Project description:BackgroundThe benefit of remote ischemia preconditioning (RIPreC) in pediatric cardiac surgery is unclear. The objective of this systematic review and meta-analysis was to examine the effectiveness of RIPreC in reducing the duration of mechanical ventilation and intensive care unit (ICU) length of stay after pediatric cardiac surgery.MethodsWe searched PubMed, EMBASE and the Cochrane Library from inception to December 31, 2022. Randomized controlled trials comparing RIPreC versus control in children undergoing cardiac surgery were included. The risk of bias of included studies was assessed using the Risk of Bias 2 (RoB 2) tool. The outcomes of interest were postoperative duration of mechanical ventilation and ICU length of stay. We conducted random-effects meta-analysis to calculate weighted mean difference (WMD) with 95% confidence interval (CI) for the outcomes of interest. We performed sensitivity analysis to examine the influence of intraoperative propofol use.ResultsThirteen trials enrolling 1,352 children were included. Meta-analyses of all trials showed that RIPreC did not reduce postoperative duration of mechanical ventilation (WMD -5.35 h, 95% CI -12.12-1.42) but reduced postoperative ICU length of stay (WMD -11.48 h, 95% CI -20.96- -2.01). When only trials using propofol-free anesthesia were included, both mechanical ventilation duration (WMD -2.16 h, 95% CI -3.87- -0.45) and ICU length of stay (WMD -7.41 h, 95% CI -14.77- -0.05) were reduced by RIPreC. The overall quality of evidence was moderate to low.ConclusionsThe effects of RIPreC on clinical outcomes after pediatric cardiac surgery were inconsistent, but both postoperative mechanical ventilation duration and ICU length of stay were reduced in the subgroup of children not exposed to propofol. These results suggested a possible interaction effect of propofol. More studies with adequate sample size and without intraoperative propofol use are needed to define the role of RIPreC in pediatric cardiac surgery.
Project description:ObjectiveIschemic preconditioning (IPC) has gradually been promoted in clinical practice to lower the risk of cardiovascular surgery and postoperative complications. We investigated the role of IPC on vascular endothelial function and the relationship between IPC, flow-mediated dilation (FMD), and brachial artery diameter (BAD).MethodsSystematic searches were conducted in PubMed, Medline, Cochrane Library, Embase, and Scopus databases from their inception to March 20, 2020. This research included randomized controlled trials (RCTs) with adults, and the values of FMD and BAD were considered as the primary outcomes. Ten studies comprising 292 participants were included in the meta-analysis.ResultsRegarding FMD, we observed beneficial effects of IPC on endothelial function (standardized mean difference (SMD): 1.82; 95% confidence interval (CI): 0.64, 3.01; p < 0.001; I 2 = 89.9%). However, the available evidence did not indicate that IPC affected BAD (SMD: 0.08; 95% CI: -0.03, 0.18; p > 0.05; I 2 = 76.5%).ConclusionsOur meta-analysis indicated a significant effect of IPC on the endothelial function of the blood vessels, affecting FMD but not BAD.
Project description:Remote ischemic preconditioning (RIPC) protects organs from ischemia-reperfusion injury. Recent trials showed that RIPC improved gas exchange in patients undergoing lung or cardiac surgery. We performed a systematic search to identify randomized controlled trials involving RIPC in surgery under general anesthesia. The primary outcome was the PaO2/FIO2 (P/F) ratio at 24 h after surgery. Secondary outcomes were A-a DO2, the respiratory index, duration of postoperative mechanical ventilation (MV), incidence of acute respiratory distress syndrome (ARDS), and serum cytokine levels. The analyses included 71 trials comprising 7854 patients. Patients with RIPC showed higher P/F ratio than controls (mean difference [MD] 36.6, 95% confidence interval (CI) 12.8 to 60.4, I2 = 69%). The cause of heterogeneity was not identified by the subgroup analysis. Similarly, A-a DO2 (MD 15.2, 95% CI - 29.7 to - 0.6, I2 = 87%) and respiratory index (MD - 0.17, 95% CI - 0.34 to - 0.01, I2 = 94%) were lower in the RIPC group. Additionally, the RIPC group was weaned from MV earlier (MD - 0.9 h, 95% CI - 1.4 to - 0.4, I2 = 78%). Furthermore, the incidence of ARDS was lower in the RIPC group (relative risk 0.73, 95% CI 0.60 to 0.89, I2 = 0%). Serum TNFα was lower in the RIPC group (SMD - 0.6, 95%CI - 1.0 to - 0.3 I2 = 87%). No significant difference was observed in interleukin-6, 8 and 10. Our meta-analysis suggested that RIPC improved oxygenation after surgery under general anesthesia.Clinical trial number: This study protocol was registered in the University Hospital Medical Information Network (registration number: UMIN000030918), https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000035305.
Project description:Ischemic preconditioning (IPC) is a potent renoprotective strategy which has not yet been translated successfully into clinical practice, in spite of promising results in animal studies. We performed a unique systematic review and meta-analysis of animal studies to identify factors modifying IPC efficacy in renal ischemia/reperfusion injury (IRI), in order to enhance the design of future (clinical) studies. An electronic literature search for animal studies on IPC in renal IRI yielded fifty-eight studies which met our inclusion criteria. We extracted data for serum creatinine, blood urea nitrogen and histological renal damage, as well as study quality indicators. Meta-analysis showed that IPC reduces serum creatinine (SMD 1.54 [95%CI 1.16, 1.93]), blood urea nitrogen (SMD 1.42 [95% CI 0.97, 1.87]) and histological renal damage (SMD 1.12 [95% CI 0.89, 1.35]) after IRI as compared to controls. Factors influencing IPC efficacy were the window of protection (<24 h = early vs. ? 24 h = late) and animal species (rat vs. mouse). No difference in efficacy between local and remote IPC was observed. In conclusion, our findings show that IPC effectively reduces renal damage after IRI, with higher efficacy in the late window of protection. However, there is a large gap in study data concerning the optimal window of protection, and IPC efficacy may differ per animal species. Moreover, current clinical trials on RIPC may not be optimally designed, and our findings identify a need for further standardization of animal experiments.
Project description:BackgroundIn recent decades, liver transplantation (LTx) has increased the survival and quality of life of patients with end-stage organ failure. Unfortunately, LTx is limited due to the shortage of donors. A lot of effort is put into finding new ways to reduce ischemia-reperfusion injury (IRI) in liver grafts to increase the number of suitable organs procured from expanded-criteria donors (ECD). The aim of this study was to systematically review the literature reporting LTx outcomes when using ischemic preconditioning (IPC) or remote ischemic preconditioning (RIPC) to reduce IRI in liver grafts.MethodsA literature search was performed in the MEDLINE, Web of Science, and EMBASE databases. The following combination was used: "Liver" OR "Liver Transplantation" AND "Ischemic preconditioning" OR "occlusion" OR "clamping" OR "Pringle." The following outcome data were retrieved: the rates of graft primary nonfunction (PNF), retransplantation, graft loss, and mortality; stay in hospital and the intensive care unit; and postoperative serum liver damage parameters.ResultsThe initial search retrieved 4,522 potentially relevant studies. After evaluating 17 full-text articles, a total of 9 randomized controlled trials (RCTs) were included (7 IPC and 2 RIPC studies) in the qualitative synthesis; the meta-analysis was only performed on the data from the IPC studies. RIPC studies had considerable methodological differences. The meta-analysis revealed the beneficial effect of IPC when comparing postoperative aspartate aminotransferase (AST) corresponding to a statistically lower mortality rate in the IPC group (odds ratio [OR] 0.51; 95% confidence interval [CI] 0.27-0.98; p = 0.04).ConclusionIPC lowers postoperative AST levels and reduces the mortality rate; however, data on the benefits of RIPC are lacking.
Project description:Multiple randomized controlled trials of remote ischemic preconditioning (RIPC) prior to cardiac surgery have failed to demonstrate clinical benefit. The aim of this updated meta-analysis was to evaluate the effect of RIPC on outcomes following cardiac surgery.Searches of PubMed, Cochrane, EMBASE, and Web of Science databases were performed for 1970 to December 13, 2015. Randomized controlled trials comparing RIPC with a sham procedure prior to cardiac surgery performed with cardiopulmonary bypass were assessed. All-cause mortality, acute kidney injury (AKI), and myocardial infarction were the primary outcomes of interest. We identified 21 trials that randomized 5262 patients to RIPC or a sham procedure prior to undergoing cardiac surgery. The majority of patients were men (72.6%) and the mean or median age ranged from 42.3 to 76.3 years. Of the 9 trials that evaluated mortality, 188 deaths occurred out of a total of 4210 randomized patients, with 96 deaths occurring in 2098 patients (4.6%) randomized to RIPC and 92 deaths occurring in 2112 patients (4.4%) randomized to a sham control procedure, demonstrating no significant reduction in all-cause mortality (risk ratio [RR], 0.987; 95% CI, 0.653-1.492, P=0.95). Twelve studies evaluated AKI in 4209 randomized patients. In these studies, AKI was observed in 516 of 2091 patients (24.7%) undergoing RIPC and in 577 of 2118 patients (27.2%) randomized to a sham procedure. RIPC did not result in a significant reduction in AKI (RR, 0.839; 95% CI, 0.703-1.001 [P=0.052]). In 6 studies consisting of 3799 randomized participants, myocardial infarction occurred in 237 of 1891 patients (12.5%) randomized to RIPC and in 282 of 1908 patients (14.8%) randomized to a sham procedure, resulting in no significant reduction in postoperative myocardial infarction (RR, 0.809; 95% CI, 0.615-1.064 [P=0.13]). A subgroup analysis was performed a priori based on previous studies suggesting that propofol may mitigate the protective benefits of RIPC. Three studies randomized patients undergoing cardiac surgery to RIPC or sham procedure in the absence of propofol anesthesia. Most of these patients were men (60.3%) and the mean or median age ranged from 57.0 to 70.6 years. In this propofol-free subgroup of 434 randomized patients, 71 of 217 patients (32.7%) who underwent RIPC developed AKI compared with 103 of 217 patients (47.5%) treated with a sham procedure. In this cohort, RIPC resulted in a significant reduction in AKI (RR, 0.700; 95% CI, 0.527-0.930 [P=0.014]). In studies of patients who received propofol anesthesia, 445 of 1874 (23.7%) patients randomized to RIPC developed AKI compared with 474 of 1901 (24.9%) who underwent a sham procedure. The RR for AKI was 0.928 (95% CI, 0.781-1.102; P=0.39) for RIPC versus sham. There was no significant interaction between the two subgroups (P=0.098).RIPC does not reduce morbidity or mortality in patients undergoing cardiac surgery with cardiopulmonary bypass. In the subgroup of studies in which propofol was not used, a reduction in AKI was seen, suggesting that propofol may interact with the protective effects of RIPC. Future studies should evaluate RIPC in the absence of propofol anesthesia.
Project description:This study aimed to determine the effect of short-term remote ischemic preconditioning (RIPC) on coronary blood flow and microcirculation function using the quantitative flow ratio (QFR) and index of microcirculatory resistance (IMR). We randomly divided 129 patients undergoing coronary angiography (CAG) into RIPC and control groups. Following the first CAG, we randomly divided the patients further into the unilateral upper limb and lower limb groups for four cycles of ischemia/reperfusion circulation; subsequently, we performed the second CAG. During each CAG, contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and IMR (in patients with cardiac syndrome X) were calculated and compared. We measured 253 coronary arteries in 129 patients. Compared to the control group, the average cQFR of the RIPC group increased significantly after RIPC. Additionally, 23 patients with cardiac syndrome X (IMR > 30) were included in this study. Compared to the control group, IMR and the difference between cQFR and fQFR (cQFR-fQFR) both decreased significantly after receiving RIPC. The application of RIPC can increase coronary blood flow and improve coronary microcirculation function.
Project description:Remote ischemic conditioning (RIC), including pre-conditioning (RIPC, before the ischemic event), per-conditioning (RIPerC, during the ischemic event), and post-conditioning (RIPostC, after the ischemic event), protects the liver in animal hepatic ischemia-reperfusion injuries models. However, several questions regarding the optimal timing of intervention and administration protocols remain unanswered. Therefore, the preclinical evidence on RIC in the HIRI models was systematically reviewed and meta-analyzed in the present review to provide constructive and helpful information for future works. In the present review, 39 articles were identified by searching the PubMed, OVID, Web of Science and Embase databases spanned from database inception to July 2024. According to the preferred reporting items for systematic reviews and meta-analyses guidelines, data were extracted independently by two researchers. The primary outcomes evaluated in this study were those directly related to liver injury, such as alanine transaminase (ALT), aspartate transaminase (AST) and liver histopathology. The risk of bias was assessed using the risk of bias tool of the SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE). The findings were expressed as standardized mean difference (SMD) and analyzed using random-effects models. Egger's test was used to evaluate the publication bias. RIC significantly reduced the changes in ALT, AST and liver histopathology (all P<0.00001). These effects had two peaks, with the first peak of RIPerC/RIPostC occurring earlier, regardless of models and species. RIPerC/RIPostC exerted significant effects on changes in ALT and AST [ALT SMD (95% confidence interval (CI]): RIPC -1.97 (-2.40, -1.55) vs. -2.78 (-3.77, -1.78); P=0.142; AST SMD (95%CI): RIPC -1.45 (-1.90, -0.99) vs. -2.13 (-2.91, -1.34); P=0.142], and RIPC had a greater effect on liver histopathology change [SMD (95%CI): RIPC -2.68 (-3.67, -1.69) vs. -1.58 (-2.24, -0.92); P=0.070]; however, no interactions were observed between the two groups in the meta-regression analysis. RIC is the most effective in experimental HIRI, using a 10-25-min dose. These outcomes suggest that RIC may be a promising strategy for treating HIRI; however, future studies using repeated doses in animal models with comorbidities will present novel ideas for its therapeutic application. The protocol of present study was registered with PROSPERO (CRD42023482725).
Project description:Stroke is a leading cause of mortality and disability worldwide. Transient ischemic attack (TIA) is defined as transient brain ischemia with temporary neurological deficits. In animal models, prior TIA seems to enhance brain ischemic tolerance to withstand further ischemic events, which might be explained by brain preconditioning. Thus, this review aims to formulate evidence of whether TIAs can induce positive preconditioning and enhance the functional outcomes in patients suffering from subsequent ischemic strokes. Five databases were searched (PubMed, Embase, SAGE, Web of Science, and Scopus), and twelve studies were included in the quantitative analysis. Studies were eligible when comparing patients with acute ischemic stroke (AIS) and previous TIA with those with AIS without TIA. Comparisons included the National Institute of Health Stroke Scale (NIHSS) score at admission and 7 days from the stroke event, modified Rankin score (mRS), and Trial of ORG 10,172 in Acute Stroke Treatment (TOAST) classification. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were used to describe our results using the random effect model. Our results revealed that patients with stroke and prior TIAs had lower NIHSS scores at admission than those without prior TIAs. However, the NIHSS score was not significantly different between the two groups at 7 days. Furthermore, there was no statistically significant difference between both groups in terms of mortality. Despite the differences in the admission mRS score groups, patients with prior TIAs had lower mRS scores at discharge.
Project description:BackgroundIschemic preconditioning (IPC) of the heart is a protective strategy in which a brief ischemic stimulus immediately before a lethal ischemic episode potently limits infarct size. Although very promising in animal models of myocardial infarction, IPC has not yet been successfully translated to benefit for patients.ObjectiveTo appraise all preclinical evidence on IPC for myocardial infarction and identify factors hampering translation.Methods and resultsUsing systematic review and meta-analysis, we identified 503 animal studies reporting infarct size data from 785 comparisons between IPC-treated and control animals. Overall, IPC reduced myocardial infarction by 24.6% [95%CI 23.5, 25.6]. Subgroup analysis showed that IPC efficacy was reduced in comorbid animals and non-rodents. Efficacy was highest in studies using 2-3 IPC cycles applied <45 minutes before myocardial infarction. Local and remote IPC were equally effective. Reporting of study quality indicators was low: randomization, blinding and a sample size calculation were reported in 49%, 11% and 2% of publications, respectively.ConclusionsTranslation of IPC to the clinical setting may be hampered by the observed differences between the animals used in preclinical IPC studies and the patient population, regarding comorbidity, sex and age. Furthermore, the IPC protocols currently used in clinical trials could be optimized in terms of timing and the number of ischemic cycles applied. In order to inform future clinical trials successfully, future preclinical studies on IPC should aim to maximize both internal and external validity, since poor methodological quality may limit the value of the preclinical evidence.