1-4) in the GDHT group compared with the control group (GOS 5, 66% versus 44%; GOS 1-4, 34% versus 56%; P=0.025). There was no significant difference in mortality between the groups. CONCLUSIONS GDHT reduced the rate of DCI after subarachnoid hemorrhage with a better functional outcome (GOS=5) 3 months after discharge. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01832389.
Fibrinogen concentrate in cardiovascular surgery: a meta-analysis of randomized controlled trials
Li J Y, Gong J, Zhu F, Moodie J, Newitt A, Uruthiramoorthy L, Cheng D, Martin J
Anesthesia and Analgesia. 2018;127((3):):612-621
BACKGROUND Postoperative bleeding remains a frequent complication after cardiovascular surgery and may contribute to serious morbidity and mortality. Observational studies have suggested a relationship between low endogenous plasma fibrinogen concentration and increased risk of postoperative blood loss in cardiac surgery. Although the transfusion of fibrinogen concentrate has been increasing, potential benefits and risks associated with perioperative fibrinogen supplementation in cardiovascular surgery are not fully understood. METHODS PubMed, Cochrane Library, Ovid MEDLINE, Embase, Web of Science, and China National Knowledge Infrastructure were searched on January 15, 2017, with automated updates searched until February 15, 2018, to identify all randomized controlled trials (RCTs) of fibrinogen concentrate, whether for prophylaxis or treatment of bleeding, in adults undergoing cardiovascular surgery. All RCTs comparing fibrinogen infusion versus any other comparator (placebo/standard of care or another active comparator) in adult cardiovascular surgery and reporting at least 1 predefined clinical outcome were included. The random-effects model was used to calculate risk ratios and weighted mean differences (95% confidence interval [CI]) for dichotomous and continuous variables, respectively. Subgroup analyses by fibrinogen dose and by baseline risk for bleeding were preplanned. RESULTS A total of 8 RCTs of fibrinogen concentrate in adults (n = 597) of mixed risk or high risk undergoing cardiovascular surgery were included. Compared to placebo or inactive control, perioperative fibrinogen concentrate did not significantly impact risk of all-cause mortality (risk ratio, 0.41; 95% CI, 0.12-1.38; I = 10%; P = .15). Fibrinogen significantly reduced incidence of allogeneic red blood cell transfusion (risk ratio, 0.64; 95% CI, 0.49-0.83; I = 0%; P = .001). No significant differences were found for other clinical outcomes. Subgroup analyses were unremarkable when analyzed according to fibrinogen dose, time of infusion initiation, mean cardiopulmonary bypass time, and rotational thromboelastometry/fibrinogen temogram use (all P values for subgroup interaction were nonsignificant). CONCLUSIONS Current evidence remains insufficient to support or refute routine perioperative administration of fibrinogen concentrate in patients undergoing cardiovascular surgery. Fibrinogen concentrate may reduce the need for additional allogeneic blood product transfusion in cardiovascular surgery patients at high risk or with evidence of bleeding. However, no definitive advantage was found for reduction in risk of mortality or other clinically relevant outcomes. The small number of clinical events within existing randomized trials suggests that further well-designed studies of adequate power and duration to measure all-cause mortality, stroke, myocardial infarction, reoperation, and thromboembolic events should be conducted. Future studies should also address cost-effectiveness relative to standard of care.
Should transfusion trigger thresholds differ for critical care versus perioperative patients? A meta-analysis of randomized trials
Chong MA, Krishnan R, Cheng D, Martin J
Critical Care Medicine. 2017;46((2):):252-263
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OBJECTIVE To address the significant uncertainty as to whether transfusion thresholds for critical care versus surgical patients should differ. DESIGN Meta-analysis of randomized controlled trials. SETTING Medline, EMBASE, and Cochrane Library searches were performed up to 15 June 2016. PATIENTS Trials had to enroll adult surgical or critically ill patients for inclusion. INTERVENTIONS Studies had to compare a liberal versus restrictive threshold for the transfusion of allogeneic packed RBCs. MEASUREMENTS AND MAIN RESULTS The primary outcome was 30-day all-cause mortality, sub-grouped by surgical and critical care patients. Secondary outcomes included myocardial infarction, stroke, renal failure, allogeneic blood exposure, and length of stay. Odds ratios and weighted mean differences were calculated using random effects meta-analysis. To assess whether subgroups were significantly different, tests for subgroup interaction were used. Subgroup analysis by trials enrolling critically ill versus surgical patients was performed. Twenty-seven randomized controlled trials (10,797 patients) were included. In critical care patients, restrictive transfusion resulted in significantly reduced 30-day mortality compared with liberal transfusion (odds ratio, 0.82; 95% CI, 0.70-0.97). In surgical patients, a restrictive transfusion strategy led to the opposite direction of effect for mortality (odds ratio, 1.31; 95% CI, 0.94-1.82). The subgroup interaction test was significant (p = 0.04), suggesting that the effect of restrictive transfusion on mortality is statistically different for critical care (decreased risk) versus surgical patients (potentially increased risk or no difference). Regarding secondary outcomes, for critically ill patients, a restrictive strategy resulted in reduced risk of stroke/transient ischemic attack, packed RBC exposure, transfusion reactions, and hospital length of stay. In surgical patients, restrictive transfusion resulted in reduced packed RBC exposure. CONCLUSIONS The safety of restrictive transfusion strategies likely differs for critically ill patients versus perioperative patients. Further trials investigating transfusion strategies in the perioperative setting are necessary.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.
Randomized double-blind safety comparison of intravenous iron dextran versus iron sucrose in an adult non-hemodialysis outpatient population: A feasibility study
Louzada ML, Hsia CC, Al-Ani F, Ralley F, Xenocostas A, Martin J, Connelly SE, Chin-Yee IH, Minuk L, Lazo-Langner A
Bmc Hematology. 2016;16:7.
BACKGROUND Intravenous iron therapy is a treatment option for iron deficient patients who are intolerant to oral iron or where oral iron is ineffective, but with possible adverse effects. Currently, prospective studies comparing different intravenous iron formulations are needed to determine safety and efficacy of these agents. METHODS We conducted a prospective, double-blind, randomized controlled trial (RCT) to assess the feasibility of a trial comparing the safety of high molecular weight intravenous iron dextran, Infufer(R), with intravenous iron sucrose, Venofer(R), in non-hemodialysis adult outpatients. Primary outcome was the occurrence of immediate severe drug reactions. RESULTS We enrolled 143 patients in a one-year period. Overall, 45/143 (31.5 %) patients (20 iron dextran, 25 iron sucrose) developed 48 infusion reactions (14 immediate, 28 delayed, and 3 both). The risk of an immediate reaction was similar in both groups, 9/73 (12.3 %) iron dextran versus 8/70 (11.4 %) iron sucrose, RR = 0.93 (95 % CI; 0.38 to 2.27). The risk of a delayed reaction was significantly higher in the iron sucrose group 22/70 (31.4 %) versus the iron dextran group 9/73 (12.3 %), RR = 2.55 (95 % CI; 1.26 to 5.15; p = 0.0078). CONCLUSION In this limited feasibility study, no major differences in immediate reactions were seen, but a significantly higher number of delayed reactions were seen in the iron sucrose group. Further, under our assumptions and design a full RCT to evaluate the safety of different intravenous iron preparations is not feasible. Future studies should consider modifying the clinical outcomes, utilize multiple centers, and consider other emerging parenteral iron formulations. (ClinicalTrials.gov NCT005936197 January 3, 2008).
Drug, devices, technologies, and techniques for blood management in minimally invasive and conventional cardiothoracic surgery: a consensus statement from the International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS) 2011
Menkis AH, Martin J, Cheng DC, Fitzgerald DC, Freedman JJ, Gao C, Koster A, Mackenzie GS, Murphy GJ, Spiess B, et al
Innovations: Technology & Techniques in Cardiothoracic & Vascular Surgery. 2012;7((4):):229-41.
OBJECTIVE The objectives of this consensus conference were to evaluate the evidence for the efficacy and safety of perioperative drugs, technologies, and techniques in reducing allogeneic blood transfusion for adults undergoing cardiac surgery and to develop evidence-based recommendations for comprehensive perioperative blood management in cardiac surgery, with emphasis on minimally invasive cardiac surgery. METHODS The consensus panel short-listed the potential topics for review from a comprehensive list of potential drugs, devices, technologies, and techniques. The process of short-listing was based on the need to prioritize and focus on the areas of highest importance to surgeons, anesthesiologists, perfusionists, hematologists, and allied health care involved in the management of patients who undergo cardiac surgery whether through the conventional or minimally invasive approach. MEDLINE, Cochrane Library, and Embase databases were searched from their date of inception to May 2011, and supplemental hand searches were also performed. Detailed methodology and search strategies are outlined in each of the subsequently published systematic reviews. In general, all relevant synonyms for drugs (antifibrinolytic, aprotinin, [Latin Small Letter Open E]-aminocaproic acid, tranexamic acid [TA], desmopressin, anticoagulants, heparin, antiplatelets, anti-Xa agents, adenosine diphosphate inhibitors, acetylsalicylic acid [ASA], factor VIIa [FVIIa]), technologies (cell salvage, miniaturized cardiopulmonary bypass (CPB) circuits, biocompatible circuits, ultrafiltration), and techniques (transfusion thresholds, minimally invasive cardiac or aortic surgery) were searched and combined with terms for blood, red blood cells, fresh-frozen plasma, platelets, transfusion, and allogeneic exposure. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of each recommendation. RESULTS AND RECOMMENDATIONS Database search identified more than 6900 articles, with 4423 full-text randomized controlled trials assessed for eligibility, and the final 125 systematic reviews and meta-analyses were used in the consensus conference. The results of the consensus conference, including the evidence-based statements and the recommendations, are outlined in the text, with references given for the relevant evidence that formed the basis for the statements and recommendations. RECOMMENDATIONS FOR ANTIFIBRINOLYTICS The lysine analogs ?-aminocaproic acid (Amicar) and tranexamic acid (TA) reduce exposure to allogeneic blood inpatients undergoing on-pump cardiac surgery. These agents are recommended to be used routinely as part of a blood conservation strategy especially in patients at risk of undergoing onpump cardiac surgery (Class I, Level A). It is important not to exceed maximum TA total dosages (50Y100mg/kg) because of potential neurotoxicity in the elderly and open-heart procedures (Class IIb, Level C). Aprotinin is not recommended in adult cardiac surgery until further studies on its safety profile have been performed (Class III, Level A). RECOMMENDATIONS FOR TA IN OFF-PUMP CORONARY ARTERY BYPASS Tranexamic acid may be recommended as part of a blood conservation strategy in high risk patients undergoing off-pump coronary artery bypass (OPCAB) surgery (Class I, Level A).Tranexamic acid dosing in OPCAB surgery needs further study particularly with regard to possible neurotoxicity such as seizures.In addition, the benefit-risk ratio in OPCAB needs further eludication because of the lower inherent risk for bleeding in this group (Class IIb, Level C). RECOMMENDATIONS FOR DDAVP DDAVP can be considered for prophylaxis in coronary artery bypass grafting (CABG) surgery, in particular, for patients onASA within 7 days or prolonged CPB more than 140 minutes (Class IIa, Level A). Caution should be used with the DDAVP infusion rate to avoid significant systemic hypotension (Class I, Level A). RECOMMENDATIONS FOR TOPICAL HEMOSTATICS The routine use of topical antifibrinolytics in cardiac surgery is
The efficacy of an intraoperative cell saver during cardiac surgery: a meta-analysis of randomized trials
Wang G, Bainbridge D, Martin J, Cheng D
Anesthesia and Analgesia. 2009;109((2):):320-30.
BACKGROUND Cell salvage may be used during cardiac surgery to avoid allogeneic blood transfusion. It has also been claimed to improve patient outcomes by removing debris from shed blood, which may increase the risk of stroke or neurocognitive dysfunction. In this study, we sought to determine the overall safety and efficacy of cell salvage in cardiac surgery by performing a systematic review and meta-analysis of published randomized controlled trials. METHODS A comprehensive search was undertaken to identify all randomized trials of cell saver use during cardiac surgery. MEDLINE, Cochrane Library, EMBASE, and abstract databases were searched up to November 2008. All randomized trials comparing cell saver use and no cell saver use in cardiac surgery and reporting at least one predefined clinical outcome were included. The random effects model was used to calculate the odds ratios (OR, 95% confidence intervals [CI]) and the weighted mean differences (WMD, 95% CI) for dichotomous and continuous variables, respectively. RESULTS Thirty-one randomized trials involving 2282 patients were included in the meta-analysis. During cardiac surgery, the use of an intraoperative cell saver reduced the rate of exposure to any allogeneic blood product (OR 0.63, 95% CI: 0.43-0.94, P = 0.02) and red blood cells (OR 0.60, 95% CI: 0.39-0.92, P = 0.02) and decreased the mean volume of total allogeneic blood products transfused per patient (WMD -256 mL, 95% CI: -416 to -95 mL, P = 0.002). There was no difference in hospital mortality (OR 0.65, 95% CI: 0.25-1.68, P = 0.37), postoperative stroke or transient ischemia attack (OR 0.59, 95% CI: 0.20-1.76, P = 0.34), atrial fibrillation (OR 0.92, 95% CI: 0.69-1.23, P = 0.56), renal dysfunction (OR 0.86, 95% CI: 0.41-1.80, P = 0.70), infection (OR 1.25, 95% CI: 0.75-2.10, P = 0.39), patients requiring fresh frozen plasma (OR 1.16, 95% CI: 0.82-1.66, P = 0.40), and patients requiring platelet transfusions (OR 0.90, 95% CI: 0.63-1.28, P = 0.55) between cell saver and noncell saver groups. CONCLUSIONS Current evidence suggests that the use of a cell saver reduces exposure to allogeneic blood products or red blood cell transfusion for patients undergoing cardiac surgery. Subanalyses suggest that a cell saver may be beneficial only when it is used for shed blood and/or residual blood or during the entire operative period. Processing cardiotomy suction blood with a cell saver only during cardiopulmonary bypass has no significant effect on blood conservation and increases fresh frozen plasma transfusion.
Reinfusion of mediastinal blood after heart surgery
Martin J, Robitaille D, Perrault LP, Pellerin M, Page P, Searle N, Cartier R, Hebert Y, Pelletier LC, Thaler HT, et al
Journal of Thoracic & Cardiovascular Surgery. 2000;120((3):):499-504.
BACKGROUND Several authors studying autotransfusion of shed mediastinal blood in patients undergoing heart operations have published conflicting results regarding reduction of the need for homologous blood transfusion. The effect on coagulation parameters is also unclear. METHODS In a prospective randomized study, 198 patients who underwent coronary artery bypass grafting or a valvular operation were divided into 2 groups: a group with autotransfusion of shed mediastinal blood after an operation and a control group. Continuous reinfusion of mediastinal blood was done until no drainage was present or for a period of 12 hours after the operation. The amount of blood lost and autotransfused, the number of homologous blood products transfused, and the coagulation parameters were monitored. RESULTS The number of patients requiring homologous blood transfusion was significantly different between the 2 groups (54/98 [55%] in autotransfused patients vs 73/100 [73%] in the control group, P =.01). The number of re-explorations for excessive bleeding was similar in the 2 groups (7/98 [7.1%] vs 8/100 [8%]), but the amount of blood collected postoperatively was higher in the autotransfused patients compared with control patients (1200 +/- 201 mL vs 758 +/- 152 mL, P =.0007). Coagulation parameters analyzed and complication rates were similar in the 2 groups after the operations. CONCLUSION Autotransfusion of shed mediastinal blood reduces the need for homologous blood transfusion in patients undergoing various cardiac operations. The cause of increased shed blood in patients undergoing autotransfusion remains unclear.