Bar Graphs & Blood Banks…

“Red cell transfusion rates for CPB patients are the highest and most variable amongst all surgical patients.”

Editor’s Note:

This discussion comes up so often, it borders on the ridiculous- because there has never really been any closure or academic consensus regarding transfusion thresholds- and the point at which we decide we are “going to have to pull the trigger”, avoid a stroke or major coagulopathy but at what implied cost to the patient (in terms of morbidity)?

We are all too familiar with the process of retrospective finger pointing, and the shrill investigation associated with bar graphs and spreadsheets that point in one’s general direction, waggin with a cautionary note-  that your transfusing too many patients, blah blah blah.

None of those pretty little charts take into account the multivariate factors that lead to the decision to transfuse.  Comparing two clinicians and their transfusion habits- is like comparing apples to oranges, and is a pointless argument.

With all that said- below is a very well written piece that is worth taking the time to read.

Have fun 🙂


What Transfusion Trigger is Indicated?

By David Mazer, MD, FRCPC

Cardiac surgery is one of the most frequent surgical procedures, with over 300,000 procedures in the United States each year.  Anemia is frequent in these patients related to pre-existing conditions, bleeding and hemodilution during cardiopulmonary bypass (CPB).  Patients undergoing cardiac surgery receive a high proportion of red cell transfusions – approximately 14% to 20% of the entire blood supply is administered to cardiac surgical patients.  Although transfusion may potentially be beneficial, there is lack of clear evidence regarding its benefit.  In addition, it is costly and may also lead to considerable mortality and morbidity. Randomized controlled trials have been shown to reduce transfusion in critically ill patients because these patients can tolerate anemia.  However, the safety of restrictive triggers has not been clearly demonstrated and the results from other populations may not be applicable to patients undergoing cardiac surgery because moderate to severe anemia in cardiac surgery has been shown to be harmful. An expert panel of the National Heart Lung and Blood Institute (NHLBI) has declared that the comparison of liberal and restrictive transfusion strategies in patients undergoing cardiac surgery is one of the “top 10” clinical trials that “would most critically impact and significantly optimize the utilization of blood components”

The uncertainty regarding optimal red cell transfusion trigger is further highlighted by the following observations: 1) both anemia and transfusions are independent predictors of morbidity and mortality in cardiac surgery patients.  2) there are a large number of patients undergoing these procedures who are exposed to anemia and transfusion 3) unnecessary transfusions may be administered because of the lack of high quality evidence, and  4) current trials in cardiac surgery have so far all been underpowered to detect a clinically relevant difference in important outcomes.  In addition, red cell transfusion rates for these patients are the highest and most variable amongst all surgical patients. A study using the Society of Thoracic Surgeons (STS) Adult Surgery database of over 100,000 patients having isolated primary CABG reported red cell transfusion rates ranging from 7.8% to 92.8%.  Previous reports have shown that this variation is mostly attributable to individual physician practice and hospital policy, rather than to patient factors.  Since both anemia and transfusion are associated with adverse outcome, the proper decision regarding transfusion should be based on when the risks of anemia outweigh the risks of transfusion.


Risks of Anemia:

Acute anemia is associated with increased mortality.  This is most likely related to impaired oxygen delivery and tissue hypoxia. Since more than 99% of the blood oxygen content is transported on hemoglobin, severe anemia leads to inadequate tissue oxygen delivery, tissue hypoxia, organ failure, and death. Although there are reports of patients surviving very low hemoglobin levels, the mortality rate in acute anemia is directly related to the reduction in hemoglobin. In animals and humans, acute reduction in hemoglobin is sensed at the cellular level and leads to adaptive cardiovascular responses to optimize tissue oxygen delivery.

These responses include 1) increased cardiac output (CO) that is proportional to the degree of anemia; 2) reduced systemic vascular resistance with organ-specific vasodilation to facilitate preferential perfusion of vital organs, including the heart and brain; and 3) increased tissue oxygen extraction. In addition, anemia leads to activation of hypoxic cellular mechanisms which are directed at maintaining oxygen homeostasis and sustaining organism survival.

These mechanisms include neuronal nitric oxide synthase (nNOS), erythropoietin, and hypoxia inducible factor (HIF).  Under normal conditions the heart extracts approximately 60 to 70% of oxygen delivered.  Although other organs can increase oxygen extraction to compensate for reduced oxygen delivery; the only compensatory mechanism for the heart is increasing myocardial blood flow by coronary vasodilatation. This increased susceptibility to anemia may be accentuated when there is a limited capacity to increase blood flow such as in patients with coronary stenoses, myocardial hypertrophy, aortic valve disease or other circulatory abnormalities.  This is highlighted by the recent MINT trial in which patients with acute coronary syndrome who were randomized to a restrictive transfusion protocol (8.0 g/L or symptoms) had a higher mortality than those randomized to a more liberal strategy (10 g/L).  In addition, during cardiopulmonary bypass (CPB), the acute hemodilution that occurs has been shown to reduce oxygenation in the brain, heart, kidney, intestine, and muscle, although the threshold hemoglobin concentration below which inadequate oxygen delivery during CPB would occur has not been determined. Hemodilution during CPB has been associated with increased risk of stroke at hemoglobin concentrations less than 8.3 g/dL and renal insufficiency at hemoglobin levels less than 7.0 g/dL.  This may be accentuated by non-physiological non-pulsatile flow during CPB.


Risks of Transfusion:

Mortality in transfused patients has been demonstrated to be higher than non-transfused in patients who are critically ill patients, have gastrointestinal hemorrhage, and who have cardiac surgery.  The increased mortality in observational studies is at least in part attributable to confounding by indication in that transfused patients are generally sicker than non-transfused patients.  Nonetheless, there are a number of complications related to transfusion that are associated with considerable morbidity and mortality. Non-infectious risks from transfusion such as TRALI are thought to occur more frequently in patients having cardiac surgery, perhaps because of increased systematic and pulmonary inflammation, and are associated with a high case fatality rate (5 to 13%)  Due to the volume of red cells transfused, pulmonary edema and fluid overload have also been shown to occur more frequently in patients with critical illness and cardiovascular disease who were transfused at a hemoglobin concentration of 10 g/dL compared to a hemoglobin concentration of 7 g/dL.  In addition, administrative errors resulting in hemolytic transfusion reactions can be life-threatening.  Unnecessary transfusions also have an impact on the care of patients. Although the risk of acquiring the human immune deficiency virus and hepatitis C virus is now very low (1:2,000,000 to 1:8,000,000), new emerging pathogens are a constant threat to the blood supply. Optimum utilization of blood components is important since there is a continuous strain on blood systems because of increased blood utilization and demographically driven decreased donations. Additionally, the cost of blood is increasing, so unnecessary transfusions result in increased resource utilization.

Current guidelines for transfusion are only helpful at the extremes of hemoglobin values.  For example, both the STS and ASA guidelines recommend transfusion of red blood cells when the hemoglobin is below 6.0 g/dL, and NOT transfusing when the hemoglobin exceeds 10 g/dL; between those triggers, the value of transfusion is variable and uncertain.  In addition, most guidelines readily acknowledge the lack of high quality evidence to support any transfusion recommendations.  Other physiologic triggers (such as symptoms, heart rate, Sv02, cerebral oximetry, ECG, lactate, metHb) have been suggested, but they have not been validated in sufficiently powered clinical comparison studies.

There are few randomized controlled studies of transfusion triggers in cardiac surgery.  Overall these studies have not been adequately powered to detect a difference in adverse events in cardiac surgery, and the majority did not address intraoperative hemoglobin thresholds.  There are three ongoing or recently completed trials examining hemoglobin concentrations for transfusion in this patient population. One trial randomized patients only in the postoperative period (TITRe-2 ISRCTN70923932; n=2000) and thus is missing the intraoperative period when anemia has been shown to lead to increased morbidity and mortality The second trial (NCT00651573)  is randomizing a heterogeneous population including several who are unlikely to receive a transfusion.  The third trial (TRICS III  NCT02042898; n~3600) is a global RCT comparing a restrictive vs liberal transfusion strategy in moderate to high risk patients during and after cardiac surgery with CPB.  The primary outcome is a composite of death MI, stroke and renal failure.  Enrollment has just begun.

Selected References:


  1. Bennett-Guerrero E, et al. Variation in use of blood transfusion in coronary artery bypass graft surgery. 2010 Oct 13;304(14):1568-75.
  2. Carson JL, et al.Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion.Cochrane Database Syst Rev. 2012 Apr 18;4:CD002042
  3. Carson JL, et al. Liberal or restrictive transfusion in high-risk patients after hip surgery. N Engl J Med. 2011 Dec 29;365(26):2453-62.
  4. Carson JL, et al. Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease. Am Heart J. 2013 Jun;165(6):964-971
  5. Chiavetta JA, et al. A survey of red cell use in 45 hospitals in Central Ontario, Canada. Transfusion, 1996; 36: 699-706.
  6. Corwin HL, et al. The CRIT Study: Anemia and blood transfusion in the critically ill-current clinical practice in the United States. Critical Care Medicine 2004; 32: 39-52.
  7. Dupuis J-Y, et al. Transfusion practices among patients who did and did not predonate autologous blood before elective cardiac surgery. CMAJ 1999 Apr 6;160(7):997-1002.
  8. Hajjar LA, et al. Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial. JAMA. 2010 Oct 13;304(14):1559-67.
  9. Hare GMT, et al. Risks of anemia and related management strategies: can perioperative blood management improve patient safety? Canadian Journal of Anesthesia. 2014 in press.
  10. Hébert PC, et al; Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group. Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases? Crit Care Med 2001 Feb;29(2):227-34.
  11. Hebert PC, et al. A multicenter, randomized controlled clinical trial of transfusion requirements in critical care. New Engl J Med 1999; 340: 409-17.
  12. Jonas RA, et al. The influence of hemodilution on outcome after hypothermic cardiopulmonary bypass: results of a randomized trial in infants. Journal Thoracic Cardiovascular Surgery 2003:125: 1765-74.
  13. Josephson CD, et al; State-of-the Science Symposium Transfusion Medicine Committee. A multidisciplinary “think tank”: the top 10 clinical trial opportunities in transfusion medicine from the National Heart, Lung, and Blood Institute-sponsored 2009 state-of-the-science symposium. Transfusion 2011 Apr;51(4):828-41
  14. Karkouti K, et a;. Risk Associated With Preoperative Anemia in Cardiac Surgery A Multicenter Cohort Study. Circulation 2008; 117: 478-484.
  15. Karkouti K, et al. Hemodilution during cardiopulmonary bypass is an independent risk factor for acute renal failure in adult cardiac surgery. J Thorac Cardiovasc Surg 2005 Feb;129(2):391-400.
  16. Karkouti K, et al. Low hematocrit during cardiopulmonary bypass is associated with increased risk of perioperative stroke in cardiac surgery. Ann Thorac Surg 2005 Oct;80(4):1381-7.
  17. Karkouti K, et al. Advance targeted transfusion in anemic cardiac surgical patients for kidney protection: an unblinded randomized pilot clinical trial. Anesthesiology. 2012 Mar;116(3):613-21.
  18. Koch CG, et al. Transfusion in coronary artery bypass grafting is associated with reduced long-term survival. Annals of Thoracic Surgery 2006;81(5):1650-7.
  19. Koch CG, et al. Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting. Critical Care Medicine 2006;34:1608-16.
  20. Kuduvalli M, et al. Effect of peri-operative red blood cell transfusion on 30-day and 1-year mortality following coronary artery bypass surgery. Eur J Cardiothorac Surg. 2005 Apr;27(4):592-8.
  21. O’Brien SF, et al. Current incidence and estimated residual risk of transfusion-transmitted infections in donations made to Canadian Blood Services. Transfusion 2007;47(2):316-25.
  22. Ranucci M, et al. Hematocrit on cardiopulmonary bypass and outcome after coronary surgery in nontransfused patients. Ann Thorac Surg 2010 Jan;89(1):11-7.
  23. Shander A, et al. Activity-based costs of blood transfusions in surgical patients at four hospitals. Transfusion 2010 Apr;50(4):753-65.
  24. Shehata N, et al. The proportion of variation in perioperative transfusion decisions in Canada attributable to the hospital. Can J Anaesth. 2007 Nov;54(11):902-7.
  25. Shehata N, et al .A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery. Transfusion. 2012 Jan;52(1):91-9.
  26. Shehata N, et al. Blood transfusion and cardiac surgery.JAMA. 2011 Jan 26;305(4):357-8; author reply 358-9.
  27. Shehata N, et al. Factors affecting perioperative transfusion decisions in patients with coronary artery disease undergoing coronary artery bypass surgery. Anesthesiology 2006;105(1):19-27.
  28. Shehata N, et al. Risk factors for red cell transfusion in adults undergoing coronary artery bypass surgery: a systematic review. Vox Sang 2007 Jul;93(1):1-11.
  29. Silliman CC, et al. Transfusion-related acute lung injury. Blood. 2005 Mar 15;105(6):2266-73.
  30. Singal RK, et al. Biologically variable bypass reduces enzymuria after deep hypothermic circulatory arrest. Ann Thorac Surg. 2006 Oct;82(4):1480-8.
  31. Society of Thoracic Surgeons Blood Conservation Guideline Task Force, Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion. Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. Annals of Thoracic Surgery 2007 May;83(5 Suppl):S27-86.
  32. Society of Thoracic Surgeons Blood Conservation Guideline Task Force,; Society of Cardiovascular Anesthesiologists Special Task Force on Blood Transfusion. 2011 update to the Society of Thoracic Surgeons and the Society of Cardiovascular Anesthesiologists blood conservation clinical practice guidelines. Ann Thorac Surg. 2011 Mar;91(3):944-82.
  33. Surgenor SD, et al. The association of perioperative red blood cell transfusions and decreased long-term survival after cardiac surgery. Anesthesia Analgesia 2009;108:1741-6.
  34. Swaminathan M, et al. The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery. Ann Thorac Surg 2003; 76:784-792.
  35. Tsui AK, et al. Reassessing the risk of hemodilutional anemia: Some new pieces to an old puzzle. Canadian J Anaesthesia 2010 Aug;57(8):779-91.
  36. Villanueva C,. Transfusion strategies for acute upper gastrointestinal bleeding.N Engl J Med. 2013 Jan 3;368(1):11-21.
  37. Vincent JL, et al. Anemia and blood transfusion in critically ill patients. JAMA 2002; 288: 1499-1507.