Clinical practice guideline: Red blood cell transfusion in adult trauma and critical care*

Objective: To develop a clinical practice guideline for red blood cell transfusion in adult trauma and critical care. Design: Meetings, teleconferences and electronic-based communication to achieve grading of the published evidence, discussion and consensus among the entire committee members. Methods: This practice management guideline was developed by a joint taskforce of EAST (Eastern Association for Surgery of Trauma) and the American College of Critical Care Medicine (ACCM) of the Society of Critical Care Medicine (SCCM). We performed a comprehensive literature review of the topic and graded the evidence using scientific assessment methods employed by the Canadian and U.S. Preventive Task Force (Grading of Evidence, Class I, II, III; Grading of Recommendations, Level I, II, III). A list of guideline recommendations was compiled by the members of the guidelines committees for the two societies. Following an extensive review process by external reviewers, the final guideline manuscript was reviewed and approved by the EAST Board of Directors, the Board of Regents of the ACCM and the Council of SCCM. Results: Key recommendations are listed by category, including (A) Indications for RBC transfusion in the general critically ill patient; (B) RBC transfusion in sepsis; (C) RBC transfusion in patients at risk for or with acute lung injury and acute respiratory distress syndrome; (D) RBC transfusion in patients with neurologic injury and diseases; (E) RBC transfusion risks; (F) Alternatives to RBC transfusion; and (G) Strategies to reduce RBC transfusion. Conclusions: Evidence-based recommendations regarding the use of RBC transfusion in adult trauma and critical care will provide important information to critical care practitioners.

[1]  J. Vincent,et al.  Time course of hemoglobin concentrations in nonbleeding intensive care unit patients , 2003, Critical care medicine.

[2]  R. Fowler,et al.  Blood conservation for critically ill patients. , 2004, Critical care clinics.

[3]  G. Rubenfeld,et al.  Acute lung injury in patients with subarachnoid hemorrhage: Incidence, risk factors, and outcome , 2006, Critical care medicine.

[4]  U. Sachs,et al.  The pathogenesis of transfusion‐related acute lung injury (TRALI) , 2007, British journal of haematology.

[5]  A. Cayuela,et al.  Transfusion of erythrocyte concentrates produces a variable increment on cerebral oxygenation in patients with severe traumatic brain injury , 2006, Intensive Care Medicine.

[6]  Tzong-Hae Lee,et al.  Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients. , 1999, Blood.

[7]  J. Boldt,et al.  The influence of allogeneic red blood cell transfusion compared with 100% oxygen ventilation on systemic oxygen transport and skeletal muscle oxygen tension after cardiac surgery. , 2004, Anesthesia and analgesia.

[8]  H. Baker,et al.  Stored Packed Red Blood Cell Transfusion Up-regulates Inflammatory Gene Expression in Circulating Leukocytes , 2007, Annals of surgery.

[9]  J. Lorente,et al.  Effects of blood transfusion on oxygen transport variables in severe sepsis , 1993, Critical care medicine.

[10]  E. Moore,et al.  Blood transfusion and the two-insult model of post-injury multiple organ failure. , 2001, Shock.

[11]  J. Zimmerman Use of blood products in sepsis: An evidence-based review , 2004, Critical care medicine.

[12]  K. Sihler,et al.  Anemia of Inflammation in Critically Ill Patients , 2008, Journal of intensive care medicine.

[13]  A. Paterson,et al.  The association of biologically active lipids with the development of transfusion‐related acute lung injury: a retrospective study , 1997, Transfusion.

[14]  R. Weiskopf,et al.  Critical Oxygen Delivery in Conscious Humans Is Less Than 7.3 ml O2 · kg−1 · min−1 , 2000, Anesthesiology.

[15]  P. L. Le Roux,et al.  Packed red blood cell transfusion increases local cerebral oxygenation* , 2005, Critical care medicine.

[16]  R. Gamelli,et al.  Effect of blood transfusion on outcome after major burn injury: A multicenter study* , 2006, Critical care medicine.

[17]  R. Gamelli,et al.  Effect of blood transfusion on outcome after major burn injury: A multicenter study , 2007 .

[18]  S. Vaslef,et al.  Massive transfusion exceeding 50 units of blood products in trauma patients. , 2002, The Journal of trauma.

[19]  C. McCollum,et al.  Cost-effectiveness of cell salvage and alternative methods of minimising perioperative allogeneic blood transfusion: a systematic review and economic model. , 2006, Health technology assessment.

[20]  T. Babineau,et al.  Reevaluation of current transfusion practices in patients in surgical intensive care units. , 1992, American journal of surgery.

[21]  M. Yaffe,et al.  Proteomics and systems biology approaches to signal transduction in sepsis. , 2003, Critical care medicine.

[22]  E. Moore,et al.  Plasma from aged stored red blood cells delays neutrophil apoptosis and primes for cytotoxicity: abrogation by poststorage washing but not prestorage leukoreduction. , 2001, The Journal of trauma.

[23]  E. Nemeth Iron regulation and erythropoiesis , 2008, Current opinion in hematology.

[24]  R. Giugliano,et al.  Association of Hemoglobin Levels With Clinical Outcomes in Acute Coronary Syndromes , 2005, Circulation.

[25]  P. T. Phang,et al.  Oxygen consumption is independent of changes in oxygen delivery in severe adult respiratory distress syndrome. , 1991, The American review of respiratory disease.

[26]  J. Minei,et al.  Inflammation and the host response to injury, a large-scale collaborative project: patient-oriented research core-standard operating procedures for clinical care: VI. Blood glucose control in the critically ill trauma patient. , 2007, The Journal of trauma.

[27]  J. Minei,et al.  Inflammation and the host response to injury, a large-scale collaborative project: Patient-oriented research core-standard operating procedures for clinical care. IV. Guidelines for transfusion in the trauma patient. , 2006, The Journal of trauma.

[28]  M. Alberts,et al.  Higher Hemoglobin is Associated with Less Cerebral Infarction, Poor Outcome, and Death after Subarachnoid Hemorrhage , 2006, Neurosurgery.

[29]  M. Kollef,et al.  Red blood cell transfusion and ventilator-associated pneumonia: A potential link? , 2004, Critical care medicine.

[30]  E. Moore,et al.  TRANSFUSION OF THE INJURED PATIENT: PROCEED WITH CAUTION , 2004, Shock.

[31]  M. Haupt,et al.  The effect of fluid loading, blood transfusion, and catecholamine infusion on oxygen delivery and consumption in patients with sepsis. , 1986, The American review of respiratory disease.

[32]  J. Dunne,et al.  Allogenic blood transfusion in the first 24 hours after trauma is associated with increased systemic inflammatory response syndrome (SIRS) and death. , 2004, Surgical infections.

[33]  T. Fabian,et al.  Improved survival of critically ill trauma patients treated with recombinant human erythropoietin. , 2008, The Journal of trauma.

[34]  R. Bynoe,et al.  Thrombosis of the portal venous system after splenectomy for trauma. , 2003, The Journal of trauma.

[35]  D. R. Gerber,et al.  Are Blood Transfusions Associated with Greater Mortality Rates? Results of the Sepsis Occurrence in Acutely Ill Patients Study , 2009 .

[36]  T. Walsh,et al.  Anaemia during critical illness. , 2006, British journal of anaesthesia.

[37]  H. Klein,et al.  The hazards of blood transfusion in historical perspective. , 2008, Blood.

[38]  L. Pearce,et al.  HBOC-201 vasoactivity in a phase III clinical trial in orthopedic surgery subjects--extrapolation of potential risk for acute trauma trials. , 2009, The Journal of trauma.

[39]  G. Rubenfeld,et al.  Effects of leukoreduced blood on acute lung injury after trauma: A randomized controlled trial* , 2008, Critical care medicine.

[40]  R. Gamelli,et al.  EFFECT OF TRANSFUSION ON OXYGEN TRANSPORT IN CRITICALLY ILL PATIENTS , 1996, Shock.

[41]  T. Wobbes,et al.  Transfusion of red cells is associated with increased incidence of bacterial infection after colorectal surgery: a prospective study , 1997, Transfusion.

[42]  R. Califf,et al.  International variation in the use of blood transfusion in patients with non-ST-segment elevation acute coronary syndromes. , 2008, The American journal of cardiology.

[43]  J. Dale,et al.  Specimen collection volumes for laboratory tests. , 2009, Archives of pathology & laboratory medicine.

[44]  R. Prescott,et al.  Does the storage time of transfused red blood cells influence regional or global indexes of tissue oxygenation in anemic critically ill patients?* , 2004, Critical care medicine.

[45]  M. Levy,et al.  A descriptive evaluation of transfusion practices in patients receiving mechanical ventilation. , 2005, Chest.

[46]  A. Sauaia,et al.  Early predictors of postinjury multiple organ failure. , 1994, Archives of surgery.

[47]  T. Fabian,et al.  Human polymerized hemoglobin for the treatment of hemorrhagic shock when blood is unavailable: the USA multicenter trial. , 2009, Journal of the American College of Surgeons.

[48]  V. Lawrence,et al.  Perioperative blood transfusion and postoperative mortality. , 1998, JAMA.

[49]  D. Christiani,et al.  Clinical predictors of and mortality in acute respiratory distress syndrome: Potential role of red cell transfusion* , 2005, Critical care medicine.

[50]  Sunil V. Rao,et al.  Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes. , 2004, JAMA.

[51]  H. Silverman,et al.  Gastric tonometry in patients with sepsis. Effects of dobutamine infusions and packed red blood cell transfusions. , 1992, Chest.

[52]  T. Ryan,et al.  Perioperative predictors of extubation failure and the effect on clinical outcome after cardiac surgery. , 1999, Critical care medicine.

[53]  J. Cade,et al.  Blood Usage in an Australian Intensive Care Unit: Have We Met Best Practice Goals? , 2004, Anaesthesia and intensive care.

[54]  Robert W. Taylor,et al.  Impact of allogenic packed red blood cell transfusion on nosocomial infection rates in the critically ill patient* , 2002, Critical care medicine.

[55]  M. Levy,et al.  Surviving Sepsis Campaign: International guidelines for management of severe sepsis and septic shock: 2008 , 2007, Intensive Care Medicine.

[56]  A. Nathens,et al.  Leukoreduction of blood transfusions does not diminish transfusion‐associated microchimerism in trauma patients , 2006, Transfusion.

[57]  R. Murray,et al.  Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment. , 2006, Health technology assessment.

[58]  George Wells,et al.  Is a restrictive transfusion strategy safe for resuscitated and critically ill trauma patients? , 2004, The Journal of trauma.

[59]  M. Gutiérrez,et al.  Risk factors for renal dysfunction in the postoperative course of liver transplant , 2004 .

[60]  J. Kramer,et al.  Oxygen Reverses Deficits of Cognitive Function and Memory and Increased Heart Rate Induced by Acute Severe Isovolemic Anemia , 2002, Anesthesiology.

[61]  R. Pickering,et al.  Mechanical methods of reducing blood transfusion in cardiac surgery: randomised controlled trial , 2002, BMJ : British Medical Journal.

[62]  J. Stollings,et al.  Oxygen Therapeutics: Oxygen Delivery Without Blood , 2006, Pharmacotherapy.

[63]  J. Minei,et al.  Allogeneic blood transfusion increases the risk of postoperative bacterial infection: a meta-analysis. , 2002, The Journal of trauma.

[64]  C. Chapman,et al.  Single hospital experience of TRALI , 2003, Transfusion.

[65]  L. Napolitano,et al.  Efficacy of blood transfusion in the critically ill: does age of blood make a difference? , 2004, Critical care medicine.

[66]  J. Minei,et al.  Inflammation and the Host Response to Injury, a large-scale collaborative project: patient-oriented research core--standard operating procedures for clinical care. III. Guidelines for shock resuscitation. , 2006, The Journal of trauma.

[67]  J. Morton,et al.  Association of bacterial infection and red blood cell transfusion after coronary artery bypass surgery. , 2002, The Annals of thoracic surgery.

[68]  D. O'Hare,et al.  Arterial blood sampling practices in intensive care units in England and Wales , 2001, Anaesthesia.

[69]  M. Kollef,et al.  Transfusion practice and blood stream infections in critically ill patients. , 2005, Chest.

[70]  Carolyn Shaffer,et al.  Diagnostic blood loss in mechanically ventilated patients. , 2007, Heart & lung : the journal of critical care.

[71]  M. Levy,et al.  The CRIT Study: Anemia and blood transfusion in the critically ill—Current clinical practice in the United States* , 2004, Critical care medicine.

[72]  K. Mandragos,et al.  Recombinant human erythropoietin therapy in critically ill patients: a dose-response study [ISRCTN48523317] , 2005, Critical care.

[73]  S. Moore,et al.  Diagnostic and pathogenetic considerations in transfusion‐related acute lung injury , 1985, Transfusion.

[74]  H. Krumholz,et al.  Blood transfusion in elderly patients with acute myocardial infarction. , 2001, The New England journal of medicine.

[75]  P. Cabrales,et al.  Microvascular perfusion upon exchange transfusion with stored red blood cells in normovolemic anemic conditions , 2004, Transfusion.

[76]  G. Quesada García,et al.  Risk factors for renal dysfunction in the postoperative course of liver transplant , 2004, Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society.

[77]  A. Meyer,et al.  Blood transfusion is an independent predictor of increased mortality in nonoperatively managed blunt hepatic and splenic injuries. , 2005, The Journal of trauma.

[78]  G. Mostafa,et al.  Age, Blood Transfusion, and Survival after Trauma , 2004, The American surgeon.

[79]  S. Woolf,et al.  Use of epoetin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[80]  E. Vamvakas,et al.  Transfusion and postoperative pneumonia in coronary artery bypass graft surgery: effect of the length of storage of transfused red cells , 1999, Transfusion.

[81]  J. Widness,et al.  Reduction in Red Blood Cell Transfusions Using a Bedside Analyzer in Extremely Low Birth Weight Infants , 2005, Journal of Perinatology.

[82]  T. Fabian,et al.  Efficacy and safety of epoetin alfa in critically ill patients. , 2007, The New England journal of medicine.

[83]  M. Zahid,et al.  Impact of blood transfusions in patients presenting with anemia and suspected acute coronary syndrome. , 2007, The American journal of cardiology.

[84]  M. Corwin,et al.  Efficacy of recombinant human erythropoietin in critically ill patients admitted to a long-term acute care facility: A randomized, double-blind, placebo-controlled trial* , 2006, Critical care medicine.

[85]  J. Bender,et al.  Blood transfusion and oxygen consumption in surgical sepsis , 1991, Critical care medicine.

[86]  J. Stockman Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death: A Meta-analysis , 2010 .

[87]  S. Conrad,et al.  Cardiovascular and metabolic response to red blood cell transfusion in critically ill volume-resuscitated nonsurgical patients. , 1990, Critical care medicine.

[88]  J. Wahr,et al.  The Use of Bovine Hemoglobin Glutamer-250 (Hemopure®) in Surgical Patients: Results of a Multicenter, Randomized, Single-Blinded Trial , 2002, Anesthesia and analgesia.

[89]  A. E. Horvath,et al.  Practice parameter for the use of fresh-frozen plasma, cryoprecipitate, and platelets. Fresh-Frozen Plasma, Cryoprecipitate, and Platelets Administration Practice Guidelines Development Task Force of the College of American Pathologists. , 1994, JAMA.

[90]  P. Offner Age of blood: does it make a difference? , 2004, Critical care.

[91]  D. Stevenson,et al.  Reduction in Red Blood Cell Transfusions Among Preterm Infants: Results of a Randomized Trial With an In-Line Blood Gas and Chemistry Monitor , 2005, Pediatrics.

[92]  B. Toth,et al.  A clinical evaluation of a blood conservation device in medical intensive care unit patients , 1993, Critical care medicine.

[93]  A. Carlson,et al.  Retrospective evaluation of anemia and transfusion in traumatic brain injury. , 2006, The Journal of trauma.

[94]  L. Napolitano Scope of the problem: epidemiology of anemia and use of blood transfusions in critical care , 2004, Critical care.

[95]  J. Doyle,et al.  Anemia, transfusions and hospital outcomes among critically ill patients on prolonged acute mechanical ventilation: a retrospective cohort study , 2008, Critical care.

[96]  G. Murphy,et al.  Safety and efficacy of perioperative cell salvage and autotransfusion after coronary artery bypass grafting: a randomized trial. , 2004, The Annals of thoracic surgery.

[97]  C. Ince,et al.  The impact of storage on red cell function in blood transfusion. , 2007, Best practice & research. Clinical anaesthesiology.

[98]  R. McLeod,et al.  Allogeneic Red Blood Cell Transfusion Is an Independent Risk Factor for the Development of Postoperative Bacterial Infection , 2000, Vox sanguinis.

[99]  J. Vincent,et al.  Anemia and blood transfusion in critically ill patients. , 2002, JAMA.

[100]  E. Schmid,et al.  Factors influencing the individual effects of blood transfusions on oxygen delivery and oxygen consumption* , 1999, Critical care medicine.

[101]  E. Vamvakas Meta-analysis of randomized controlled trials investigating the risk of postoperative infection in association with white blood cell-containing allogeneic blood transfusion: the effects of the type of transfused red blood cell product and surgical setting. , 2002, Transfusion medicine reviews.

[102]  S. Vieira,et al.  Acute lung injury and acute respiratory distress syndrome at the intensive care unit of a general university hospital in Brazil , 2002, Intensive Care Medicine.

[103]  R. Fowler,et al.  Blood conservation in the intensive care unit , 2003, Critical care medicine.

[104]  W. Sibbald,et al.  Effects of storage on efficacy of red cell transfusion: When is it not safe? , 2003, Critical care medicine.

[105]  M. Somerfield,et al.  Use of epoetin and darbepoetin in patients with cancer: 2007 American Society of Hematology/American Society of Clinical Oncology clinical practice guideline update. , 2008, Blood.

[106]  Arthur S Slutsky,et al.  Transfusion requirements in critical care : a pilot study , 1995 .

[107]  E. Moore,et al.  Hemoglobin-Based Oxygen Carriers in Trauma Care: Scientific Rationale for the US Multicenter Prehosptial Trial , 2006, World Journal of Surgery.

[108]  F. Verdú,et al.  [Risks of blood transfusion]. , 1981, Actas urologicas espanolas.

[109]  B. Wiggs,et al.  Increased concentrations of plasma lactate predict pathologic dependence of oxygen consumption on oxygen delivery in patients with adult respiratory distress syndrome , 1990 .

[110]  J. Cade,et al.  The Influence of a Blood Conserving Device on Anaemia in Intensive Care Patients , 2003, Anaesthesia and intensive care.

[111]  W. Knaus,et al.  Evaluating laboratory usage in the intensive care unit: patient and institutional characteristics that influence frequency of blood sampling. , 1997, Critical care medicine.

[112]  S. Brett,et al.  Silent myocardial ischaemia and haemoglobin concentration: a randomized controlled trial of transfusion strategy in lower limb arthroplasty , 2006, Vox sanguinis.

[113]  E. Moore,et al.  Insights from studies of blood substitutes in trauma. , 2005, Shock.

[114]  E. Ivers,et al.  Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock , 2001 .

[115]  Edward Abraham,et al.  Transfusion-related acute lung injury: definition and review. , 2005, Critical care medicine.

[116]  R. Burns,et al.  Autotransfusion utilization in abdominal trauma. , 1997, The American surgeon.

[117]  M. Busch,et al.  Transfusion-associated microchimerism: a new complication of blood transfusions in severely injured patients. , 2007, Seminars in hematology.

[118]  F. Sonnenberg,et al.  Risk of bacterial infection associated with allogeneic blood transfusion among patients undergoing hip fracture repair , 1999, Transfusion.

[119]  D. Coyle,et al.  Clinical outcomes following institution of the Canadian universal leukoreduction program for red blood cell transfusions. , 2003, JAMA.

[120]  S. E. Lucking,et al.  Dependence of oxygen consumption on oxygen delivery in children with hyperdynamic septic shock and how oxygen extraction , 1990, Critical care medicine.

[121]  U. Sachs,et al.  Pulmonary Transfusion Reactions , 2008, Transfusion Medicine and Hemotherapy.

[122]  E. Moore,et al.  The first randomized trial of human polymerized hemoglobin as a blood substitute in acute trauma and emergent surgery. , 1998, Journal of the American College of Surgeons.

[123]  E. Vamvakas,et al.  Deleterious clinical effects of transfusion-associated immunomodulation: fact or fiction? , 2001, Blood.

[124]  M. Silver Anemia in the long-term ventilator-dependent patient with respiratory failure. , 2005, Chest.

[125]  E. Moore,et al.  Increased rate of infection associated with transfusion of old blood after severe injury. , 2002, Archives of surgery.

[126]  G. Wells,et al.  Does transfusion practice affect mortality in critically ill patients? Transfusion Requirements in Critical Care (TRICC) Investigators and the Canadian Critical Care Trials Group. , 1997, American journal of respiratory and critical care medicine.

[127]  S. Leal-Noval,et al.  Transfusion of blood components and postoperative infection in patients undergoing cardiac surgery. , 2001, Chest.

[128]  T L Petty,et al.  Acute respiratory distress in adults. , 1967, Lancet.

[129]  P. Gunter Practice Guidelines for Blood Component Therapy , 1996 .

[130]  D. Triulzi Transfusion-related acute lung injury: an update. , 2006, Hematology. American Society of Hematology. Education Program.

[131]  J. Stubbs Alternatives to blood product transfusion in the critically ill: Erythropoietin , 2006, Critical care medicine.

[132]  M. Lamy,et al.  The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. , 1994, American journal of respiratory and critical care medicine.

[133]  G. Wells,et al.  A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. , 1999, The New England journal of medicine.

[134]  J. Marshall,et al.  Transfusion requirements in critical care. A pilot study. Canadian Critical Care Trials Group. , 1995, JAMA.

[135]  J. Vincent,et al.  Efficacy of allogeneic red blood cell transfusions. , 2007, Best practice & research. Clinical anaesthesiology.

[136]  K. Boffard,et al.  Intraoperative Blood Salvage in Penetrating Abdominal Trauma: a Randomised, Controlled Trial , 2006, World Journal of Surgery.

[137]  H. Corwin The role of erythropoietin therapy in the critically ill. , 2006, Transfusion medicine reviews.

[138]  M. Saeed,et al.  Risk factors for ARDS in patients receiving mechanical ventilation for > 48 h. , 2008, Chest.

[139]  J. Marshall,et al.  Effect of a liberal versus restrictive transfusion strategy on mortality in patients with moderate to severe head injury , 2006, Neurocritical care.

[140]  M. Busch,et al.  Microchimerism in transfused trauma patients is associated with diminished donor-specific lymphocyte response. , 2005, The Journal of trauma.

[141]  Timothy C Fabian,et al.  Acute Respiratory Distress Syndrome in Blunt Trauma: Identification of Independent Risk Factors , 2002, The American surgeon.

[142]  O. Gajic,et al.  Pulmonary edema after transfusion: How to differentiate transfusion-associated circulatory overload from transfusion-related acute lung injury , 2006, Critical care medicine.

[143]  Irwin Gratz,et al.  Polymerized bovine hemoglobin solution as a replacement for allogeneic red blood cell transfusion after cardiac surgery: results of a randomized, double-blind trial. , 2002, The Journal of thoracic and cardiovascular surgery.

[144]  Thomas M Scalea,et al.  Blood transfusion, independent of shock severity, is associated with worse outcome in trauma. , 2003, The Journal of trauma.

[145]  G. Rubenfeld,et al.  THE EFFECTS OF LEUKOREDUCED BLOOD TRANSFUSION ON INFECTION RISK FOLLOWING INJURY: A RANDOMIZED CONTROLLED TRIAL , 2006, Shock.

[146]  O. Gajic,et al.  The accuracy of natriuretic peptides (brain natriuretic peptide and N‐terminal pro‐brain natriuretic) in the differentiation between transfusion‐related acute lung injury and transfusion‐related circulatory overload in the critically ill , 2009, Transfusion.

[147]  E. Vamvakas,et al.  Allogeneic blood transfusion and postoperative duration of mechanical ventilation: effects of red cell supernatant, platelet supernatant, plasma components and total transfused fluid , 2002, Vox sanguinis.

[148]  A. Shorr,et al.  Red blood cell transfusions and the risk of acute respiratory distress syndrome among the critically ill: a cohort study , 2007, Critical care.

[149]  E. Moore,et al.  Clinical utility of human polymerized hemoglobin as a blood substitute after acute trauma and urgent surgery. , 1997, The Journal of trauma.

[150]  Y. Amoateng-Adjepong,et al.  Predictors of extubation outcome in patients who have successfully completed a spontaneous breathing trial. , 2001, Chest.

[151]  D. Köhler,et al.  Blood transfusion and lung function in chronically anemic patients with severe chronic obstructive pulmonary disease. , 1998, Critical care medicine.

[152]  Sibu P Saha,et al.  Perioperative blood transfusion and blood conservation in cardiac surgery: the Society of Thoracic Surgeons and The Society of Cardiovascular Anesthesiologists clinical practice guideline. , 2007, The Annals of thoracic surgery.

[153]  D. Ouellette The impact of anemia in patients with respiratory failure. , 2005, Chest.

[154]  T. Walsh,et al.  Red cell transfusion practice following the transfusion requirements in critical care (TRICC) study: prospective observational cohort study in a large UK intensive care unit , 2003, Vox sanguinis.

[155]  T. Lesnick,et al.  Transfusion‐related acute lung injury and pulmonary edema in critically ill patients: a retrospective study , 2006, Transfusion.

[156]  T. Walsh,et al.  Red cell requirements for intensive care units adhering to evidence‐based transfusion guidelines , 2004, Transfusion.

[157]  J. Vincent,et al.  Pharmacokinetics and pharmacodynamics of once-weekly subcutaneous epoetin alfa in critically ill patients: Results of a randomized, double-blind, placebo-controlled trial* , 2006, Critical care medicine.

[158]  I. Chin-Yee,et al.  WBC reduction reduces storage‐associated RBC adhesion to human vascular endothelial cells under conditions of continuous flow in vitro , 2003, Transfusion.

[159]  Andrew D. Rosenberg,et al.  Practice Guidelines for Blood Component Therapy: A Report by the American Society of Anesthesiologists Task Force on Blood Component Therapy , 1996, Anesthesiology.

[160]  E. Moore,et al.  Age of transfused blood is an independent risk factor for postinjury multiple organ failure. , 1999, American journal of surgery.

[161]  S. Cohn Oxygen therapeutics in trauma and surgery. , 2003, The Journal of trauma.

[162]  W J Sibbald,et al.  Effect of stored-blood transfusion on oxygen delivery in patients with sepsis. , 1993, JAMA.

[163]  Jeffrey S. Young,et al.  Blood Transfusions Correlate with Infections in Trauma Patients in a Dose-Dependent Manner , 2002, The American surgeon.

[164]  O. Habler,et al.  Hyperoxic Ventilation in Critical Dilutional Anemia: Intestinal O2Transport and Tissue Oxygenation , 2004 .

[165]  M. Busch,et al.  Blood transfusion is associated with donor leukocyte microchimerism in trauma patients. , 2004, The Journal of trauma.

[166]  Sunil V. Rao,et al.  The implications of blood transfusions for patients with non-ST-segment elevation acute coronary syndromes: results from the CRUSADE National Quality Improvement Initiative. , 2005, Journal of the American College of Cardiology.

[167]  P. Marik,et al.  Gastric intramucosal pH changes after volume replacement with hydroxyethyl starch or crystalloid in patients undergoing elective abdominal aortic aneurysm repair. , 1997, Journal of critical care.

[168]  R. Skeate,et al.  Distinguishing between transfusion related acute lung injury and transfusion associated circulatory overload , 2007, Current opinion in hematology.

[169]  H. Doughty,et al.  A study of blood loss from phlebotomy in renal medical inpatients , 2009, Transfusion medicine.

[170]  D. Fergusson,et al.  Transfusion of leukoreduced red blood cells may decrease postoperative infections: two meta-analyses of randomized controlled trials , 2004, Canadian journal of anaesthesia = Journal canadien d'anesthesie.

[171]  Robert W. Taylor,et al.  Red blood cell transfusions and nosocomial infections in critically ill patients* , 2006, Critical care medicine.

[172]  M. Muñoz,et al.  Documento «Sevilla» de Consenso sobre Alternativas a la Transfusión de Sangre Alogénica , 2006 .

[173]  D. Fuchs,et al.  Erythropoietin response is blunted in critically ill patients. , 1997, Intensive care medicine.

[174]  B. Riou,et al.  Intraoperative autologous transfusion in emergency surgery for spine trauma. , 1994, The Journal of trauma.

[175]  A. Sauaia,et al.  Blood Transfusion: An Independent Risk Factor for Postinjury Multiple Organ Failure , 1997 .

[176]  D. Demetriades,et al.  Blood transfusion in critically injured patients: a prospective study. , 2006, Injury.

[177]  M. Levy,et al.  Anemia and blood transfusion in trauma patients admitted to the intensive care unit. , 2003, The Journal of trauma.

[178]  S. Conrad,et al.  Effect of red cell transfusion on oxygen consumption following fluid resuscitation in septic shock. , 1990, Circulatory shock.

[179]  J. Montaner,et al.  Pathologic dependence of oxygen consumption on oxygen delivery in acute respiratory failure secondary to AIDS-related Pneumocystis carinii pneumonia. , 1990, Chest.

[180]  Perioperative Blood Transfusion and Postoperative Mortality , 1998 .

[181]  R. Winslow,et al.  Current status of oxygen carriers (‘blood substitutes’): 2006 , 2006, Vox sanguinis.

[182]  E. Vamvakas Possible mechanisms of allogeneic blood transfusion-associated postoperative infection. , 2002, Transfusion medicine reviews.

[183]  Denise Rossato Silva,et al.  Acute lung injury and acute respiratory distress syndrome at the intensive care unit of a general university hospital in Brazil. An epidemiological study using the American-European Consensus Criteria. , 2002, Intensive care medicine.

[184]  Sunil V. Rao,et al.  Transfusion practice and outcomes in non-ST-segment elevation acute coronary syndromes. , 2008, American heart journal.

[185]  T. Petty,et al.  Ashbaugh DG, Bigelow DB, Petty TL, Levine BE. Acute respiratory distress in adults. The Lancet, Saturday 12 August 1967. , 2005, Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine.

[186]  K. Langa,et al.  Allogeneic blood transfusions explain increased mortality in women after coronary artery bypass graft surgery. , 2006, American heart journal.

[187]  H. Winn,et al.  Blood transfusion and increased risk for vasospasm and poor outcome after subarachnoid hemorrhage. , 2004, Journal of neurosurgery.

[188]  A. Shorr,et al.  Transfusion practice and nosocomial infection: assessing the evidence , 2005, Current opinion in critical care.

[189]  W. Howland,et al.  Hemodynamic oxygen transport and 2,3-diphosphoglycerate changes after transfusion of patients in acute respiratory failure , 2004, Intensive Care Medicine.

[190]  Robert A Levine,et al.  Geometric Determinants of Functional Tricuspid Regurgitation: Insights From 3-Dimensional Echocardiography , 2006, Circulation.

[191]  A. Casbard,et al.  The impact of universal leukodepletion of the blood supply on hemovigilance reports of posttransfusion purpura and transfusion‐associated graft‐versus‐host disease , 2007, Transfusion.

[192]  Andrew D. Rosenberg,et al.  Practice guidelines for perioperative blood transfusion and adjuvant therapies: An updated report by the American Society of Anesthesiologists Task Force on perioperative blood transfusion and adjuvant therapies , 2006 .

[193]  Anemia and blood transfusion in the critically ill , 2011 .

[194]  A. Nathens Massive transfusion as a risk factor for acute lung injury: association or causation? , 2006, Critical care medicine.

[195]  K. Eckardt,et al.  Important role of nondiagnostic blood loss and blunted erythropoietic response in the anemia of medical intensive care patients* , 1999, Critical care medicine.

[196]  P. Barie,et al.  Diagnosis and management of iron-related anemias in critical illness , 2006, Critical care medicine.

[197]  W. Sibbald,et al.  Transfusing red blood cells stored in citrate phosphate dextrose adenine-1 for 28 days fails to improve tissue oxygenation in rats. , 1997, Critical care medicine.

[198]  Vladimir Cerny,et al.  Correction: Management of bleeding following major trauma: a European guideline , 2007, Critical care.

[199]  L. Napolitano Hemoglobin-based oxygen carriers: first, second or third generation? Human or bovine? Where are we now? , 2009, Critical care clinics.

[200]  L. Napolitano,et al.  Efficacy of red blood cell transfusion in the critically ill. , 2004, Critical care clinics.

[201]  G. LaMuraglia,et al.  The reduction of the allogenic transfusion requirement in aortic surgery with a hemoglobin-based solution. , 2000, Journal of vascular surgery.

[202]  T. Walsh,et al.  Prevalence of ischaemic heart disease at admission to intensive care and its influence on red cell transfusion thresholds: multicentre Scottish Study. , 2005, British journal of anaesthesia.

[203]  B. Smoller,et al.  Phlebotomy for diagnostic laboratory tests in adults. Pattern of use and effect on transfusion requirements. , 1986, The New England journal of medicine.

[204]  P. Keegan,et al.  Continuing Reassessment of the Risks of Erythropoiesis-Stimulating Agents in Patients with Cancer , 2008, Clinical Cancer Research.

[205]  J. Marshall,et al.  Is a low transfusion threshold safe in critically ill patients with cardiovascular diseases? , 2001, Critical care medicine.

[206]  G. Foulke,et al.  Effective measures for reducing blood loss from diagnostic laboratory tests in intensive care unit patients. , 1989, Critical care medicine.

[207]  C. Sprung,et al.  Are Blood Transfusions Associated with Greater Mortality Rates?: Results of the Sepsis Occurrence in Acutely Ill Patients Study , 2008, Anesthesiology.

[208]  M. Bueter,et al.  Transfusion-related acute lung injury (TRALI)—an important, severe transfusion-related complication , 2006, Langenbeck's Archives of Surgery.

[209]  E. Vamvakas,et al.  Transfusion‐associated cancer recurrence and postoperative infection: meta‐analysis of randomized, controlled clinical trials , 1996, Transfusion.

[210]  M. Corwin,et al.  Nutritional deficiencies and blunted erythropoietin response as causes of the anemia of critical illness. , 2001, Journal of critical care.

[211]  G. Horowitz,et al.  Reducing adult phlebotomy blood loss with the use of pediatric-sized blood collection tubes. , 1989, American journal of clinical pathology.

[212]  Liang Li,et al.  Morbidity and mortality risk associated with red blood cell and blood-component transfusion in isolated coronary artery bypass grafting* , 2006, Critical care medicine.

[213]  R. Groom,et al.  Intraoperative Red Blood Cell Transfusion During Coronary Artery Bypass Graft Surgery Increases the Risk of Postoperative Low-Output Heart Failure , 2006, Circulation.

[214]  E. Knobel,et al.  Red blood cell transfusion does not increase oxygen consumption in critically ill septic patients , 2001, Critical care.

[215]  K. Gubler,et al.  Efficacy of recombinant human erythropoietin in the critically ill patient: A randomized, double-blind, placebo-controlled trial* , 2001, Critical care medicine.

[216]  J. Paramo,et al.  Spanish consensus statement on alternatives to allogeneic transfusions: the 'Seville document' , 2006 .

[217]  C. Silliman,et al.  Transfusion-related acute lung injury: epidemiology and a prospective analysis of etiologic factors. , 2003, Blood.

[218]  D. Annane,et al.  Practice parameters for hemodynamic support of sepsis in adult patients: 2004 update , 2004, Critical care medicine.

[219]  L. Napolitano Current status of blood component therapy in surgical critical care , 2004, Current opinion in critical care.

[220]  Jan O Friedrich,et al.  Anemia, transfusion, and phlebotomy practices in critically ill patients with prolonged ICU length of stay: a cohort study , 2006, Critical care.

[221]  J. Berlin,et al.  Effect of anaemia and cardiovascular disease on surgical mortality and morbidity , 1996, The Lancet.

[222]  G. Martin,et al.  The role of acute blood transfusion in the development of acute respiratory distress syndrome in patients with severe trauma. , 2005, The Journal of trauma.

[223]  S. Dzik,et al.  Clinical and molecular basis of transfusion-induced immunomodulation: summary of the proceedings of a state-of-the-art conference. , 2001, Transfusion medicine reviews.

[224]  M. Popovsky Pulmonary consequences of transfusion: TRALI and TACO. , 2006, Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis.

[225]  E. Moore,et al.  Stored red blood cells selectively activate human neutrophils to release IL-8 and secretory PLA2. , 2000, Shock.

[226]  D. Stoltzfus,et al.  The effect of arterial lines on blood-drawing practices and costs in intensive care units. , 1995, Chest.

[227]  L. Napolitano Cumulative risks of early red blood cell transfusion. , 2006, The Journal of trauma.

[228]  S. Brett,et al.  Blood component use in critically ill patients , 2002, Anaesthesia.

[229]  R. Weiskopf,et al.  Acute Severe Isovolemic Anemia Impairs Cognitive Function and Memory in Humans , 2000, Anesthesiology.

[230]  P. Holland,et al.  Transfusion-related acute lung injury: report of a clinical look-back investigation. , 2002, JAMA.

[231]  F. Machado,et al.  EVALUATION OF BLOOD TRANSFUSION EFFECTS ON MIXED VENOUS OXYGEN SATURATION AND LACTATE LEVELS IN PATIENTS WITH SIRS / SEPSIS , 2005 .

[232]  P. Holland,et al.  Noninfectious serious hazards of transfusion. , 2002, Current hematology reports.

[233]  C. Bekes Efficacy of recombinant human erythropoietin in critically ill patients admitted to a long-term acute care facility: A randomized, double-blind, placebo-controlled trial , 2008 .

[234]  E. Moore,et al.  The life-sustaining capacity of human polymerized hemoglobin when red cells might be unavailable. , 2002, Journal of the American College of Surgeons.

[235]  M. Levy,et al.  Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. , 2002, JAMA.

[236]  M. Pollack,et al.  Effect of blood transfusion on oxygen consumption in pediatric septic shock. , 1990, Critical care medicine.

[237]  T. Fabian,et al.  Transfusions result in pulmonary morbidity and death after a moderate degree of injury. , 2005, The Journal of trauma.

[238]  K. Sosnowski,et al.  Highly Conservative Phlebotomy in Adult Intensive Care— A Prospective Randomized Controlled Trial , 2006, Anaesthesia and intensive care.

[239]  D. Cook,et al.  Do blood transfusions improve outcomes related to mechanical ventilation? , 2001, Chest.

[240]  R. McLeod,et al.  Allogeneic Red Blood Cell Transfusion Is an Independent Risk Factor for the Development of Postoperative Bacterial Infection , 2000, Vox Sanguinis.

[241]  D. Fergusson,et al.  Clinical consequences of red cell storage in the critically ill , 2006, Transfusion.

[242]  M. Aminoff,et al.  Acute isovolemic anemia impairs central processing as determined by P300 latency , 2005, Clinical Neurophysiology.

[243]  P. Marik,et al.  Efficacy of red blood cell transfusion in the critically ill: A systematic review of the literature* , 2008, Critical care medicine.

[244]  W. Markiewicz,et al.  Impact of red blood cell transfusion on clinical outcomes in patients with acute myocardial infarction. , 2008, The American journal of cardiology.

[245]  A. Sauaia,et al.  A 12-year prospective study of postinjury multiple organ failure: has anything changed? , 2005, Archives of surgery.

[246]  Stephen M Cohn,et al.  Predictors of Mortality in Trauma Patients , 2004, The American surgeon.

[247]  T. Ganz,et al.  Iron imports. IV. Hepcidin and regulation of body iron metabolism. , 2006, American journal of physiology. Gastrointestinal and liver physiology.

[248]  P. Barie,et al.  Failure of red blood cell transfusion to increase oxygen transport or mixed venous PO2 in injured patients. , 1982, The Journal of trauma.

[249]  S. Leal-Noval,et al.  Influence of Erythrocyte Concentrate Storage Time on Postsurgical Morbidity in Cardiac Surgery Patients , 2003, Anesthesiology.

[250]  S. Timmons The life-saving properties of blood Mitigating cerebral insult after traumatic brain injury , 2006, Neurocritical care.