Effect of Remote Ischemic Preconditioning on Myocardial Injury in Noncardiac Surgery: The PRINCE Randomized Clinical Trial
Abstract
BACKGROUND: Major noncardiac surgery is associated with high rates of postoperative myocardial injury and other complications. Remote ischemic preconditioning (RIPC) was reported to decrease these complication rates. 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 mm Hg. The primary end point 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 patients to RIPC and 614 to sham RIPC. The most frequent surgical procedures were abdominal or intrathoracic surgeries (406 patients [33.6%]). RIPC was applied to the upper limb in 1014 patients (84.8%) and to the lower limb in 182 patients (15.2%). Postoperative myocardial injury occurred in 215 of 566 patients (38.0%) in the RIPC group and in 223 of 596 patients (37.4%) in the sham RIPC group (relative risk, 1.02 [95% CI, 0.88–1.18; P =0.84). There were no significant differences in the rate of any secondary outcomes. We observed 11 episodes of limb petechiae (10 [1.7%] in the RIPC group versus one [0.2%] in the sham RIPC group) and 34 (6.0%) hospital readmissions in the RIPC group versus 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. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02427867.
Article Details
Authors (121)
Levan Berikashvili
V.A. Negovsky Scientific Research Institute of General Reanimatology, Moscow, Russia (L. Berikashvili, K.K., P.R., A.S., V.L.).
Alessandro Belletti
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Francesco Meroi
Department of Emergency, University Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale “Santa Maria della Misericordia,” Udine, Italy (F. Meroi, T.B.).
Stefano Fresilli
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Aituar Kabibulatov
Astana Medical University, Kazakhstan (A. Kabibulatov, A. Konkayev).
Andrea Russo
Sergey Efremov
Saint-Petersburg State University Hospital, St. Petersburg, Russia
Lini Wang
Department of Anesthesiology and Perioperative Medicine, Anesthesia Clinical Research Center, Xijing Hospital, Xi’an, China (L.W., C.L.).
Simone Vietri
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy (M.G., G. Lombardi, M.P., F. Monaco, A.B., S.F., G.G., F.M.O., R. Lembo, S.V., F.D., R. Labanca, M. Marmiere, A.P., L. Beretta, G.M., A.Z., G. Landoni, S.T.).
Elena Momesso
Department of Anesthesiology and Intensive Care, ULSS 4 Veneto Orientale, San Donà di Piave, Italy (E.M.).
Filippo D’Amico
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Kristina Kadantseva
V.A. Negovsky Scientific Research Institute of General Reanimatology, Moscow, Russia (L. Berikashvili, K.K., P.R., A.S., V.L.).
Rosa Labanca
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Pavel Ryzhkov
V.A. Negovsky Scientific Research Institute of General Reanimatology, Moscow, Russia (L. Berikashvili, K.K., P.R., A.S., V.L.).
Marilena Marmiere
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Valerii Subbotin
Loginov Moscow Clinical Scientifiс Center, Moscow, Russia (K.K., V.S.).
Alessandro Pruna
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Nerlep Rana
Department of Anesthesiology, Ospedale Regionale di Lugano, Switzerland (N.R.).
Francesca Livi
Department of Anesthesia and Critical Care, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy (F.L.).
Hugo Mantilla-Gutierrez
Fundación Cardioinfantil-Instituto de Cardiología, Bogotá, Colombia (H.M.-G.).
Ivan Situm
Marco Micali
Anaesthesia and Intensive Care, E.O. Ospedali Galliera, Genoa, Italy (C.B., M. Micali).
Stefano Bosso
Anesthesia and Intensive Care Unit Department, “Cardinal Massaia” Hospital, Asti, Italy (A. Roasio, S.B.).
Anastasia Smirnova
V.A. Negovsky Scientific Research Institute of General Reanimatology, Moscow, Russia (L. Berikashvili, K.K., P.R., A.S., V.L.).
Giuseppe Fresta
Department of Anesthesia, Pain Medicine and Intensive Care Unit, Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS, Rome, Italy (A. Russo, G.F.).
Andrey Cherednichenko
Saint-Petersburg State University Hospital, Russia (S.E., A.C.).
Luigi Beretta
Giacomo Monti
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Francesco Corradi
Department of Surgical, Medical, Molecular Pathology and Critical Care Medicine, University of Pisa, Italy (F.C.).
Maurizio Cecconi
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy (M.G., M.C.).
Andrey Yavorovskiy
I.M. Sechenov First Moscow State Medical University of the Russian Ministry of Health, Moscow, Russia (A.Y., V.L.).
Matteo Aldo Bonizzoni
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Tiziana Cabrini
Francesca Cavenago
Benedetta Chiodi
Edoardo Cristallo
Jacopo D’Andria Ursoleo
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Noemi De Piccoli
Francesco Deni
Sara Fiorito
Rosario Losiggio
Renato Meani
Elena Moizo
Cristina Nakhnoukh
Francesco Giuseppe Nisi
Lisa Notarianni
Anita Nutta
Domenico Pontillo
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Erica Ronca
Tommaso Scquizzato
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Luisa Zaraca
Özgün Ömer Asiller
Marta Veneziano
Federico Ghignone
Vincenzo Bosco
Giuseppe Neri
Assyia Kadralinova
Nazerke Zhanarystan
Augusta Danella
Lorenzo Foti
Alessandra Besozzi
Laura Pasin
Jelena Lesanovis
Milica Stojicic
Michela Gandini
Marco Gemma
Michele Introna
Carolina Sassorossi
Yamume Tshomba
Renato Ricciardi
Felix Ramon Montes
Pavel Bagdasarov
Daria Yavorovskaya
Federico Piccioni
Andrea Pradella
Roman Mikhey
Yuki Kotani
Sergey Ushakov
Ekaterina Svetalkina
Massimo Zambon
Paolo Maino
Valeria Govorushkina
Maxim Monastyrnyy
Nicoletta Boffa
Maria Carmen Guarino
Ante Erceg
Federico Faitini
Daniele Orso
Cono Alberto Lanza
Martina Baiardo Redaelli
Desjan Filolli
Katia Donadello
Ekaterina Chernevskaya
Mikhail Yadgarov
Baobao Gao
Xue Yang
Massimiliano Greco
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy (M.G., M.C.).
Gaetano Lombardi
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy (M.G., G. Lombardi, M.P., F. Monaco, A.B., S.F., G.G., F.M.O., R. Lembo, S.V., F.D., R. Labanca, M. Marmiere, A.P., L. Beretta, G.M., A.Z., G. Landoni, S.T.).
Marina Pieri
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Rosalba Lembo
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy (M.G., G. Lombardi, M.P., F. Monaco, A.B., S.F., G.G., F.M.O., R. Lembo, S.V., F.D., R. Labanca, M. Marmiere, A.P., L. Beretta, G.M., A.Z., G. Landoni, S.T.).
Lian Kah Ti
Department of Anaesthesia, National University Hospital, Singapore
Chong Lei
Department of Anesthesiology and Perioperative Medicine, Anesthesia Clinical Research Center, Xijing Hospital, Xi’an, China
Aidos Konkayev
Astana Medical University, Kazakhstan (A. Kabibulatov, A. Konkayev).
Tiziana Bove
Department of Emergency, University Hospital of Udine, Azienda Sanitaria Universitaria Friuli Centrale Santa Maria della Misericordia, Udine, Italy
Alberto Zangrillo
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Giovanni Landoni
Rinaldo Bellomo
Department of Critical Care, University of Melbourne, Melbourne, VIC, Australia
Remo Daniel Covello
Anesthesia and Intensive Care Unit, Emergency Department, Busto Arsizio Hospital, ASST Valle Olona, Busto Arsizio, Italy (R.D.C.).
Stefano Turi
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Claudia Brusasco
Anaesthesia and Intensive Care, E.O. Ospedali Galliera, Genoa, Italy (C.B., M. Micali).
Agostino Roasio
Anesthesia and Intensive Care Unit Department, “Cardinal Massaia” Hospital, Asti, Italy (A. Roasio, S.B.).
Fabrizio Monaco
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Giuseppe Giardina
Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan
Federico Mattia Oliva
Department of Anesthesia and Intensive Care, IRCCS (Istitituto di Ricovero e Cura a Carattere Scientifico) San Raffaele Scientific Institute, Milan, Italy (S.T., F.M.O., R.L., G.L., D.P.).
Fabio Guarracino
Department of Cardiothoracic and Vascular Anesthesia and Intensive Care, Azienda Ospedaliero Universitaria Pisana, Pisa, Italy
Lorenzo Schiavoni
Pasquale Sansone
Department of Women, Child and General and Specialized Surgery, University of Campania “L. Vanvitelli,” Naples, Italy (P.S.).
Valery Likhvantsev
Federal Clinical and Research Center of Intensive Care and Rehabilitation, Moscow
Antonio Pisano
Alessandro Putzu
Carolina Soledad Romero Garcia