1. Physiology of Acute Anemia John R. Feiner, MD Department of Anesthesia and Perioperative Care University of California, San Francisco

2. Issues with Donation Acute hypovolemiaAcute hypovolemia –Loss of 450 mL of whole blood –This is the same no matter what level of hemoglobin the person starts with Acute anemiaAcute anemia –Once the person’s volume is restored, which happens fairly rapidly, the issue is simply one of acute anemia

3. Tolerance of Acute Anemia Physiology of Acute AnemiaPhysiology of Acute Anemia –Very distinct from anemia in patients

4. Our Studies Over 10 years of studying volunteers with acute isovolemic hemodilution to Hb < 7 g/dLOver 10 years of studying volunteers with acute isovolemic hemodilution to Hb < 7 g/dL Purpose was to understand compensation for and tolerance of acute anemiaPurpose was to understand compensation for and tolerance of acute anemia Interested in transfusion decisions-- physiological transfusion thresholdsInterested in transfusion decisions-- physiological transfusion thresholds However, this created great experience in understanding acute anemiaHowever, this created great experience in understanding acute anemia

5. Basic Physiology 32 volunteers and patients hemodiluted with 5% albumin and their autologous plasma to target Hb ≈ 5 g/dL32 volunteers and patients hemodiluted with 5% albumin and their autologous plasma to target Hb ≈ 5 g/dL Age: 19 - 69 yrsAge: 19 - 69 yrs 16 male, 16 female16 male, 16 female Physiological parameters measured with pulmonary artery catheter and arterial linePhysiological parameters measured with pulmonary artery catheter and arterial line Weiskopf et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA (1998) vol. 279 (3) pp. 217-21

6. Oxygen Delivery Weiskopf et al. JAMA (1998) vol. 279 (3) pp. 217-21

7. Oxygen Delivery Compensation for anemia is quite complete and remarkable at higher hemoglobin concentrationCompensation for anemia is quite complete and remarkable at higher hemoglobin concentration No increase in oxygen extraction even occurs until more extreme anemiaNo increase in oxygen extraction even occurs until more extreme anemia

8. Cardiac Output Weiskopf et al. JAMA (1998) vol. 279 (3) pp. 217-21

9. Cardiac Output Cardiac output completely compensates for the decreased oxygen carrying capacity at higher hemoglobin concentrationCardiac output completely compensates for the decreased oxygen carrying capacity at higher hemoglobin concentration Not till much lower levels of hemoglobin (≈8 g/dL) is compensation less that completeNot till much lower levels of hemoglobin (≈8 g/dL) is compensation less that complete

10. Heart Rate Weiskopf et al. JAMA (1998) vol. 279 (3) pp. 217-21

11. Heart Rate Increase Heart rate increase approximately 4 beats/min/g Hb at restHeart rate increase approximately 4 beats/min/g Hb at rest The majority of the compensation is heart rate, with the rest from stroke volumeThe majority of the compensation is heart rate, with the rest from stroke volume This is minimal added stress to compensate for anemiaThis is minimal added stress to compensate for anemia

12. Other Outcomes FatigueFatigue –No significant symptoms until ≈ 7 g/dL Cognitive changesCognitive changes –Significant changes for Hb < 7 g/dL

13. Old Blood vs. New Blood Two studies where our subjects donated 2 units total, 1 week apart, 2-3 weeks prior to being studiedTwo studies where our subjects donated 2 units total, 1 week apart, 2-3 weeks prior to being studied This is similar to extra blood donationsThis is similar to extra blood donations Total of 50+ subjects went through this protocol between the two studiesTotal of 50+ subjects went through this protocol between the two studies Weiskopf et al. Fresh blood and aged stored blood are equally efficacious in immediately reversing anemia-induced brain oxygenation deficits in humans. Anesthesiology (2006) vol. 104 (5) pp. 911-20 Weiskopf et al. Fresh and Stored Red Blood Cell Transfusion Equivalently Induce Sub- Clinical Pulmonary Gas Exchange Deficit in Normal Humans. Submitted.

14. Hemoglobin Changes

15. Two Unit Donation These subjects who donated 2 units 1 week apart had no subjective symptoms or problemsThese subjects who donated 2 units 1 week apart had no subjective symptoms or problems Note that 2 unit donation in female subjects produced more significant anemiaNote that 2 unit donation in female subjects produced more significant anemia

16. What Sensitive Outcomes? ExerciseExercise –Might be able to detect small changes in VO 2 max –Subjective changes in exercise capacity in good athletes Doubtful if one could find any other measurable effect of decreased Hb at higher levelsDoubtful if one could find any other measurable effect of decreased Hb at higher levels

17. Anemia in Patients Information on risks of anemia in people with anemia not relevantInformation on risks of anemia in people with anemia not relevant Anemia is highly associated with multiple comorbidities, and is likely associated with adverse outcomes largely through this associationAnemia is highly associated with multiple comorbidities, and is likely associated with adverse outcomes largely through this association Note that producing higher levels of hemoglobin with erythropoietin treatment is not helpful and may have adverse consequencesNote that producing higher levels of hemoglobin with erythropoietin treatment is not helpful and may have adverse consequences

18. Conclusions Acute anemia is well compensated and tolerated by healthy humansAcute anemia is well compensated and tolerated by healthy humans We have only been able to find measurable effects at very low hemoglobin levelsWe have only been able to find measurable effects at very low hemoglobin levels