doi: 10.1161/CIRCULATIONAHA.107.716654
(Circulation. 2007;116:458-460.)
© 2007 American Heart Association, Inc.
Editorial |
To Transfuse or Not to Transfuse
From Christiana Care Health System, The Center for Heart and Vascular Health, Newark Del.
Correspondence to Timothy J. Gardner, MD, Christiana Care Health System, The Center for Heart and Vascular Health, 4745 Ogletown-Stanton Rd, Newark DE 19718. E-mail tgardner{at}christianacare.org
Key Words: Editorials • blood cells • anemia • bypass • transfusions
Preoperative anemia in a patient requiring cardiac surgery generally is not considered an independent risk factor for an unfavorable outcome. Older and sicker patients, especially women, are more likely to be anemic, but these patients often are at higher risk because of other coexisting comorbidities. It is these other comorbidities and risk factors that are accounted for in most risk-prediction models of patients undergoing heart surgery. The present report by Kulier et al1 demonstrates that anemia itself is a risk factor and that the degree of risk is proportional to the level of anemia. This finding, however, uncovers a common dilemma in the management of cardiac surgery patients. The controversy revolves around whether and even how best to deal with the anemia that is encountered in most cardiac surgery patients before, during, and after the surgery. This "transfusion" dilemma is a result of many equally compelling reports on the detrimental effects of blood transfusions in critically ill postoperative patients, including specific reports in cardiac surgery populations.
Article p 471
It is well recognized that moderate to severe preoperative anemia, with hemoglobin (Hb) levels of 10 g/dL or less, can complicate what would otherwise be a straightforward cardiac operation. The hemodilution that occurs as a result of the pump priming volume required to establish cardiopulmonary bypass may not be tolerated by anemic patients without the addition of red blood cells (RBCs) to the prime or to the pump circuit once bypass has begun. In addition, tolerable levels of anemia in the perioperative and early postoperative phase for younger cardiac surgery patients may not be tolerated in older patients who are prone to excessive vasodilation and inadequate cerebral or renal perfusion in the perioperative period without RBC transfusion and better oxygen-delivery capacity. Overshadowing these considerations has been the suggestion by some that perioperative RBC transfusion can be used as a quality-of-care process indicator for CABG patients. The suggestion is that RBC transfusion–free management during or after cardiac surgery represents "best practice."2 Imagine a similar dilemma if the administration of perioperative antibiotic prophylaxis targeting the 1% to 3% surgical infection risk were challenged because of the predictability of specific complications associated with the use of potent antibiotics, such as hypersensitivity allergic reactions, organ toxicity, and nonsusceptible bacterial overgrowth.
In the present context of the increasing incidence of preoperative anemia in the relentlessly aging population of cardiac surgery patients, the present report1 from the Multicenter Study of Perioperative Ischemia (MCSPI) and the Ischemia Research Educational Foundation (IREF), founded several years ago by Dennis Mangano and colleagues,3 is quite timely. This study was based on hard clinical data obtained from more than 4800 patients operated on at 70 institutions around the world. Their complex analyses, however, raise questions and even create confusion about the truly independent consequence of preoperative anemia on outcomes in CABG patients. For example, their data analysis demonstrates that lower-risk anemic patients, so characterized by progressive risk factor summing as assessed by the EuroSCORE method,4 had an increase in noncardiac complications (renal or cerebral). Anemia was not, however, an independent predictor of adverse cardiac events in these patients. In the higher-risk anemic patients, as identified by use of the EuroSCORE method, they conclude that preoperative anemia, defined as an Hb level of <11 g/dL, is an independent risk factor that influences all adverse postoperative events. Even in a study population of >4800 patients, fewer than 30% qualified as anemic by the RBC levels defined by the authors (for males, Hb <13 g/dL, and for females, Hb <12 g/dL). The questionable reliability of assessing the independent contribution of anemia versus associated comorbid factors should be acknowledged, especially when the significance of the anemia is variably related to the level of Hb. In addition, as noted above, the preoperative Hb level does not reliably predict either the intraoperative or postoperative Hb levels.
So, let us review the "horns" of this therapeutic dilemma. There are convincing reports that RBC transfusion to various subgroups of critically ill patients is associated with poorer outcomes. Hebert and associates5 in the Canadian Critical Care Trials Group concluded that a restrictive transfusion policy may be superior to liberal transfusion practice in critically ill euvolemic patients with Hb <9 g/dL, with the possible exception of patients with ongoing myocardial ischemia. Rao and associates,6 however, when analyzing the effect of RBC transfusion on patients from 3 large international trials of patients with acute coronary syndromes, found that blood transfusion was associated with higher mortality even after adjustment for other predictive factors for death. Corwin and associates7 in the CRIT study reported on the pattern and consequences of transfusion practices in nearly 5000 patients in intensive care units. They noted that anemia is common in such patients, that RBC transfusions are frequent, and that the number of RBC units transfused is an independent predictor of poor outcomes. In a large population study of transfused patients served by a single blood center in the United Kingdom, those patients who received transfusion had reduced survival compared with that estimated in early population studies, which the authors speculate may have been the result of increased use of transfusions in older patients.8 Explanations for this transfusion-related mortality risk, especially in the acutely ill population, include factors such as acute lung injury, immunosuppression, and transmission of new infections.8–10
Of particular interest in the context of the present report by Kulier et al1 are published reports of a direct relationship between perioperative RBC transfusions and poor outcomes after cardiac surgery. In 1999, Michalopoulos and associates11 described a relationship in their cardiac surgery patients between the number of blood transfusions and early hospital mortality. Engoren et al12 described an association of perioperative blood transfusion and increased long-term mortality in their CABG patients. Koch and associates13 at the Cleveland Clinic, examining the outcomes of >10 000 CABG patients, reported that perioperative RBC transfusions in CABG patients were associated with a risk-adjusted reduction in survival both in the early period (up to 6 months) after operation and late after operation. In another analysis reported from the Cleveland Clinic on >15 000 patients who underwent cardiovascular operations, Banbury et al10 demonstrated that the risk of postoperative infection increased with each unit of transfused blood.
Along with this evidence of an association between perioperative RBC transfusions and worse early and late outcomes after cardiac surgery, however, there are many reports of the consequences of severe anemia for cardiac surgery patients. Karkouti and associates14 from the University of Toronto reported that the nadir hematocrit concentration during operation on cardiopulmonary bypass, at which maximum hemodilution is observed, was associated with the development of acute renal failure that required dialysis. Habib and associates15 reported on the same association of hemodilutional anemia, transfusion, and renal injury in CABG patients. The negative significance of procedure-related renal insufficiency on outcome after cardiac surgery is well documented.16 In addition, although yet to be demonstrated conclusively in cardiac surgery patients, the detrimental effects of acute severe isovolemic anemia on neurological function has been described.17 The possible relationship between renal insufficiency, neurological injury, and the induction of isovolemic anemia during cardiac procedures that use cardiopulmonary bypass is very intriguing. In addition, it is quite compelling to consider studying whether RBC transfusion at this stage in the operative course would obviate the renal and cerebral injury that has been seen.
What options are available to deal with preoperative anemia in the patient who must undergo cardiac surgery? To begin with, and as a consequence of the present report,1 we should include anemia in our risk-prediction models, because there is increasing evidence from this report and earlier studies noted above that severe preoperative anemia may be an independent and additive risk factor for poor outcomes, both early and late, after cardiac surgery. There are other options as well, short of preoperative RBC transfusion. For patients whose surgery can be postponed, erythropoiesis-stimulating agents are an option. For some anemic patients, the use of off-pump CABG should be considered. For patients requiring cardiac surgery with cardiopulmonary bypass, bypass pumps that require minimal priming volumes and result in less dilution of the patient’s blood volume and that do not exacerbate the patient’s anemic state at the onset of extracorporeal support should be used. For all patients undergoing cardiac surgery, the aggressive perioperative and postoperative blood conservation techniques that were developed and promoted so well in the 1990s should be utilized to the fullest extent possible.18 Despite the validation of these techniques and the demonstration that many patients tolerate transient anemia in the first several weeks after surgery as Hb levels are restored with simple iron therapy, there may have been some recent slippage in the avoidance of extraneous or unnecessary RBC transfusions. The real need for transfusion is especially questionable in patients who receive a single RBC unit, an occurrence in 12.5% of the CABG patients at the Cleveland Clinic.13
What will be a hopeful and significant consequence of the present report, however, is a renewal of the goal to clarify the dilemma posed above, that is, should the anemic patient be transfused before surgery? Goodnough et al19 raised this question more than 10 years ago in their report "On the Need for Improved Transfusion Indicators in Cardiac Surgery." Kulier and associates1 provide a related comment in the present report: "(While) the independent association of RBC transfusion with adverse outcome has been described previously, the beneficial effects of RBC transfusions have not yet been precisely described in defined subsets of anemic patients undergoing heart surgery." We agree with this conclusion, especially for patients with severe preoperative anemia and with concurrent high-risk profiles. Despite polarized positions on the benefits and risks of perioperative transfusions among physicians caring for cardiac surgery patients, there is equipoise on the question of how to deal with severe preoperative anemia. This issue may be a very appropriate one to be addressed by the new Clinical Network for Cardiothoracic Surgical Investigations (U01; http://grants.nih.gov/grants/guide/rfa-files/RFA-HL-06-005.html) that has just been established by the National Heart, Lung, and Blood Institute.
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Acknowledgments |
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Disclosures
None.
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Footnotes |
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The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.
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References |
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 Top References |
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2. Lee LY, DeBois W, Krieger KH, Isom OW. Transfusion therapy and blood conservation. In: Cohn LH, Edmunds LH Jr, eds. Cardiac Surgery in the Adult. New York, NY: McGraw-Hill; 2003: 389–400.
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