Effect of remote ischaemic preconditioning on clinical outcomes in patients undergoing cardiac bypass surgery: a randomised controlled clinical trial (original) (raw)
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Is remote ischaemic preconditioning of benefit to patients undergoing cardiac surgery?
Interactive CardioVascular and Thoracic Surgery, 2012
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was whether remote ischaemic preconditioning (RIPC) is of benefit to patients undergoing cardiac surgery. Altogether, more than 264 papers were found using the reported search, 16 of which represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. We conclude that RIPC is a safe protocol which could potentially be used in cardiac surgery to provide additional cardiac protection against ischaemia reperfusion injury, although it may not be appropriate for patients on K + ATPase channel blockers (sulphonylureas) as they seem to eliminate the effect of RIPC. In our study, we found two meta-analyses of cardiac surgery with or without RIPC. Both unequivocally showed 0.81 and 0.74 standardized mean reduction in myocardial necrosis markers in patients receiving RIPC and cardiac or vascular surgery. No difference in perioperative myocardial infarction incidence or 30-day mortality were found. In adult cardiac surgery, we found 11 randomized control trials (RCTs) ranging in size from 45 to 162 patients. Two representative studies reported no difference in postoperative cardiac troponin I concentration in RIPC vs. controls. In one of the studies (CABG ± RIPC) no additional benefit could have been observed for RIPC regarding intra-aortic balloon pump usage (controls 8.5 vs. RIPC 7.5%), inotropic support (39 vs. 50%) or vasoconstrictor usage (66 vs. 64%). On the other hand, in the other study [CABG ± AVR (aortic valve replacement) ± RIPC] significant reduction of troponin I at 8 h postoperatively (controls, 2.90 µg/l vs. RIPC, 2.54 µg/l, P = 0.043) was shown. Marked reduction in cardiac necrosis markers was also found in several smaller RCTs concerning coronary artery bypass grafting (CABG) patients receiving RIPC preoperatively: with cold crystalloid cardioplegia (44.5% reduction), with cross-clamping and fibrillation (43% reduction) and with cold blood cardioplegia (42.4% reduction). The proof of concept trials summarized here give some early evidence that RIPC may potentially provide some reduction in myocardial injury. If confirmed, in future clinical studies this technique may one day lead to a method to reduce reperfusion injury in clinical practice.
2012
Objective To investigate the cardioprotective efficacy of remote ischaemic preconditioning (RIPC) in cardiac surgery. Design We have performed a systematic search of MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials to identify randomized controlled trials involving RIPC. Setting Randomized controlled trials of RIPC in open cardiac surgery patients. Main outcome measures Meta-analysis was performed with the primary outcome the standardized mean difference between intervention and control groups in 12 hour postoperative troponin concentration. Heterogeneity was examined by fixed effects meta-regression. Results Ten studies with a total of 693 participants were included in the meta-analysis. RIPC reduced troponin levels 12 hours after surgery compared with control. The fixed and random effects differences were 0.35 (95% CI 0.19 to 0.51) and 0.53 (95% CI 0.18-0.88) respectively. However, important heterogeneity was present. Fixed effects metaregression partially accounted for heterogeneity based on whether studies had full blinding, comprising blinding of patients, surgeons, anaesthetists and investigators. Studies with incomplete or no blinding demonstrated a larger estimate of effect, 0.74 (95% CI 0.47 to 1.00) compared to those with full blinding, 0.13 (95% CI-0.07 to 0.33). Conclusions Although our analysis suggests RIPC may result in cardiac protection during cardiac surgery, the effect was most marked in studies without full blinding, with a smaller and statistically nonsignificant effect in fully blinded studies. We propose that further double blind randomized controlled trials investigating the cardioprotective effects of RIPC in cardiac surgery are required to resolve the current clinical uncertainty.
Remote ischaemic preconditioning in coronary artery bypass surgery: a meta-analysis
Heart, 2012
Aim Randomised trials exploring remote ischaemic preconditioning (RIPC) in patients undergoing coronary artery bypass graft (CABG) surgery have yielded conflicting data regarding potential cardiovascular and renal protection, and are individually flawed by small sample size. Methods Three investigators independently searched the MEDLINE, EMBASE and Cochrane databases to identify randomised trials testing RIPC in patients undergoing CABG. Results Nine studies with 704 patients were included. Standardised mean difference of troponin I and T release showed a significant decrease (À0.36 (95% CI À0.62 to À0.09)). This difference held true after excluding the trials with cross-clamp fibrillation, the study with offpump CABG and studies using a flurane as anaesthetic agent (À0.41 (95% CI À0.69 to À0.12), À0.38 (95% CI À0.70 to À0.07) and À0.37 (95% CI À0.63 to À0.12), respectively). A similar trend was also obtained for patients with multivessel disease (À0.41 (95% CI À0.73 to À0.08)). The trials evaluating postoperative creatinine reported a non-significant reduction (0.02 (95% CI À0.09 to 0.13)). Moreover, the length of in-hospital stay was not influenced by the kind of treatment (weighted mean difference 0.27 (95% CI À0.24 to 0.79)). Conclusion RIPC reduced the release of troponin in patients undergoing CABG. Larger randomised trials are needed to clarify the presence of a causal relationship between RIPC-induced troponin release and clinical adverse events.
PubMed, 2016
Background: The cardioprotective effect of ischemic preconditioning has been known for many years. Since the temporary ischemia in the heart may cause lethal cardiac effects, the idea of creating ischemia in organs far from the heart such as limbs was raised as remote ischemic preconditioning (RIPC). We hypothesized that the extension of RIPC has more cardioprotective effect in patients undergoing coronary artery bypass graft (CABG) surgeries. Methods: In this triple-blind randomized clinical trial study, 96 patients were randomly divided into 3 groups and two blood pressure cuffs were placed on both upper and lower extremities. In group A, only upper extremity cuff and in group B upper limb and lower limb cuff was inflated intermittently and group C was the control group. RIPC was induced with three 5-min cycles of cuff inflation about 100 mmHg over the initial systolic blood pressure before starting cardiopulmonary bypass. The primary endpoints were troponin I and creatine phosphokinase-myoglobin isoenzyme (CK-MB). Results: Six hours after the termination of CPB, there was a peak release of the troponin I level in all groups (group A=4.90 ng/ml, group B=4.40 ng/ml, and group C=4.50 ng/ml). There was a rise in plasma CK-MB in all groups postoperatively and there were not any significant differences in troponin I and CK-MB release between the three groups. Conclusion: RIPC induced by upper and lower limb ischemia does not reduce postoperative myocardial enzyme elevation in adult patients undergoing CABG. Trial registration number: IRCT2012071710311N1.
Background: Trials of remote ischemic pre-conditioning (RIPC) have suggested this intervention reduces complications of angioplasty and coronary artery by-pass grafting (CABG). The aim of this work was to conduct a systematic review and meta-analysis of the effects of RIPC on mortality and myocardial damage in patients undertaking coronary artery bypass grafting with/without valve surgery. Methods: A systematic review and subsequent meta-analysis of randomized controlled trials of RIPC versus usual care or sham RIPC was performed. Results: Eighteen studies, totalling 4551 participants were analysed. RIPC reduced post troponin release as indicated by area under the curve at 72 h (μg·L −1 ) Mean Difference (MD) − 3.72 (95% CI − 3.92 to − 3.53, p b 0.00001). However there was no significant difference between RIPC and control when mortality odds ratio (OR) 1.27 (95% CI 0.87 to 1.86, p = 0.22); the incidence of new onset atrial fibrillation OR 0.82 (95% CI 0.67 to 1.01, p = 0.06); inotropic support OR 1.27 (95% CI 0.84 to 1.91, p = 0.25); intensive care unit stay in days MD − 0.02 (95% CI − 0.12 to 0.07, p = 0.61); Hospital stay in days MD 0.18 (95% CI − 0.30 to 0.66, p = 0.47) and serum creatinine MD −0.00 (95% CI −0.07 to 0.07, p = 0.97) were compared. Conclusions: RIPC reduces does not confer any clinical benefit in patients undertaking CABG with/without valve surgery.
International Journal of Cardiology, 2016
Background: Remote ischemic preconditioning (RIPC) has been associated with reduced risk of myocardial injury in patients undergoing cardiovascular surgery, but uncertainty about clinical outcomes remains, particularly in the light of 2 recent large randomized clinical trials (RCTs) which were neutral. We performed a meta-analysis to evaluate the efficacy of RIPC on clinically relevant outcomes in patients undergoing cardiovascular surgery. Methods: We searched PubMed, Cochrane CENTRAL, EMBASE, EBSCO, Web of Science and CINAHL databases from inception through November 30, 2015. RCTs that compared the effects of RIPC vs. control in patients undergoing cardiac and/or vascular surgery were selected. We calculated summary random-effect odds ratios (ORs) and 95% confidence intervals (CI). Results: The analysis included 5652 patients from 27 RCTs. RIPC reduced the risk of myocardial infarction (MI) (OR 0.72, 95% CI, 0.52 to 1.00; p = 0.05; number needed to treat (NNT) = 42), acute renal failure (OR 0.73, 95% CI, 0.53 to 1.00; p = 0.05; NNT = 44) as well as the composite of all cause mortality, MI, stroke or acute renal failure (OR 0.60, 95% CI, 0.39 to 0.90; p = 0.01; NNT = 25). No significant difference between RIPC and the control groups was observed for the outcome of all-cause mortality (OR 1.10, 95% CI, 0.81 to 1.51). Randomization to RIPC group was also associated with significantly shorter hospital stay (weighted mean difference −0.15 days; 95% CI −0.27 to −0.03 days). Conclusions: RIPC did not decrease overall mortality, but was associated with less MI and acute renal failure and shorter hospitalizations in patients undergoing cardiac or vascular surgery.
Clinical Research in Cardiology, 2012
Background Novel cardioprotective strategies are required to improve clinical outcomes in high risk patients undergoing coronary artery bypass graft (CABG) ± valve surgery. Remote ischemic preconditioning (RIC), in which brief episodes of non-lethal ischemia and reperfusion are applied to the arm or leg, has been demonstrated to reduce perioperative myocardial injury following CABG ± valve surgery. Whether RIC can improve clinical outcomes in this setting is unknown and is investigated in the effect of remote ischemic preconditioning on clinical outcomes (ERICCA) trial in patients undergoing CABG surgery. (ClinicalTrials.gov Identifier: NCT01247545). Methods The ERICCA trial is a multicentre randomized double-blinded controlled clinical trial which will recruit 1,610 high-risk patients (Additive Euroscore C 5) undergoing CABG ± valve surgery using blood cardioplegia via 27 tertiary centres over 2 years. The primary combined endpoint will be cardiovascular death, non-fatal myocardial infarction, coronary revascularization and stroke at 1 year. Secondary endpoints will include peri-operative myocardial and acute kidney injury, intensive care unit and hospital stay, inotrope score, left ventricular ejection fraction, changes of quality of life and exercise tolerance. Patients will be randomized to receive after induction of anesthesia either RIC (4 cycles of 5 min inflation to 200 mmHg and 5 min deflation of a blood pressure cuff placed on the upper arm) or sham RIC (4 cycles of simulated inflations and deflations of the blood pressure cuff). Implications The findings from the ERICCA trial have the potential to demonstrate that RIC, a simple, non-invasive and virtually cost-free intervention, can improve clinical outcomes in higher-risk patients undergoing CABG ± valve surgery. Keywords Remote preconditioning Á Ischaemia Á Reperfusion Á Clinical trial Á CABG surgery Background Coronary heart disease (CHD) is the leading cause of death and disability worldwide and accounts for 3.8 million of men and 3.4 million of women deaths every year. CABG surgery remains the procedure of choice for coronary artery revascularization in patients with multi-vessel coronary artery disease. Currently, high-risk CHD patients are being operated on due to the aging population, the increasing prevalence of co-morbidities such as diabetes, hypertension, valve disease and the presence of more complex D. J. Hausenloy and L. Candilio are joint first authors.
Circulation Journal, 2012
Background: Myocardial injury is associated with an adverse outcome after off-pump coronary artery bypass graft surgery (OPCAB). The authors conducted a randomized controlled trial to evaluate whether remote ischemic preconditioning (RIPC) with remote ischemic postconditioning (RIPostC) reduces myocardial injury in patients undergoing OPCAB. Methods and Results: Seventy patients scheduled for OPCAB were randomly assigned to an RIPC+RIPostC group (n=35) or a control group (n=35). In the RIPC+RIPostC group, 4 cycles of 5-min ischemia and 5-min reperfusion were done on a lower limb before anastomoses (RIPC) and after anastomoses (RIPostC). RIPC+RIPostC significantly reduced postoperative serum troponin I levels (P=0.001). The area under the curve for postoperative troponin I was 48.7% lower in the RIPC+RIPostC group (median [interquartile range], 21.3 h • ng-1 • ml-1 , 16.5-53.1 h • ng-1 • ml-1 vs. 41.5 h • ng-1 • ml-1 , 24.6-90.2 h • ng-1 • ml-1 , P=0.020). There was no significant difference in creatinine levels and PaO2/FiO2 ratios between the 2 groups. Conclusions: RIPC+RIPostC by lower limb ischemia decreased postoperative myocardial enzyme elevation by almost half postoperatively in patients undergoing OPCAB.
2016
Background Novel cardioprotective strategies are required to improve clinical outcomes in higher-risk patients undergoing coronary artery bypass graft (CABG) with or without valve surgery. Remote ischaemic preconditioning (RIPC) in which brief episodes of non-lethal ischaemia and reperfusion are applied to the arm or leg has been demonstrated to reduce perioperative myocardial injury (PMI) following CABG with or without valve surgery. Objective To investigate whether or not RIPC can improve clinical outcomes in this setting in the Effect of Remote Ischaemic preconditioning on Clinical outcomes in patients undergoing Coronary Artery bypass graft surgery (ERICCA) study in patients undergoing CABG surgery. Design Multicentre, double-blind, randomised sham controlled trial. Setting The study was conducted across 30 cardiothoracic centres in the UK between March 2010 and March 2015. Participants Eligible patients were higher-risk adult patients (aged > 18 years of age; additive Europe...