TY - JOUR

T1 - Effect of Remote Ischemic Preconditioning on Myocardial Injury in Noncardiac Surgery

T2 - the PRINCE Randomized Clinical Trial

AU - PRINCE Study Group

AU - Greco, Massimiliano

AU - Lombardi, Gaetano

AU - Brusasco, Claudia

AU - Pieri, Marina

AU - Roasio, Agostino

AU - Monaco, Fabrizio

AU - Berikashvili, Levan

AU - Belletti, Alessandro

AU - Meroi, Francesco

AU - Fresilli, Stefano

AU - Kabibulatov, Aituar

AU - Giardina, Giuseppe

AU - Russo, Andrea

AU - Oliva, Federico Mattia

AU - Efremov, Sergey

AU - Lembo, Rosalba

AU - Wang, Lini

AU - Vietri, Simone

AU - Momesso, Elena

AU - D'Amico, Filippo

AU - Kadantseva, Kristina

AU - Labanca, Rosa

AU - Ryzhkov, Pavel

AU - Marmiere, Marilena

AU - Subbotin, Valery

AU - Pruna, Alessandro

AU - Rana, Nerlep

AU - Livi, Francesca

AU - Mantilla-Gutierrez, Hugo

AU - Guarracino, Fabio

AU - Schiavoni, Lorenzo

AU - Šitum, Ivan

AU - Micali, Marco

AU - Bosso, Stefano

AU - Smirnova, Anastasia

AU - Fresta, Giuseppe

AU - Cherednichenko, Andrey

AU - Beretta, Luigi

AU - Monti, Giacomo

AU - Ti, Lian Kah

AU - Sansone, Pasquale

AU - Corradi, Francesco

AU - Cecconi, Maurizio

AU - Yavorovskiy, Andrey

AU - Lei, Chong

AU - Konkayev, Aidos

AU - Bove, Tiziana

AU - Likhvantsev, Valery

AU - Zangrillo, Alberto

AU - Landoni, Giovanni

PY - 2025/10/28

Y1 - 2025/10/28

N2 - BACKGROUND: Major noncardiac surgery carries high rates of postoperative myocardial injury and other complications. Remote ischemic preconditioning (RIPC) was reported to decrease these complications. However, such supportive evidence lacks robustness.METHODS: In a multinational, double-blind trial, we randomly assigned adult high-risk patients undergoing noncardiac surgical procedures to receive RIPC or sham-RIPC after the induction of general anesthesia and before surgery. RIPC involved three 5-minute ischemic cycles, each followed by 5 minutes of reperfusion, using a blood-pressure cuff inflated to 200 mmHg. The primary endpoint was the rate of myocardial injury defined by an increase in postoperative troponin levels above the highest 99th percentile of reference values. Secondary outcomes included myocardial infarction, stroke, acute kidney injury, need for intensive care unit, length of hospital stay and 30-day all-cause mortality.RESULTS: We recruited 1213 patients in 25 hospitals and 8 countries. We randomly assigned 599 to RIPC and 614 to sham-RIPC. The most frequent surgical procedures were abdominal and intrathoracic surgeries (406 patients, 33.6%). RIPC was applied to the upper limb in 1,014 patients (84.8%) and to the lower limb in 182 patients (15.2%). Postoperative myocardial injury occurred in 215/566 patients (38.0%) in the RIPC group and in 223/596 patients (37.4%) in the sham-RIPC group (relative risk, 1.02; 95% confidence interval, 0.88 to 1.18; P=0.84). There were no significant differences in the rate of any secondary outcomes. We observed eleven episodes of limb petechiae (10 [1.7%] in the RIPC group vs 1 [0.2%] in the sham-RIPC group) and 34 (6.0%) hospital readmissions in the RIPC group vs 20 (3.5%) in the sham-RIPC group.CONCLUSIONS: Among adult patients undergoing noncardiac surgery, RIPC did not reduce myocardial injury or other postoperative complications.

AB - BACKGROUND: Major noncardiac surgery carries high rates of postoperative myocardial injury and other complications. Remote ischemic preconditioning (RIPC) was reported to decrease these complications. However, such supportive evidence lacks robustness.METHODS: In a multinational, double-blind trial, we randomly assigned adult high-risk patients undergoing noncardiac surgical procedures to receive RIPC or sham-RIPC after the induction of general anesthesia and before surgery. RIPC involved three 5-minute ischemic cycles, each followed by 5 minutes of reperfusion, using a blood-pressure cuff inflated to 200 mmHg. The primary endpoint was the rate of myocardial injury defined by an increase in postoperative troponin levels above the highest 99th percentile of reference values. Secondary outcomes included myocardial infarction, stroke, acute kidney injury, need for intensive care unit, length of hospital stay and 30-day all-cause mortality.RESULTS: We recruited 1213 patients in 25 hospitals and 8 countries. We randomly assigned 599 to RIPC and 614 to sham-RIPC. The most frequent surgical procedures were abdominal and intrathoracic surgeries (406 patients, 33.6%). RIPC was applied to the upper limb in 1,014 patients (84.8%) and to the lower limb in 182 patients (15.2%). Postoperative myocardial injury occurred in 215/566 patients (38.0%) in the RIPC group and in 223/596 patients (37.4%) in the sham-RIPC group (relative risk, 1.02; 95% confidence interval, 0.88 to 1.18; P=0.84). There were no significant differences in the rate of any secondary outcomes. We observed eleven episodes of limb petechiae (10 [1.7%] in the RIPC group vs 1 [0.2%] in the sham-RIPC group) and 34 (6.0%) hospital readmissions in the RIPC group vs 20 (3.5%) in the sham-RIPC group.CONCLUSIONS: Among adult patients undergoing noncardiac surgery, RIPC did not reduce myocardial injury or other postoperative complications.

KW - Adult

KW - Aged

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Ischemic Preconditioning/methods

KW - Male

KW - Middle Aged

KW - Myocardial Infarction/prevention & control

KW - Myocardial Reperfusion Injury/prevention & control

KW - Postoperative Complications/prevention & control

KW - Surgical Procedures, Operative/adverse effects

KW - Treatment Outcome

U2 - 10.1161/circulationaha.125.075254

DO - 10.1161/circulationaha.125.075254

M3 - Article

C2 - 40511609

VL - 152

SP - 1194

EP - 1205

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 17

ER -