Preoperative anemia management in the coronavirus disease (COVID-19) era

Abstract

Central MessageCOVID-19 has led to a deferral of cardiac surgical cases and an opportunity to optimize preoperative anemia, while improving patient care, reducing cost, and conserving our tenuous blood supply.See Commentaries on pages 95 and 97. COVID-19 has led to a deferral of cardiac surgical cases and an opportunity to optimize preoperative anemia, while improving patient care, reducing cost, and conserving our tenuous blood supply. See Commentaries on pages 95 and 97. The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes the disease COVID-19 and is responsible for a global pandemic with more than 30,000,000 affected patients worldwide with a significant mortality exceeding 1,000,000.1An interactive web-based dashboard to track COVID-19 in real time.https://coronavirus.jhu.edu/map.htmlDate: 2020Date accessed: September 25, 2020Google Scholar Certain underserved segments of the population are particularly hard hit, conferring severe risk of exposure and adverse outcomes.2Mendy A. Apewokin S. Wells A.A. Morrow A.L. Factors associated with hospitalization and disease severity in a racially and ethnically diverse population of COVID-19 patients.medRxiv. June 17, 2020.; ([Epub ahead of print])https://doi.org/10.1101/2020.06.25.20137323Crossref Scopus (0) Google Scholar The tragic human toll is unprecedented and resembles the flu epidemic that occurred more than 100 years ago. The current outbreak impacted the global economy and placed a tremendous strain on all health care systems. In addition to its obvious impact on intensive care unit (ICU) beds, ventilators, and personal protective equipment, there are major effects on the supply chain for much-needed supplies to address the pandemic. The rapid spread of COVID-19 had a profound impact on blood donations, blood supplies, and potentially on blood safety.3Cai X. Ren M. Chen F. Li L. Lei H. Wang X. Blood transfusion during the COVID-19 outbreak.Blood Transfus. 2020; 18: 79-82PubMed Google Scholar The long, possibly asymptomatic incubation period (1-14 days) of COVID-19 has created immense challenges in procuring safe and adequate blood donations. Blood products are a critical component of emergency preparedness. In addition, the implementation of enhanced donor screening, and deferral strategies to maintain a safe donating environment, have limited the donor pool. The nationwide curtailment strategy to limit spread resulted in the cancelling of more than 4000 volunteer blood donation drives, which account for more than 80% of the blood collected by the American Red Cross, and a deficit of more than 130,000 donations in a few weeks' time.4Raturi M. Kusum A. The active role of a blood center in outpacing the transfusion transmission of COVID-19.Transfus Clin Biol. 2020; 27: 96-97Crossref PubMed Scopus (12) Google Scholar,5Shander A. Goobie S.M. Warner M.A. Aapro M. Bisbe E. Perez-Calatayud A.A. et al.The essential role of patient blood management in a pandemic: a call for action.Anesth Analg. 2020; 131: 74-85Crossref PubMed Scopus (94) Google Scholar This multifactorial impact on our nation's blood supply led to a call to action from the Director of the US Food and Drug Administration's (FDA) Center for Biologics Evaluation and Research that urged people to start turning out in force to give blood. In an effort to increase the donor pool, the FDA on April 2, 2020, modified certain donor eligibility criteria without compromising the safety of the blood supply.6Coronavirus (COVID-19) update: FDA provides updated guidance to address the urgent need for blood during the pandemic.https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-provides-updated-guidance-address-urgent-need-blood-during-pandemicDate: 2020Date accessed: August 20, 2020Google Scholar The declining donor pool is only one factor impacting the national blood supply. Nationwide curtailment strategies also impacted the supply chain of manufacturing supplies needed to maintain blood services. Travel restrictions, factory closings, and decreased manufacturing output will further impact the ability to maintain the blood supply.5Shander A. Goobie S.M. Warner M.A. Aapro M. Bisbe E. Perez-Calatayud A.A. et al.The essential role of patient blood management in a pandemic: a call for action.Anesth Analg. 2020; 131: 74-85Crossref PubMed Scopus (94) Google Scholar While there is no direct evidence that COVID-19, or any other coronaviruses of concern (severe acute respiratory syndrome, Middle East respiratory syndrome coronavirus), can be transmitted through blood or blood components, there is still a theoretical risk of transmission through blood transfusion, especially with a relatively longer asymptomatic phase. Reports from China show that the detection of viral RNA in the blood of patients infected with COVID-19 is common, but no reports have shown infection of recipients of platelets or red blood cell (RBC) transfusions from donors diagnosed with COVID-19, despite documented examples of transfusion of blood products from infected donors.7Cho H.J. Koo J.W. Roh S.K. Kim Y.K. Suh J.S. Moon J.H. et al.COVID-19 transmission and blood transfusion: a case report.J Infect Public Health. 2020; 13: 1678-1679Crossref PubMed Scopus (60) Google Scholar In addition, the detection of viral RNA by polymerase chain reaction is not the same as detection of intact live infective virus.8Chang L. Yan Y. Wang L. Coronavirus disease 2019: coronaviruses and blood safety.Transfus Med Rev. 2020; 34: 75-80Crossref PubMed Scopus (404) Google Scholar It seems clear that the transfusion dynamics of transmission and infection related to COVID-19 are incompletely understood.9Stanworth S.J. New H.V. Apelseth T.O. Brunskill S. Cardigan R. Doree C. et al.Effects of the COVID-19 pandemic on supply and use of blood for transfusion.Lancet Haematol. 2020; 7: e756-e764Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar The challenges faced by the blood bank establishment during the COVID-19 pandemic are to maintain and protect the safety of the blood supply. However, the variables that must be considered and not easily controlled are the use and the demand for blood components. Small studies suggest that the pandemic itself has not resulted in an increased requirement for blood transfusions, especially in patients with mild COVID-19 infection. A small review did show a 36.8% requirement for packed red blood cell (PRBC) transfusion in patients with COVID-19 in the ICU with lesser requirements for fresh-frozen plasma and platelets, except in the small extracorporeal membrane oxygenation population.10Fan B.E. Ong K.H. Chan S.S.W. Young B.E. Chong V.C.L. Chen S.P.C. et al.Blood and blood product use during COVID-19 infection.Am J Hematol. 2020; 95: E158-E160Crossref PubMed Scopus (30) Google Scholar The demand for blood components further decreased in the early stage of the pandemic, by the almost-universal postponing of elective operations, with the net result of lessening the impact on blood inventory. In fact, during early May, greater than 50% of the respondents to an AABB hospital transfusion services survey reported increased inventory wastage due to the impact of COVID-19, while by June many hospital transfusion services were unable to meet their typical inventory needs from their blood suppliers (Figure 1) and have implemented inventory-management strategies to deal with shortages.11AABB COVID-19 weekly hospital transfusion services survey: week 21 snapshot.http://www.aabb.org/advocacy/regulatorygovernment/Documents/AABB-COVID-19-Impact-Survey-Snapshot.pdfDate: 2020Date accessed: August 22, 2020Google Scholar The geographic variation in disease incidence enabled regional redistribution of blood components to areas more profoundly impacted by the decrease in supply. In addition, many transfusion services implemented blood order triage plans to ensure the appropriate use of blood components and considered plans to arbitrarily extend platelet expiration to 7 days from 5 days if necessary.12Pagano M.B. Hess J.R. Tsang H.C. Staley E. Gernsheimer T. Sen N. et al.Prepare to adapt: blood supply and transfusion support during the first 2 weeks of the 2019 novel coronavirus (COVID-19) pandemic affecting Washington State.Transfusion. 2020; 60: 908-911Crossref PubMed Scopus (116) Google Scholar A recent guideline from the National Blood Transfusion Committee in England proposed a triage tool to guide the ethical allocation of blood components for massive hemorrhage in the setting of severe blood shortage, such as the COVID-19 pandemic.13Doughty H. Green L. Callum J. Murphy M.F. National Blood Transfusion Committee Triage tool for the rationing of blood for massively bleeding patients during a severe national blood shortage: guidance from the National Blood Transfusion Committee.Br J Haematol. 2020; 191: 340-346Crossref PubMed Scopus (18) Google Scholar The greatest concern regarding the impact of COVID-19 on our nation's blood supply revolves around the gradual reopening of society accompanied by the resumption of elective surgery. This increase in surgical volume will likely be accompanied by an increase in blood use, with a delayed replenishment of the blood inventory. Donor recruitment for blood donation will likely be hampered by existing social containment and mitigation policies, potential donor fears, as well as the shift in resources to prioritize convalescent plasma transfusion will continue to impact an already strained inventory.11AABB COVID-19 weekly hospital transfusion services survey: week 21 snapshot.http://www.aabb.org/advocacy/regulatorygovernment/Documents/AABB-COVID-19-Impact-Survey-Snapshot.pdfDate: 2020Date accessed: August 22, 2020Google Scholar These concerns occurred in some regions of the nation, where there is currently only a 1- or 2-day supply of blood instead of the usual 1- to 2-week inventory.14COVID-19 pandemic leading to blood supply shortages. Transfusion news.https://transfusionnews.com/2020/03/17/covid-19-pandemic-leading-to-blood-supply-shortages/Date: 2020Date accessed: May 16, 2020Google Scholar Regional voluntary redistribution of blood components may alleviate some of the strain, but only to a limited extent, given its short shelf-life.15Sussman J.S. Coronavirus disease 2019 (COVID-19) poses challenges for the U.S. blood supply. Congressional research service 2020.https://crsreports.congress.gov/product/pdf/IN/IN11238Date: 2020Date accessed: May 16, 2020Google Scholar The impact of COVID-19 on resources required an unprecedented restructuring of health care to continue our commitment to patient care, in addition to planning for the care of all patients in the weeks and months ahead. Many surgical societies developed guidance statements to enable postponing of elective operations during the peak of the pandemic. The rationale for postponing elective operations starting in mid-March 2020 was based on the urgent need to preserve and redirect limited resources and personnel for the treatment of patients with COVID-19. The American College of Surgeons guidance specifically highlighted blood conservation as a key component of this initiative:•Blood conservation. The nation's blood supply is dropping due to the elimination of blood drives and other factors. Minimizing elective procedures that require blood will help to preserve this resource.14COVID-19 pandemic leading to blood supply shortages. Transfusion news.https://transfusionnews.com/2020/03/17/covid-19-pandemic-leading-to-blood-supply-shortages/Date: 2020Date accessed: May 16, 2020Google Scholar The Society of Thoracic Surgeons (STS) COVID-19 Taskforce and the Workforce for Adult Cardiac and Vascular Surgery released a tiered patient guidance statement to address the changing cardiac surgery landscape, emphasizing the acute needs of the cardiac surgical patient in relation to the prevalence of COVID-19 at their institution.16Haft J.W. Atluri P. Alawadi G. Engelman D.T. Grant M.C. Hassan A. et al.Adult cardiac surgery during the COVID-19 pandemic: a tiered patient triage guidance statement.Ann Thorac Surg. 2020; 110: 697-700Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar Ultimately, the prioritization of these goals will maximize the number of lives saved. The STS database defines operative categories of elective, urgent, and emergent/salvage surgery. These definitions required a re-examination during the COVID-19 era.17Clark R.E. The Society of Thoracic Surgeons national database status report.Ann Thorac Surg. 1994; 57: 20-26Abstract Full Text PDF PubMed Google Scholar While there is an obvious risk in delaying definitive cardiac operations in patients with significant cardiovascular disease, these risks are balanced by the multitude and far-reaching risks of performing surgery during a pandemic. The STS guidance document provides a detailed tiered approach to balancing these factors based on the underlying cardiovascular disease and the impact of COVID-19 on the institution's operative capacity, with the flexibility to adapt to the dynamic landscape of the pandemic and unique patients' needs.16Haft J.W. Atluri P. Alawadi G. Engelman D.T. Grant M.C. Hassan A. et al.Adult cardiac surgery during the COVID-19 pandemic: a tiered patient triage guidance statement.Ann Thorac Surg. 2020; 110: 697-700Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar George and colleagues18George I. Salna M. Kobsa S. Deroo S. Kriegel J. Blitzer D. et al.The rapid transformation of cardiac surgery practice in the coronavirus disease 2019 (COVID-19) pandemic: insights and clinical strategies from a center at the epicenter.Ann Thorac Surg. 2020; 110: 1108-1118Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar created their own classification to time cardiac surgery during the pandemic depending on case type and urgency. This balancing act of risk versus benefit is not necessarily a new paradigm shift for the physician/surgeon, who must constantly balance the risk and timing of an intervention versus delaying a procedure to further optimize a patient before surgery. One important risk factor that is often dismissed before surgery is preoperative anemia. Perioperative anemia is a common condition, present in up to 40% of patients, and associated with a nearly 5-fold increase in the odds of postoperative mortality.19Beattie W.S. Karkouti K. Wijeysundera D.N. Tait G. Risk associated with preoperative anemia in noncardiac surgery: a single-center cohort study.Anesthesiology. 2009; 110: 574-581Crossref PubMed Scopus (312) Google Scholar It is often considered an abnormal laboratory value that can easily be corrected with a blood transfusion. However, preoperative anemia is an important independent risk factor for perioperative morbidity and mortality in cardiac surgery, and this risk is exacerbated by the current default treatment of allogenic transfusion.20Karkouti K. Wijeysundera D.N. Beattie W.S. Reducing bleeding in cardiac surgery. I. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study.Circulation. 2008; 117: 478-484Crossref PubMed Scopus (355) Google Scholar This is especially pertinent as our nation's blood supply is at a critical inventory level, but is also an opportunity to improve patient outcomes by incorporating patient blood management (PBM) strategies for anemia management into our daily cardiac surgery practice. PBM is defined by Society for the Advancement of Blood Management as the timely application of evidence-based medical and surgical concepts designed to maintain hemoglobin (Hgb) concentration, optimize hemostasis, and minimize blood loss to improve patient outcome.21Frietsch T. Shander A. Faraoni D. Hardy J.F. Patient blood management is not about blood transfusion: it is about patients' outcomes.Blood Transfus. 2019; 17: 331-333PubMed Google Scholar This initiative to address preoperative anemia, a cornerstone of PBM, is not new, and numerous societies support the importance of the identification and management of preoperative anemia,22Society of Thoracic Surgeons Blood Conservation Guideline Task Force Ferraris V.A. Brown J.R. Despotis G.J. Hammon J.W. Reece T.B. et al.2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines.Ann Thorac Surg. 2011; 91: 944-982Abstract Full Text Full Text PDF PubMed Scopus (987) Google Scholar,23Raphael J. Mazer C.D. Subramani S. Schroeder A. Abdalla M. Ferreira R. et al.Society of Cardiovascular Anesthesiologists Clinical practice improvement advisory for management of perioperative bleeding and hemostasis in cardiac surgery patients.Anesth Analg. 2019; 129: 1209-1221Crossref PubMed Scopus (73) Google Scholar especially during a pandemic.5Shander A. Goobie S.M. Warner M.A. Aapro M. Bisbe E. Perez-Calatayud A.A. et al.The essential role of patient blood management in a pandemic: a call for action.Anesth Analg. 2020; 131: 74-85Crossref PubMed Scopus (94) Google Scholar In fact, Muñoz and colleagues,24Munoz M. Acheson A.G. Auerbach M. Besser M. Habler O. Kehlet H. et al.International consensus statement on the peri-operative management of anaemia and iron deficiency.Anaesthesia. 2017; 72: 233-247Crossref PubMed Scopus (406) Google Scholar in their international consensus statement on perioperative management of anemia and iron deficiency, advocated that major nonurgent surgery should be postponed to allow the diagnosis and treatment of anemia and iron deficiency. Muñoz and colleagues25Muñoz M. Ariza D. Gómez-Ramírez S. Preoperative anemia in elective cardiac surgery: prevalence, risk factors, and influence on postoperative outcome.Transfus Altern Transfus Med. 2010; 11: 47-56Crossref Scopus (24) Google Scholar estimated the prevalence of preoperative anemia at 36.5% in patients undergoing elective cardiac surgery, and Klein and colleagues26Klein A.A. Collier T.J. Brar M.S. Evans C. Hallward G. Fletcher S.N. et al.The incidence and importance of anaemia in patients undergoing cardiac surgery in the UK—the first Association of Cardiothoracic Anaesthetists national audit.Anaesthesia. 2016; 71: 627-635Crossref PubMed Scopus (108) Google Scholar found the incidence among more than 19,000 patients undergoing cardiac surgery in the United Kingdom to be 31% and independently associated with worse outcomes, including ICU, hospital length of stay, and mortality. Karski and colleagues27Karski J.M. Mathieu M. Cheng D. Carroll J. Scott G.J. Etiology of preoperative anemia in patients undergoing scheduled cardiac surgery.Can J Anaesth. 1999; 46: 979-982Crossref PubMed Scopus (43) Google Scholar found iron-deficiency anemia to be the second most common cause of anemia following hospital-acquired anemia in cardiac surgery patients, whereas folate deficiency was present in less than 5% of the patients and vitamin B12 is relatively uncommon worldwide. Deficiencies in vitamin B12 or folate should be treated if identified, and empiric supplementation of vitamin B12 and folate were part of a recent protocol managing iron deficiency anemia in preoperative cardiac surgery patients.28Spahn D.R. Schoenrath F. Spahn G.H. Seifert B. Stein P. Theusinger O.M. et al.Effect of ultra-short-term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery: a prospective randomised trial.Lancet. 2019; 393: 2201-2212Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar A more recent meta-analysis confirmed that patients with anemia received more transfusions than patients without anemia and that preoperative anemia was associated with an increased risk of stroke, acute kidney injury, infection, and other complications.20Karkouti K. Wijeysundera D.N. Beattie W.S. Reducing bleeding in cardiac surgery. I. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study.Circulation. 2008; 117: 478-484Crossref PubMed Scopus (355) Google Scholar,29Padmanabhan H. Siau K. Curtis J. Ng A. Menon S. Luckraz H. et al.Preoperative anemia and outcomes in cardiovascular surgery: systematic review and meta-analysis.Ann Thorac Surg. 2019; 108: 1840-1848Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar, 30Hung M. Besser M. Sharples L.D. Nair S.K. Klein A.A. The prevalence and association with transfusion, intensive care unit stay and mortality of pre-operative anaemia in a cohort of cardiac surgery patients.Anaesthesia. 2011; 66: 812-818Crossref PubMed Scopus (91) Google Scholar, 31Kulier A. Levin J. Moser R. Rumpold-Seitlinger G. Tudor I.C. Snyder-Ramos S.A. et al.Impact of preoperative anemia on outcome in patients undergoing coronary artery bypass graft surgery.Circulation. 2007; 116: 471-479Crossref PubMed Scopus (357) Google Scholar, 32van Straten A.H. 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Cotrufo M. et al.Preoperative anemia in patients undergoing coronary artery bypass grafting predicts acute kidney injury.J Thorac Cardiovasc Surg. 2009; 138: 965-970Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar, 36Kazmierski J. Kowman M. Banach M. Fendler W. Okonski P. Banys A. et al.Incidence and predictors of delirium after cardiac surgery: results from the IPDACS Study.J Psychosom Res. 2010; 69: 179-185Crossref PubMed Scopus (178) Google Scholar In a recent study by LaPar and colleagues,37LaPar D.J. Hawkins R.B. McMurry T.L. Isbell J.M. Rich J.B. Speir A.M. et al.Preoperative anemia versus blood transfusion: which is the culprit for worse outcomes in cardiac surgery?.J Thorac Cardiovasc Surg. 2018; 156: 66-74.e2Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar 33,411 patients undergoing coronary artery bypass grafting (CABG) were investigated to determine the relative association between preoperative hematocrit (Hct) level versus PRBC transfusion on postoperative outcomes. After risk adjustment, PRBC transfusion demonstrated stronger associations with postoperative mortality (odds ratio [OR]; 4.3, P < .0001), renal failure (OR, 6.3; P < .0001), and stroke (OR, 2.4; P < .0001). A 1-point increase in preoperative Hct was associated with a decreased probability of mortality (OR, 0.97; P = .0001) and renal failure (OR, 0.94; P < .0001) and, as expected, a strong association was observed between preoperative Hct and the likelihood for PRBC transfusion (P < .001).37LaPar D.J. Hawkins R.B. McMurry T.L. Isbell J.M. Rich J.B. Speir A.M. et al.Preoperative anemia versus blood transfusion: which is the culprit for worse outcomes in cardiac surgery?.J Thorac Cardiovasc Surg. 2018; 156: 66-74.e2Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar An editorial by Gaetano Paone38Paone G. Anemia, transfusion, and outcome: both are bad...does it really matter which is worse?.J Thorac Cardiovasc Surg. 2018; 156: 75-76Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar on this study simply stated that “anemia is bad, transfusion is worse, and both together are worse than either one alone,” and the real emphasis should be on avoiding the conditions that lead to transfusion. The challenge to patient outcome is to sort out the relative contributions of preoperative, intraoperative, and postoperative anemia, in addition to the additive risk of RBC transfusion. While the exact etiologies of the adverse effects of transfusion and anemia are not clear, the evidence that transfusion in the cardiac surgical population is not benign and should be used cautiously is clear. These challenges remain in the era of COVID-19 and require additional investigation.36Kazmierski J. Kowman M. Banach M. Fendler W. Okonski P. Banys A. et al.Incidence and predictors of delirium after cardiac surgery: results from the IPDACS Study.J Psychosom Res. 2010; 69: 179-185Crossref PubMed Scopus (178) Google Scholar It is clear that preoperative anemia places cardiac surgical patients at a greater risk of postoperative adverse outcomes.39Loor G. Koch C.G. Sabik III, J.F. Li L. Blackstone E.H. Implications and management of anemia in cardiac surgery: current state of knowledge.J Thorac Cardiovasc Surg. 2012; 144: 538-546Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar The fact that preoperative anemia is one of the few potentially modifiable risk factors should trigger efforts to optimize Hgb preoperatively. It is likely that preoperative Hgb levels should be included in future risk models such as the European System for Cardiac Operative Risk Evaluation and the STS Predicted Risk of Mortality. In addition to improvements in postoperative patient outcome, there may be short-term benefits to the evaluation and treatment of anemia as seen in the heart failure and chronic kidney disease population.40Anker S.D. Kirwan B.A. van Veldhuisen D.J. Filippatos G. Comin-Colet J. Ruschitzka F. et al.Effects of ferric carboxymaltose on hospitalisations and mortality rates in iron-deficient heart failure patients: an individual patient data meta-analysis.Eur J Heart Fail. 2018; 20: 125-133Crossref PubMed Scopus (227) Google Scholar,41Levin A. Stevens P.E. Bilous R.W. Coresh J. De Francisco A.L.M. De Jong P.E. et al.Kidney disease: improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease.Kidney Int Suppl. 2013; 3: 1-150Abstract Full Text Full Text PDF Scopus (1565) Google Scholar A 2019 meta-analysis that included 10 randomized controlled trials (RCTs) of patients with heart failure and iron-deficiency anemia had improvements in New York Heart Association class, reduced hospitalizations, improved exercise tolerance, left ventricular ejection fraction, and serum markers of heart failure and inflammation.42Zhou X. Xu W. Xu Y. Qian Z. Iron supplementation improves cardiovascular outcomes in patients with heart failure.Am J Med. 2019; 132: 955-963Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar It must be emphasized that preoperative anemia management is a multifaceted paradigm that entails a combination of red cell enhancement, careful evaluation of anemia etiologies, and thoughtful intraoperative and postoperative management. Focus on a single strategy to the exclusion of a multifaceted approach is insufficient and lacks evidence base.43Meybohm P. Westphal S. Ravn H.B. Ranucci M. Agarwal S. Choorapoikayil S. et al.Perioperative anemia management as part of PBM in cardiac surgery—a narrative updated review.J Cardiothorac Vasc Anesth. 2020; 34: 1060-1073Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar Evidence-based findings suggest that preoperative anemia is associated with adverse outcomes from cardiac operations,29Padmanabhan H. Siau K. Curtis J. Ng A. Menon S. Luckraz H. et al.Preoperative anemia and outcomes in cardiovascular surgery: systematic review and meta-analysis.Ann Thorac Surg. 2019; 108: 1840-1848Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar and in noncardiac surgery, evidence for parenteral iron administration in patients with absolute and functional iron deficiency or anemia is stronger.44Ellermann I. Bueckmann A. Eveslage M. Buddendick H. Latal T. Niehoff D. et al.Treating anemia in the preanesthesia assessment clinic: results of a retrospective evaluation.Anesth Analg. 2018; 127: 1202-1210Crossref PubMed Scopus (26) Google Scholar, 45Yang Y. Li H. Li B. Wang Y. Jiang S. Jiang L. Efficacy and safety of iron supplementation for the elderly patients undergoing hip or knee surgery: a meta-analysis of randomized controlled trials.J Surg Res. 2011; 171: e201-e207Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar, 46Meybohm P. Herrmann E. Steinbicker A.U. Wittmann M. Gruenewald M. Fischer D. et al.Patient blood management is associated with a substantial reduction of red blood cell utilization and safe for patient's outcome: a prospective, multicenter cohort study with a noninferiority design.Ann Surg. 2016; 264: 203-211Crossref PubMed Scopus (141) Google Scholar, 47ten Broeke R. Bravenboer B. Smulders F.J. Iron deficiency before and after bariatric surgery: the need for iron supplementation.Neth J Med. 2013; 71: 412-417PubMed Google Scholar However, the evidence base for delaying surgery for preoperative treatment of anemia to improve cardiac surgical outcomes is confusing. A Cochrane review looked at the use of iron supplementation in anemic patients before surgery and suggested that the preoperative use of iron supplementation did not show a clinically significant reduction in the proportion of trial participants who received an allogeneic blood transfusion compared to no iron therapy. However, the quality of the evidence was low and the researchers commented that future higher quality of evidence will likely change the results of their review.48Ng O. Keeler B.D. Mishra A. Simpson J.A. Neal K. Al-Hassi H.O. et al.Iron therapy for preoperative anaemia.Cochrane Database Syst Rev. 2019; 12: CD011588PubMed Google Scholar Recently, the long-awaited PREVENTT (Preoperative Intrav