1. A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery P. Meybohm, B. Bein, O. Brosteanu, J. Cremer, M. Gruenewald, C. Stoppe, M. Coburn, G. Schaelte, A. B.ning, B. Niemann, J. Roesner, F. Kletzin, U. Strouhal, C. Reyher, R. Laufenberg ‑ Feldmann, M. Ferner, I.F. Brandes, M. Bauer, S.N. Stehr, A. Kortgen, M. Wittmann, G. Baumgarten, T. Meyer ‑ Treschan, P. Kienbaum, M. Heringlake, J. Sch.n, M. Sander, S. Treskatsch, T. Smul, E. Wolwender, T. Schilling, G. Fuernau, D. Hasenclever, and K. Zacharowski, for the RIPHeart Study Collaborators* N Engl J Med 2015;373:1397-407. DOI: 10.1056/NEJMoa1413579 R2. 이성곤 /pf. 김우식

2. Back-ground Cardiac surgery  risk of end-organ ischemic & reperfusion injury. Remote ischemic preconditioning(RIPC) : is reported to help remote vital organs withstand a subsequent prolonged ischemic event ? Proof-of-concept trials  Myocardial and kidney injury ↓ (btw. RIPC & control groups ); but. small samples.  Large, randomized this study

3. Method(1) **Trial Design and Oversight : Screened & underwent randomization during (2011.1~ 2014.5) (German 14 university hospitals) Prospective, randomized, double-blind, multicenter, parallel-group controlled trial :1403 patients undergoing cardiac surgery, randomization  Perioperative death, as assessed with the use of the logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE). EuroSCORE : 17 pre-operative items of information about the pt. and the planned type of surgery and uses logistic regression.  Calculate the risk of death within 30 days after surgery.  Higher score ?  Higher risk of death.

4. Method(2) **Patients ≥ 18 years who were scheduled for elective cardiovascular surgery Exclusion criteria : Specific surgical procedures (e.g., off-pump heart surgery or urgent surgery) and severe organ dysfunction(e.g. EF <30% or severe renal failure). **Intervention and Blinding : RIPC at least 15 mm Hg higher than the patient’s actual SAP VS sham RIPC dummy arm was used for similar cycles To ensure double blinding, the intervention was performed on patients who were already anesthetized

5. Method(3)

6. Method(3) ** Primary and Secondary End Points Primary end point : death from any cause, ~D/C (~14 days) ① Nonfatal MI : biomarker (e.g., Tn) values ≥ 5 times the 99th percentile of the normal reference range + one or more of the following (new pathologic Q waves or new LBBB within the 1st 72 hours after surgery, standard clinical criteria for MI from 72 hours ischemia by TTE or CAG, or diagnosed at autopsy.) ② Stroke : any new, temporary or permanent, focal or global neurologic deficit, evaluated according to the National Institutes of Health Stroke Scale ( ≥4 points on a scale of 0 ~ 42, higher scores  greater severity) or autopsy. ③ ARF: sCr ≥ 2 or more from baseline, or urine output < 0.5 ml/kg/hr for 12 hours, use of RRT, or evidence of autopsy. Secondary end points: at 30, 90 days, and 12 mo. after surgery duration of mechanical ventilation, length of stay in the ICU and total hospital stay, levels of TnT and TnI, Cr. level, new onset of A-fib, and incidence of post-op. delirium

7. 218 42 did not receive the assinged interventoin 1385 1) Study population Excluded from the per-protocol analysis for the following reasons : 142 received an inadequate intervention (e.g., the cuff pressure was too low or was applied for too short a time), : 41 received volatile anesthetics, : 10 underwent a different type of surgery (e.g., off-pump CAB surgery) : 51 exclusion criteria (e.g., prev. MI ≤7 days or severe COPD)

8. Result(2) 437/1385 (31.3%) ≥ 6 437/1385 (31.3%) ≥ 6 383/1385 (27.7%) 383/1385 (27.7%)

9. Result(3)

10. Supplementary appendix 1243

11. 10(85.2%) 9(85.0%) (84.5%) (84.4%) Result(4)

12. Result(5)

13. Cumulative Incidence of Composite Components. A. Death of any cause (p=0.76) B.MI (p=0.11) C.Stroke (p=0.27) D. ARF (p=0.29)

16. Conclusion In conclusion, in our large-scale, double-blind, multicenter trial, no significant difference was observed between upper-limb RIPC and a sham intervention with respect to the rate of postoperative myocardial infarction, stroke, renal failure, and death within 90 days after elective cardiac surgery.