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IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele. Pharmacological pre-emptive strategies for cardiac surgery : give me the magic bullet , please. INTERCEPT 2009 S Donato Milanese, Milan, April 17h 2009. Speaker: Landoni G.

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Pharmacological pre-emptive strategies for cardiac surgery : give me the magic bullet , please


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    1. IRCCS Ospedale San Raffaele Milano Università Vita-Salute San Raffaele Pharmacologicalpre-emptivestrategiesforcardiacsurgery: give me the magicbullet, please INTERCEPT 2009 S Donato Milanese, Milan, April 17h 2009 Speaker: Landoni G

    2. MAGIC BULLETS TO REDUCE MORTALITY IN CARDIAC SURGERY • THERE ARE NO GUIDELINES • THERE IS NO CONSENSUS CONFERENCE • THERE IS NO LARGE RANDOMIZED CONTROLLED STUDY ADEQUATELY POWERED TO SUGGEST A REDUCTION IN MORTALITY

    3. AN OVERVIEW OF META-ANALYSIS • PEXELIZUMAB • LEVOSIMENDAN • FENOLDOPAM • VOLATILE AGENTS (Intercept 2006)

    4. MAGIC BULLET PEXELIZUMAB LEVOSIMENDAN FENOLDOPAM VOLATILE AGENTS NNT TO PREVENT ONE DEATH 100 12 19 or 26 84 AN OVERVIEW OF META-ANALYSIS

    5. LEVOSIMENDAN 1

    6. LEVOSIMENDAN 2

    7. Description of the ten studies included in the meta-analysis. * CABG: coronary artery bypass graft † CPB: cardiopulmonary bypass ‡ OPCABG: off-pump coronary artery bypass graft

    8. Number of patients and interventions of included studies. † CPB: cardiopulmonary bypass # LCOS: low cardiac output syndrome

    9. Levosimendan and Mortality in Cardiac Surgery

    10. Levosimendan and Mortality in Cardiac Surgery • 11/235=4.7% v 26/205=12.7% • P=0.007 • NNT = 12

    11. Levosimendan and Myocardial Infarction

    12. Evidence! LEVOSIMENDAN VS CONTROLMyocardial Infarction in cardiac surgery • 2/183=1.1% v 9/153=5.9% • P=0.04

    13. Levosimendan and Acute Renal FailureNNT = 6

    14. LEVOSIMENDAN 2

    15. VOLATILE ANESTHETICS FENOLDOPAM DESMOPRESSIN ESMOLOL LEVOSIMENDAN VALVOLE PERCUTANEE landoni.giovanni@hsr.it www.itacta.org 4 200 AIFA 2006 34 1.000 MINISTRY 2008 3 200 3 200 10 1.000 3 150 ITACTA ONGOING RCTsTOPICS HOSPITALS PATIENTS GRANTS

    16. AIM OF THE STUDY To evaluate the renoprotective action of fenoldopam in a selected high-risk group of patients undergoing cardiac surgery

    17. RESULTS • Post-operative data

    18. Am J Kidney Dis. 2007;4956-68. IF 4.4

    19. Fenoldopam and Death in Critically ill patients 81/487(17%) versus 109/531 (21%) p=0.01 NNT=26

    20. Pooled estimates of risk for need for renal replacement therapy 34/526 (6%) versus 59/570 (10%) p=0.007 NNT=26

    21. Fenoldopam and Death in Cardiovascular Surgery 28/503 (6%) versus 55/503 (11%) p=0.002 NNT=19

    22. Fenoldopam and renal replacement therapy in cardiovascular surgery 30/528 (6%) versus 71/531 (13%) p<0.001 NNT=13

    23. VOLATILE ANESTHETICS FENOLDOPAM DESMOPRESSIN ESMOLOL LEVOSIMENDAN VALVOLE PERCUTANEE landoni.giovanni@hsr.it www.itacta.org 4 200 AIFA 2006 34 1.000 MINISTRY 2008 3 200 3 200 10 1.000 3 150 ITACTA ONGOING RCTsTOPICS HOSPITALS PATIENTS GRANTS

    24. FENO-HSR FENOLDOPAM E INSUFFICIENZA RENALE

    25. DESIGN • Fenoldopam vs placebo • randomized • double blind • multicenter (32 centers, 1000 patients)

    26. Which patients? “R” (RIFLE) after cardiac surgery Serum creatinine increase by 50% or Urinary output <0,5 ml/kg/h for 6 h Planned ICU stay > 24 hours

    27. AIM OF THE STUDY Reduction of the need for renal replacement therapy From 10% to 5%

    28. DESFLURANEversusPROPOFOL(fentanyl-based cardiac anesthesia)

    29. Troponin I after OFF-PUMP CABG

    30. Troponin I after CABG (CPB)

    31. Troponin I after MITRAL SURGERY

    32. Volatile Anesthetics

    33. META-ANALYSIS(cardiac anaesthesia) • 22 randomized studies (15 CPB-CABG; 6 OP-CABG; 1 mitral valve surgery) • 1922 patients (904 TIVA and 1018 DES or SEVO) • 16 studies administered volatile anesthetics throughout all the procedure (6 studies for 5-30 minutes)

    34. Evidence! Mortality

    35. Evidence! Mortality • 4/977=0.4% v 14/872=1.6% • NNT=84 • RRR=(1,6-0,4)/1,6=75% • OR: 0.31(0.12-0.80) • P=0.02

    36. Evidence! Myocardial infarction

    37. Evidence! Myocardial infarction • 24/979=2.4% v 45/874=5.1% • NNT=37 • RRR: (5.1-2.4)/5.1 = 53% • OR: 0.51(0.32-0.84) • p=0.008