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CA-3 lecture on Anemia and Transfusion
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The Transfusion Trigger: When Should You Give Red Cells?
Harriet W. Hopf, MDProfessor of Anesthesiology
University of Utah
Goals To understand
the effect of anemia on oxygen transport mechanisms that compensate for anemia the risks of transfusion the concept of a transfusion trigger
Objective Participants will be able persuasively to
defend their decision to transfuse / not to transfuse red cells
Why Transfuse Red Cells?
Why Transfuse Red Cells? To maintain O2 delivery to organs To prevent inadequate O2 consumption
How Do We Measure Need? Ideal
Tissue oxygen Good-- but not practical
O2ER (VO2/DO2) Madjdpour and Spahn. BJA 2005; 95:33-42
Real Hemoglobin Hemodynamics
Physiologic Effects of Anemia
Why is there a wide range of “normal” and “acceptable” hemoglobin?
Physiologic Effects of Anemia Compensate by increased cardiac output
CO = HR X SV HR increases 4 bpm / g Hb SV increases as well
Increased contractility (active) Decreased SVR (passive) Increased venous return (passive)
Weiskopf et al. Transfusion 2003; 43: 235-40
Physiologic Effects of Anemia Under anesthesia, no HR increase Increased CO is from increased SV
Majdpour and Spahn. BJA 2005; 95:33-42.
Fick’s Principle
Fick’s Principle
CO = VO2 / AVDO2
AVDO2 = CaO2-CvO2
CO2 = SO2(HbX1.34) + PO2(0.003) mL O2 / dL blood
Does Dissolved Oxygen Matter?
Hemoglobin bound oxygen
Hb (g/dL)
PaO2 (mmHg)14 10 7 3
CaO2
100
18.76 13.40 9.38 4.02
50018.76 13.40 9.38 4.02
200018.76 13.40 9.38 4.02
Dissolved Oxygen
Hb (g/dL)
PaO2 (mmHg)14 10 7 3
CaO2
100
0.30 0.30 0.30 0.30
5001.50 1.50 1.50 1.50
20006.00 6.00 6.00 6.00
Putting it all together
Hb (g/dL)
PaO2 (mmHg)14 10 7 3
CaO2
100
18.76
0.30
19.06
13.40
0.30
13.70
9.38
0.30
9.68
4.02
0.30
4.32
500
18.76
1.50
20.26
13.40
1.50
14.90
9.38
1.50
10.88
4.02
1.50
5.52
2000
18.76
6.00
24.76
13.40
6.00
19.40
9.38
6.00
15.38
4.02
6.00
10.02
Does Dissolved Oxygen Matter?
What if you can’t transfuse?
What if you can’t transfuse? Administer 100% oxygen
Equivalent to 1-1.5 g/dL Hb 1 g Hb fully saturated = 1.34 mL O2
PaO2 500 mm Hg = 1.5 mL O2
PaO2 300 mm Hg = 0.9 mL O2
Weiskopf et al. Anesthesiology, 96(4), 871-7, 2002.
Dissolved Oxygen Matters!!!
Hb (g/dL)
PaO2 (mmHg)14 10 7 3
CaO2
100
18.76
0.30
19.06
13.40
0.30
13.70
9.38
0.30
9.68
4.02
0.30
4.32
500
18.76
1.50
20.26
13.40
1.50
14.90
9.38
1.50
10.88
4.02
1.50
5.52
2000
18.76
6.00
24.76
13.40
6.00
19.40
9.38
6.00
15.38
4.02
6.00
10.02
What Happens to AVDO2?
Normal AVDO2 using Fick’s Equation Hb 14 g/dL
CO 50 dL / min (5 Lpm) VO2 250 mL O2 / min
AVDO2 = 250/50 = 5 CaO2 19 mL O2/dL blood CvO2 14 mL O2/dL blood p50 CvO2 = 7
What if AVDO2 Doesn’t Change?
Hb (g/dL)
PaO2 (mmHg)14 10
CaO2
100
18.76
0.30
19.06
13.40
0.30
13.70
13.7 - 5 = 8.7
Close enough to 7!!!
What Happens to AVDO2? Assume CO can increase
Hb 7 g/dL CO 100 dL / min (10 Lpm) VO2 250 mL O2 / min
AVDO2 = 250/100 = 2.5
What if AVDO2 Does Change?
Hb (g/dL)
PaO2 (mmHg)14 10 7
CaO2
100
18.76
0.30
19.06
13.40
0.30
13.70
9.38
0.30
9.68
CvO2
AVDO2 = 514.06 8.70 4.68
CvO2
AVDO2 = 2.516.56 11.20 7.18
What if you can’t transfuse?
Maximize CaO2
FiO2 1.0 Hyperbaric oxygen (intermittent)
Minimize VO2
Intubate Paralyze Sedate Cool (?) to 35.5C
What if you can’t transfuse? Maximize CO
Volume Goal is isovolemia Consider TEE guidance Don’t measure Hb!
Don’t use dopamine Increased VO2 mostly cardiac
Dissolved Oxygen Matters!!!
Hb (g/dL)
PaO2 (mmHg)14 10 7 3
CaO2
100
18.76
0.30
19.06
13.40
0.30
13.70
9.38
0.30
9.68
4.02
0.30
4.32
500
18.76
1.50
20.26
13.40
1.50
14.90
9.38
1.50
10.88
4.02
1.50
5.52
2000
18.76
6.00
24.76
13.40
6.00
19.40
9.38
6.00
15.38
4.02
6.00
10.02
Risks of Transfusion Infection
HIV 1: 500K-1500K HBV 1:30K-200K HCV 1: 2000K-3000K Bacterial 1:28K-43K Malaria 1:4000K vCJD Recent reports
Majdpour and Spahn. BJA 2005; 95:33-42.
Risks of Transfusion Transfusion Reaction 1:13K Mistransfusion 1:14K-18K TRALI 1:5K-529K
Expensive Limited supply
Majdpour and Spahn. BJA 2005; 95:33-42.
Risks of Transfusion Cancer recurrence Surgical site infection Mortality
Role for leucoreduction? Old vs. new blood?
Koch et al, NEJM 358:1229, 2008 Weiskopf et al, Anesth. 104:911, 2006
Majdpour and Spahn. BJA 2005; 95:33-42.
Transfusion Guidelines Are there guidelines?
ASA Guidelines, Anesth 105:198-208, 2006.
Are they based on data? “strongly agree” transfuse < 6 g/dL “strongly agree” don’t transfuse >10g/dL
How good are physicians at following them?
Joint Commission Patient Blood Management Performance Measures Project
Transfusion Consent RBC Transfusion Indication Plasma Transfusion Indication Platelet Transfusion Indication Blood Administration Indication Preoperative Anemia Screen Preoperative Blood Type / Antibody Screen
http://www.jointcommission.org/patient_blood_management_performance_measures_project/
Transfusion Trigger Really a TARGET not a TRIGGER Healthy patient
7 g / dL Cardiopulmonary disease
10 g / dL (?8-9) Prevent tachycardia
What does this mean? Healthy patient, Hb 14 g/dL Assume 500 mL (1 unit) whole blood loss = 1
g/dL Hb decrease Assume volume replaced EBL >3500 mL before consider transfusion
How low can you go? Unmedicated, healthy volunteers at rest
Hb 5 g / dL No VO2-DO2 dependency Fatigued Mild cognitive impairment
Slightly slower and less accurate Still in normal range Reversed by RBC transfusion at Hb 7 g/dL Reversed by 100% O2 via NRB
Weiskopf et al. Anesthesiology, 96(4), 871-7, 2002.
What about surgical patients? Anemia increases 30-day mortality, CV
complications, and LOS Non-cardiac surgery
Polycythemia similar effects Wu et al. JAMA 297:2481, 2007 (98% men)
Colorectal surgery ~50% women but not analyzed separately Leichtle et al, J Am Coll Surg 212:187, 20011
Cardiac surgery Koch et al, Crit Care Med 34:1608, 2008
How Should We Manage Anemia?
Is anemia a marker for disease or inherently causative?
Preoperative treatment: 2 weeks oral iron (200 mg) reduces transfusion
9.4 vs 27.4%, p<0.05 Okuyama et alSurg Today 35:36, 2005
ESA reduces transfusion, increases DVT Laupacis and Fergusson, Transfus Med 8:309, 1998
How Should We Manage Anemia?
Is anemia a marker for disease or inherently causative?
Risk-adjusted, propensity-matched ≥4 U blood predicts increases:
Mortality Infection LOS
Dunne et al, J Surg Res 102:237, 2002
Critical Care Transfusion RCT
838 patients, Hb <9 g/dL, within 72 h of admit Trigger <7 Target 7-9 Trigger <10 Target 10-12
Hebert et al. NEJM, 1999; 340:409-17.
Critical Care Transfusion RCT
Trigger30d Mortality
<7 g / dL <10 g/dL P value
Overall 18.7 23.3 0.11
APACHE II <21
8.7 16.1 0.03
Age <55 yr 5.7 13 0.02
CV Disease 20.5 22.9 0.69
Table 3. Unadjusted Rates of Outcomes and Adjusted Results of Cox Regression Predicting 30-Day Death and Death or Recurrent Myocardial Infarction Using Transfusion as a Time-Dependent
Covariate.
Rao, S. V. et al. JAMA 2004;292:1555-1562
Copyright restrictions may apply.
HCT 25% best cut-off for transfusion
Individualize Transfusion target (7 vs. 10 vs. 8…) Acute vs. chronic anemia Rate of bleeding Hemodynamics
What about ADLs? Should target differ in men and women?
Summary Transfusions of RBC can be life-saving Also cause serious morbidity and mortality Individualize therapy
Underlying disease Adequacy of compensatory responses Rate of bleeding Starting point