Dataset Information

Preoperative endothelial dysfunction for the prediction of acute kidney injury after cardiac surgery using cardiopulmonary bypass: a pilot study based on a second analysis of the MONS study.

ABSTRACT:

Background

Up to 42% of patients develop acute kidney injury (AKI) after cardiac surgery. The aim of this study was to describe the relationship between preoperative microcirculatory function and postoperative AKI after cardiac surgery using cardiopulmonary bypass (CPB).

Methods

The prospective observational cohort MONS enrolled 60 patients scheduled for valvular (n = 30, 50%) or coronary (n = 30, 50%) surgery using CPB. Preoperative microcirculation was assessed during preoperative consultation from January 2019 to April 2019 at the University Hospital of Angers, France, using endothelium-dependent and endothelium-independent reactivity tests on the forearm (iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP), respectively). Skin blood flow was measured by laser speckle contrast imaging. The primary endpoint was the occurrence of AKI according to the KDIGO classification during the hospital stay.

Results

Forty-three (71.7%) patients developed AKI during the in-hospital follow-up, and 15 (25%) were classified as KDIGO stage 1, 20 (33%) KDIGO stage 2, and 8 (13%) KDIGO stage 3. Regarding preoperative microcirculation, a higher peak amplitude of vasodilation in response to iontophoresis of ACh was found in patients with postoperative occurrence of AKI (35 [20-49] vs 23 [9-44] LSPU, p = 0.04). Iontophoresis of SNP was not significantly different according to AKI occurrence (34 [22-49] vs 36 [20-50] LSPU, p = 0.95). In a multivariable model, the preoperative peak amplitude at iontophoresis of ACh was independently associated with postoperative AKI (OR 1.045 [1.001-1.092], p = 0.045).

Conclusions

The preoperative peak amplitude of endothelium-dependent vasodilation is independently associated with the postoperative occurrence of AKI.

Trial registration

Clinical-Trials.gov, NCT03631797. Registered 15 August 2018, https://clinicaltrials.gov/ct2/show/NCT03631797.

SUBMITTER: Abrard S

PROVIDER: S-EPMC10903056 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Publications

Preoperative endothelial dysfunction for the prediction of acute kidney injury after cardiac surgery using cardiopulmonary bypass: a pilot study based on a second analysis of the MONS study.

Abrard Stanislas S Streichenberger Antoine A Riou Jérémie J Hersant Jeanne J Rineau Emmanuel E Jacquet-Lagrèze Matthias M Fouquet Olivier O Henni Samir S Rimmelé Thomas T

Perioperative medicine (London, England) 20240229 1

<h4>Background</h4>Up to 42% of patients develop acute kidney injury (AKI) after cardiac surgery. The aim of this study was to describe the relationship between preoperative microcirculatory function and postoperative AKI after cardiac surgery using cardiopulmonary bypass (CPB).<h4>Methods</h4>The prospective observational cohort MONS enrolled 60 patients scheduled for valvular (n = 30, 50%) or coronary (n = 30, 50%) surgery using CPB. Preoperative microcirculation was assessed during preoperati ...[more]

PMID: 38424616

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Project description:ObjectivesCardiopulmonary bypass-induced endothelial dysfunction has been inferred by changes in pulmonary vascular resistance, alterations in circulating biomarkers, and postoperative capillary leak. Endothelial-dependent vasomotor dysfunction of the systemic vasculature has never been quantified in this setting. The objective of the present study was to quantify acute effects of cardiopulmonary bypass on endothelial vasomotor control and attempt to correlate these effects with postoperative cytokines, tissue edema, and clinical outcomes in infants.DesignSingle-center prospective observational cohort pilot study.SettingPediatric cardiac ICU at a tertiary children's hospital.PatientsChildren less than 1 year old requiring cardiopulmonary bypass for repair of a congenital heart lesion.InterventionNone.Measurements and main resultsLaser Doppler perfusion monitoring was coupled with local iontophoresis of acetylcholine (endothelium-dependent vasodilator) or sodium nitroprusside (endothelium-independent vasodilator) to quantify endothelial-dependent vasomotor function in the cutaneous microcirculation. Measurements were obtained preoperatively, 2-4 hours, and 24 hours after separation from cardiopulmonary bypass. Fifteen patients completed all laser Doppler perfusion monitor (Perimed, Järfälla, Sweden) measurements. Comparing prebypass with 2-4 hours postbypass responses, there was a decrease in both peak perfusion (p = 0.0006) and area under the dose-response curve (p = 0.005) following acetylcholine, but no change in responses to sodium nitroprusside. Twenty-four hours after bypass responsiveness to acetylcholine improved, but typically remained depressed from baseline. Conserved endothelial function was associated with higher urine output during the first 48 postoperative hours (R = 0.43; p = 0.008).ConclusionsCutaneous endothelial dysfunction is present in infants immediately following cardiopulmonary bypass and recovers significantly in some patients within 24 hours postoperatively. Confirmation of an association between persistent endothelial-dependent vasomotor dysfunction and decreased urine output could have important clinical implications. Ongoing research will explore the pattern of endothelial-dependent vasomotor dysfunction after cardiopulmonary bypass and its relationship with biochemical markers of inflammation and clinical outcomes.

Project description:IntroductionGlucagon-like peptide-1 receptor agonists reduce insulin requirements and improve glucose control when administered before cardiac surgery. An increase in endogenous insulin release is the most likely mechanism, but this has never been studied in the setting of cardiac surgery. We hypothesized that liraglutide increases pancreatic insulin secretion during cardiac surgery with cardiopulmonary bypass (CPB).MethodsWe performed a planned prospective substudy of a multicenter randomized-controlled trial (GLOBE trial, NTR6323). Patients undergoing cardiac surgery with CPB were randomized to receive either two preoperative subcutaneous injections of liraglutide or a matching placebo. We measured hormone concentrations before and after surgery, including insulin, glucagon, C-peptide and free fatty acid (FFA), and calculated HOMA-B, HOMA-IR and insulin/glucagon ratios. We compared between-group and before and after surgery differences in outcomes.ResultsMetabolic hormone concentrations were measured in 37 participants. HOMA-B revealed that liraglutide increased insulin secretion relative to glycemia (258 ± 179 vs 116 ± 180, difference (95% CI): 142 (24-261), P = 0.004). While insulin, C-peptide and glucagon levels did not differ significantly between groups, the insulin/glucagon ratios were significantly higher in the liraglutide group (preoperatively: 1.09 ± 0.45 vs 0.79 ± 0.35 difference (95% CI): -0.30 (-0.57 to -0.03), P = 0.039). Overall, postoperative insulin levels decreased >60% from preoperative insulin levels (55 ± 31 to 21 ± 9.8, difference (95% CI): -29 (-36 to -22), P < 0.001).ConclusionPreoperative liraglutide administration increased beta-cell function, measured as HOMA-B, and higher insulin/glucagon ratios. These results could explain the lower glucose and FFA concentrations in the liraglutide-treated patients. Interestingly, in both groups, we observed a remarkable drop in insulin and other hormone levels over the course of surgery.

Project description:Endothelial activation leading to vascular barrier dysfunction and organ failure is a well-recognized complication of cardiovascular surgery with cardiopulmonary bypass (CPB). The endothelial-specific angiopoietin-Tie2 ligand-receptor system has been identified as a non-redundant regulator of endothelial activation. Binding of angiopoietin-2 (Ang-2) to the Tie2 receptor antagonizes Tie2 signaling and renders the endothelial barrier responsive to pro-inflammatory cytokines. We aimed to study the time course and potential triggering factors of Ang-2 release after CPB, as well as the association of Ang-2 changes with surrogates of increased vascular permeability, organ dysfunction, and outcome.Serum levels of Ang-2 from 25 adult patients (140 screened) were measured before and at 0, 12, and 24h following CPB procedure by in-house immuno-luminometric assay (ILMA), and compared with indices of organ dysfunction, duration of mechanical ventilation (MV), length of stay (LOS) in the intensive care unit (ICU), and hospital mortality. The effect of Ang-2 was studied in vitro by incubating high Ang-2 patient serum with endothelial cells (EC).Ang-2 levels steadily increased from 2.6 ± 2.4 ng/mL at 0 h up to 7.3 ± 4.6 ng/mL at 24h following CPB (P<0.001). The release of Ang-2 correlated with the duration of CPB, aortic cross-clamp time, and post-CPB lactate levels. Changes in Ang-2 during follow-up correlated with partial pressure of oxygen in arterial blood (PaO(2))/fraction of inspired oxygen (FiO(2)) ratio, alveolar-arterial oxygen tension difference (AaDO(2)), hemodynamics, fluid balance, and disease severity measures. Ang-2 levels at 12h predicted the duration of MV, ICU-LOS, and hospital mortality. High Ang-2 patient sera disrupted EC architecture in vitro, an effect reversed by treatment with the competitive Tie2 ligand angiopoietin-1 (Ang-1).Collectively, our results suggest that Ang-2 is a putative mediator of endothelial barrier dysfunction after CPB. These findings suggest that targeting the Ang/Tie2 pathway may mitigate organ dysfunction and improve outcome in patients undergoing CPB.

Project description:BackgroundCardiopulmonary bypass (CPB) surgery initiates a systemic inflammatory response, which is associated with postoperative morbidity and mortality. Hemoadsorption (HA) of cytokines may suppress inflammatory responses and improve outcomes. We tested a new sorbent used for HA (CytoSorb™; CytoSorbents Europe GmbH, Berlin, Germany) installed in the CPB circuit on changes of pro- and anti-inflammatory cytokines levels, inflammation markers, and differences in patients' perioperative course.MethodsIn this first pilot trial, 37 blinded patients were undergoing elective CPB surgery at the Medical University of Vienna and were randomly assigned to HA (n = 19) or control group (n = 18). The primary outcome was differences of cytokine levels (IL-1β, IL-6, IL-18, TNF-α, and IL-10) within the first five postoperative days. We also analyzed whether we can observe any differences in ex vivo lipopolysaccharide (LPS)-induced TNF-α production, a reduction of high-mobility box group 1 (HMGB1), or other inflammatory markers. Additionally, measurements for fluid components, blood products, catecholamine treatment, bioelectrical impedance analysis (BIA), and 30-day mortality were analyzed.ResultsWe did not find differences in our primary outcome immediately following the HA treatment, although we observed differences for IL-10 24 hours after CPB (HA: median 0.3, interquartile range (IQR) 0-4.5; control: not traceable, P = 0.0347) and 48 hours after CPB (median 0, IQR 0-1.2 versus not traceable, P = 0.0185). We did not find any differences for IL-6 between both groups, and other cytokines were rarely expressed. We found differences in pretreatment levels of HMGB1 (HA: median 0, IQR 0-28.1; control: median 48.6, IQR 12.7-597.3, P = 0.02083) but no significant changes to post-treatment levels. No differences in inflammatory markers, fluid administration, blood substitution, catecholamines, BIA, or 30-day mortality were found.ConclusionsWe did not find any reduction of the pro-inflammatory response in our patients and therefore no changes in their perioperative course. However, IL-10 showed a longer-lasting anti-inflammatory effect. The clinical impact of prolonged IL-10 needs further evaluation. We also observed strong inter-individual differences in cytokine levels; therefore, patients with an exaggerated inflammatory response to CPB need to be identified. The implementation of HA during CPB was feasible.Trial registrationClinicalTrials.gov: NCT01879176, registration date: June 7, 2013.

Project description:BackgroundCurrent diagnostic strategies for acute kidney injury (AKI) after cardiac surgery with cardiopulmonary bypass (CPB) are nonspecific and limited. Previously, we demonstrated that circulating microparticles (MPs) in patients with valve heart disease (VHD) and congenital heart diseases (CHD) induce endothelial dysfunction and neutrophil chemotaxis, which may result in kidney injury. We also found that circulating MPs increase after cardiac surgery with CPB and are related to cardiac function. However, the relationship between circulating MPs and AKI after CPB is unknown.MethodsEighty-five patients undergoing cardiac surgery with CPB were enrolled. Patients were divided into AKI and non-AKI groups based on the serum creatinine levels at 12 h and 3 d post-CPB. Circulating MPs were isolated from plasma, and their levels including its subtypes were detected by flow cytometer. Independent risk factors for the CPB-associated AKI (CPB-AKI) were determined by multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis was used to measure the prognostic potential of CPB-AKI.ResultsThe morbidity of AKI at 12 h and 3 d after cardiac surgery with CPB was 40% and 31.76%, respectively. The concentrations of total MPs and platelet-derived MPs (PMP) remained unchanged at 12 h and then increased at 3 d post-CPB, while that of endothelial-derived MPs (EMP) increased at both time points. In patients with AKI, PMP and EMP were elevated compared with the patients without AKI. However, no significant change was detected on monocyte-derived MPs (MMP) at 12 h and 3 d post-CPB. The logistic regression analysis showed that EMP was the independent risk factor for AKI both at 12 h and 3 d post-CPB. The area under ROC for the concentrations of EMP at 12 h and 3 d post-CPB was 0.86 and 0.91, with the specificity up to 0.88 and 0.91, respectively.ConclusionsCirculating EMP may serve as a potential biomarker of AKI after cardiac surgery with CPB.

Dataset Information

Preoperative endothelial dysfunction for the prediction of acute kidney injury after cardiac surgery using cardiopulmonary bypass: a pilot study based on a second analysis of the MONS study.

Background

Methods

Results

Conclusions

Trial registration

Publications

Preoperative endothelial dysfunction for the prediction of acute kidney injury after cardiac surgery using cardiopulmonary bypass: a pilot study based on a second analysis of the MONS study.

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