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ICU Cornerstone: Changing our view of blood transfusions
Critical Care volume 6, Article number: 291 (2002)
Blood transfusions are commonly administered to critically ill patients, but deciding when to transfuse a particular patient is often difficult and necessitates careful consideration of both the potential benefits and risks. This commentary briefly discusses some of the considerations both for and against blood transfusion in the setting of critical illness and reviews a landmark clinical trial in this area. Finally, we reflect on the changes in attitudes towards the transfusion of blood and blood products that have taken place over the last 20 years.
Blood transfusions have long been a common component of the therapy of critically ill patients, yet knowing when a particular patient will benefit from a transfusion has not always been clear . Until recently, the 'optimal' hemoglobin concentration in critically ill patients was empirically set at 10 g/dl, and most patients in critical care units received transfusions during their stay in the unit [2,3]. There was no evidence from clinical trials to support this practice, but some studies had demonstrated a pathologic dependence of oxygen consumption (VO2) on oxygen delivery (DO2) in conditions like sepsis and acute respiratory distress syndrome . These observations spawned the hope that increasing DO2 might improve tissue oxygenation and ultimately decrease mortality. Most of the clinical trials that attempted to increase DO2 did so using inotropes or vasoactive drugs, and demonstrated no benefit in clinical outcomes [5,6]. In both the experimental and control groups of these studies, hemoglobin was maintained at 10 g/dl (or hematocrit >0.30), reflecting the widely accepted threshold for transfusion at the time. In the few studies that specifically looked at the effect of blood transfusions on oxygen delivery and consumption, blood tended to increase oxygen delivery but not consumption [7,8]. To complicate matters, other investigators suggested that the measurements demonstrating pathologic dependence of oxygen consumption on delivery might in fact be artifactual  as a result of mathematical coupling. There were also concerns about possible immunosuppressive  and microcirculatory  effects of blood transfusions.
Naturally, this uncertainty in the literature about the respective benefits and harms of transfusion spilled over into clinical practice. As recently as the mid-1990s, papers documented strikingly heterogeneous transfusion practices by intensivists and suggested that a high proportion of critically ill patients were apparently being transfused without any clearly predisposing factors [3,11]. This debate led to a landmark investigation into transfusion requirements in critical care [the transfusion requirements in critical care (TRICC) trial], which we believe has brought about a change in practice . This study was a multi-center, randomized, controlled trial in which euvolemic patients in the intensive care unit were randomized to either a restrictive or to a liberal transfusion policy. In the restrictive group, patients were transfused when the hemoglobin level was less than 7.0 g/dl, with a target hemoglobin level of 7.0 to 9.0 g/dl. In the liberal group, transfusions were given when the hemoglobin level was less than 10.0 g/dl, with a target range of 10.0 to 12.0 g/dl. There were a number of exclusion criteria including patients with ongoing bleeding or chronic anemia and patients undergoing cardiac surgery. The study enrolled over 800 patients and demonstrated no difference in 30-day mortality rates between the two groups. In-patient mortality was significantly lower in the restrictive transfusion group, and subgroup analyses in patients <55 years of age or in those with acute physiological and chronic health evaluation (APACHE) II scores ≤ 20 favored the restrictive transfusion strategy. The average number of units of blood transfused was 54% lower in the restrictive group than in the liberal group. The implications of this study were that the classic transfusion threshold of 10 g/dl  was unnecessarily high for many patients in the critical care unit, and that excessive transfusion might be harmful.
Although the results of this trial cannot be generalized to patients with acute coronary syndromes  or to patients specified in the exclusion criteria, the practical effect of this trial has been to lower the transfusion threshold to 7 g/dl for many patients. For those patients with a hemoglobin level above 7 g/dl, this trial has put the onus on clinicians to justify blood transfusion.
Notwithstanding the momentous and influential nature of this study, it is likely that this shift in attitudes towards blood transfusion had its roots earlier and elsewhere. No clinician in practice in the last 20 years could miss the hesitation and frank apprehension in the public consciousness engendered by the widely publicized infectious hazards of the transfusion of blood products. This underlying trepidation, spanning continents and cultures [15,16,17], spurred the careful examination of blood transfusion practices that would culminate in the TRICC trial. Even before the TRICC trial, physicians were becoming more reluctant to transfuse blood; the critical care literature from the mid-1990s demonstrates striking reductions in transfusion use in patients with burns  or trauma . Indeed, if there was any key moment that changed clinical practice, one could argue that it was a simple two-page report that appeared almost 20 years ago in Morbidity and Mortality Weekly Report. Entitled 'Possible transfusion-associated Acquired Immune Deficiency Syndrome (AIDS) – California', the case report  was a harbinger of the transfusion-associated AIDS epidemic. Two decades later, even after significant improvements in the field of transfusion medicine which have made transfusion safer than ever, patients and their physicians will never view transfusion of blood and blood products in quite the same way.
APACHE = acute physiological and chronic health evaluation
DO2 = oxygen delivery
TRICC = transfusion requirements in critical care
VO2 = oxygen consumption.
Cane RD: Hemoglobin: how much is enough? Crit Care Med 1990, 18: 1046-1047.
Czer LSC, Shoemaker WC: Optimal hematocrit value in critically ill postoperative patients. Surg Gynecol Obstet 1978, 147: 363-368.
Corwin HL, Parsonnet KC, Gettinger A: RBC transfusion in the ICU – is there a reason? Chest 1995, 108: 767-771.
Russell JA, Phang PT: The oxygen delivery/consumption controversy–approaches to management of the critically ill. Am J Respir Crit Care Med 1994, 149: 533-537.
Hayes MA, Timmins AC, Yau EHS, Palazzo M, Hinds CJ, Watson D: Elevation of systemic oxygen delivery in the treatment of critically ill patients. N Engl J Med 1994, 330: 1717-1722. 10.1056/NEJM199406163302404
Gattinoni L, Brazzi L, Pelosi P, Latini R, Tognoni G, Pesenti A, Fumagalli R, for the SvO2 Collaborative Group: A trial of goal-oriented hemodynamic therapy in critically ill patients. N Engl J Med 1995, 333: 1025-1032. 10.1056/NEJM199510193331601
Lorente JA, Landin L, De Pablo R, Renes E, Rodriguez-Diaz R, Liste D: Effects of blood transfusion on oxygen transport variables in severe sepsis. Crit Care Med 1993, 21: 1312-1318.
Dietrich KA, Conrad SA, Hebert CA, Levy GL, Romero MD: Cardiovascular and metabolic response to red blood cell transfusion in critically ill volume-resuscitated nonsurgical patients. Crit Care Med 1990, 18: 940-944.
Jenson LS, Anderson AJ, Christiansen PM, Hokland P, Juhl CO, Madsen G: Postoperative infection and natural killer cell function following transfusion in patients undergoing elective colorectal surgery. Br J Surg 1992, 79: 513-516.
Marik PE, Sibbald WJ: Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993, 269: 3024-3029. 10.1001/jama.269.23.3024
Hébert PC, Wells G, Martin C, Tweeddale M, Marshall J, Blajch-man M, Pagliarello G, Schweitzer I, Calder L: A Canadian survey of transfusion practices in critically ill patients. Crit Care Med 1998, 26: 482-487. 10.1097/00003246-199803000-00019
Hébert PC, Wells G, Blajchman MA, Marshall J, Martin C, Pagliarello G, Tweeddale M, Schweitzer I, Yetisir E, and the Transfusion Requirements in Critical Care Investigators for the Canadian Critical Care Trials Group: A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. N Engl J Med 1999, 340: 409-417. 10.1056/NEJM199902113400601
McCrossan L, Masterson G: Blood transfusion in critical illness. Br J Anaesth 2002, 88: 6-9. 10.1093/bja/88.1.6
Hébert PC, Yetisir E, Martin C, Blajchman MA, Wells G, Marshall J, Tweeddale M, Pagliarello G, Schweitzer I, and the 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, 29: 227-234. 10.1097/00003246-200102000-00001
Dorozynski A: Tainted blood affair threatens French Government. Br Med J 1992, 14: 1177.
Watts J: Japanese official found guilty in HIV-blood trial. Lancet 2001, 358: 1166. 10.1016/S0140-6736(01)06317-6
Capen K: Informed consent and blood transfusions: What does Krever's interim report mean to doctors? CMAJ 1995, 152: 1663-1665.
Mann R, Heimbach DM, Engrav LH, Foy H: Changes in transfusion practices in burn patients. J Trauma 1994, 37: 220-222.
Farion KJ, McLellan BA, Boulanger BR, Szalai JP: Changes in red cell transfusion practice among adult trauma victims. J Trauma 1998, 44: 583-587.
CDC: Possible transfusion-associated acquired immune deficiency syndrome (AIDS) – California. MMWR Morb Mortal Wkly Rep 2000, 31: 652-654.
Supported by grants from the Canadian Institutes of Health Research to G. Downey. G. Downey holds the R. Fraser Elliott Chair in Transplantation Research from the Toronto General Hospital of the University Health Network, and a Canada Research Chair in Respiration from the Canadian Institutes of Health Research.
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Lee, W.L., Downey, G.P. ICU Cornerstone: Changing our view of blood transfusions. Crit Care 6, 291 (2002). https://doi.org/10.1186/cc1512
- blood transfusion
- critical care