“Parsimonious RBC Transfusion: State of the Art”

Moises Auron, MD, FAAP, FACP Assistant Professor of Medicine and Pediatrics

Disclosure of Financial Relationships
• Dr. Auron has no relationships with entities producing, marketing, re-selling, or distributing health care goods or services consumed by, or used on, patients.

Outline
• Anemia Physiology • Current evidence for transfusion medicine • Adverse effects of blood utilization

It is right to say……
• The safest transfusion is the one that is avoided • The best transfusion is the one that is avoided
• What is the evidence? • What is the comparison?

Physiology
Pre-load After-load Contractility Stroke volume (SV)

SV x Heart rate = Cardiac output (CO) •CaO2 = SaO2 x 1.34 x Hb + [PaO2 x 0.003] •DO2 = CO x CaO2 •O2ER = VO2/DO2 (~20-30%) •DO2crit = < 7.3 ml O2/kg/min
Madjdpour C, et al. Crit Care Med 2006; 34[Suppl.]:S102–S108.

Physiology

Acute response to Anemia Central – ↑ CO Regional – Redistribution

Microcirculation –capillary recruitment

http://www.frca.co.uk/article.aspx?articleid=100345 Shander A, et al. Brit J Anaesth 2011;107 (S1): i41–i59.

Outline
• Anemia Physiology • Current evidence for transfusion medicine • Adverse effects of blood utilization

Anemia tolerance: what is the ideal hemoglobin level?
• Cardiovascular effect - Coronary artery disease - Valvular disease - Elderly patient • CNS effects • Effects on splachnic and renal perfusion

Preoperatory Anemia and Cardiovascular Disease
Retrospective (N = 1958) Jehovah's witnesses > 18a

Mortality 1.3% (Hb > 12)
Mortality 33.3% (Hb < 6)

Carson JL. Lancet 1996; 348: 1055–60.

N = 5065 4804 were not transfused before surgery Hb < 11 – increase in postop adverse effects (renal, CNS (P=0.001)) Specially in patients with EUROSCORE > 4 Circulation. 2007;116: 471-479. http://www.euroscore.org

N = 1,136,201 1996-1997

Journal of Cardiac Failure. 2004:10(6)467-72.

• •

N = 227 425 patients (69 229 preoperatory anemia) Postoperative mortality (30 days) (OR 1.42, 95% CI 1.31-1.54) - Mild Anemia (OR 1.41, 1.30-1.53) - Moderate-severe Anemia (OR 1.44, 1.29-1.60) Postoperative morbidity (30 days) (OR 1.35, 1.30-1.40) - Mild Anemia (OR 1.31, 1.26-1.36) - Moderate-severe Anemia (1.56, 1.47-1.66)

Lancet 2011; 378: 1396–407.

What is my cut-off Hemoglobin value to transfuse?
• 10/30? - Based in “experience” - Not supported by evidence • Indiscriminate use of blood - USA: 15 million pRBC/year - Global: 85 million pRBC/year

Carson JL, et al. Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB. Ann Int Med 2012.

Hb 12.6±0.2 to 9.9 ±0.2 g/dl N = 90 (60 hemodilution)

Anesth Analg 1996;82:687-94.

- Hemoglobin 13±1.3 to 9.3±1 g/dl - No left ventricle dysfunction or hemodynamic instability. Crit Care Med. 2005 Mar;33(3):591-7.

Hb 9.1 g/dL  Increase C.I, C.O, and pre-load indexes - Less viscosity increases venous return, pre-load  increase stroke voume - Consider in patients with preserved LV function
Anaesthesia, 2004;59:1170–1177.

Increase in C.I and O2 extraction (VO2/DO2) - Independent of baseline rhythm

Anaesthesia, 1998;53:20-24.

N = 20 Age +/- S.E.M. = 76 y/o (66-85) Excluded: Hx of CAD, valvular cardiomyopathy, non-sinus rhythm, LBBB, betablocker use, Hb < 10 g/dL.

Isovolumetric hemodilution was well tolerated in elderly down to 8.8 +/- 0.3 g/dL
Anesth Analg 1996;82:681-6.

Horizontal addition

Immediate memory

There is no difference between time of reaction (speed and precision of processing information) or in immediate Delayed memory Numeric substitution and delayed memory between Hemoglobin of 7 g/dL vs. 14 g/dL.

Anesthesiology. 2000;92:1646-52.

There is no difference in reaction time in patients with Hemoglobin of 5.7 g/dL who used supplemental O2 (PaO2 > 350 mm Hg equals to increase Hb ~ 2-3 g/dL  reverse effects of acute anemia
N = 31 healthy volunteers (28 y/o +/- 4) Tests: verbal and standard memory; computerized neuropsychological Basal hemoglobin 12.7 g/dL  hemodilution to 5.7 g/dL

Anesthesiology 2002; 96:871–7.

Renal and splachnic perfusion
• Studies in animals (dogs) • Normovolemic hemodilution - Hct 30 - Hb 7 g/dL • Preserve adequate renal perfusion and blood distribution

Habler O, et al. Eur J Med Res 1997;2:419–424. Meier J, et al. Clin Physiol Funct Imaging 2005; 25: 158-65.

18% vs. 23%

TRICC Study N = 838 Hb < 9.0 g/dL Euvolemic Restrictive – Hb < 7 g/dL (N = 418) Liberal – Hb < 10 g/dL (N = 420)

8.7% vs. 16.1% 5.7% vs. 13%

NEJM 1999;340(6):409-17.

• • • • •

TRIPICU Study (non-inferiority) N = 637 hemodinamically stable children 320 – Transfused for Hb < 7.0 g/dL 317 – Transfused for Hb < 9.5 g/dL No significant difference in prognostic markers (death, infections, inpatient stay in ICU).

N Engl J Med 2007;356:1609-19.

Patients > 50 y/o
10 g/dL 8 g/dL

N Engl J Med 2011;365:2453-62.

Liberal – Hct 30.6% Conservative – Hct 27.9%

Am J Cardiol 2011;108:1108 –1111.

HR 3.94; (95% CI, 3.26-4.75)

N = 24112 Acute coronary syndromes

Studies: GUSTOIIb, PURSUIT, PARAGON B

Rao SV, et al. JAMA 2004. 292(13):1555-62.

N = 1410 (370 with anemia) 110 (30%) were transfused

Am J Cardiol 2007;99:1119 –1121.

J Surg Research. 2002; 102:237–244.

Complication Inpatient mortality Mortality at 1 year Prolonged intubation (>72h) Renal failure Sepsis

Blood > 14 d (%) 2.8% 11%

Blood < 14 d (%) 1.7% 7%

P 0.004 0.001

9.7% 2.7% 4.0%

5.6% 1.6% 2.8%

0.001 0.003 0.01

N Engl J Med 2008;358:1229-39.

Changes in aging blood
• RBC age rapidly in refrigeration – 75% viable at 24hs • Decreased ATP and 2,3 DPG • Loss of membrane phospholipids • Progressive structural rigidity  echinocytes at 14-21 days Poor tissue delivery of O2

Holme S. Transfus Apher Sci 2005;33:55–61. Hovav T, et al. Transfusion 1999; 39(3):277-81.

Physiologic factors that indicate blood transfusion
Hypotension and tachycardia – refractory to euvolemia New ST depression > 0.1 mV New ST elevation > 0.2 mV New LV free wall motion abnormality (Echocardiogram) PVO2 < 25 mmHg O2ER > 50% SVO2 < 50% Decrease VO2 > 10%

Crit Care Med 2006; 34[Suppl.]:S102–S108

Hemoglobin levels that indicate blood transfusion
All patients Patients > 80 y/o CAD/CHF SaO2 < 90% Catabolic state 7 7-8 8 8 7-8

Crit Care Med 2006; 34[Suppl.]:S102–S108

Transfusion limits: Guidelines
Society ASA BCSH (British Committee of Hematology Standards) Australian and NZ Society of Blood Transfusion ESC (European Society of Cardiology) SCCM/ACCM AABB (American Assoc of Blood Banking) Year 1996
2001 2001 2007 2009 2012

Hb Limit (g/dL) 6
7 7 8 7 7

Anesthesiology. 1996;84:732-47. http://www.nhmrc.gov.au/guidelines/publications/cp78 (2001) Napolitano LM, et al. J Trauma. 2009;67:1439-42.

Murphy MF, et al. Br J Haematol. 2001;113:24-31. Bassand JP, et al. Eur Heart J. 2007;28:1598-660. Carson JL, et al. Ann Int Med 2012 (online first).

Transfusion restriction and mortality

Carson JL, et al. Transfus Med Rev. 2002;16(3):187-99.

• Transfusion restrictive strategy • Critical patients – consider transfusion if Hb < 7 g/dL • Post-op surgical patients - consider transfusion if Hb < 8 g/dL or if symptomatic (angina; orthostatic hypotension; tachycardia refractory to IVF resuscitation, CHF)
Carson JL, et al. Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB. Ann Int Med 2012.

Outline
• Anemia Physiology • Current evidence for transfusion medicine • Adverse effects of blood utilization

Blood transfusion: Risks

Carson JL, et al. Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB. Ann Int Med 2012.

Blood transfusion: Risks
• Infections: HCV, HBV, HIV, HTLV, XMRV • Immunologic reactions: - Non-hemolytic febrile reaction - Early and delayed hemolytic reactions - Anaphylaxis - Urticaria • TRALI • TACO • TRIM (↑ infections) • XMRV – Chronic fatigue syndrome?
Meiers J. Transfus Med Hemother 2012;39:98–103 http://www.frca.co.uk/article.aspx?articleid=100902

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