Abstract and Introduction
Abstract
Aims The aim of this study was to evaluate whether remote ischaemic preconditioning (RIPC) combined with remote ischaemic postconditioning (RIPostC) improves the clinical outcomes of patients undergoing cardiac surgery.
Methods and results From June 2009 to November 2010, 1280 patients who underwent elective cardiac surgery were randomized into the RIPC with RIPostC group or the control group in the morning of the surgery. In the RIPC with RIPostC group, four cycles of 5-min ischaemia and 5-min reperfusion were administered twice to the upper limb—before cardiopulmonary bypass (CPB) or coronary anastomoses for RIPC and after CPB or coronary anastomoses for RIPostC. The primary endpoint was the composite of major adverse outcomes, including death, myocardial infarction, arrhythmia, stroke, coma, renal failure or dysfunction, respiratory failure, cardiogenic shock, gastrointestinal complication, and multiorgan failure. Remote ischaemic preconditioning with RIPostC did not reduce the composite outcome compared with the control group (38.0 vs. 38.1%, respectively; P = 0.998) and there was no difference in each major adverse outcome. The intensive care unit and hospital stays were not different between the two groups. However, in the off-pump coronary artery bypass surgery subgroup, multivariate logistic regression analysis revealed that RIPC with RIPostC was related to increased composite outcome (odds ratio: 1.54; 95% confidence interval: 1.02–2.30; P = 0.038).
Conclusion Remote ischaemic preconditioning with RIPostC by transient upper limb ischaemia did not improve clinical outcome in patients who underwent cardiac surgery.
Clinical Trial Registration clinicaltrials.gov, NCT00997217.
Introduction
Brief sublethal ischaemia activates a robust protective system against ischaemic reperfusion injury for a specific time window. Following the first identification of ischaemic preconditioning by Murry et al., ischaemic preconditioning has been shown to provide powerful protective effects on ischaemic reperfusion injury in animal and in vitro studies. Given the predictive time window for ischaemic reperfusion injury, ischaemic preconditioning seemed to be particularly suitable in cardiac surgeries during which ischaemic reperfusion-related complications are frequent. However, ischaemic preconditioning is an invasive technique using repeated aorta cross-clamp or coronary artery occlusion. There have been continued trials to improve the classic ischaemic preconditioning technique.
In early clinical studies, remote ischaemic preconditioning (RIPC) showed impressive results. In RIPC, brief sublethal ischaemia applied to remote organs or tissues induced systemic protection and significantly attenuated postoperative troponin elevation in cardiac and non-cardiac surgery patients. The RIPC techniques used in these studies were very simple, inexpensive, and non-invasive. Remote ischaemic preconditioning is considered a promising cardioprotective technique for cardiac surgery patients. However, there have been some contradictory results, in which RIPC did not reduce perioperative troponin release. Although RIPC is expected to exert a systemic protective effect, several studies of the effect of RIPC on renal failure have failed to show a significant benefit.
In the present study, we hypothesized that RIPC with RIPostC (remote ischaemic postconditioning) would improve clinical outcomes by decreasing perioperative complications in patients undergoing cardiac surgery. To evaluate this hypothesis, we conducted a prospective randomized controlled study in patients undergoing cardiac surgery.