A systematic review and meta-analysis of the cardioprotective effects of remote ischaemic preconditioning in open cardiac surgery (original) (raw)
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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.
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.
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.
Heart (British Cardiac Society), 2015
Objectives Remote ischaemic preconditioning (RIPC), using brief cycles of limb ischaemia/reperfusion, is a non-invasive, low-cost intervention that may reduce perioperative myocardial injury (PMI) in patients undergoing cardiac surgery. We investigated whether RIPC can also improve short-term clinical outcomes. Methods One hundred and eighty patients undergoing elective coronary artery bypass graft (CABG) surgery and/ or valve surgery were randomised to receive either RIPC (2-5 min cycles of simultaneous upper arm and thigh cuff inflation/deflation; N=90) or control (uninflated cuffs placed on the upper arm and thigh; N=90). The study primary end point was PMI, measured by 72 h area under the curve (AUC) serum high-sensitive troponin-T (hsTnT); secondary end point included short-term clinical outcomes.
2013
Summary Objectives: To systematically review and assess the existing evidence for the applicability of remote ischemic preconditioning (rIPC) in cardiac surgery. Material and methods: Major biomedical databases: Medline, Cochrane, etc. were searched. All randomized controlled trials (RCTs) comparing rIPC and standard myocardial protection in patients submitted to cardiac surgery were included if they reported at least one of the outcomes of interest: myocardial injury markers, postoperative inotropic support, or length of ICU stay. Results: 991 patients were included in the analysis. rIPC was shown to reduce myocardial injury markers postoperatively by –0.63 SMD [–0.99 to –0.28] and postoperative inotropic requirement by –0.40 SMD [–0.66 to –0.16] in the adult patients submitted to cardiac surgery. There has been significant, yet correctable, heterogeneity of the primary outcome of interest, and the available RCTs were small sample studies. Conclusions: This meta-analysis provides e...
International Journal of Cardiology, 2014
Background: A number of 'proof-of-concept' trials suggest that remote ischaemic preconditioning (RIPC) reduces surrogate markers of end-organ injury in patients undergoing major cardiovascular surgery. To date, few studies have involved hard clinical outcomes as primary end-points. Methods: Randomised clinical trials of RIPC in major adult cardiovascular surgery were identified by a systematic review of electronic abstract databases, conference proceedings and article reference lists. Clinical end-points were extracted from trial reports. In addition, trial principal investigators provided unpublished clinical outcome data. Results: In total, 23 trials of RIPC in 2200 patients undergoing major adult cardiovascular surgery were identified. RIPC did not have a significant effect on clinical end-points (death, peri-operative myocardial infarction (MI), renal failure, stroke, mesenteric ischaemia, hospital or critical care length of stay). Conclusion: Pooled data from pilot trials cannot confirm that RIPC has any significant effect on clinically relevant end-points. Heterogeneity in study inclusion and exclusion criteria and in the type of preconditioning stimulus limits the potential for extrapolation at present. An effort must be made to clarify the optimal preconditioning stimulus. Following this, large-scale trials in a range of patient populations are required to ascertain the role of this simple, cost-effective intervention in routine practice.
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.
Trials, 2015
Background: Patients undergoing vascular surgery procedures constitute a 'high-risk' group. Fatal and disabling perioperative complications are common. Complications arise via multiple aetiological pathways. This mechanistic redundancy limits techniques to reduce complications that target individual mechanisms, for example, anti-platelet agents. Remote ischaemic preconditioning (RIPC) induces a protective phenotype in at-risk tissue, conferring protection against ischaemia-reperfusion injury regardless of the trigger. RIPC is induced by repeated periods of upper limb ischaemia-reperfusion produced using a blood pressure cuff. RIPC confers some protection against cardiac and renal injury during major vascular surgery in proof-of-concept trials. Similar trials suggest benefit during cardiac surgery. Several uncertainties remain in advance of a full-scale trial to evaluate clinical efficacy. We propose a feasibility trial to fully evaluate arm-induced RIPC's ability to confer protection in major vascular surgery, assess the incidence of a proposed composite primary efficacy endpoint and evaluate the intervention's acceptability to patients and staff.
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.