Ammar Alsughayir TM Fellow The University of Ottawa April 9 th 2008

1. Ammar Alsughayir TM Fellow The University of Ottawa April 9th 2008

2. Background • Considerable evidence suggest that transfusion increased the risk of serious complications and death in critically ill especially those undergoing cardiac surgery . • The risk is even increased further if transfused with old blood

3. Methods • Patients • Only Adults ( 18 years and older ) • Cardiac surgery • Coronary artery bypass grafting • Cardiac valve surgery or • Combination • Cleveland clinic • 1998-2006

4. Methods • Only patients who received newer blood • Red blood cells who were stored for 14 days or less • Those who received older blood • RCC stored for more than 14 days • Exclusion from the study of those who received a mixture of both

5. Methods • Blood conservative techniques • EACA • Cardiotomy suction • No uniform protocol for perioperative transfusion • Blood bank practice is to provide the oldest blood available

6. Data sources • 3 Data sources • Cleveland Clinic anesthesia registry • Baseline demographic • Perioperative variables ( prospectively collected ) • Cardiovascular information registry • Additional variables • Blood banks database • Storage time of RCC • ABO Blood type • Leucoreduction status

7. The primary end point Composite of serious adverse events in-hospital death myocardial infarction, asystole, ventricular tachycardia or fibrillation, tamponade, femoral or aortic dissection, renal failure, sepsis, respiratory insufficiency, pulmonary embolism, pneumonia, cerebral vascular accident, coma Secondary end point The long term survival Complications

8. Statistical Analysis • Two-sample tests. • Baseline characteristics, operative factors, and univariate outcomes were compared between the 2 groups • The Wilcoxon rank-sum test & chi-square test • were used for group comparisons among continuous and categorical variables. • the dose–response relationship between the storage time of blood and the composite outcome • Summary variable for the storage time • To adjust for potential confounders • Kaplan–Meier analysis was used to examine differences in unadjusted survival

9. Results • Age of Red Cells • The newer and older blood units were delineated by the median storage time (i.e., 15 days), the number of patients receiving newer units and the number receiving older units were nearly equal.

10. The numbers of units transfused per patient The mean duration of storage per number of red-cell units transfused Red cell age

11. The distribution of ABO blood types, both for the recipients and for the units transfused, differed between the two groups) patients given newer blood were less likely to receive leukocyte-reduced red cell units were less likely to receive leukocyte-reduced red cell units often classified as NYH class IV and had a smaller body-surface area

12. slightly more patients in the older blood group had preoperative • mitral regurgitation (67.3% vs. 64.1%, P = 0.01), • abnormal left ventricular function (63.1% vs. • 57.9%, P<0.001), • and peripheral vascular disease)

13. Greater in-hospital mortality more likely to need prolonged ventilatory support More likely to have renal failure OR Septicemia multisystem organ failure composite outcome of multiple serious adverse events Complications

14. This unadjusted relationship indicates a trend, toward an association between blood storage time and the composite outcome. remained significant after adjustment for the baseline risk factors The dose–response relationship

15. The 1-year survival rate was 92.6% for the group receiving newer blood and 89.0% for the group receiving older blood The 1-year survival rate was 92.6% for the group receiving newer blood and 89.0% for the group receiving older blood

16. it would be necessary to restrict blood-storage time to 2 weeks or less for 28 ptns undergoing cardiac surgery to prevent one death during the first year after the operation. • most deaths occurred within the first 6 postoperative months

17. Discussion • “storage lesion” • is an amalgamation of reversible and irreversible changes that begin after 2 to 3 weeks of storage

18. “storage lesion”

19. “storage lesion” • The effects of prolonged storage on red cells include • decreased deformability, which can impede microvascular flow; • depletion of (2,3-DPG), which shifts the oxyhemoglobin dissociation curve to the left and reduces oxygen delivery • increased adhesiveness and aggregability • Reduction in the concentrations of nitric oxide and • adenosine triphosphate • accumulation of proinflammatory bioactive substances

20. “storage lesion”

21. “storage lesion”

22. “storage lesion” • It happened that the median red-cell storage time was 15 days, so that a 2-week cut off resulted in two groups of nearly equal size

23. The effect of red-cell age on outcomes • Inverse association between changes in gastric intramucosal pH and the age of transfused blood for patients who received red cells stored for more than 15 days • evidence of splanchnic ischemia developed in patients given older blood Marik PE,. Effect of stored blood transfusion on oxygen delivery in patients with sepsis. JAMA 1993

24. The effect of red-cell age on outcomes • Other studies demonstrated association between an increased duration of storage and • multiorgan failure • infectious complications, • and death

25. Discussion • Other investigations, however, showed no relationship between the duration of red-cell storage and adverse outcomes

26. examined broad outcome measures, such as length of stay 30-day mortality The authors reported similar outcomes in both groups; however, there were only a small number of outcome events

27. Discussion • “duration of storage” becomes difficult to define meaningfully if more than 1 unit is used. • Previous investigators have used • average, • median, • maximum duration of storage

28. Discussion • “imbalance in confounding” variables among groups under comparison when group assignment is not at random. • The provision of units of blood by a blood bank is not a random process • the blood bank is not blinded to the identity of transfusion recipients, and staff may become aware of the specific blood requirements of a rapidly bleeding patient.

29. Discussion • the blood bank routinely prepared 2 to 4 units of red cells the evening before planned surgical procedures and delivered them to the operating rooms the morning of surgery • a majority of patients received 1 or 2 units of blood, amounts not associated with active bleeding

30. Discussion • the number and distribution of units transfused in the two groups were fully balanced, and • the number of units was included as a variable in the multivariable modeling; therefore, • the adverse effects of transfusion per se do not confound the conclusion that outcomes are worse with older blood

31. Discussion • About half of all patients undergoing cardiac surgery are given blood, typically 1 or 2 units • The relative risk of postoperative death is increased by 30% in patients given blood that has been stored for more than 2 weeks

32. Conclusion • maintaining an adequate blood supply depends on the balance between blood donation and use • Improving donation • a reduction in the amount of blood transfused • the development of newer methods of blood storage to retard the progression of storage-related changes • inventory optimization

33. Conclusion • Further investigation will be necessary, however, before any substantial changes in blood banking practices can be considered for broad implementation on the basis of these data.

34. Critical Appraisal • Observational study • Randomized? no • Follow-up complete? yes • Blinded? NO • Blood bank is not blinded

35. Critical Appraisal • Groups similar at end of study ? Yes • Was follow-up sufficiently long and complete? yes • How would the results of this study change my clinical practice? NO • Is an observational study • Have great impact on the cost of blood • Need more RCTs

36. Thanks QUESTIONS??