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