Update on Transfusion Practice Where’s the Evidence? Connie Lorette Calvin, PhD, CRNA, APRN Northeastern University History • Richard Lower (1631-1691) – Performed the first transfusion (animal to animal) in 1665 – Lamb to human 1667 • 1667 Jean Baptist Denis – Lambs blood – Calves blood • 1774 – – Lavoisier - Role of oxygen in respiration – Priestley – RBC as oxygen carriers • 1818 - first human to human transfusion – James Blundell Karl Landsteiner 1930 Nobel Prize Laureate • 1900 – Landsteiner – A-B-O • 1902– Sturli & DeCastello – AB • 1940-Landsteiner – Rh typing Lewisohn’s Method of Transfusion 1913 Blood is collected in a citrated flask….…...and immediately transfused. Enculturation of Transfusion • Blood is a “life giving force” • 1-800-save a life 1971 - 1987 • Red cell transfusion more than doubled • Platelet transfusion grew 50 fold • Risk of hepatitis transmission was approximately 1/100 U transfused • HIV / AIDS • Is transfusion beneficial Transfusion Trigger • • • • Hemoglobin 10gm/dl Hematocrit 30% Blood loss of 15% of circulating blood volume Clinical presentation • Risk:Benefits “Safest Blood” • Voluntary blood donation – self exclusion • Surrogate tests • NAT • Does transfusion of banked blood improve outcome for patients? Infectious Risk of Transfusion Pathogen Estimate Risk Per Unit Hepatitis A Unknown - <1:1million Hepatitis B 1 : 277,000 Hepatitis C 1 : 1,930,000 HIV - 1 1 : 2,135,000 HTLV -I, II 1 : 2,993,000 CMV Infrequent in leukocyte reduced components West Nile 1 : 350,000 Infectious Risk of Transfusion Pathogen Estimated Risk Per Unit Bacterial contamination 1:5 million RBC 1:100,000 per apheresis or pooled platelet unit Malaria < 1:1 million Babesia < 1:1 million regional Chagas Disease Unknown presumably < 1:1 million Variant Creutzfeldt-Jacob Disease 3 reported case in UK Troublesome Events! • Alloimmunization (platelets – Leukocytes - RBC) • HLA – antigens – Granulocyte – platelet – RBC specific • Allergic reactions • Febrile reactions • ABT – related mortality – TRALI – TAS – HTRs – TTI • What are the costs of these? Mean annual # of ABT related deaths from 3 leading causes Eleftherios et al., 2010 TRALI -Transfusion Related Acute Lung Injury • All plasma containing blood products • Non-cardiogenic pulmonary edema – 1-2 hours post-transfusion – Dyspnea -cough - fever • Misdiagnosed - TACO – Volume overload – Cardiogenic pulmonary edema • Multiparous donors – HLA sensitization Hemolytic Transfusion Reactions • ABO – ABO antigens and/or antibodies to other RBC antigens. • Acute = 24 hours • Delayed > 24 hours • Non-ABO – RBC antibodies • Jkb, Jka, Kell, Fya, Fyb, E, Jsa, I Eleftherios et al., 2010 Percent of HTR deaths ABO versus Non-ABO Transfusion Associated Sepsis • Bacterial contamination • Platelets – highest – Decreased with single-donor • Organisms – – – – Staphylococcus epidermidis E-coli Staphylococcus aureus Bacillus cereus Transfusion Related Immunomodulation - TRIM • APCs and plasma – – – – – Non-specific immunosuppression Antigen-specific immunosuppression Impaired T-cell mediated immunity Decreased macrophage Altered cytokine • Renal allografts – better outcomes • Tumor recurrence • Reduction in survival – WBCs – HLA – CD4 – Helper T-cell Leukocyte Reduction • Non-hemolytic transfusion reactions • CMV transmission • HLA alloimmunization • Capraro et al. – Infection rate – 90-day mortality – Length of ICU stay Benefits??? Oxygen Transports • Blood flow - CO • Arterial O2 content – DO2 = CO X CaO2 • Transportation – Hemoglobin – Plasma – DO2 = CO X (%Sat X 1.39 X [Hb]) Impact of Anemia • CRIT • NNE – Lowest hct on bypass = increased mortality and incidence of heart failure – However blood transfusions = increased need for mechanical and inotropic support • Nadir hgb following MI predicts mortality – Aronson et al. 2007 Adaption to Anemia • Shift in oxyhemoglobin dissociation curve – Right - synthesis 2,3-DPG • Hemodynamic alterations – CO • Microcirculatory alterations – Vascular tone • Renin-angiotensin-aldosterone system Impact of Preop Anemia on Postop Adverse Events • Cardiac surgical patients n=5065 • Low preop hgb = Comorbidities = adverse cardiac events • Anemia = adverse postop neurologic and renal outcomes – Kulier et al. 2007 • Preoperative anemia and intraoperative blood transfusion were both independent risk factors for adverse outcomes. • Incidence increased significantly as a function of numbers of units of RBCs transfused Efficacy of RBC transfusion • DO2 and utilization = improved outcomes • Delivery - Stored RBC – Low p50 – shift oxygen dissociation curve – left – Depletion 2,3, DPG – Depletion ATP • Oxygen utilization – Organ level – Hemodynamics and oxygen transport parameters Anemia and Transfusion • Anemia predicts adverse outcomes • Current transfusion practice provides no benefit or is harmful • Ischemic complications were not decreased with blood transfusion – Murphy et al. 2007 • Patients who received blood that was stored for more than 2 weeks prior to transfusion had a statistically significant increase in in-hospital mortality, prolonged intubation, renal failure and sepsis or septicemia – Koch 2007 Storage Lesions Biochemical Changes • • • • • • • • • Lactate = 1.6 - 30.1 mmol/L pH = 7.2 - 6.6 2,3-DPG ATP GSH K+ = 3.9 - 78 mEq/L SNO-Hb Ionized Calcium and magnesium = 0 Free Hemoglobin Regulation of microvascular perfusion mediated by Hemoglobin + NO Low pO2 Release Low pH ATP Storage Lesions Biomechanical • • • • • Hemolysis Membrane area Osmotic fragility RBC adhesion Deformability Storage Lesions Oxidative • • • • Hemoglobin oxidation Hemoglobin denaturation Lipid peroxidation Bioactive Substance – – – – Cytokines Histamines Lipids Soluble HLA Storage • Morphologic • Biochemical • Storage duration – – – – – – Increased mortality Increased length of stay in ICU/Hospital Multiple organ failure TRALI Increased infections Impaired tissue oxygen utilization Benefits • Hemorrhagic shock • Critically ill do not tolerate anemia • Goal – Increase DO2 – Increase VO2 Efficacy of RBC Transfusion in the Critically Ill • RBC transfusion did not improve VO2 • RBC transfusion was not associated with improvements in clinical outcomes • RBC transfusion was associated with worse outcomes • Factors to identify patients who may benefit • Lack of efficacy related to – – – – – Adherence of stored RBCs Nitric Oxide binding Donor leukocytes Inflammatory response Decreased red cell deformability Large Randomized Controlled Trials • Restrictive strategies vs. liberal strategies – Carson et al. 1996 • No data demonstrating that allogeneic RBCs increase oxygen carrying capacity – Hebert et al. 1997 • Mortality rate was doubled for patients receiving perioperative transfusion – Engoren et al. 2002 • The number of RBC units transfused is an independent predictor of worse clinical outcome – Corwin et al. 2004 – Corwin et al. 2007 Transfusion (1-2 U) Does Not Increase Oxygen Delivery!! • The influence of allogeneic RBC transfusion compared with 100% oxygen ventilation on systemic oxygen transport and skeletal muscle oxygen tension after cardiac surgery • O2 - not the blood transfusion increased tissue oxygen levels Suttner et al. (2004) anesth analg 99: 2-11 Rejuvenation • Post-storage metabolic manipulations • Mixture of pyruvate – inosine – phosphate – adenine – Rejuvesol (Cytosol Laboratory Inc) • 37°C incubation followed by cell washing [24] • Restored ATP • Elevated 2,3-DPG Goals • Reduce hemolysis • Reduce dead-on-arrival RBC – Iron toxicity – Vasoconstriction via NO scavenging • Maintain deformability / prevent aggregation – Prevent capillary blockage • Maintenance of high ATP – 2,3, DPG – SNO-hb • Minimize oxidative damage • Prevent release, and/or remove bio-active substances – Prevention of TRALI • Leukoreduction, irradiation, pathogen-reduction, etc. Hemoglobin Solutions • Limited duration of action • Half life 10 - 30 minutes • High colloidal osmotic pressure – 7 g/dL • Vasoactive properties • Oxygen affinity • Dissociation into dimers Acute Normovolemic Hemodilution • Conserved RBC Mass • Improved Oxygenation • Preservation of Hemostasis Other Autologous Transfusions • Intraoperative blood collection – Cell saver – shed blood • Postoperative blood collection – Shed blood Recombinant Factor VIIa • Approved for hemophilia patients • Enhances thrombin generation on activated platelets • Cost – exorbitant $15,000.00 • Thrombotic complications DDAVP • • • • Dose: 0.3 mcg/kg over ½ hour Release of factor VIII and vWF Enhances platelet adhesion to the vessel wall Shortens the prolonged aPTT and bleeding time Conclusion • Benefits of transfusion are theoretical • Risks of transfusion are fact • Transfusion of allogeneic blood represents a major risk for immunosuppression and adverse outcome • Transfusion must be considered carefully • Accept lower transfusion thresholds • Alternatives to RBC transfusion References Spiess BD. 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