The effect of remote ischaemic preconditioning on postoperative cardiac and inflammatory biomarkers in pancreatic surgery: a randomized controlled trial.
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SUBMITTER: van Zeggeren L
PROVIDER: S-EPMC8065964 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Despite advances in surgery support there are unmet needs for cardiopulmonary bypass (CPB) patients being at risk of perioperative ischemia. Remote ischemic preconditioning (RIPC) is considered as adjuvant therapy, but its effects are still underexplored. Thus, we monitored transcriptomic responses from the RIPC procedure during and after cardiac surgery in a pilot study, comprising 34 samples and 10 for validation from patients. We systematically compared the response between CTRL and RIPC including individual effects and dynamics. We gratefully acknowledge the support from the study participants as part of the clinical trial (ClinicalTrials.gov ID: NCT01067703). Different individual and time-resolved patterns were found for preconditioned patients (RIPC) comprising alternated cytokine, ribosomal and stress related genes. This was confirmed by a tailored method for ranking candidates by integrating variance and expression changes at once.
2017-09-01 | GSE58270 | GEO
Project description:RationaleRemote ischaemic preconditioning (RIPC) is a novel cardioprotective strategy that uses brief intermittent limb ischaemia to protect the myocardium and other organs from perioperative ischaemic damage. The precise mechanism through which this protective effect occurs is unknown, but potentially could be related to changes in blood-borne mediators such as cytokines.ObjectiveTo determine whether RIPC alters inflammatory cytokine expression in a double-blind, randomised, controlled trial of patients undergoing high-risk cardiac surgery.Methods and resultsSerum interleukin (IL)-6, IL-8, and IL-10 levels from 95 patients randomised to RIPC (n=47) or control treatment (n=48) were measured preoperatively, and 1, 2, 3, 6 and 12?h after cross-clamp removal. Systemic concentrations of all cytokines were increased from baseline following surgery, and, compared with simple procedures, complex surgeries were associated with significantly higher release of IL-6 (ratio of mean area under the curves 1.54 (95% CI 1.02 to 2.34), p=0.04) and IL-10 (1.97 (1.16 to 3.35), p=0.012). No significant difference in mean cytokine levels between the RIPC and control groups was detected at any time point, irrespective of the type of surgery undergone.ConclusionsHigh levels of IL-6, IL-8 and IL-10 are produced during high-risk cardiac surgery, and RIPC does not alter these elevated perioperative cytokine concentrations. Identification of factors that influence the ability to induce RIPC-mediated cardioprotection should be the priority of future research.Trial registrationis in the Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au; ACTRN12609000965202).
| S-EPMC4832611 | biostudies-literature
Project description:AimsRemote ischaemic preconditioning (RIPC) by inducing brief ischaemia in distant tissues protects the heart against myocardial ischaemia-reperfusion injury (IRI) in children undergoing open-heart surgery, although its effectiveness in adults with comorbidities is controversial. The effectiveness and mechanism of RIPC with respect to myocardial IRI in children with tetralogy of Fallot (ToF), a severe cyanotic congenital cardiac disease, undergoing open heart surgery are unclear. We hypothesized that RIPC can confer cardioprotection in children undergoing ToF repair surgery.Methods and resultsOverall, 112 ToF children undergoing radical open cardiac surgery using cardiopulmonary bypass (CPB) were randomized to either a RIPC group (n = 55) or a control group (n = 57). The RIPC protocol consisted of three cycles of 5-min lower limb occlusion and 5-min reperfusion using a cuff-inflator. Serum inflammatory cytokines and cardiac injury markers were measured before surgery and after CPB. Right ventricle outflow tract (RVOT) tissues were collected during the surgery to assess hypoxia-inducible factor (Hif)-1α and other signalling proteins. Cardiac mitochondrial injury was assessed by electron microscopy. The primary results showed that the length of stay in the intensive care unit (ICU) was longer in the control group than in the RIPC group (52.30 ± 13.43 h vs. 47.55 ± 10.34 h, respectively, P = 0.039). Patients in the control group needed longer post-operative ventilation time compared to the RIPC group (35.02 ± 6.56 h vs. 31.96 ± 6.60 h, respectively, P = 0.016). The levels of post-operative serum troponin-T at 12 and 18 h, CK-MB at 24 h, as well as the serum h-FABP levels at 6 h, after CPB were significantly lower, which was coincident with significantly higher protein expression of cardiac Hif-1α, p-Akt, p-STAT3, p-STAT5, and p-eNOS and less vacuolization of mitochondria in the RIPC group compared to the control group.ConclusionIn ToF children undergoing open heart surgery, RIPC attenuates myocardial IRI and improves the short-term prognosis.
| S-EPMC6018784 | biostudies-literature
Project description:There is limited evidence on the effect of remote ischaemic preconditioning (RIPC) following non-cardiac surgery. The aim of this study was to investigate the effect of RIPC on morbidity following intra-abdominal cancer surgery. We conducted a double blinded pilot randomised controlled trial that included 47 patients undergoing surgery for gynaecological, pancreatic and colorectal malignancies. The patients were randomized into an intervention (RIPC) or control group. RIPC was provided by intermittent inflations of an upper limb tourniquet. The primary outcome was feasibility of the study, and the main secondary outcome was postoperative morbidity including perioperative troponin change and the urinary biomarkers tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 (TIMP-2*IGFBP-7). The recruitment target was reached, and the protocol procedures were followed. The intervention group developed fewer surgical complications at 30 days (4.5% vs. 33%), 90 days (9.5% vs. 35%) and 6 months (11% vs. 41%) (adjusted p 0.033, 0.044 and 0.044, respectively). RIPC was a significant independent variable for lower overall postoperative morbidity survey (POMS) score, OR 0.79 (95% CI 0.63 to 0.99) and fewer complications at 6 months including pulmonary OR 0.2 (95% CI 0.03 to 0.92), surgical OR 0.12 (95% CI 0.007 to 0.89) and overall complications, OR 0.18 (95% CI 0.03 to 0.74). There was no difference in perioperative troponin change or TIMP2*IGFBP-7. Our pilot study suggests that RIPC may improve outcomes following intra-abdominal cancer surgery and that a larger trial would be feasible.
| S-EPMC8999621 | biostudies-literature
Project description:Remote ischaemic preconditioning (RIPC) has been shown to have a protective role on vital organs exposed to reperfusion injury. The aim of this systematic review was to evaluate the effects of non-invasive RIPC on clinical and biochemical outcomes in patients undergoing non-cardiac surgery. A systematic literature search of PubMed, EMBASE, Scopus, and Cochrane databases was carried out in February 2020. RCTs investigating the effect of non-invasive RIPC in adults undergoing non-cardiac surgery were included. Meta-analyses and trial sequential analyses (TSAs) were performed on cardiovascular events, acute kidney injury, and short- and long-term mortality. Some 43 RCTs including 3660 patients were included. The surgical areas comprised orthopaedic, vascular, abdominal, pulmonary, neurological, and urological surgery. Meta-analysis showed RIPC to be associated with fewer cardiovascular events in non-cardiac surgery (13 trials, 1968 patients, 421 events; odds ratio (OR) 0.68, 95 per cent c.i. 0.47 to 0.96; P = 0.03). Meta-analyses of the effect of RIPC on acute kidney injury (12 trials, 1208 patients, 211 events; OR 1.14, 0.78 to 1.69; P = 0.50; I2 = 9 per cent), short-term mortality (7 trials, 1239 patients, 65 events; OR 0.65, 0.37 to 1.12; P = 0.12; I2 = 0 per cent), and long-term mortality (4 trials, 1167 patients, 9 events; OR 0.67, 0.18 to 2.55; P = 0.56; I2 = 0 per cent) showed no significant differences for RIPC compared with standard perioperative care in non-cardiac surgery. However, TSAs showed that the required information sizes have not yet been reached. Application of RIPC to non-cardiac surgery might reduce cardiovascular events, but not acute kidney injury or all-cause mortality, but currently available data are inadequate to confirm or reject an assumed intervention effect.
| S-EPMC7970092 | biostudies-literature
Project description:BackgroundRemote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery.MethodsWe conducted a prospective, randomized, double-blind, controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomized either to RIPC or to control group. Primary endpoint was postoperative neurocognitive dysfunction 5-7 days after surgery assessed by a comprehensive test battery. Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD (1 SD criterion) or if the combined Z score was 1.96 or greater (Z score criterion).ResultsAccording to 1 SD criterion, 52% of control and 46% of RIPC patients had cognitive deterioration 5-7 days after surgery (p = 0.753). The summarized Z score showed a trend to more cognitive decline in the control group (2.16±5.30) compared to the RIPC group (1.14±4.02; p = 0.228). Three months after surgery, incidence and severity of neurocognitive dysfunction did not differ between control and RIPC. RIPC tended to decrease postoperative troponin T release at both 12 hours [0.60 (0.19-1.94) µg/L vs. 0.48 (0.07-1.84) µg/L] and 24 hours after surgery [0.36 (0.14-1.89) µg/L vs. 0.26 (0.07-0.90) µg/L].ConclusionsWe failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery. Therefore, definitive large-scale multicenter trials are needed.Trial registrationClinicalTrials.gov NCT00877305.
| S-EPMC3669352 | biostudies-literature
Project description:BackgroundDespite advances in perioperative care, elective major vascular surgical procedures still carry a significant risk of morbidity and mortality. Remote ischaemic preconditioning (RIPC) is the temporary blocking of blood flow to vascular beds remote from those targeted by surgery. It has the potential to provide local tissue protection from further prolonged periods of ischaemia. However, the efficacy and safety of RIPC in people undergoing major vascular surgery remain unknown. This is an update of a review published in 2011. OBJECTIVES: To assess the benefits and harms of RIPC versus no RIPC in people undergoing elective major vascular and endovascular surgery.Search methodsThe Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov to 1 April 2022.Selection criteriaWe included all randomised controlled trials that evaluated the role of RIPC in reducing perioperative mortality and morbidities in people undergoing elective major vascular or endovascular surgery.Data collection and analysisWe collected data on the characteristics of the trial, methodological quality, and the remote ischaemic preconditioning stimulus used. Our primary outcome was perioperative mortality, and secondary outcomes included myocardial infarction, renal impairment, stroke, hospital stay, limb loss, and operating time or total anaesthetic time. We analysed the data using random-effects models. For each outcome, we calculated the risk ratio (RR) or mean difference (MD) with a 95% confidence interval (CI) based on an intention-to-treat analysis. In addition, we used GRADE to assess the certainty of the evidence for each outcome.Main resultsWe included 14 trials which randomised a total of 1295 participants (age range: 64.5 to 76 years; 84% male; study periods ranged from 2003 to 2019). In general, the included studies were at low to unclear risk of bias for most risk of bias domains. The certainty of evidence of main outcomes was moderate due to imprecision of results, moderate heterogeneity, or possible publication bias. We found that RIPC made no clear difference in perioperative mortality compared with no RIPC (RR 1.41, 95% CI 0.59 to 3.40; I2 = 0%; 10 studies, 965 participants; moderate-certainty evidence). Similarly, we found no clear difference between the two groups for myocardial infarction (RR 0.82, 95% CI 0.49 to 1.40; I2 = 7%; 11 studies, 1001 participants; moderate-certainty evidence), renal impairment (RR 1.07, 95% CI 0.62 to 1.86; I2 = 40%; 12 studies, 1054 participants; moderate-certainty evidence), stroke (RR 0.33, 95% CI 0.04 to 3.15; I2 = 0%; 4 studies, 392 participants; moderate-certainty evidence), limb loss (RR 0.74, 95% CI 0.05 to 10.61; I2 = 32%; 3 studies, 322 participants; low-certainty evidence), hospital stay (MD -0.94 day, 95% CI -1.95 to 0.07; I2 = 17%; 7 studies, 569 participants; moderate-certainty evidence), and operating time or total anaesthetic time (MD 5.76 minutes, 95% CI -3.25 to 14.76; I2 = 44%; 10 studies, 803 participants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Overall, compared with no RIPC, RIPC probably leads to little or no difference in perioperative mortality, myocardial infarction, renal impairment, stroke, hospital stay, and operating time, and may lead to little or no difference in limb loss in people undergoing elective major vascular and endovascular surgery. Adequately powered and designed randomised studies are needed, focusing in particular on the clinical endpoints and patient-centred outcomes.
| S-EPMC9841888 | biostudies-literature
Project description:BackgroundChildren undergoing cardiac surgery are at risk for acute kidney injury (AKI) and cardiac dysfunction. Opportunity exists in protecting end organ function with remote ischemic preconditioning. We hypothesize this intervention lessens kidney and myocardial injury.MethodsWe conducted a randomized, double blind, placebo controlled trial of remote ischemic preconditioning in children undergoing cardiac surgery. Pre-specified end points are change in creatinine, estimated glomerular filtration rate, development of AKI, B-type natriuretic peptide and troponin I at 6, 12, 24, 48, 72 h post separation from bypass.ResultsThere were 45 in the treatment and 39 patients in the control group, median age of 3.5 and 3.8 years, respectively. There were no differences between groups in creatinine, cystatin C, eGFR at each time point. There was a trend for a larger rate of decrease, especially for cystatin C (p = 0.042) in the treatment group but the magnitude was small. AKI was observed in 21 (54%) of control and 16 (36%) of treatment group (p = 0.094). Adjusting for baseline creatinine, the odds ratio for AKI in treatment versus control was 0.31 (p = 0.037); adjusting for clinical characteristics, the odds ratio was 0.34 (p = 0.056). There were no differences in natriuretic peptide or troponin levels between groups. All secondary end points of clinical outcomes were not different.ConclusionsThere is suggestion of RIPC delivering some kidney protection in an at-risk pediatric population. Larger, higher risk population studies will be required to determine its efficacy. Trial registration and date: Clinicaltrials.gov NCT01260259; 2021.
| S-EPMC10765905 | biostudies-literature
Project description:Endothelial dysfunction result from inflammation and excessive production of reactive oxygen species as part of the surgical stress response. Remote ischemic preconditioning (RIPC) potentially exerts anti-oxidative and anti-inflammatory properties, which might stabilise the endothelial function after non-cardiac surgery. This was a single centre randomised clinical trial including 60 patients undergoing sub-acute laparoscopic cholecystectomy due to acute cholecystitis. Patients were randomised to RIPC or control. The RIPC procedure consisted of four cycles of five minutes of ischaemia and reperfusion of one upper extremity. Endothelial function was assessed as the reactive hyperaemia index (RHI) and circulating biomarkers of nitric oxide (NO) bioavailability (L-arginine, asymmetric dimethylarginine (ADMA), L-arginine/ADMA ratio, tetra- and dihydrobiopterin (BH4 and BH2), and total plasma biopterin) preoperative, 2-4 h after surgery and 24 h after surgery. RHI did not differ between the groups (p = 0.07). Neither did levels of circulating biomarkers of NO bioavailability change in response to RIPC. L-arginine and L-arginine/ADMA ratio was suppressed preoperatively and increased 24 h after surgery (p < 0.001). The BH4/BH2-ratio had a high preoperative level, decreased 2-4 h after surgery and remained low 24 h after surgery (p = 0.01). RIPC did not influence endothelial function or markers of NO bioavailability until 24 h after sub-acute laparoscopic cholecystectomy. In response to surgery, markers of NO bioavailability increased, and oxidative stress decreased. These findings support that a minimally invasive removal of the inflamed gallbladder countereffects reduced markers of NO bioavailability and increased oxidative stress caused by acute cholecystitis.
| S-EPMC10047371 | biostudies-literature
Project description:BackgroundRemote 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.MethodsPatients 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.ResultsWe 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).InterpretationRemote 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 registrationClinicalTrials.gov, no. NCT01071265.
| S-EPMC4786386 | biostudies-literature