The document discusses blood transfusion in the ICU, including: - The history of blood transfusion and evolution of transfusion medicine. - Controversy around transfusion triggers in the ICU, with studies showing increased risks with liberal transfusion strategies. - Risks of blood transfusion including infections, TRALI, and immunomodulation effects. - Specific transfusion guidelines and considerations for septic patients, bleeding patients, and massive transfusion situations.

1. BLOOD TRANSFUSION IN ICU
By
Dr.Sherif Badrawy
Critical Care Registrar

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

3. EVOLUTION OF TRANSFUSION

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. BLOOD
TRANSFUSION

7. 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).

8. 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

9. Anemia VS blood transfusion in ICU

10. ✪ 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

11. ✪ 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

12. ✪ 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

13. ❂ 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

14. ❂ 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

15. ❂ 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. DOES OLD BLOOD IMPROVE
OXYGEN CONTENT?

17. 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

18. TRANSFUSION TRIGGER
Acceptable hemoglobin concentration
Risk of blood transfusion Risk of low hemoglobin

19. 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

20. 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. TRANSFUSION TRIGGERS IN NON-BLEEDING
PATIENTS

22. 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

23. 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

24. • 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

25. 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. ❋ A CANADIAN PAEDIATRIC STUDY
❋ MIRRORED THE FINDINGS OF TRICC, BUT
WITH MODS AS THE PRIMARY OUTCOME

29. 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

30. 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

31. 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

32. 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

33. • 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

34. • 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

35. TRANSFUSION TRIGGERS IN BLEEDING
PATIENTS

36. 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

37. 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

38. HARM FROM BLOOD TRANSFUSION
✺ Conclusion
• Blood transfusion is an independent risk factor for:
• morbidity and mortality
• ICU admission
• Hospital LOS
• Increased cost

39. • 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.

40. Massive Transfusion

41. MASSIVE TRANSFUSION
• Settings
• Trauma
• Obstetric
• Surgical

42. 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

43. “BLOODY VICIOUS CYCLE”

44. 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

45. 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)

46. 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

47. 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

48. TRALI

49. 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

50. ♛ 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

51. ♛ 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

52. 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

53. 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

54. 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®)

55. 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

56. 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

57. • 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

58. 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.

59. - 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)

60. 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.

61. 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

62. 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.

63. 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]