Implications and management of anemia in cardiac surgery: Current state of knowledge
2012; Elsevier BV; Volume: 144; Issue: 3 Linguagem: Inglês
10.1016/j.jtcvs.2012.04.014
ISSN1097-685X
AutoresGabriel Loor, Colleen G. Koch, Joseph F. Sabik, Liang Li, Eugene H. Blackstone,
Tópico(s)Cardiac and Coronary Surgery Techniques
ResumoDecreasing oxygen delivery during and after cardiopulmonary bypass (CPB) can adversely affect patient outcomes. Balancing morbidities associated with anemia, red blood cell (RBC) transfusion, pharmaceuticals to prevent fibrinolysis, and reoperations for bleeding poses a dilemma. One would optimally balance these factors to minimize patient risk. Uncertainty in defining an optimal transfusion threshold, a trigger for reoperation, and a strategy for use of pharmaceuticals is evidenced by the considerable variability in clinical practice worldwide.1Snyder-Ramos S.A. Mohnle P. Weng Y.S. Bottiger B.W. Kulier A. Levin J. et al.The ongoing variability in blood transfusion practices in cardiac surgery.Transfusion. 2008; 48: 1284-1299Crossref PubMed Scopus (120) Google Scholar, 2Bennett-Guerrero E. Zhao Y. O'Brien S.M. Ferguson Jr., T.B. Peterson E.D. Gammie J.S. et al.Variation in use of blood transfusion in coronary artery bypass graft surgery.JAMA. 2010; 304: 1568-1575Crossref PubMed Scopus (365) Google Scholar Therefore, to gain insight to inform surgical practice, we have brought together current knowledge of the association of preoperative anemia, intraoperative anemia, blood transfusion, and measures to address blood loss with adverse outcomes after cardiac surgery. The World Health Organization defines anemia as a hemoglobin level less than 13 g/dL in men and less than 12 g/dL in women. By that measure, prevalence of preoperative anemia in patients undergoing cardiac surgery ranges from 16% to 54%, with severe anemia (hemoglobin < 10 g/dL) in 5.5%.3Hung 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, 4Kulier 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 (359) Google Scholar, 5van Straten A.H. Hamad M.A. van Zundert A.J. Martens E.J. Schonberger J.P. de Wolf A.M. Preoperative hemoglobin level as a predictor of survival after coronary artery bypass grafting: a comparison with the matched general population.Circulation. 2009; 120: 118-125Crossref PubMed Scopus (130) Google Scholar Patients presenting with low hemoglobin are more susceptible to end-organ ischemia; however, oxygen demands on CPB vary, and it is unclear what hemoglobin level is adequate. Nonetheless, several large observational studies suggest that preoperative anemia is associated with increased noncardiac morbidity and mortality after CPB (Table 1).Table 1Investigations examining effect of preoperative anemia on postoperative outcomesInvestigationDesignnEffectZindrou et al6Zindrou D. Taylor K.M. Bagger J.P. Preoperative haemoglobin concentration and mortality rate after coronary artery bypass surgery.Lancet. 2002; 359: 1747-1748Abstract Full Text Full Text PDF PubMed Scopus (123) Google ScholarObservational2059Increased mortalityHung et al3Hung 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 ScholarObservational2688Increased transfusion requirement, ICU stay, and mortalityvan Straten et al5van Straten A.H. Hamad M.A. van Zundert A.J. Martens E.J. Schonberger J.P. de Wolf A.M. Preoperative hemoglobin level as a predictor of survival after coronary artery bypass grafting: a comparison with the matched general population.Circulation. 2009; 120: 118-125Crossref PubMed Scopus (130) Google ScholarObservational10,626Increased mortalityRanucci et al7Ranucci M. Conti D. Castelvecchio S. Menicanti L. Frigiola A. Ballotta A. et al.Hematocrit on cardiopulmonary bypass and outcome after coronary surgery in nontransfused patients.Ann Thorac Surg. 2010; 89: 11-17Abstract Full Text Full Text PDF PubMed Scopus (82) Google ScholarObservational3003Prolonged ventilation, renal insufficiency, stroke, reoperationsKarkouti et al9Karkouti K. Wijeysundera D.N. Beattie W.S. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study.Circulation. 2008; 117: 478-484Crossref PubMed Scopus (356) Google ScholarObservational3500Increased in-hospital death, stroke, or acute kidney injuryKulier et al4Kulier 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 (359) Google ScholarObservational5065Neurologic, renal, and GI complicationsDe Santo et al8De Santo L. Romano G. Della Corte A. de Simone V. Grimaldi F. 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 ScholarObservational1214Postoperative renal insufficiencyKazmierski et al10Kazmierski 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: 179-185Abstract Full Text Full Text PDF PubMed Scopus (178) Google ScholarObservational563Postoperative deliriumICU, Intensive care unit; GI, gastrointestinal. Open table in a new tab ICU, Intensive care unit; GI, gastrointestinal. Zindrou and colleagues6Zindrou D. Taylor K.M. Bagger J.P. Preoperative haemoglobin concentration and mortality rate after coronary artery bypass surgery.Lancet. 2002; 359: 1747-1748Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar performed an observational study of 2059 patients undergoing isolated coronary artery bypass grafting (CABG) that showed that patients with a preoperative hemoglobin of 10 g/dL or less had a 5-fold higher in-hospital mortality than those with a greater hemoglobin concentration. This was confirmed by multivariable analysis. However, this study may have been confounded by RBC transfusion, which was not considered in the analysis. Likewise, van Straten and colleagues5van Straten A.H. Hamad M.A. van Zundert A.J. Martens E.J. Schonberger J.P. de Wolf A.M. Preoperative hemoglobin level as a predictor of survival after coronary artery bypass grafting: a comparison with the matched general population.Circulation. 2009; 120: 118-125Crossref PubMed Scopus (130) Google Scholar from the Dutch Central Bureau for Statistics performed an observational study of 10,626 patients who underwent CABG. Preoperative anemia, as defined by the World Health Organization, was an independent risk factor for increased early (<30 days) mortality and higher degree of preoperative anemia for higher late mortality. Preoperative hemoglobin of 14.5 g/dL or greater in men and 13.5 g/dL in women was associated with an 88% survival at 8 years, whereas a value less than 12 g/dL in men and less than 11 g/dL in women was associated with a 55% survival at 8 years. This study did not factor intraoperative anemia or use of RBC transfusion into the analysis. To account for transfusion as a potential confounder, Ranucci and colleagues7Ranucci M. Conti D. Castelvecchio S. Menicanti L. Frigiola A. Ballotta A. et al.Hematocrit on cardiopulmonary bypass and outcome after coronary surgery in nontransfused patients.Ann Thorac Surg. 2010; 89: 11-17Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar reviewed 3003 consecutive patients undergoing isolated CABG without perioperative RBC transfusion and found no association between preoperative anemia and postoperative mortality. However, they reported a 5-fold greater unadjusted occurrence of major morbidity in patients with a preoperative hematocrit (HCT) of 33% or less versus 42% or greater. After risk adjustment, preoperative HCT and lowest HCT on CPB were associated with an increased postoperative occurrence of prolonged ventilation, renal insufficiency, stroke, and reoperation. Several additional studies have identified an association between preoperative anemia and postoperative morbidity. A multicenter observational study by Kulier and colleagues4Kulier 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 (359) Google Scholar demonstrated that preoperative anemia (hemoglobin <13 g/dL) was associated with increased neurologic, renal, and gastrointestinal complications. Anemia was not associated with more cardiac complications, although these events were related to perioperative RBC transfusion. De Santo and colleagues8De Santo L. Romano G. Della Corte A. de Simone V. Grimaldi F. 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 studied a cohort of 1214 cardiac surgical patients and found that preoperative anemia was an independent risk factor for postoperative renal insufficiency. Karkouti and colleagues9Karkouti K. Wijeysundera D.N. Beattie W.S. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study.Circulation. 2008; 117: 478-484Crossref PubMed Scopus (356) Google Scholar evaluated 3500 consecutive cardiac surgery cases for the association of preoperative anemia (hemoglobin <12 g/dL) with the composite outcome of death, stroke, and acute renal insufficiency. Adjusted odds ratio for the composite outcome was 1.8 for patients with preoperative anemia. Kazmierski and colleagues10Kazmierski 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: 179-185Abstract Full Text Full Text PDF PubMed Scopus (178) Google Scholar examined the relationship of preoperative anemia to the prevalence of postoperative delirium (16%), adjudicated by 2 independent psychiatrists, on the basis of the criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. After adjustment for various risk factors, preoperative anemia was an independent risk factor for postoperative delirium. The association of preoperative anemia with adverse postoperative events is not limited to cardiac surgery. In a study of 227,425 patients undergoing a variety of general and vascular surgical procedures reported in the American College of Surgeons' National Surgical Quality Improvement Program database, Musallam and colleagues11Musallam K.M. Tamim H.M. Richards T. Spahn D.R. Rosendaal F.R. Habbal A. et al.Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study.Lancet. 2011; 378: 1396-1407Abstract Full Text Full Text PDF PubMed Scopus (758) Google Scholar found that even mild levels of anemia (HCT 29% to 36% in women and 29% to 39% in men) were associated with a substantial increase in adverse events. Anemic patients had a 42% higher adjusted mortality and 35% higher adjusted composite morbidity than nonanemic patients. A retrospective analysis of 7759 noncardiac surgical cases by Beattie and colleagues12Beattie 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 (314) Google Scholar showed a prevalence of anemia (hemoglobin < 12 g/dL) of 39% that was associated with a 2.3-fold higher risk of death. Thus, preoperative anemia places patients undergoing cardiac and noncardiac surgery at risk of postoperative mortality and morbidity, and the magnitude of that risk increases with increasing degree of preoperative anemia. Sorting out the relative contribution of preoperative, intraoperative, and postoperative anemia to this risk, in addition to the contribution of RBC transfusion and management of anemia, is difficult. Nonetheless, preoperative anemia should raise the suspicion that these patients will be at higher risk for adverse postoperative outcomes. How can one best manage patients with preoperative anemia without the use of blood transfusions? There are 2 aspects to this: one is to optimize hemoglobin level and the other is to avoid risk factors for bleeding. For the former, reversible causes of anemia, such as occult gastrointestinal bleeding, should be ruled out and addressed. Surgery should be delayed to allow correction of anemia whenever possible. Patients with volume overload should be diuresed adequately, and iron supplementation should be instituted. Elective operations should be delayed for at least 2 weeks to allow optimization of preoperative hemoglobin. Administration of erythropoietin (EPO) has been suggested as a way to promote erythropoiesis in anemic patients several days before cardiac surgery.13Ferraris V.A. Brown J.R. Despotis G.J. Hammon J.W. Reece T.B. Saha S.P. 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 (990) Google Scholar Although recombinant EPO increases RBC mass, it has not been demonstrated to reduce the need for RBC transfusion in cardiac surgery,14D'Ambra M.N. Gray R.J. Hillman R. Jones J.W. Kim H.C. Rawitscher R. et al.Effect of recombinant human erythropoietin on transfusion risk in coronary bypass patients.Ann Thorac Surg. 1997; 64: 1686-1693Abstract Full Text Full Text PDF PubMed Scopus (67) Google Scholar and for specific patient populations, some have expressed concern that it may contribute to adverse outcomes.15Unger E.F. Thompson A.M. Blank M.J. Temple R. Erythropoiesis-stimulating agents–time for a reevaluation.N Engl J Med. 2010; 362: 189-192Crossref PubMed Scopus (225) Google Scholar, 16Besarab A. Bolton W.K. Browne J.K. Egrie J.C. Nissenson A.R. Okamoto D.M. et al.The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin.N Engl J Med. 1998; 339: 584-590Crossref PubMed Scopus (1879) Google Scholar EPO may lead to overcorrection of anemia in patients with chronic kidney disease and is associated with increased occurrence of cardiovascular events.17Singh A.K. Szczech L. Tang K.L. Barnhart H. Sapp S. Wolfson M. et al.Correction of anemia with epoetin alfa in chronic kidney disease.N Engl J Med. 2006; 355: 2085-2098Crossref PubMed Scopus (2273) Google Scholar, 18Drueke T.B. Locatelli F. Clyne N. Eckardt K.U. Macdougall I.C. Tsakiris D. et al.Normalization of hemoglobin level in patients with chronic kidney disease and anemia.N Engl J Med. 2006; 355: 2071-2084Crossref PubMed Scopus (1781) Google Scholar Other side effects include worsening hypertension and increased risk of thrombosis.19Felker G.M. Adams Jr., K.F. Gattis W.A. O'Connor C.M. Anemia as a risk factor and therapeutic target in heart failure.J Am Coll Cardiol. 2004; 44: 959-966Abstract Full Text Full Text PDF PubMed Scopus (231) Google Scholar Moreover, the 2011 update to the Society of Thoracic Surgeons recommendations on blood conservation address several interventions for reducing risk of bleeding in high-risk patients undergoing cardiac surgery.13Ferraris V.A. Brown J.R. Despotis G.J. Hammon J.W. Reece T.B. Saha S.P. 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 (990) Google Scholar These should be applied to patients with preoperative anemia. Although a complete review of this topic is beyond the scope of this article, several important points should be highlighted. For instance, drugs that inhibit platelet P2Y12 receptors, such as clopidogrel, ticlopidine, prasugrel, and ticagrelor, should be avoided when feasible. Desmopressin should be considered for patients with evidence of platelet dysfunction. Use of platelets or fresh-frozen plasma (FFP) must be balanced against the hazards of transfusing blood products. Factor IX concentrates may be helpful in patients with hemophilia B or for prophylaxis in Jehovah's Witness patients who are anemic at baseline.20Bolliger D. Sreeram G. Duncan A. Molinaro R.J. Szlam F. Chen E.P. et al.Prophylactic use of factor IX concentrate in a Jehovah's Witness patient.Ann Thorac Surg. 2009; 88: 1666-1668Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar Further discussion of risks and benefits of RBC transfusions is detailed below. Several factors contribute to intraoperative anemia: CPB priming volume, crystalloid solutions, and bleeding due to technical factors or coagulopathy. Investigators have demonstrated that the lowest HCT on CPB is associated with adverse patient outcomes. Habib and colleagues21Habib R.H. Zacharias A. Schwann T.A. Riordan C.J. Durham S.J. Shah A. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed?.J Thorac Cardiovasc Surg. 2003; 125: 1438-1450Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar reported that postoperative morbidity and mortality were greater in patients with a nadir HCT less than 22%. This was supported by their multivariable analysis; however, they did not control for RBC transfusion. Their subsequent study of 1760 patients undergoing isolated CABG concluded that intraoperative HCT less than 24% was associated with increased renal insufficiency independently of use of RBC transfusion.22Habib R.H. Zacharias A. Schwann T.A. Riordan C.J. Engoren M. Durham S.J. et al.Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: implications on operative outcome.Crit Care Med. 2005; 33: 1749-1756Crossref PubMed Scopus (241) Google Scholar This effect was exacerbated by increased CPB duration and transfusion. Ranucci and colleagues7Ranucci M. Conti D. Castelvecchio S. Menicanti L. Frigiola A. Ballotta A. et al.Hematocrit on cardiopulmonary bypass and outcome after coronary surgery in nontransfused patients.Ann Thorac Surg. 2010; 89: 11-17Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar performed an investigation of nontransfused cardiac surgical patients and showed that nadir HCT on CPB was a risk factor for postoperative major morbidity but not mortality. The regional observational study by Defoe and colleagues23DeFoe G.R. Ross C.S. Olmstead E.M. Surgenor S.D. Fillinger M.P. Groom R.C. et al.Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.Ann Thorac Surg. 2001; 71: 769-776Abstract Full Text Full Text PDF PubMed Scopus (313) Google Scholar of 6980 patients undergoing isolated CABG identified nadir HCT during CPB as a risk factor for in-hospital mortality, intra- or postoperative placement of an intra-aortic balloon pump, and return to CPB. Adjusted mortality for patients with an HCT less than 19% was approximately twice that of patients with a nadir HCT 25% or greater (3.9% vs 1.6%; P < .001). In a randomized trial by Jonas and colleagues,24Jonas R.A. Wypij D. Roth S.J. Bellinger D.C. Visconti K.J. du Plessis A.J. et al.The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants.J Thorac Cardiovasc Surg. 2003; 126: 1765-1774Abstract Full Text Full Text PDF PubMed Scopus (329) Google Scholar 74 patients undergoing CPB for congenital disorders were assigned to a lower HCT strategy (22% ± 2.9%) and 73 patients were assigned to a higher strategy (27.8% ± 3.2%). In an intent-to-treat analysis, the lower HCT group had greater cardiac dysfunction and serum lactate levels and higher total body water. At 1 year, Psychomotor Development Index scores were lower in the lower HCT group. Mortality was similar. Swaminathan and colleagues25Swaminathan M. Phillips-Bute B.G. Conlon P.J. Smith P.K. Newman M.F. Stafford-Smith M. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery.Ann Thorac Surg. 2003; 76: 784-792Abstract Full Text Full Text PDF PubMed Scopus (211) Google Scholar showed that nadir HCT during CPB was associated with higher peak change in serum creatinine and highest postoperative creatinine. Other risk factors for postoperative change in creatinine included higher preoperative creatinine, lower preoperative HCT, and RBC transfusion. Karkouti and colleagues26Karkouti K. Djaiani G. Borger M.A. Beattie W.S. Fedorko L. Wijeysundera D. et al.Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery.Ann Thorac Surg. 2005; 80: 1381-1387Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar investigated the influence of nadir HCT during CPB on postoperative stroke in more than 10,000 patients requiring CPB for cardiac surgical procedures. Prevalence of postoperative stroke was 1.0% (n = 110/10,949). Patients experiencing a stroke had a lower nadir HCT (21 ± 3.0 g/dL) than those who did not (23 ± 5.0 g/dL). After risk adjustment, each percentage decrease in nadir HCT was associated with a 10% increase in risk of a postoperative stroke (P = .002). RBC transfusion was also a risk factor for stroke.26Karkouti K. Djaiani G. Borger M.A. Beattie W.S. Fedorko L. Wijeysundera D. et al.Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery.Ann Thorac Surg. 2005; 80: 1381-1387Abstract Full Text Full Text PDF PubMed Scopus (201) Google Scholar Yet not all studies have shown that intraoperative anemia is associated with adverse patient outcomes. von Heymann and colleagues27von Heymann C. Sander M. Foer A. Heinemann A. Spiess B. Braun J. et al.The impact of an hematocrit of 20% during normothermic cardiopulmonary bypass for elective low risk coronary artery bypass graft surgery on oxygen delivery and clinical outcome–a randomized controlled study [ISRCTN35655335].Crit Care. 2006; 10: R58Crossref PubMed Scopus (44) Google Scholar randomized 54 patients undergoing normothermic CPB to a mean HCT of 20% versus 25%. Calculated oxygen delivery in the low versus high HCT groups was similar: 647 ± 200 versus 760 ± 180 mL/m2/min, respectively. Oxygen consumption, blood lactate levels, cardiac index, vasopressor requirements, and morbidities, including stroke, renal failure, and respiratory failure, were similar. A randomized study by Berger and colleagues28Berger K. Sander M. Spies C.D. Weymann L. Buhner S. Lochs H. et al.Profound haemodilution during normothermic cardiopulmonary bypass influences neither gastrointestinal permeability nor cytokine release in coronary artery bypass graft surgery.Br J Anaesth. 2009; 103: 511-517Crossref PubMed Scopus (9) Google Scholar exposed 23 patients to an HCT range of 19% to 21% and 24 patients to an HCT range of 24% to 26%. They found that gastrointestinal permeability and expression of inflammatory cytokines were similar. However, neither study was powered for detecting a difference in these outcomes. Evidence supports the notion that intraoperative anemia is associated with adverse neurologic, renal, cardiac, and pulmonary outcomes. Increased length of stay and possibly increased mortality are also associated with a lower nadir HCT (Table 2). A summary of data points from the literature suggests an inflection point around an HCT of 20% to 24%, below which morbidity and mortality increase substantially (Figure 1).Table 2Investigations examining effect of intraoperative anemia on postoperative outcomesGroupsDesignnEffectHabib et al21Habib R.H. Zacharias A. Schwann T.A. Riordan C.J. Durham S.J. Shah A. Adverse effects of low hematocrit during cardiopulmonary bypass in the adult: should current practice be changed?.J Thorac Cardiovasc Surg. 2003; 125: 1438-1450Abstract Full Text Full Text PDF PubMed Scopus (333) Google ScholarObservational5000Increased mortality and pulmonary, neurologic, renal, and cardiac morbidityHabib et al22Habib R.H. Zacharias A. Schwann T.A. Riordan C.J. Engoren M. Durham S.J. et al.Role of hemodilutional anemia and transfusion during cardiopulmonary bypass in renal injury after coronary revascularization: implications on operative outcome.Crit Care Med. 2005; 33: 1749-1756Crossref PubMed Scopus (241) Google ScholarObservational1760Increased renal injuryRanucci et al7Ranucci M. Conti D. Castelvecchio S. Menicanti L. Frigiola A. Ballotta A. et al.Hematocrit on cardiopulmonary bypass and outcome after coronary surgery in nontransfused patients.Ann Thorac Surg. 2010; 89: 11-17Abstract Full Text Full Text PDF PubMed Scopus (82) Google ScholarObservational3003Major morbidity: prolonged ventilation, surgical reoperation, mediastinitis, renal dysfunction, strokeDeFoe et al23DeFoe G.R. Ross C.S. Olmstead E.M. Surgenor S.D. Fillinger M.P. Groom R.C. et al.Lowest hematocrit on bypass and adverse outcomes associated with coronary artery bypass grafting. Northern New England Cardiovascular Disease Study Group.Ann Thorac Surg. 2001; 71: 769-776Abstract Full Text Full Text PDF PubMed Scopus (313) Google ScholarObservational6980Mortality, low output heart failureJonas et al24Jonas R.A. Wypij D. Roth S.J. Bellinger D.C. Visconti K.J. du Plessis A.J. et al.The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants.J Thorac Cardiovasc Surg. 2003; 126: 1765-1774Abstract Full Text Full Text PDF PubMed Scopus (329) Google ScholarRandomized controlled trial147Decreased cardiac index and psychomotor development; increased serum lactate and total body waterSwaminathan et al25Swaminathan M. Phillips-Bute B.G. Conlon P.J. Smith P.K. Newman M.F. Stafford-Smith M. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery.Ann Thorac Surg. 2003; 76: 784-792Abstract Full Text Full Text PDF PubMed Scopus (211) Google ScholarObservational1404Renal insufficiencyKarkouti et al26Karkouti K. Djaiani G. Borger M.A. Beattie W.S. Fedorko L. Wijeysundera D. et al.Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery.Ann Thorac Surg. 2005; 80: 1381-1387Abstract Full Text Full Text PDF PubMed Scopus (201) Google ScholarObservational10,949StrokeBahrainwala et al58Bahrainwala Z.S. Grega M.A. Hogue C.W. Baumgartner W.A. Selnes O.A. McKhann G.M. et al.Intraoperative hemoglobin levels and transfusion independently predict stroke after cardiac operations.Ann Thorac Surg. 2011; 91: 1113-1118Abstract Full Text Full Text PDF PubMed Scopus (44) Google ScholarObservational617Increased risk of strokevon Heymann et al27von Heymann C. Sander M. Foer A. Heinemann A. Spiess B. Braun J. et al.The impact of an hematocrit of 20% during normothermic cardiopulmonary bypass for elective low risk coronary artery bypass graft surgery on oxygen delivery and clinical outcome–a randomized controlled study [ISRCTN35655335].Crit Care. 2006; 10: R58Crossref PubMed Scopus (44) Google ScholarRandomized controlled trial54Similar oxygen delivery and morbidityBerger et al28Berger K. Sander M. Spies C.D. Weymann L. Buhner S. Lochs H. et al.Profound haemodilution during normothermic cardiopulmonary bypass influences neither gastrointestinal permeability nor cytokine release in coronary artery bypass graft surgery.Br J Anaesth. 2009; 103: 511-517Crossref PubMed Scopus (9) Google ScholarRandomized controlled trial47Similar GI permeability and inflammatory responseGI, Gastrointestinal. Open table in a new tab GI, Gastrointestinal. Among methods used to prevent or correct intraoperative anemia in patients undergoing cardiac surgery are antifibrinolytics, cell salvage, ultrafiltration, and RBC transfusion. If anemia leads to adverse outcomes after cardiac surgery, these methods should decrease morbidity and mortality. Yet several studies have reported increased morbidity associated with many of these interventions. The Society of Thoracic Surgeons blood conservation update gave a class I recommendation for the use of lysine analogues during cardiac surgery.13Ferraris V.A. Brown J.R. Despotis G.J. Hammon J.W. Reece T.B. Saha S.P. 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 (990) Google Scholar Antifibrinolytics reduce blood loss and RBC use in cardiac surgical patients.29Henry D.A. Moxey A.J. Carless P.A. O'Connell D. McClelland B. Henderson K.M. et al.Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion.Cochrane Database Syst Rev. 2001; : CD001886PubMed Google Scholar E-aminocaproic acid and tranexamic acid are the most commonly used agents; aprotonin is no longer used in adult cardiac surgery because of an unfavorable safety profile.30Fergusson D.A. Hebert P.C. Mazer C.D. Fremes S. MacAdams C. Murkin J.M. et al.A comparison of aprotinin and lysine analogues in high-risk cardiac surgery.N Engl J Med. 2008; 358: 2319-2331Crossref PubMed Scopus (873) Google Scholar, 31Mangano D.T. Miao Y. Vu
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