Presented by: Maggie Savelberg On: February 18, 2009

1. Effects of Shed Mediastinal Blood on Cardiovascular and Pulmonary Function: A Randomized and Double Blind Study Presented by: Maggie Savelberg On: February 18, 2009

2. 1 Problem: Suction Blood Good? 4 3 2 Overview: Objective & Methods Results & Future Implications Limitations of Paper

3. Identification of a Problem I: Recirculation and retransfusion of shed mediastinal and pericardial blood (since 1978) has been associated with decreased homeostasis and increased morbidity Principle Findings (1995) : - ↑ thombin-antithrombin III levels - significant ↓ in post-op blood - ↑ tissue-type plasminogen activator loss (p<0.005) - ↑ fibrin degradation products - ↓ blood product use - ↑ free plasma hemoglobin Retransfusion of sucker blood = ↑ wound bleeding Ann Thorac Surg 1995;59:901-907

4. Identification of a Problem II: • Principle Findings (2000) : • - ↑endotoxin in pooled pericardial blood • (p<0.05) • proposed reinfusion as a possible • contributor to overall SIR • ↑[endotoxin] = respiratory failure, • renal failure, bleeding disorders, and • neurological dysfunction. Perfusion 2000;15:427-431

5. Identification of a Problem IV: Principle Findings (2004) : - significant ↑ TNF-α , IL-6, C3a in retransfusion group (p<0.001) - ↑volume retransfusion blood = ↑TNF-α levels = ↓ Hgb post-operatively Annals of Thoracic Surgery 2004;78:54-59

6. Interactive Cardiovascular and Thoracic Surgery 2009; Identification of a Problem III: Principle Findings (2008) : - lipid-microemboli size ranged from 10- 60µm which have been linked to poor neurological outcome following CPB. - ↑ concentration following cannulation and in shed blood from the pleura - Found in arterial side of HLM circuit ↑ lipid microemboli in pericardial sucker blood bleeding = link to ↓ neurological outcome

7. I. Objective: • Determine within subset of Cardiotomy Trial patients the effects of cardiotomy • blood processing on identified endpoints; • a) cardiovascular function • b) pulmonary mechanics • c) gas exchange Clinical identifiers of patient status/health Annals of Thoracic Surgery 2008;86:1167-74

8. 77 77 II. Methods:Study Design Patient Population: - 266 patients - non-emergent CABG and/or AV replacement - on-pump CPB - exclusions: neurological deficits pre-op coagulopathy bleeding diathesis thrombocytopenia renal insufficiency hepatic insufficiency - Control: received unprocessed shed mediastinal blood. - Treatment: received processed shed mediastinal blood. 266 patients Control Treatment 136 133 Additional Testing

9. II. Methods:Study Design Randomization: - computer generated randomization - allocation presented in sealed envelope to perfusionist by research coordinator just prior to giving heparin before CPB. - all members of the surgical team were unaware due to positioning of opaque drape - intraoperative decisions to transfuse blood products were made by anesthesia who again, were unaware of treatment assignment.

10. Treatment Control II. Methods: Intraoperative Protocol Interventional Plan: CPB Strategy: - narcotic based anesthetic - heparin for ACT >400 sec - CPB (roller pump, 43µm art filter closed venous reservoir) - prime (1,300mL) RL solution - bypass flows maintained at 2.4 – 3.2 L/min/m2 - antegrade cardioplegia & topical cooling - body temperature 34ºC, re-warmed to 37ºC Study Interventions: Sucker blood ↓ Circuit ↓ Patient Sucker blood ↓ Cell Saver ↓ LD Filter ↓ Circuit ↓ Patient

11. Baseline / Intraoperative characteristics similar Cardiotomy blood volume collected similar in both groups (p= 0.21) Patient Population III. Results: A Summary

12. Analyzed before, during and after CPB No difference in indices of mechanical pulmonary function or gas exchange b/t groups. Pulmonary Function III. Results: A Summary Variables Measured Tidal Volume Peak Inspiratory Pressure Positive End Expiratory Pressure Compliance **Arterial pO2 **Pulmonary Shunt (Qs/Qt %) **DO2 index **Oxygen Extraction Ratio (%) **Alveolar-arterial oxygen gradient Impairments in red starred ** variables (same in both the control and treatment groups)

13. Processed Sucker Blood Cardiovascular Effects III. Results: A Summary ↓ PVR + SVR ↑ Cardiac Index (p = 0.004) ↓duration myocardial Ischemia (p =0.02) ↑ hgb levels (p=0.003) being in processed group • Processed ● Unprocessed multivariate analysis revealed only independent pre/intra operative factors attributed to improved post-op cardiac index. ↑ Unprocessed sucker volume = ↓ cardiac hemodynamics

14. Clinical Outcomes Results: A Summary No ∆ in mortality ↑ creatine kinase in unprocessed group BUT troponin levels similar Unprocessed Processed P-value

15. Conclusion: & Future Implications Principle Findings : - Processing (centrifugal washing & leukocyte depleting filtration) of cardiotomy blood = no effect on mechanical pulmonary function = no effect on indices of pulmonary gas exchange - However, significant hemodynamic changes were observed as a result of cardiotomy blood processing. = ↓ PVR and SVR (approximately by 30%) = ↑ CI = trend toward ↓ ventilation time - Individualized Perfusion: (tailored approach) Benefits may to process suctioned blood in patients with poor LV vs. those with good LV function who are high risk of bleeding complications (further complicate bleeding by loss of PLT and coagulation factors from cell saver)

16. Limitation #2 Limitation #1 Limitation #3 IV. Limitations: • “Processing” consisted of both centrifugal washing & lipid/leukocyte reduction • To which do we • attribute the outcomes? • Use of cell saver associated with loss of coagulation factors and PLTs. • Perhaps looking at chest tube loss post-operatively, and blood product use? Could have done the same evaluation with a group of patients just discarding suction blood if it is a small volume.

17. Thank You! Please feel free to post questions/comments to OSCP site for discussion.