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Age of Transfused Blood: Short-Term Age of Transfused Blood: Short-Term Mortality and Long-Term Survival after Mortality and Long-Term Survival after
Cardiac SurgeryCardiac Surgery
Mark Stafford-Smith, MD, CM, FRCPC, FASEProfessor of AnesthesiologyDivision of Cardiothoracic Anesthesia & Critical Care MedicineDuke Heart Center, Durham, NC
Thursday May 1, 2008FDA Blood Products Advisory Committee
91st Annual MeetingRockville, MD
Disclosure:
No financial relationships to disclose pertinent to the content of this
CME presentation
Consultant for Polymedix Inc.
Age of Transfused Blood: Short-term Mortality Age of Transfused Blood: Short-term Mortality and Long-term Survival after Cardiac Surgeryand Long-term Survival after Cardiac Surgery
http://www.resource4thepeople.com/defectivedrugs/avandia.html
Problems for Established Therapeutic Problems for Established Therapeutic InterventionsInterventions
Efficacy vs. SafetyEfficacy vs. Safety2002 - estrogen/medroxyprogesterone acetate vs. myocardial infarction
http://www.fda.gov/cder/drug/safety/WHI_statement.htm
http://washingtontimes.com/national/20040208-123823-1958r.htm
2004 - SSRI antidepressants, teen suicide link
2005 - cyclooxygenase 2 inhibitor (Vioxx) vs. myocardial infarction
http://www.fda.gov/cder/drug/infopage/cox2/NSAIDdecisionMemo.pdf
McEvoy et al. Anesth Analg 2007; 105:949-962
2007 - rosiglitazone (Avandia) vs. myocardial infarction
2008 - aprotinin (Trasylol) vs. postop kidney dysfunction and mortality
Ho et al. Crit Care Med 2003;31:S687-97
2003 - UK – SHOT analysis, TRALI and plasma donor gender
Liberal versus Restrictive TransfusionLiberal versus Restrictive Transfusion
Hébert et al. New Engl J Med 1999;340:409-17
N=838 critically ill patients Hb<9.0g/dLRandomized to one of two groups within 72h of ICU admission
Transfusion StrategyRestrictive – trigger <7.0g/dL, target 7-9Liberal – trigger <10g/dL, target 10-12
n=78,974 elderly (>65y) with MIcrude 30-day mortality correlated with decreasing admission Hct
3,680 (4%) received a transfusion
Wu W-C et al N Engl J Med 2001;345;1230-6
Myocardial Infarction and TransfusionMyocardial Infarction and Transfusion
Odds ratio for 30 day mortalityfor patients who received a blood transfusion as compared to those who did not.
Ho et al. Crit Care Med 2003;31:S687-97
Mortality in-hosp, 30d. - meta-analysis (15 trials)
60d, 90d no association leukored vs. non Vox Sang 2002;82:141-149
Multiorgan failure - trauma patients, prospective cohorttransfusion Arch Surg 1997;132:620-5
Mortality 24h/in-hosp - trauma patients, prospective
and LOS ICU/Hosp transfusion J Trauma 2003;54:898-907
ICU mortality and - postop cardiac surgery patients, prospective cohort
mechanical ventilation transfusion Anesthesiology 2003;98:815-22
Harm Associated with TransfusionHarm Associated with Transfusion
30 day mortality - critically ill patients, prospective RCTrestrictive vs. liberal N Engl J Med 1999;340:409-17
28 day / ICU mortality - critically ill patients, prospective cohort
and LOS transfusion JAMA 2002;288:1499-1507
(cardiac surgery subgroup (3RCTs) – leukoreduced reduced 22-66 months mortality)
Age Distribution of Transfused BloodAge Distribution of Transfused Blood
DeSimone et al. Anesth Analg 2005;100:SCA7
VanMatre et al. Anesth Analg 2007;104:SCA23
20% of packed red cells are transfused > 28 days old
10-38% packed red cells transfused within 2 days of expiry
Vamvakas et al. Transfusion 2000;40:101-9
Ho et al. Crit Care Med 2003;31:S687-97
Adverse Changes (“Storage Lesion”)Adverse Changes (“Storage Lesion”)in Stored Red Blood Cellsin Stored Red Blood Cells
Bennett-Guerrero et al PNAS 2007;43:17063-8
Ho et al. Crit Care Med 2003;31:S687-97
Prolonged Storage and Outcomes after Red Cell Prolonged Storage and Outcomes after Red Cell TransfusionTransfusion
Length of ICU stay - 698 septic patients, retrospectiveblood >14days Clin Invest Med 1994;17:B21
Mortality - 31 septic patients, retrospectiveblood >16days Can J Anaesth 1997;44:1256-61
Multiorgan failure - trauma patients, prospective cohort#units >14days, >21days Am J Surg 1999;178:570-2
Postop pneumonia - 416 CABG surgery patients, retrospectiveage of blood Transfusion 1999;39:701-10
Gastric pH - septic patients, prospectiveblood >16days JAMA 1993;269:3024-3029
Major infections - cardiac surgery patients, retrospectiveage of oldest unit Anesthesiology 2003;98:815-22
Longer storage of blood + WBC’s → greater accumulation of WBC-derived cytokines
Interaction between Leukoreduction and Interaction between Leukoreduction and Blood StorageBlood Storage
http://images.encarta.msn.com/xrefmedia/sharemed/targets/images/pho/35a5c/35A5C297.jpg
Postop pneumonia - 416 CABG surgery patients, retrospectiveage of blood, non- vs. leukored Transfusion 1999;39:701-10
Hebert et al. Anesth Analg 2005;100:1433-8
- 57 transfused ICU/cardiac surgery patients- Canadian Medical Centers
Standard group- Median age transfusion 19 days
Experimental group- Median age transfusion 19 days
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
Koch et al. New Engl J Med 2008;358:1229-39
- single institution- transfused CABG, Valve or CABG/Valve surgery patients- June 30, 1998 - January 30, 2006
- 2,872 patients - blood stored <14 days (8,802 units)- 3,130 patients - blood stored >14 days (10,782 units)
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
- Propensity-adjusted, multivariable logistic regression analysis to examine the association of storage age on postoperative mortality
- Kaplan-Meier and Brownstone Decompensation method to assess association of storage age on long-term survival
Koch et al. New Engl J Med 2008;358:1229-39
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
Koch et al. New Engl J Med 2008;358:1229-39
Koch et al. New Engl J Med 2008;358:1229-39
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
Koch et al. New Engl J Med 2008;358:1229-39
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
Koch et al. New Engl J Med 2008;358:1229-39
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
Koch et al. New Engl J Med 2008;358:1229-39
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
Koch et al. New Engl J Med 2008;358:1229-39
Age of Stored Blood and Long-Term SurvivalAge of Stored Blood and Long-Term Survival
- single institution- 4643 transfused CABG surgery patients- September 1993 - June 2002
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
DeSimone et al. Anesth Analg 2005;100:SCA7VanMatre et al. Anesth Analg 2007;104:SCA23
30 Day Mortality N (deaths) P value
All units ≤ 14 1.68 1605 (27) 0.14
All units > 14 2.38 2187 (52)
Oldest unit ≤ 14 1.68 1605 (27) 0.003
Oldest unit > 14 3.15 2984 (94)
Oldest unit ≤ 14 1.68 1605 (27) <0.0001
Oldest unit >14, ≤ 28 2.42 1774 (43)
Oldest unit >28 4.21 1210 (51)
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
- Propensity-adjusted, multivariable logistic regression analysis to examine the association of storage age of the oldest transfusion on postoperative mortality
- Cubic-Splines analysis to assess for curvilinear relationships
- Kaplan-Meier method to assess the association of storage age of the oldest transfusion on long-term survival
DeSimone et al. Anesth Analg 2005;100:SCA7VanMatre et al. Anesth Analg 2007;104:SCA23
DeSimone et al. Anesth Analg 2005;100:SCA7
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
VanMatre et al. Anesth Analg 2007;104:SCA23
Age of Stored Blood and Post-Cardiac Surgery Age of Stored Blood and Post-Cardiac Surgery Mortality RiskMortality Risk
“…the COX-2 saga has served to demonstrate that an approach (to drug development) based on studies powered to showeffectiveness, no longer meets societal expectations for a comprehensive review of acceptable drug safety.”
Stafford-Smith Can J Anaesth 2006;53:973-977