11 surgical bleeding and transfusions


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  • 04/16/10 04:05
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  • 11 surgical bleeding and transfusions

    1. 1. Surgical Bleeding and Transfusions: The Issues in 2004 Chief, Dept of Anesthesiology, Critical Care and Hyperbaric Medicine Englewood Hospital & Medical Center and Associate Clinical Professor, Mount Sinai School of Medicine Aryeh Shander, MD, FCCM, FCCP
    2. 2. Objectives <ul><ul><li>Risks of bleeding, subsequent hypovolemia, and acute anemia </li></ul></ul><ul><ul><ul><li>Compensatory mechanisms </li></ul></ul></ul><ul><ul><ul><ul><li>Macrocirculation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Microcirculation </li></ul></ul></ul></ul><ul><ul><ul><li>Morbidity & mortality </li></ul></ul></ul><ul><ul><li>Risks of transfusions </li></ul></ul>
    3. 3. Surgical Bleeding Vessel interruption Surgical repair Bleeding contained No need for further action Delay in repair Bleeding stops Surgical repair Clotting Factor consumption Impaired clotting Transfusion of blood products SIRS Transfusion related complications
    4. 4. Consequences of untreated Hypovolemia <ul><li>American College of Surgeons (ACS) </li></ul><ul><li>Advance Trauma Life Support (ATLS) </li></ul><ul><li>Society of Critical Care Medicine (SCCM) </li></ul>Failure of the circulatory system to maintain adequate cellular perfusion
    5. 5. Bleeding and Hemorrhage <ul><li>Macrocirculation </li></ul><ul><ul><li>Compensation </li></ul></ul><ul><ul><li>Shifting of blood flow </li></ul></ul><ul><li>Microcirculatory response </li></ul><ul><ul><li>Cellular adaptation </li></ul></ul><ul><ul><li>Phenotype survival </li></ul></ul>SIR
    7. 7. Human Hemorrhage and Blood Pressure 25-30% bleed (n=6) Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81
    8. 8. Human Hemorrhage and Heart Rate 25-30% bleed (n=6) Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81
    9. 9. 25-30% bleed (n=6) p=0.002 Human Hemorrhage and Gastric Perfusion Hamilton-Davies C et al, Intensive Care Med 1997;23:276-81
    10. 10. <ul><li>Deliberate perioperative increase of DO2 >600 ml/min/m 2 using volume loading and dopexamine in RCT </li></ul><ul><li>Protocol (dopexamine) group had higher DO2 preop and postop (p<0.001) </li></ul>Boyd O. JAMA 1993;270:2699-2707. “ Fluid” + Dobutamine / High Risk Surgery
    11. 11. “ Fluid” + Dobutamine / High Risk Surgery % Lobo et al, Crit Care Med 2000;28:3396-3404. * * p<0.05 *
    12. 12. Surgery, trauma and the inflammatory response <ul><ul><li>Surgical trauma: hyperinflammation versus immunosuppression? Menger MD, Vollmar B. Langenbecks Arch Surg 2004;389:475-84. </li></ul></ul><ul><ul><ul><li>Surgery Vs. Trauma effect on ICAM and VCAM </li></ul></ul></ul><ul><ul><ul><li>Local (surgery) Vs. Systemic (trauma) Pro and inflammatory response </li></ul></ul></ul><ul><ul><li>The role of interleukin-10 in the regulation of the systemic inflammatory response following trauma-hemorrhage Schneider CP et al, Biochim Biophys Acta 2004;1689:22-32. </li></ul></ul><ul><ul><ul><li>Protective role </li></ul></ul></ul><ul><ul><ul><li>Damaging role </li></ul></ul></ul>
    13. 13. Risks of Anemia
    14. 14. Anemia in CVD <ul><li>Hgb =  Mortality in CVD </li></ul><ul><li>Carson/Gould – 300 Pts with Hgb <8 gm/dL - Stratified </li></ul><ul><ul><li>Carson JL et al, Lancet 1996;348:1055-60 </li></ul></ul><ul><li>Hgb < 9.5 g/dL = high risk with CVD </li></ul><ul><ul><li>Hebert PC at al, Am J Respir Crit Care Med 1997;155:1618-23 </li></ul></ul><ul><li>Hgb < 7.0 g/dL acceptable with normal coronary circulation </li></ul>
    15. 15. Low Hct and Adverse Outcome <ul><li>Lowest CPB HCT of <14% in low risk patients and <17% in high risk patients associated with doubling of mortality risk (Fang WC, Circulation 1997) </li></ul><ul><li>Below 23%, CPB HCT is inversely related to mortality (Defoe GR, Ann Thorac Surg 2001) </li></ul><ul><li>In postop cardiac surgical pts, inverse relationship exists between hemoglobin and major morbidity (Hardy JF, Br J Anaesth 1998) </li></ul><ul><li>Perioperative vital organ dysfunction, short- and intermediate-term mortality increased with lowest HCT <22% (Habib RH, J Thorac Cardiovasc Surg 2003) </li></ul>
    16. 16. Blood transfusion in Elderly Patients with Acute Myocardial Infarction Wu WC et al, NEJM 2001;345:1230-36 <ul><li>Cooperative Cardiovascular Project </li></ul><ul><ul><ul><li>234,769 total patients 78,974 (33.6%) included </li></ul></ul></ul><ul><ul><ul><li>CMS ICD-9 discharge code for MI and anemia </li></ul></ul></ul><ul><ul><ul><li>Anemia – WHO definition Hct of 39% or less </li></ul></ul></ul><ul><ul><ul><li>Hct in the first 24 hrs </li></ul></ul></ul><ul><ul><ul><li>30 day mortality </li></ul></ul></ul><ul><ul><li>3324 (4.2%) had Hct less than 30% </li></ul></ul><ul><ul><ul><li>These patients had more trauma, surgery, internal bleeding, coexisting diseases, DNR, shock and less treatments ( β blockers ASA etc.) </li></ul></ul></ul><ul><ul><li>3680 (4.7%) of the cohort received transfusions </li></ul></ul>
    17. 18. Low Hct and Adverse Outcome <ul><li>Retrospective database reviews </li></ul><ul><li>These studies did not assess impact of transfusion or preoperative hematocrit </li></ul><ul><li>Lowest HCT groups were transfused at a significantly higher rate </li></ul><ul><li>Prospective, randomized trial results supporting these conclusions not available </li></ul>
    18. 19. Risks of Blood Transfusions
    19. 20. Blood Transfusion: The Global Picture <ul><li>>82,000,000 units donated per annum world wide </li></ul><ul><li>In the US, ~12,500,000 units of RBCs transfused </li></ul><ul><li>That’s one unit every 25 seconds! </li></ul>WHO 2003
    20. 21. Risk and Prevention of Bloodborne Diseases <ul><li>43% of WHO participating countries (191) test their blood for </li></ul><ul><ul><li>HIV </li></ul></ul><ul><ul><li>HCV </li></ul></ul><ul><ul><li>HBV </li></ul></ul><ul><li>13,000,000 units per annum are not tested! </li></ul><ul><li>20% of the world ’ s population uses 80% of the safe blood supply </li></ul>WHO 2003
    21. 22. Risks Associated With Blood Transfusions <ul><ul><li>Clerical error </li></ul></ul><ul><ul><li>Transfusion reactions </li></ul></ul><ul><ul><li>Viral/bacterial infection </li></ul></ul><ul><ul><li>Immunomodulation </li></ul></ul>DHHS Jan, 2002
    22. 23. SHOT - Serious Hazards Of Transfusions 366 Reported &quot;Complications&quot; Blood Delivery Error 52% Acute Reaction 15% Delayed Reaction 14% GVHD 2% TRALI 8% Purpura 6% Disease 3% LM Williamson et al, BMJ 1999;319:16-19 <ul><li>ABO – clerical associated complications 1:16,000 1 </li></ul><ul><li>Krombach J et al, Human Error: The Persisting Risk of Blood Transfusion. Anesth Analg 2002;94:154-156 </li></ul>
    23. 24. Transfusion Safety in Hospitals <ul><li>Linden JV et al. A report of104 transfusion errors in </li></ul><ul><li>NY State. Transfusion 1992;32:601-6 1:12,000 </li></ul><ul><li>Robillard P et al. ABO incompatible transfusions, </li></ul><ul><li>acute and delayed hemolytic reaction in </li></ul><ul><li>Quebec. Transfusion 2002;42:25s 1:13,000 </li></ul><ul><li>Baele PL et al. Bedside transfusion errors. </li></ul><ul><li>A prospective survey by the Belgium SAnGUIS group. </li></ul><ul><li>Vox Sang 1994;66:117-21 1:400 </li></ul>
    24. 26. Decline in HIV, HBV, and HCV Risks of Transmission Through Transfusion Adapted from Busch MP et al, JAMA 2003;289:959-62. Aubuchon JP, Transfusion 2004;44:1377-1383. Risk of Infection per Unit Transfused 1:100 1:1000 1:10,000 1:100,000 1:1,000,000 1:10,000,000 1983 1985 1987 1989 1991 1993 1995 1997 1999 2001 Year Revised Donor Deferral Criteria Non-A, Non-B Hepatitis Surrogate Testing HIV Antibody Screening HCV Antibody Screening p24 Antigen Testing HCV and HIV Nucleic Acid Testing HIV HCV HBV Clerical 1:12,000 Bacteria 1:2,000 TRALI 1:5,000
    25. 27. Potential Risks to the Blood supply <ul><li>Simian Foamy Virus (SFV) </li></ul><ul><li>West Nile virus </li></ul><ul><li>vCJD </li></ul><ul><li>Trypanosoma Cruzi </li></ul>
    26. 28. TRALI <ul><li>1:2000 transfused patients </li></ul><ul><li>FDA reports as the third most prevalent transfusion related mortality, after hemolysis and sepsis </li></ul><ul><li>Associated with: whole blood, RBC, platelets, FFP and cryo. </li></ul><ul><li>CHF – ARDS, fleeting or devastating </li></ul><ul><li>Two prominent theories </li></ul><ul><ul><li>HLA class I and possible II, and monocyte antigens </li></ul></ul><ul><ul><li>20% of women with multiple gestations carry class I antigens </li></ul></ul><ul><ul><li>Mixture of predisposition and infusion of blood related lipid derived mediators </li></ul></ul>
    27. 29. Risks of Allogeneic Blood ‘ TRIM’ Transfusion Related Immune Modulation
    28. 30. Immune Effects of Blood <ul><li>Immunologic effects of autologous/allogenic blood Tx </li></ul><ul><ul><li>Decreased T-cell proliferation </li></ul></ul><ul><ul><li>Decreased CD3, CD4, CD8 T-cells </li></ul></ul><ul><ul><li>Increased soluble cytokine receptor </li></ul></ul><ul><ul><ul><li>sTNF-R, sIL-2R </li></ul></ul></ul><ul><ul><li>Increased serum neopterin </li></ul></ul><ul><ul><li>Increased cell-mediated lympholysis </li></ul></ul><ul><ul><li>Increased TNF-alfa </li></ul></ul><ul><ul><li>Increased suppressor T-cell activity </li></ul></ul><ul><ul><li>Reduced natural killer cell activity </li></ul></ul>McAlister FA et al, Br J Surg 1998;85:171-8. Innerhofer P et al, Transfusion 1999;39:1089-96.
    29. 31. Immune modulation <ul><li>Allogeneic transfusion may enhance tumor recurrence following colorectal cancer resection (Heiss MM, J Clin Oncol 1994) </li></ul><ul><li>Allogeneic transfusion is associated with prolonged hospital LOS (Vamvakas EC, Transfusion 2000) </li></ul><ul><li>Allogeneic transfusion is associated with increased risk of bacterial infection (  35%) and pneumonia (  52%) (Carson JL, Transfusion 1999) </li></ul><ul><li>Length of storage of transfused RBCs was associated with postoperative pneumonia following CABG surgery, 5% per unit (Vamvakas EC, Transfusion 1999) </li></ul>
    30. 32. Donor Leukocytes <ul><li>Persistence of donor WBCs in trauma patients for up to 1.5 years after an allogeneic blood transfusion </li></ul><ul><li>‘ Survival of donor leukocyte subpopulations in immunocompetent transfusion recipients: frequent long-term microchimerism in severe trauma patients ’ </li></ul><ul><li>2 x 10 9 WBCs in one unit of packed red blood cells </li></ul><ul><li>1 x 10 8 WBCs – c entrifuged, buffy coat depleted </li></ul><ul><li>1–5 x 10 6 WBCs – l eukocyte filter, leukocyte-depleted </li></ul>Lee TH et al, Blood 1999;93:3127 – 3139
    31. 33. Mortality Rates Are Lower When Leukocyte - Reduced Blood Is Used Leukocyte reduction results in a significant reduction of mortality in patients undergoing cardiac surgery van de Watering LMG et al, Circulation 1998;97:562 – 568 Mortality Rate (%) 7.8% 3.3% n=914 Bc=306 Ff=305 Sc=303
    32. 34. A prospective, randomized clinical trial of universal WBC reduction <ul><li>Men = 704 (49.4%) </li></ul><ul><li>Age = 69.4 (39.8, 84.3) </li></ul><ul><li>Surgical pts. (62%) </li></ul><ul><li>Non-surg. pts. 542 (38%) </li></ul><ul><li>Men = 675 (49.8%) </li></ul><ul><li>Age = 69.6 (42.0, 84) </li></ul><ul><li>Surgical pts. (60.5%) </li></ul><ul><li>Non-surg. pts. 535 (39.5%) </li></ul>Control Leukoreduced No demographic differences between groups N=2780 Dzik WH et al, Transfusion 2002;42:1114-22.
    33. 35. Primary outcomes <ul><li>In-hospital death 121 (8.5%) </li></ul><ul><li>LOS from the first transfusion avg. 10.6 days + 14.5 </li></ul><ul><li>Total hospital cost avg. $29,800 + $33.2K </li></ul><ul><li>median = $19,500) </li></ul><ul><li>Nonprophylactic antibiotic use after transfusion (days) 5.1 </li></ul><ul><li>In-hospital death 122 (9.0%) </li></ul><ul><li>LOS from the first transfusion avg. 10.3 days + 13.7 </li></ul><ul><li>Total hospital cost avg. </li></ul><ul><li>$29,000 + $34K </li></ul><ul><li>(median = $19,200) </li></ul><ul><li>Nonprophylactic antibiotic use after transfusion (days) 4.5 </li></ul>Control Leukoreduced Dzik WH et al, Transfusion 2002;42:1114-22.
    34. 36. The Impact of PRBCs on Nosocomial Infection Rates in ICU <ul><ul><li>Retrospective database study of 1,717 patients using Project IMPACT </li></ul></ul><ul><ul><li>NI rates of 3 groups were compared: </li></ul></ul><ul><ul><ul><li>Entire cohort </li></ul></ul></ul><ul><ul><ul><li>Transfusion group </li></ul></ul></ul><ul><ul><ul><li>Nontransfusion group </li></ul></ul></ul><ul><ul><li>Patients stratified for age, gender, and probability of survival using Mortality Prediction Model (MPM-0) scores </li></ul></ul>Taylor RW et al, Crit Care Med 2002;30:1-6.
    35. 37. Nosocomial Infection Rates in Critically Ill Patients N = 1,717 n = 416 n = 1,301 P < .05 Adjusted for severity of illness using MPM-0 scores, age, gender (Project IMPACT). Taylor RW et al, Crit Care Med 2002;30:2249-54. For each unit of PRBCs given, the odds of infection is increased by a factor of 1.5
    36. 38. Mortality Rates in Critically Ill Patients N = 1,717 n = 416 n = 1,301 P < .05 Taylor RW et al, Crit Care Med 2002;30:2249-54.
    37. 39. Transfusion and Outcome <ul><li>Retrospective, database study of long-term outcome in 1,915 patients after primary CABG </li></ul><ul><li>Excluded for death within 30 days of surgery </li></ul><ul><li>546 patients transfused during hospitalization were matched by propensity score (age, gender, size, LOS, perfusion time and STS risk) with patients not transfused and 5-year mortality compared </li></ul><ul><li>5-year mortality twice as high in transfused patients </li></ul><ul><li>After correction for comorbidity, 5-year mortality remained 70%higher in transfused group (p<0.001) </li></ul>Engoren et al, Ann Thorac Surg 2002;74:1180-6
    38. 40. Univariate association rates of stroke and death in CABG with platelet transfusion Patients (%) STROKE DEATH Spiess BD et al, Transfusion 2004;44:1143-1148 N=1720/248 from 6 RCT for Aprotinin FDA approval
    39. 41. Summary <ul><li>Risks </li></ul><ul><ul><li>Infectious vs. non-infectious </li></ul></ul><ul><li>Outcome data </li></ul><ul><ul><li>Morbidity </li></ul></ul><ul><ul><ul><li>Infection </li></ul></ul></ul><ul><ul><ul><li>MOF </li></ul></ul></ul><ul><ul><li>Mortality – </li></ul></ul><ul><li>Mechanism </li></ul><ul><ul><li>WBC mediated </li></ul></ul><ul><ul><li>RBC mediated </li></ul></ul><ul><ul><li>Platelet/plasma </li></ul></ul><ul><li>Storage lesion </li></ul><ul><li>Combination </li></ul>