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 [Latin Small Letter Open E]-aminocaproic acid (Amicar) and tranexamic acid (TA) reduce exposure to allogeneic blood in patients 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 on-pump cardiac surgery (Class I, Level A).
▪ It is importarnt not to exceed maximum TA total dosages (50–100 mg/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 on ASA 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 not recommended (Class IIa, Level A).
▪ Topical fibrin sealants may be considered in clinical situations where conventional approaches of surgical and medical improvement of hemostasis are not effective, that is, with bleeding problems more local than generalized, bearing in mind the black box warning of bovine thrombin by the US Food and Drug Administration (Class IIb, Level C).
Recommendations for FVIIa:
▪ Prophylactic use of FVIIa cannot be recommended because of a significant increase in the risk of thromboembolic events and stroke (Class IIa, Level A).
▪ Factor VIIa may be considered in clinical situations where conventional approaches of surgical and pharmacologic hemostasis have failed and uncontrollable hemorrhage poses a high risk of severe and life-threatening outcomes (Class IIb, Level B).
Recommendations for Erythropoietin Plus Iron:
▪ It is reasonable to administer erythropoietin preoperatively to increase red blood cell mass in patients who are anemic or refuse blood products (such as for Jehovah’s Witness faith) or who are likely to have postoperative anemia (Class IIa, Level A).
Recommendations for Antiplatelets Before Cardiac Surgery:
▪ Acetylsalicylic acid may be continued until surgery (Class IIa, Level B)
▪ For stable elective CABG procedures with no drug-eluting stent, stop clopidogrel 5 days before surgery (Class I, Level A).
▪ For stable elective CABG procedures with drug-eluting stents less than 1 year old, consider continuing clopidogrel or heparin as a bridge to surgery (Class IIb, Level C).
▪ Direct-acting P2Y12 receptor antagonists may be a better alternative than clopidogrel in acute coronary syndrome patients undergoing CABG surgery (Class IIa, Level B).
Recommendations for Antiplatelets After Cardiac Surgery:
▪ In stable CABG surgery (non–acute coronary syndrome patients), the routine use of postoperative clopidogrel with ASA is not warranted (Class IIb, Level B).
Recommendations for Acute Normovolemic Hemodilution:
▪ Acute normovolemic hemodilution can be considered in selected patients with adequate preoperative hemoglobin to reduce post-CPB bleeding (Class IIa, Level A).
▪ The routine use of acute normovolemic hemodilution is not recommended (Class IIb, Level B).
Recommendations for Retrograde Autologous Priming:
▪ Retrograde autologous priming is recommended as a blood conservation modality to reduce allogeneic blood transfusion for on-pump cardiac surgery (Class I, Level A).
Recommendations for Cell Salvage:
▪ Routine use of cell salvage is recommended in operations where an increased blood loss is expected (Class 1, Level A).
▪ Cell salvage should be used throughout the entire operation and not merely as a replacement for CPB cardiotomy suction (Class IIa, Level A).
Recommendations: Biocompatible CPB Circuits:
▪ The routine use of biocompatible coated CPB circuitry may be considered as part of a multimodal blood conservation program. However, the heterogeneity of surface-modified products, anticoagulation management, and CPB technique does not significantly impact surgical blood loss and transfusion needs (Class IIb, Level A).
Recommendations for Miniaturized Extracorporeal Cardiopulmonary Circuit Versus Conventional Extracorporeal Cardiopulmonary Circuit:
▪ Miniaturized extracorporeal cardiopulmonary circuit can be considered as a blood conservation technique to reduce allogeneic blood exposure (Class IIa, Level A); however, issues related to heparinization management and biocompatible coatings remain to be clarified.
Recommendations for Ultrafiltration (Continuous or Modified):
▪ Ultrafiltration may be considered for blood conservation (Class IIb, Level A); however, the impact on clinically relevant outcomes remains unknown.
Recommendations for Platelet Plasmapheresis:
▪ It is reasonable to recommend platelet plasmapheresis for blood management in cardiac surgery (Class IIa, Level A), although the impact on clinically relevant outcomes remains unknown.
Recommendations for Point-of-Care Monitoring:
▪ The evidence is too premature to recommend point-of-care technology for routine use because its use has not been shown to impact clinical outcome (Class IIb, Level A).
Recommendations for Surgical Techniques for OPCAB, Minimally Invasive Sternotomy for Aortic Valve Surgery, Minimally Invasive Sternotomy for Mitral Valve Surgery, and Transcatheter Aortic Valve Implantation:
▪ Although these minimally invasive procedures are not primarily selected for the purpose of blood management, the reduced allogeneic blood exposure should be considered in the balance of benefits and risks when selecting the appropriate surgery for patients.
From the *WRHA Cardiac Sciences Program, Department of Surgery, University of Manitoba, Winnipeg, MB Canada; †Evidence-Based Perioperative Clinical Outcomes Research (EPiCOR), Department of Anesthesia and Perioperative Medicine, Western University, London, ON Canada; ‡Inova Heart and Vascular Institute, Falls Church, VA USA; §Division of Hematology, Department of Medicine, St. Michael Hospital, Toronto, ON Canada; ∥Department of Cardiovascular Surgery, Minimally Invasive and Robotic Cardiac Surgery Center, PLA General Hospital, Beijing, China; ¶Heart and Diabetes Center NRW, Bad Oeynhausen, Germany, Ruhr-University Bochum, Germany; #Cardiac Anesthesia, WRHA/SBGH Cardiac Sciences Program, Winnipeg, MB Canada; **Glenfield Hospital, University of Leicester, Leicester, UK; ††Department of Anesthesiology, Virginia Commonwealth University/Medical College of Virginia, Richmond VA USA; and ‡‡Cardiac Surgery, Inova Heart and Vascular Institute, Falls Church, VA USA.
Accepted for publication August 29, 2012.
Supported by the International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS), which has received unrestricted educational grants from industries that produce surgical technologies and from the Department of Anesthesia & Perioperative Medicine, Western University, London, ON Canada.
Disclosure: John J. Freedman, MD, is a speaker and receives consultant fees for Ethicon Biosurgery, Markham, ON Canada; Gavin J. Murphy is a consultant to Novo Nordisk, Bagsvaerd, Denmark and Ethicon Biosurgery, Somerville, NJ USA; Niv Ad, MD, is a speaker and receives consulting fees for Medtronic, Inc., Minneapolis, MN USA, AtriCure, Inc., West Chester, OH USA, and Estech, Inc., San Ramon, CA USA. Alan H. Menkis, MD, Janet Martin, PharmD, MSc (HTA), Davy C.H. Cheng, MD, David C. Fitzgerald, CCP, Changqing Gao, MD, Andreas Koster, MD, PhD, G. Scott MacKenzie, MD, and Bruce Spiess, MD, declare no conflict of interest.
Address correspondence and reprint requests to Davy C.H. Cheng, MD, FRCPC, Department of Anesthesia and Perioperative Medicine, LHSC-University Hospital, 339 Windermere Rd, London, ON Canada N6A 5A5. E-mail: firstname.lastname@example.org.