For Doctors in a Hurry
- Clinicians lack effective preventive strategies to reduce myocardial injury occurring after major noncardiac abdominal surgery.
- The researchers conducted a randomized, sham-controlled trial involving 766 patients to evaluate a two-session remote ischemic preconditioning protocol.
- Myocardial injury occurred in 17.4 percent of the intervention group versus 17.9 percent of controls, yielding a non-significant risk ratio of 1.04.
- The authors concluded that this specific two-session preconditioning protocol failed to reduce the incidence of postoperative myocardial injury.
- Higher troponin levels observed in the intervention group require further study to determine their long-term clinical significance for patient outcomes.
Mitigating Myocardial Injury in Noncardiac Surgery
Myocardial injury after noncardiac surgery (MINS) is a common complication defined by elevated cardiac troponin levels resulting from a presumed ischaemic mechanism, and it is independently associated with increased short-term and long-term mortality [1]. Remote ischaemic preconditioning (RIPC), a technique involving brief, non-lethal cycles of limb ischaemia and reperfusion to activate innate systemic cardioprotection, has been extensively studied as a low-cost intervention to mitigate this risk [2, 3]. While some trials in cardiac surgery have demonstrated reductions in perioperative myocardial injury and improvements in short-term clinical outcomes, results in the noncardiac setting remain largely inconsistent [4, 5, 6]. This discrepancy may stem from variations in anaesthetic regimens or the timing of the ischaemic stimulus relative to the surgical insult [4, 7]. A new randomized controlled trial now examines whether a two-session protocol can effectively reduce the incidence of MINS in patients undergoing major abdominal surgery.
Dual-Phase Preconditioning Protocol and Trial Design
The researchers conducted a prospective, two-centre, observer-blinded, randomised, sham-controlled trial (NCT05733208) to evaluate whether a more intensive preconditioning regimen could overcome the inconsistent results seen in previous studies. This trial focused on the physiological observation that remote ischaemic preconditioning (RIPC) confers distinct early and delayed cardioprotection, providing two separate windows of systemic defense against ischaemic injury. The first window of protection appears within minutes and lasts for a few hours, while a second, delayed window emerges approximately 24 hours later and can persist for several days. By utilizing a two-session protocol, the investigators aimed to activate both phases of this innate protective mechanism to provide continuous coverage during the perioperative period. A total of 766 patients undergoing abdominal surgery were allocated to either a RIPC intervention or a sham procedure. The active intervention was precisely defined, consisting of four cycles of 5-minute ischaemia followed by 5-minute reperfusion applied to the upper limb using a manual blood pressure cuff. To capture both protective windows, the researchers applied the RIPC protocol twice: once 24 hours before the induction of anaesthesia and again 1 hour before anaesthesia. The control group received a sham procedure that mimicked the timing and appearance of the intervention without inducing limb ischaemia. The primary outcome was the incidence of Myocardial Injury after Noncardiac Surgery (MINS), defined according to American Heart Association criteria as a postoperative elevation in cardiac troponin levels thought to result from myocardial ischaemia without requiring the presence of clinical symptoms or electrocardiographic changes.
Patient Characteristics and Primary Outcomes
The trial enrolled a total of 766 patients undergoing abdominal surgery, providing a robust sample size to evaluate the efficacy of the dual-session preconditioning protocol. The study population had a median age of 71 years, representing a high-risk demographic typically susceptible to perioperative cardiac complications. Within this cohort, 33.7% of the participants (258 of 766) were female, ensuring the findings are applicable across a broad clinical spectrum of patients requiring major abdominal interventions. The primary outcome analysis revealed that the intensive preconditioning regimen did not provide the anticipated cardioprotection. Myocardial Injury after Noncardiac Surgery (MINS) occurred in 64 of 368 patients (17.4%) in the remote ischaemic preconditioning (RIPC) group, compared to 66 of 368 patients (17.9%) in the control group. This marginal difference was not statistically significant, as evidenced by an adjusted risk ratio for MINS of 1.04 (95% confidence interval, 0.76 to 1.41; P=0.808). These data demonstrate that the two-session RIPC protocol did not reduce the incidence of MINS in patients undergoing abdominal surgery, suggesting that targeting both the early and delayed windows of ischaemic protection does not translate into a measurable clinical benefit for this surgical population.
Secondary Cardiovascular Events and Troponin Release
Beyond the primary incidence of myocardial injury, the researchers evaluated several secondary outcomes to determine if the intervention influenced broader clinical stability. These secondary outcomes included total high-sensitivity cardiac troponin T release and a series of cardiovascular events, such as myocardial infarction, heart failure, and cardiac arrest. Despite the theoretical benefits of preconditioning, no significant differences were observed in secondary cardiovascular outcomes between groups. This lack of divergence in clinical events aligns with the primary outcome data, suggesting that the two-session remote ischaemic preconditioning protocol failed to provide a measurable protective effect against major postoperative complications in this surgical cohort. A notable and unexpected finding emerged regarding the biochemical markers of cardiac stress. Total high-sensitivity cardiac troponin T release within the first 3 postoperative days was higher in the remote ischaemic preconditioning group compared to the control group. Specifically, the median difference in troponin T release was 32 ng L-1 (95% confidence interval, 12 to 52; P=0.002). This paradoxical elevation is clinically relevant because myocardial injury after noncardiac surgery is associated with both short-term and long-term mortality. While the mechanism for this increase remains unclear, the researchers noted that the increased troponin release after remote ischaemic preconditioning warrants further investigation to determine its long-term clinical significance, particularly as it may indicate a subclinical stress response rather than the intended cardioprotection.
References
1. Wang F, Liang C, Shi J, et al. Effects of remote ischaemic preconditioning on myocardial injury after major abdominal surgery in patients at high risk for cardiovascular adverse events in China (RIPC-MAS): protocol for a randomised, sham-controlled, observer-blinded trial.. BMJ open. 2023. doi:10.1136/bmjopen-2023-073038
2. Papadopoulou A, Dickinson M, Samuels TL, Heiss C, Forni L, Creagh-Brown B. Efficacy of remote ischaemic preconditioning on outcomes following non-cardiac non-vascular surgery: a systematic review and meta-analysis.. Perioperative medicine (London, England). 2023. doi:10.1186/s13741-023-00297-0
3. Ackland GL, Pinto BB. The PRINCE trial of remote ischaemic preconditioning in noncardiac surgery to reduce myocardial injury: sign o' the times.. British journal of anaesthesia. 2026. doi:10.1016/j.bja.2025.11.005
4. Deferrari G, Bonanni A, Bruschi M, Alicino C, Signori A. Remote ischaemic preconditioning for renal and cardiac protection in adult patients undergoing cardiac surgery with cardiopulmonary bypass: systematic review and meta-analysis of randomized controlled trials.. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2018. doi:10.1093/ndt/gfx210
5. Candilio L, Malik A, Ariti C, et al. Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial.. Heart (British Cardiac Society). 2015. doi:10.1136/heartjnl-2014-306178
6. Hausenloy D, Candilio L, Evans R, et al. Effect of Remote Ischaemic preconditioning on Clinical outcomes in patients undergoing Coronary Artery bypass graft surgery (ERICCA study): a multicentre double-blind randomised controlled clinical trial. 2016. doi:10.3310/EME03040
7. Moscarelli M, Fiorentino F, Suleiman M, et al. Remote ischaemic preconditioning in isolated aortic valve and coronary artery bypass surgery: a randomized trial†.. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2019. doi:10.1093/ejcts/ezy404
