Effects of remote ischemic preconditioning in high-risk patients undergoing cardiac surgery (Remote IMPACT): a randomized controlled trial

Background:Remote ischemic preconditioning is a simple therapy that may reduce cardiac and kidney injury. We undertook a randomized controlled trial to evaluate the effect of this therapy on markers of heart and kidney injury after cardiac surgery.Methods:Patients at high risk of death within 30 days after cardiac surgery were randomly assigned to undergo remote ischemic preconditioning or a sham procedure after induction of anesthesia. The preconditioning therapy was three 5-minute cycles of thigh ischemia, with 5 minutes of reperfusion between cycles. The sham procedure was identical except that ischemia was not induced. The primary outcome was peak creatine kinase–myocardial band (CK-MB) within 24 hours after surgery (expressed as multiples of the upper limit of normal, with log transformation). The secondary outcome was change in creatinine level within 4 days after surgery (expressed as log-transformed micromoles per litre). Patient-important outcomes were assessed up to 6 months after randomization.Results:We randomly assigned 128 patients to remote ischemic preconditioning and 130 to the sham therapy. There were no significant differences in postoperative CK-MB (absolute mean difference 0.15, 95% confidence interval CI] −0.07 to 0.36) or creatinine (absolute mean difference 0.06, 95% CI −0.10 to 0.23). Other outcomes did not differ significantly for remote ischemic preconditioning relative to the sham therapy: for myocardial infarction, relative risk (RR) 1.35 (95% CI 0.85 to 2.17); for acute kidney injury, RR 1.10 (95% CI 0.68 to 1.78); for stroke, RR 1.02 (95% CI 0.34 to 3.07); and for death, RR 1.47 (95% CI 0.65 to 3.31).Interpretation:Remote ischemic precnditioning did not reduce myocardial or kidney injury during cardiac surgery. This type of therapy is unlikely to substantially improve patient-important outcomes in cardiac surgery. Trial registration: ClinicalTrials.gov, no. {"type":"clinical-trial","attrs":{"text":"NCT01071265","term_id":"NCT01071265"}}NCT01071265.Each year, 2 million patients worldwide undergo cardiac surgery. For more than 25% of these patients, the surgery is complicated by myocardial infarction (MI) and/or acute kidney injury, both of which are strongly associated with morbidity and mortality.^1–3 Preventing MI and acute kidney injury after cardiac surgery would improve survival.An important cause of MI and acute kidney injury in patients undergoing cardiac surgery is ischemia–reperfusion injury.^4,5 This type of injury begins as ischemia, which is then exacerbated by a systemic inflammatory response upon restoration of organ perfusion.⁶ Remote ischemic preconditioning may mitigate ischemia–reperfusion damage. It is accomplished by inducing, before surgery, brief episodes of ischemia in a limb, which lead to widespread activation of endogenous cellular systems that may protect organs from subsequent severe ischemia and reperfusion.^7–9Small randomized controlled trials evaluating the efficacy of remote ischemic preconditioning have had mixed results.^10–17 Interpretation of their data is difficult because of small sample sizes and heterogeneity in the preconditioning procedures and patient populations (e.g., few trials have evaluated patients at high risk of organ injury and postoperative death). Whether remote ischemic preconditioning effectively mitigates ischemia–reperfusion injury therefore remains uncertain. We undertook the Remote Ischemic Preconditioning in Cardiac Surgery Trial (Remote IMPACT) to determine whether this procedure reduces myocardial and kidney injury. We proposed that a large trial to determine the effect on clinically important outcomes would be worthwhile only if a substantial effect on myocardial or kidney injury, or both, were observed in the current study.