Comparison between Custodiol, del Nido and modified del Nido in the myocardial protection - Cardioplegia Trial: a study protocol for a randomised, double-blind clinical trial.
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ABSTRACT: Introduction
Myocardial protection is essential for successful cardiac surgery, and the search for an ideal cardioplegic solution has continued since its beginning. In this context, Custodiol, del Nido and modified del Nido are single-dose cardioplegic solutions with good safety profiles and great relevance in modern surgical practice. While these solutions have all been evaluated for their impact on patient outcomes independently, limited research exists comparing them directly. Thus, the present study aims to examine the effects of these cardioplegic solutions on myocardial protection and clinical outcomes in adult patients undergoing elective cardiac surgery. The assessment of the increase in myocardial injury biomarkers in patients submitted to all treatment methods may be considered a major strength of our study.Methods and analysis
This is a clinical trial study protocol that will compare myocardial protection and clinical outcomes among three patient groups based on which cardioplegic solution was used. Patients will be randomised to receive del Nido (n=30), modified del Nido (n=30) or Custodiol (n=30). Myocardial injury biomarkers will be measured at the baseline and 2 hours, 12 hours and 24 hours after the cardiopulmonary bypass. Clinical outcomes will be assessed during the trans operative period and the intensive care unit stay, in addition to other haematological parameters.Ethics and dissemination
This protocol and its related documents were approved by the Research Ethics Committee of the Hospital Nossa Senhora da Conceição, Brazil, registered under no. 4.029.545. The findings of this study will be published in a peer-reviewed journal in the related field.Trial registration number
RBR-7g5s66.
SUBMITTER: Almeida AS
PROVIDER: S-EPMC8422325 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundHistidine-tryptophan-ketoglutarate (HTK) and del Nido (DN) cardioplegia are intracellular-type and extracellular-type solution respectively, both can provide a long period of myocardial protection with single-dose infusion, but studies comparing the two are rare for adult cardiac surgery. This study aims to evaluate whether DN is suitable for cardioplegia in complex and high-risk valve surgery with long-term cardiac ischemia when compared with HTK.MethodsThe perioperative records of adult patients infused with DN/HTK as a cardioplegic solution who underwent complex valve surgery with an expected myocardial ischaemic duration longer than 90 min between Oct 2018 and Oct 2019 were analysed retrospectively.ResultsOf the 160 patients who received DN/HTK and underwent complex valve surgery, we propensity matched 73 pairs. Both groups achieved satisfactory cardiac arrest effects, and no significant difference was found in their cTnI and CK-MB levels within 12 to 72 h postoperatively. The DN group had a higher rate of return to spontaneous rhythm (0.88 v 0.52, P < 0.001), a lower frequency of postoperative severe arrythmias (12% v 26%, P = 0.036), a higher postoperative stroke volume (65 v 59 ml, P = 0.011) and a higher cardiac output (6.0 v 4.9 L/min, P = 0.007) as evaluated by echocardiography, fewer transfusions and shorter ICU stays (both P < 0.05). The two groups had similar inotrope usage and similar incidences of low cardiac output, morbidities and mortality. Subgroup analysis showed that when the aortic clamping time was greater than 120 min, the advantages of DN were weakened.ConclusionsDN can be safely applied to complex valve surgery, and it has a similar myocardial protection effect as HTK. Further prospective studies are required to verify these retrospective findings. Trial registration retrospectively registered.
| S-EPMC8683821 | biostudies-literature
Project description:BackgroundDel Nido cardioplegia is widely used in adult cardiopulmonary bypass surgery and has a satisfying cardioprotective effect for about 90 minutes by single dose, but the effect in patients with coronary heart disease remains confused. The purpose of this study was to examine the cardioprotective effect of del Nido cardioplegia in adult multivessel coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB).MethodsThis retrospective comparative analysis included 124 consecutive patients undergoing isolated on-pump CABG performed by a single surgeon between January 2017 and December 2020. The demographic characteristics and medical history of the included patients were collected. The included patients were divided into two groups: a del Nido cardioplegia (DN) group and a conventional multidose blood cardioplegia (BC) group. Perioperative, intraoperative, and postoperative indicators and complications were compared.ResultsCompared with the BC group, CPB and aortic cross-clamp time were significantly shorter in the DN group. In the early postoperative period, the hemoglobin concentration in the DN group was significantly higher than that in the BC group (P<0.05).ConclusionsThis study demonstrated that the application of del Nido cardioplegia in adult on-pump CABG could lead to a significantly shorter aortic cross-clamp and CPB time, as well as a higher hemoglobin concentration in the early postoperative period. The myocardial protective effect of del Nido cardioplegia is not inferior to that of conventional blood perfusion in adult on-pump CABG.
| S-EPMC8828514 | biostudies-literature
Project description:BACKGROUND:The use of cardioplegia solutions as a myocardial protection technique is essential during cardiac surgery with cardiopulmonary bypass. The del Nido cardioplegia solution (DNS) has been widely used as a myocardial preservation technique for pediatric patients undergoing cardiac surgery with cardiopulmonary bypass. Its unique pharmacological features have created growing interest for adult cardiac surgery, especially for elderly patients or those with ventricular dysfunction who are more prone to ischemia-reperfusion injury. Ever since its implementation, several retrospective studies have been published to validate the efficacy, safety, and efficiency of DNS in adult patients undergoing coronary revascularization, valve replacement, or combined procedures. Recently, a meta-analysis based on nine retrospective studies was published claiming the noninferiority of DNS compared to other conventional cardioplegia solutions. Few prospective randomized studies have been conducted whose primary outcome was the assessment of DNS clinical efficacy compared to other solutions commonly used in adult patients. OBJECTIVE:The aim of this randomized clinical trial is to assess the benefits of DNS compared to Cardi-Braun blood cardioplegia solution in clinical and biochemical terms regarding myocardial protection during adult cardiac surgery. METHODS:This is the protocol of a controlled, randomized, single-center clinical trial carried out at the Puerta de Hierro Majadahonda University Hospital in Spain. A total of 474 participants over the age of 18 years undergoing elective cardiac surgery with cardiopulmonary bypass will be assigned to groups by simple randomization to receive either DNS or Cardi-Braun blood cardioplegia solution. The primary outcome will be the differences between groups in myocardial protection in biochemical terms (ie, perioperative troponin levels) and clinical terms (ie, presence of the composite variable acute cardiovascular event). The clinical trial will be carried out under conditions of respect for the fundamental rights of the person and the ethical principles that affect biomedical research with human beings, as well as in accordance with international recommendations contained in the Declaration of Helsinki and its subsequent revisions. RESULTS:The inclusion process started in 2018. Data cleaning and analyses are expected to take place in the fall of 2020 and the results are expected in January 2021. CONCLUSIONS:This study is particularly relevant as it will be one of the first to analyze the clinical effects of del Nido cardioplegia on the basis of direct myocardial protection parameters. In light of published studies, carrying out prospective studies based on primary clinical objectives with a larger sample, high-risk patients, and longer cardiopulmonary bypass times continues to be necessary. We believe that our study addresses an important gap in the knowledge of del Nido cardioplegia in adult patient cardiac surgery and will be able to clarify the possible benefits of this method in a large population of patients undergoing these procedures. TRIAL REGISTRATION:European Union Drug Regulating Authorities Clinical Trials Database (EudraCT) 2017-005144-14; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2017-005144-14+; ClinicalTrials.gov NCT04094168; https://clinicaltrials.gov/ct2/show/NCT04094168. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/17826.
| S-EPMC7388037 | biostudies-literature
Project description:OBJECTIVES:The del Nido cardioplegia solution has been used extensively in congenital heart surgery for more than 20 years and more recently for adults. This randomized controlled trial examined whether expanding this technique to adult cardiac surgery confers benefits in surgical workflow and clinical outcome compared with blood-based cardioplegia. METHODS:Adult first-time coronary artery bypass grafting (CABG), valve, or CABG/valve surgery patients requiring cardiopulmonary bypass (CPB) were randomized to del Nido cardioplegia (n = 48) or whole blood cardioplegia (n = 41). Primary outcomes assessed myocardial preservation. Troponin I was measured at baseline, 2 hours after CPB termination, 12 and 24 hours after cardiovascular intensive care unit admission. Alpha was set at P < .001. RESULTS:Preoperative characteristics were similar between groups, including age, Society of Thoracic Surgeons risk score, CABG, and valve procedures. There was no significant difference on CPB time (97 vs 103 minutes; P = .288) or crossclamp time (70 vs 83 minutes; P = .018). The del Nido group showed higher return to spontaneous rhythm (97.7% vs 81.6%; P = .023) and fewer patients required inotropic support (65.1% vs 84.2%; P = .050), but did not reach statistical significance. Incidence of Society of Thoracic Surgeons-defined morbidity was low, with no strokes, myocardial infarctions, renal failure, or operative deaths. For del Nido group patients, troponin levels did not increase as much as for control patients (P = .040), but statistical significance was not reached. CONCLUSIONS:Evidence from this study suggests del Nido cardioplegia use in routine adult cases may be safe, result in comparable clinical outcomes, and streamline surgical workflow. The trend for troponin should be investigated further because it may suggest superior myocardial protection with the del Nido solution.
| S-EPMC5929134 | biostudies-literature
Project description:ObjectiveWhile del Nido (DN) cardioplegia is increasingly used in cardiac surgery, knowledge is limited in its safety profile for operations with prolonged crossclamp time (CCT). We have introduced a unique redosing strategy for aortic surgery: all operations use DN with a 1000-mL initiation dose (750 mL antegrade, 250 mL retrograde) composed of 1:4 blood:DN crystalloid. At 90 minutes CCT and every 30 minutes thereafter, a 250-mL dose was introduced retrograde in a 4:1 ("reverse") ratio. Additionally, at 90 minutes CCT and every 90 minutes thereafter, a reverse ratio dose of approximately 100 to 400 mL was introduced via the right coronary artery. Here, we analyze the outcomes of our unique redosing strategy used.MethodsIn total, 440 patients underwent aortic surgery between January 2015 and March 2021 under a single surgeon and received DN. Our primary end points were change in left ventricular ejection fraction (LVEF) and right ventricular systolic function based on echocardiography. Multivariable linear regression was used to analyze the relationship between CCT and outcomes.ResultsThe median was 61 years old (interquartile range, 51-69), and 23% were female. Indication was aneurysm in 65% and dissection in 24%. Median preoperative LVEF was 60% (55%-62%). Median CCT and cardiopulmonary bypass times were 135 minutes (93-165 minutes) and 181 minutes (142-218 minutes), respectively. In-hospital mortality occurred in 3%. Multivariable linear regression showed CCT was not associated with change in LVEF or change in right ventricular systolic function.ConclusionsOur unique method of redosing DN cardioplegia appears to provide safe and effective myocardial protection for aortic surgery.
| S-EPMC9255383 | biostudies-literature
Project description:Background:To analyze the protective effect of single-dose del Nido cardioplegia (DNC) in adult minimally invasive valve surgery. Methods:From January to December 2017, 165 consecutive adult patients who underwent minimally invasive valve surgery by the same team of surgeons were divided into two cohorts based on the type of cardioplegia administered during surgery: (I) single-dose DNC (DNC group (n=76, male 41, female 35) used in patients from May to December, 2017 and (II) intermittent standard 4:1 blood cardioplegia based on St.Thomas solution (SBC group, n=89, male 45, female 44) used in patients from January to April, 2017. Preoperative baseline demographics, preoperative comorbidities, operative variables, postoperative complications, and patient outcomes were collected and compared between the two groups. Results:Preoperative characteristics were shown to be similar between the two groups before and after propensity matching. Patients in the DNC group required a significantly lower volume of cardioplegia. The volume of ultrafiltration in the DNC group was substantially higher than that in the SBC group. The spontaneous return of heartbeat rate in the DNC group was considerably higher than that in the SBC group (97.0% vs. 78.8%, P=0.006). The Euroscore II in the DNC group was markedly lower than that in the SBC group (2.00 vs. 3.00, P<0.05). The level of blood urea nitrogen (BUN) in the DNC group was significantly lower than that in the SBC group (6.20 vs. 6.95, P<0.05). There were no differences in surgery procedure, cross-clamp time, bypass time, Apache score, troponin T (cTnT), brain natriuretic peptide (BNP), liver and renal function, postoperative complications or patient outcomes between two groups. Regression analysis showed that cTnT increased with the prolongation of myocardial ischemia time, and was closely related to the type of operation, but had no significant correlation with the type of cardioplegia. Conclusions:In our initial experience, single-dose DNC in adult minimally invasive valve surgery in which the cross-clamp time was mostly less than 90 min, achieved equivalent myocardial protection and clinical outcomes when compared with standard whole blood cardioplegia. In addition, single-dose DNC made the minimally invasive valve surgery procedure progress in a smoother and more convenient fashion.
| S-EPMC6626819 | biostudies-literature
Project description:BackgroundTo determine the safely and effectively of del Nido cardioplegia (DNC) in surgery for aortic root disease, with mild hypothermic cardiopulmonary bypass (CPB).MethodsFrom July to December 2017, all patients undergoing the surgery for aortic root disease (total aortic root replacement, valve-sparing aortic root replacement and replacement of aortic valve plus ascending aorta), with mild hypothermic CPB, were retrospectively reviewed at our institution. Patients were divided into two groups based on the type of cardioplegia: the classical blood cardioplegia (CBC group) and del Nido cardioplegia (DNC group). Demographics, operative details, perioperative data and postoperative complications were recorded and compared. A propensity score matching was performed in this study.ResultsThe preoperative data in DNC group were similar to CBC group. The volume of ultrafiltration was lower in DNC than CBC group (2,053.49±806.62 DNC vs. 2,666.00±967.14 CBC, P=0.001), when matched. The use of temporary pacemaker was more in DNC group (n=20, 46.5%, P=0.023), and the rate of automatic heart resuscitating was higher in the CBC group (92.0% vs. 72.1% DNC group, P=0.024, unmatched).There were no differences in in-hospital mortality, troponin T (mean 0.66 ng/mL for CBC group vs. 0.49 ng/mL for DNC group, P=0.152), left ventricular ejection fraction (mean 58.37% for CBC group vs. 60.07% for DNC group, P=0.395) or other postoperative complications between two groups, after matching. In subgroup analysis, the ultrafiltration volume was lower in DNC than CBC group (1,932.26±749.39 DNC vs. 2,640.00±996.24 CBC, P=0.004), when ACC time less than or equal to 90 minutes. The apache score was better in DNC group (4.75±3.41, P=0.041), when ACC time greater than 90 min. There were no statistical significances in other characteristics between groups.ConclusionsDNC is safe and effective for surgery for aortic root disease, not inferior to the CBC.
| S-EPMC7475601 | biostudies-literature
Project description:BackgroundDel Nido cardioplegia (DNc) was designed for superior myocardial protection during cardiopulmonary bypass (CPB). We conducted a retrospective review to explore if DNc was associated with increase in systemic ventricle dysfunction (sVD) following pediatric CPB.Methods and resultsThis single-center, retrospective study included 1534 patients undergoing CPB between 2013 and 2016, 997 prior to center-wide conversion to DNc and 537 following. The primary outcome was new postoperative ≥moderate sVD by echocardiogram. Secondary outcomes included sVD of any severity and right ventricular dysfunction. Data was evaluated by interrupted time-series analysis. Groups had similar cardiac diagnoses and surgical complexity. Del Nido cardioplegia was associated with longer median (IQR) CPB [117 (84-158) vs 108 (81-154), p = 0.04], and aortic cross-clamp [83 (55-119) vs 76 (53-106), p = 0.03], and fewer cardioplegia doses [2 (1-2) vs 3 (2-4), p < 0.0001]. Mortality was similar in both groups. Frequency of sVD was unchanged following DNc, including predetermine subgroups (neonates, infants, and prolonged cross-clamp). Logistic regression showed a significant rise in right ventricular dysfunction (OR 5.886 [95% CI: 0.588, 11.185], p = 0.03) but similar slope.ConclusionsUse of DNc was not associated with increased in reported sVD, and provided similar myocardical protection to the systemic ventricle compared to conventional cardioplegia but may possibly impact right ventricular function. Studies evaluating quantitative systolic and diastolic function are needed.
| S-EPMC9932617 | biostudies-literature
Project description:Objectivesdel Nido cardioplegia is used to pharmacologically arrest the heart during cardiac surgery and decrease reperfusion- and ischaemia-related myocardial injury. Studies have demonstrated the physiological differences between male and female hearts, potentially related to cardiac size or myocyte calcium handling; we aimed to assess for between-sex differences in clinical outcomes after receipt of del Nido cardioplegia.MethodsPatients who underwent coronary artery bypass or coronary artery bypass graft/valve surgery at our institution using del Nido cardioplegia (January 2014 to December 2019) were included (n = 2118). Clinical data were collected retrospectively. After the creation of a propensity-matched cohort (n = 1252), multivariable logistic regression was used to analyse binary postoperative outcomes, and a Gamma model was used for a continuous postoperative outcome. Our primary end-point was a composite end-point comprised of 30-day mortality and/or need for a post-bypass mechanical support device.ResultsThe final cohort included 459 females and 793 males (matched up to 1:2, all standardized mean differences <0.1). Multivariable logistic regression showed that biological sex was not associated with the composite primary end-point (odds ratio = 0.898, P = 0.779). A Gamma model indicated that there were no sex-related differences in vasoactive-inotropic scores reflecting vasopressor and inotrope usage at the time of patient operating room exit (exp[est] = 1.394, P = 0.189).ConclusionsOur findings showed no significant between-sex differences in clinical outcomes after receiving del Nido cardioplegia, suggesting adequate myocardial protection as currently administered. Further research is warranted to elicit if there are sex-based differences between cardioplegic solutions.Irb approval date (protocol number)26 May 2021 (AAAR8359).
| S-EPMC9531685 | biostudies-literature
Project description:Open heart surgery is often an unavoidable procedure for treatment of coronary artery disease. The procedure associated reperfusion injury affects postoperative cardiac performance and long-term outcome. We addressed here whether cardioplegia essential for cardiopulmonary bypass surgery activates Nrf2, a transcription factor regulating the expression of antioxidant and detoxification genes. With commonly used cardioplegic solutions, High K+, Low K+, Del Nido (DN), histidine-tryptophan-ketoglutarate (HTK) and Celsior, we found that DN causes an increase of Nrf2 protein in AC16 human cardiomyocytes. Tracing the ingredients in DN led to the discovery of KCl at the concentration above 5 mM capable of Nrf2 protein induction. The Antioxidant Response Element luciferase reporter assay confirmed Nrf2 activation by DN or KCl. Transcriptomic profiling using RNA-seq revealed that oxidation-reduction as a main gene ontology group affected by KCl. KCl indeed elevated the expression of classical Nrf2 downstream targets, including TXNRD1, AKR1C, AKR1B1, SRXN1 and G6PD. DN or KCl induced Nrf2 elevation is Ca2+ concentration dependent. We found that KCl extended the half-life of Nrf2 from 17.8 to 25.1 mins, and decreased Nrf2 protein ubiquitination. Knocking out Keap1 blocked Nrf2 induction by K+. Nrf2 induction by DN or KCl protected against ROS generation or loss of viability by H2O2. Our data support that high K+ concentration in DN cardioplegic solution can induce Nrf2 protein, which in turn mediates protection of cardiomyocytes
2023-01-01 | GSE221058 | GEO