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Blood Transfusion in ICU

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Blood Transfusion in ICU

  1. 1. BLOOD TRANSFUSION IN ICU By Dr.Sherif Badrawy Critical Care Registrar
  2. 2. HISTORY OF TRANSFUSION • Important dates: • 1665: first recorded transfusion; between dogs • In 1667, blood transfusron from sheep to male • 1795 first human-to-human transfusion • 1901. description of blood groups • World War 1: development of blood banks • 1960s-1970s: methods to separate whole blood, prevent antibody formation, and detect infections
  4. 4. SOME FACTS ABOUT BLOOD TRANSFUSION • Only absolute indication is to increase oxygen delivery to Tissues in anaemic patients- to increase oxygen carrying capacity. • It is a tissue transplantation procedure • Blood should not be used for intravascular volume expansion
  6. 6. FACTORS THAT MAY RESULT IN A PATIENT BEING POTENTIALLY CLOSER TO THE CRITICAL POINT THAN NORMAL •Reduced oxygen delivery. • (a) Decreased cardiac output: (i) Pre-morbid disease e.g.,IHD, valvular heart disease. (ii) Hypovolaemia e.g., increased capillary leak. (iii) Arrhythmias e.g., atrial fibrillation. (iv) Pulmonary embolism. (v) Specific heart muscle disease e.g., systemic inflammatory response syndrome (SIRS) related cardiomyopathy. • (b) Hypoxaemia secondary to acute respiratory failure.- (ALI)/ (ARDS).
  7. 7. FACTORS THAT MAY RESULT IN A PATIENT BEING POTENTIALLY CLOSER TO THE CRITICAL POINT THAN NORMAL Pain, stress, anxiety. Shivering. Fever. Severe infection. Sepsis/(SIRS). Trauma Surgery. Burns. Adrenergic drug infusions. Work of breathing e.g., during weaning. Convulsions. Increased oxygen consumption
  8. 8. Anemia VS blood transfusion in ICU
  9. 9. ✪ Anemia Frequency >60% of ICU patients upon admission 90% of ICU patients by day 3 in ICU 97% of ICU patients by day 8 Thomas J, Jensen L, Nahirniak S, Gibney RT. Anemia and blood transfusion practices in the critically ill: a prospective cohort review. Heart Lung. 2010;39(3):217-225. 3a
  10. 10. ✪ Anemia morbidity and mortality Associated with increased 90-day mortality in patients with chronic obstructive pulmonary disease Associated with adverse outcomes in patients with congestive heart failure, acute myocardial infarction, and chronic kidney disease Rasmussen L, Christensen S, Lenler-Petersen P, Johnsen SP.Anemia and 90-day mortality in COPD patients requiring invasive mechanical ventilation. Clin Epidemiol. 2011;3:1-5. 3b
  11. 11. ✪ Anemia Cost Associated with >twice inpatient costs in patients with chronic conditions Associated with increased length of stay in patients with heart failure Nissenson AR, Wade S, Goodnough T, Knight K, Dubois RW. Economic burden of anemia in an insured population. J Manag Care Pharm. 2005;11(7):565-574. 4a
  12. 12. ❂ Blood transfusion Frequency 20% to 62% of ICU patients receive 1 or more units of blood Taylor RW, O'Brien J, Trottier SJ, et al. Red blood cell transfusions and nosocomial infections in critically ill patients. Crit Care Med. 2006;34(9):2302-2308. 4b
  13. 13. ❂ Blood transfusion morbidity and mortality Associated with as much as a 40% increase in 30-day morbidity Associated with as much as a 38% increase in 30-day mortality Bernard AC, Davenport DL, Chang PK, Vaughan TB, ZwischenbergerJB. Intraoperative transfusion of 1 U to 2 U packed red blood cells is associated with increased 30-day mortality, surgical- site infection, pneumonia, and sepsis in general surgery patients. J Am Coll Surg. 2009;208(5):931-937. a
  14. 14. ❂ Blood transfusion Cost Associated with around 2 day increase in length of stay per transfusion Hill SR, Carless PA, Henry DA, et al. Transfusion thresholds and other strategies for guiding allogeneic red blood cell transfusion. Cochrane Database Syst Rev. 2002(2):CD002042. b
  16. 16. STORAGE DEFECTS AND MICROVASCULAR PERFUSION Decreased 2,3- DPG, ADP,NO Build-up of cytokines, Free Hb, K+, debris Poor deformability Will they improve oxygen content and delivery ? Immune suppression Infections Clinical and animal studies report contradictory findings about the oxygenation capacity of stored RBCs
  17. 17. TRANSFUSION TRIGGER Acceptable hemoglobin concentration Risk of blood transfusion Risk of low hemoglobin
  18. 18. TRANSFUSION “TRIGGER” CONTROVERSY Transfusion trigger: “hemoglobin or hematocrit level below which a blood transfusion was to be given. Most trials compared outcomes in patients transfused at Hgb thresholds between 7 and 10 g/dL” 8/24? 7/21? 10/30? Transfusion paradigms
  19. 19. TRANSFUSION LITERATURE • The current paradigm of the transfusion trigger of Hb 7 g/dL comes from the TRICC trial… • It challenged the solid belief that high hemoglobin values are safe, effective, and necessary in the critically ill. • It triggered a more focused look at the physiology of oxygen transport in the context of haemoglobin availability • It raised the question of whether transfusion has problems in its own right
  21. 21. STUDY DESIGN • The patients included were >16 years old, critically ill, normovolaemic, non-bleeding, Hb <90 within 72 h of ICU admission • MC RCT involving 25 centers over 3 years with n = 838 • The comparison groups had different Hb target ranges – these were restrictive (70-90g/L) vs liberal groups (100-120g/L), with the lower value as the transfusion threshold
  22. 22. FINDINGS • no difference in the the primary endpoint of mortality @ 30 days • increased complications in liberal strategy group • significant reduction in blood exposure in the more restrictive group • significantly lower in-hospital mortality in the less sick (APACHE 20 OR LESS: 8.7 percent in the • restrictive-strategy group and 16.1 percent in the liberal-strategy group, p = 0.03) and those aged <55y • in the restrictive transfusion strategy group
  23. 23. • The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.2 percent vs. 28.1 percent, p = 0.05). • trend to decreased survival with a restrictive strategy for patients with cardiovascular disease • no differences in duration of MV or ventilator free days
  24. 24. QUESTIONS UNANSWERED IN TRICC TRIAL ? Why liberal strategy group failed to improve mortality & rates of organ failure in critically ill ?? Possible explanations : a) greater no. of allogenic RBC units depressed host immune responses. [Hermans j et al circulation 1998] b) altered microcirculatory flow as consequence of prolonged storage times.
  26. 26. CURRENT GUIDELINES ON TRANSFUSION IN SEPSIS ◕ Maintain a haematocrit of > 30% in the presence of hypoperfusion in the first 6 hours ◕ Once tissue hypoperfusion has resolved and in the absence of extenuating circumstances, such as myocardial ischemia, severe hypoxemia, acute hemorrhage, or ischemic coronary artery disease, we recommend that red blood cell transfusion occur when the hemoglobin concentration decreases to < 7.0 g/dL to target a hemoglobin concentration of 7.0 to 9.0 g/dL in adults Surviving Sepsis Campaign
  27. 27. TRANSFUSION REQUIREMENTS IN SEPTIC SHOCK (TRISS) TRIAL • trial to evaluate the effects on mortality of leuko reduced blood transfusion at a lower versus a higher hemoglobin threshold among patients with septic shock who are in the (ICU). • multicenter, parallel-group trial • when the hemoglobin level was 7 g /dl or less (lower threshold) or when the level was 9 g /dl or less (higher threshold) during the ICU stay. ➜ Pt receives 1 unit of leuko reduced red cells
  28. 28. TRANSFUSION REQUIREMENTS IN SEPTIC SHOCK (TRISS) TRIAL Primary outcome- Death at 90 days post randomisation A significant difference in mortality was not found 43% in the lower threshold group 45% in the higher threshold group • There were no differences in ischemic events, duration of vasopressor or mechanical ventilation, and length of stay
  29. 29. TRANSFUSION REQUIREMENTS IN SEPTIC SHOCK (TRISS) TRIAL • CONCLUSIONS: Among patients with septic shock, mortality at 90 days and rates of ischemic events and use of life support were similar among those assigned to blood transfusion at a higher hemoglobin threshold and those assigned to blood transfusion at a lower threshold; the latter group received fewer transfusions
  30. 30. • Six-month mortality rates were higher in patients receiving transfusion (28.1% vs 11.7%) • protective effect of transfusion in patients with nadir hemoglobin < or =8 g/dL • transfusion was associated with increased mortality in patients with nadir hemoglobin > 8 g/dL
  31. 31. • RCT with n = 502 • HCT 30% vs HCT > 24% • no difference in mortality and severe morbidity • number of RBC’s transfused was an independent risk factor for clinical complications
  33. 33. OUTCOMES • primary outcome was mortality at 45 days: 5% vs. 9% in favour of restrictive approach • other secondary outcomes: further bleeding associated with hemodynamic instability or Hgb drop ≥2 • within 6 hours, number of RBCs transfused, cardiac complications, transfusion reactions and mean LOS
  34. 34. COMMENTARY AND CRITICISMS • Patients with major haemorrhage or low rebleeding risk were excluded • Patients had emergency upper GI endoscopy within a mean of 5 hours of admission — unrealistic in most clinical settings • Subgroup analysis suggested benefit extends beyond those with portal hypertension • the liberal arm may have benefited from hemostatic resuscitation rather than simply RBC transfusion which may cause dilutional coagulopathy
  35. 35. HARM FROM BLOOD TRANSFUSION ✺ Conclusion • Blood transfusion is an independent risk factor for: • morbidity and mortality • ICU admission • Hospital LOS • Increased cost
  36. 36. • Sepsis Occurrence in Acutely Ill Patients study was a multicenter, observational study followed up to 60 days • Transfused patients were sicker and did worse, but blood transfusion was not significantly associated with death in multivariate analysis – in fact the opposite was found.
  37. 37. Massive Transfusion
  38. 38. MASSIVE TRANSFUSION • Settings • Trauma • Obstetric • Surgical
  39. 39. MASSIVE TRANSFUSION Definitions • Replacement of one blood volume in a 24 hour period • Transfusion of >10 units RCC in 24 hours • Transfusion of 4 or more RCC within 1 hour when ongoing need is foreseeable • Replacement of >50% of the total blood volume within 3 hours
  41. 41. MASSIVE TRANSFUSION • Now recognised DIC is a significant contribution: loss of localisation ➜ microvascular damage • depletion of coagulation factors • In the massively transfused patient, ➜ platelets and impaired platelet function are the most consistent significant haematological abnormalities. Factor deficiency is initially confined to factors V and VIII
  42. 42. GET SOME HELP…. • Contact Key Personnel • surgeon/ obstetrician • Blood Bank • Haematologist • Shock/hypoperfusion is the key underlying problem ➜ fix it! • Control bleeding: • Early surgery (vs pre-op stabilisation)
  43. 43. BLOOD TRANSFUSION RISKS ✺ EARLY • TACO (transfusion associated circulatory overload) • TRALI (transfusion related acute lung injury) • haemolytic reactions (incompatibility – ABO, Rh) • fever • allergy (mild -> anaphylaxis) • infection: bacterial contamination • air embolism • hypothermia
  44. 44. BLOOD TRANSFUSION RISKS ✺ LATE • viral infection: hepatitis B (~1 in 750,000), HIV (<1 in a million), CMV • bacterial infection: Treponema pallidum, Salmonella, Yersinia, Pseudomonas, Staphylococcus spp • parasitic infection: malaria (<1 in a million), toxoplasmosis, prion infection • GVHD (graft versus host disease) • immune sensitisation • TRIM (transfusion-related immunomodulation); leading to increased risk of: infection, tumour • recurrence, activation of latent viral infections, recurrent miscarriages
  45. 45. TRALI
  46. 46. TRALI • hypoxia and bilateral pulmonary edema occurring during or within 6 h of a transfusion in the absence of other causes such as cardiac failure or intravascular volume overload • incidence is 1 in 5,000 U of plasma containing products (FFP, platelets or whole blood) • Theories • (1) donor anti-granulocytic antibodies called leukoagglutinins in plasma target recipient leucocyte antigens on neutrophils sequestered in the lungs, resulting in an immune reaction • (2) “biological response modifiers” (BRMs) such as cytokines and biologically active lipids (e.g. in aged cellular components) cause a lung-mediated response
  47. 47. ♛ MANAGEMENT OF TRALI • stop transfusion • respiratory support (may require NIV or intubation) • lung protective ventilation if intubated • haemodynamic support if needed e.g. noradrenaline • supportive care and monitoring • no evidence for steroids • inform blood bank and haematology
  48. 48. ♛ PROGNOSIS OF TRALI • most recover within 48-96 hours • radiological changes often last 7 days • mortality 5% ♛ PREVENTION of TRALI • limit transfusion of blood products • avoid donations (especially FFP) from multiparous women
  49. 49. TRANSFUSION OF OTHER BLOOD PRODUCTS • Transfusion of platelets ❁ Prophylaxis: ✾ < 10 without associated risk or < 20 with additional risk factors ✾ Keep > 50 in patients undergoing surgery or invasive procedures ✾ < 50 in massive haemorrhage and < 100 in diffuse microvascular bleeding ❁ Not appropriate if: ✾ Thrombocytopenia is due to immune mediated destruction ✾ In TTP and HUS except if continuous bleeding ✾ In uncomplicated cardiac bypass surgery
  50. 50. TRANSFUSION OF OTHER BLOOD PRODUCTS • Transfusion of Fresh frozen plasma • FFP has an INR of ~1.6 -> cannot lower below INR 1.7 • FFP must be ABO compatible • 10-20 cc/kg (4-6 units in adults) will increase factors by ~20% • FFP contains all coagulation factors in normal concentrations. • Rh factor need not be considered • there are no viable leukocytes so plasma does not carry a risk of CMV transmission or GVHD
  51. 51. TRANSFUSION OF OTHER BLOOD PRODUCTS • Indications of Fresh frozen plasma • documented coagulation factor deficiencies and active bleeding, or who are about to undergo an invasive procedure. • Deficiencies may be congenital or acquired secondary to liver disease, warfarin anticoagulation,DIC. • Recombinant or Factor VIII concentrates should be used to replace Factor VIII. • Reversal of warfarin anticoagulation with plasma is indicated only if significant bleeding or risk is present. • Rapid reversal for life threatening bleeding may be achieved with recombinant Factor VIIa (Novo7®)
  52. 52. FACTOR VIIA • recombinant protein • MECHANISM OF ACTION ➜ tissue factor + VIIa + platelets -> platelet aggregation • ➜ production of platelet-fibrin matrix ➜ haemostasis • used in massive transfusion senario’s to attempt to control intractable haemorrhage • expensive • need platelets for rFVIIa to be effective
  53. 53. EVIDENCE OF FACTOR VIIA • initially developed for haemophilia • encouraging case reports from use in trauma • may avoid problems with ongoing transfusion – disease transmission, acute lung injury, TRALI, hypothermia, acid-base disturbance, volume overload • probable publication bias -> tendency to publish cases where it has produced successful results • massive transfusion and trauma -> off licence use
  54. 54. • Multicentre RCT • n = 399 with acute intracerebral haemorrhage • single IV injection of recombinant factor VIIa (40, 80 or 160mcg/kg) VS placebo within 1 hour of their base line CT head scan. • -> significant reduction in volume of haematoma on CT @ 24 hours with therapy proportional to dose. • -> significant reduction in 30 day mortality without increase in severely disabled patients. • -> no statistically significant increase in thromboembolic events although there was a trend
  55. 55. TYPES OF RBC PRODUCTS WHOLE BLOOD : RBC+platelets+plasma proteins - indicated in hemorrhage & anemia - autologous donation prior to surgery PACKED RBC’S : 200ml of RBC’S + preservatives - each bag has Hct of 60% & approx 200 mg elemental iron. GAMMA IRRADIATED : destruction of donor T-lym. for GVHD prevention in immunocom., stem cell recepient.
  56. 56. - CMV antibody neg : used in transplant & pregnancy(high risk of CMV complications) - Leukocyte depleted : in febrile reactions,to avoid leucocyte immunization in hema tological malignancy. - Washed RBC’S : washed with NS to remove donor serum, -used in IgA def & those at high risk for anaphylaxis, - in PNH pt ( to deplete complement)
  57. 57. GRANULOCYTES - Used in profound & prolonged neutropenia secondary to marrow suppression. - Collected by : 1) filtration leukapheresis - 2) continuous flow centrifugation - Usefulness is doubted d/t : 1) inability to collect sufficient cells 2) early development of allo-immuniz.
  58. 58. CRYOPRECIPITATE contains fibrinogen,v-Wfactor,VIII,XIII,fibronectin, - conc. of fibrinogen in cryo > 10 times of FFP Indications : 1) DIC, along with FFP 2) isolated hypofibrinogenemia(<100- mg/dl) 3) platelet dysfunction not responding to DDAVP/dialysis. Dose : ~ one bag / 10 kg body weight
  59. 59. ANTI-THROMBIN CONCENTRATES : - used in anti-thrombin deficiency thrombophilia GAMMA-GLOBULINS : - in hypogammaglobulinemia, - in high doses in autoimmune diseases - SPECIFIC IMMUNOGLOBULINS : - for prophylaxis in rhesus,tetanus,zoster, Hep B.
  60. 60. CRASH-2 TRIAL : EFFECT OF TRANEXAMIC ACID ON DEATH,VASC. OCCLUSIVE EVENTS & BLOOD TRANSFUSION IN TRAUMA PATIENTS. - Early administration of tranexamic acid,an antifibrinolytic agent,to trauma patients,with or at risk of significant bleeding reduces the risk of death from hemorrhage with no apparent increase in fatal or non-fatal vascular occlusive events.(with no stastically significant difference in transfusion requirements) - DOSAGE : 1gm loading dose in 10 mins f/b infusion of 1gm over 8hrs. [lancet- 2010]