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A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass.

ABSTRACT: Cardiac surgery and cardiopulmonary bypass (CPB) are associated with a systemic inflammatory reaction that occasionally induces a life-threatening organ dysfunction caused by the dysregulated host response to the damage-associated molecular patterns (DAMPs). In severe inflammation, cell-free DNA (cfDNA) and histones are released by inflammatory cells and damaged tissue and act as DAMPs. We sought to characterize the changes in circulating cell-free DNA (cfDNA) levels during CPB. Primary outcomes were renal failure, ventilation time (>18 hr), length of stay (LOS) in the intensive care unit (ICU) (>48hr), hospital LOS (>15 days), and death. We looked for associations with blood tests and comparison to standard scores. In a prospective cohort study, we enrolled 71 patients undergoing non-emergent coronary artery bypass grafting. Blood was drawn at baseline, 20 and 40 minutes on CPB, after cross-clamp removal, and 30 minutes after chest closure. cfDNA was measured by our fast fluorescent method. Baseline cfDNA levels [796 (656-1063) ng/ml] increased during surgery, peaked after cross-clamp removal [2403 (1981-3357) ng/ml] and returned to baseline at recovery. The difference in cfDNA from 20 to 40 minutes on CPB (ΔcfDNA 40-20) inversely correlated with peripheral vascular disease (PVD), longer ventilation time, and longer ICU and hospital length of stay (LOS). Receiver operating characteristic (ROC) curve of ΔcfDNA 40-20 for long ICU-LOS (>48hr) was with an area under the curve (AUC) of 0.738 (p = 0.022). ROC AUC of ΔcfDNA 40-20 to long Hospital LOS (>15 days) was 0.787 (p = 0.006). Correction for time on CPB in a multivariate logistic regression model improved ROC-AUC to 0.854 (p = 0.003) and suggests that ΔcfDNA 40-20 is an independent risk factor. To conclude, of measured parameters, including STS and Euroscore, the predictive power of ΔcfDNA 40-20 was the highest. Thus, measurement of ΔcfDNA 40-20 may enable early monitoring of patients at higher risk. Further studies on the mechanism behind the negative association of ΔcfDNA 40-20 with PVD and outcomes are warranted.

SUBMITTER: Ishay SY

PROVIDER: S-EPMC9612555 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass.

Ishay Shlomo Yaron SY Abu-Tailakh Muhammad M Raichel Lior L Hershenhoren Tal F TF Matsa Menahem M Lev-Ran Oren O Gideon Sahar S Douvdevani Amos A

PloS one 20221027 10

Cardiac surgery and cardiopulmonary bypass (CPB) are associated with a systemic inflammatory reaction that occasionally induces a life-threatening organ dysfunction caused by the dysregulated host response to the damage-associated molecular patterns (DAMPs). In severe inflammation, cell-free DNA (cfDNA) and histones are released by inflammatory cells and damaged tissue and act as DAMPs. We sought to characterize the changes in circulating cell-free DNA (cfDNA) levels during CPB. Primary outcomes ...[more]

PMID: 36301964

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Project description:BackgroundPersistent microcirculatory dysfunction associated with increased morbidity and mortality. Interventions in the early resuscitation can be tailored to the changes of microcirculation and patient's need. However, there is usually an uncoupling of macrocirculatory and microcirculatory hemodynamics during resuscitation. Current research on the patterns of microcirculatory changes and recovery after cardiopulmonary bypass (CPB)-assisted cardiac surgery is limited. This study aimed to analyze changes in the microcirculatory parameters after CPB and their correlation with macrocirculation and to explore the characteristics of microcirculatory changes following CPB-assisted cardiac surgery.MethodsBetween December 2018 and January 2019, 24 adult patients with indwelling pulmonary artery catheters after elective cardiac surgery using CPB were enrolled in this study. Both microcirculatory and macrocirculatory parameters were collected at 0, 6, 16, and 24 hours after admission to the intensive care unit (ICU). Video images of sublingual microcirculation were analyzed to obtain the microcirculatory parameters, including total vascular density (TVD), perfused small vessel density (PSVD), the proportion of perfused small vessels (PPV), microvascular flow index (MFI), and flow heterogeneity index (HI). The characteristics of microcirculatory parameter change following cardiac surgery and the correlation between microcirculatory parameters and macroscopic hemodynamic indicators, oxygen metabolic indicators, and carbon dioxide partial pressure difference (PCO2gap) were analyzed.ResultsThere were significant differences in the changes of TVD (P=0.012) and PSVD (P=0.005) during the first 24 hours postoperatively in patients who underwent CPB-assisted cardiac surgery. The microcirculatory density parameters (TVD: r=-0.5059, P=0.0456; PVD: r=-0.5499, P=0.0273) were correlated with oxygen delivery index (DO2I) at 24 hours after surgery. The microcirculatory flow parameters (PPV: r=0.4370, P=0.0327; MFI: r=0.6496, P=0.0006; and HI: r=-0.5350, P=0.0071) had a strong correlation with PCO2gap at 0 hour after surgery.ConclusionsTVD and PSVD might be two most sensitive indicators affected by CPB-assisted cardiac surgery. There was no consistency between microcirculation and macrocirculation until 24 hours following cardiac surgery, meaning the improvement of systemic hemodynamic indicators does not guarantee correspondently improvement in microcirculation. Early controlled oxygen supply after CPB-assisted cardiac surgery may be conducive to the resuscitation of patients to a certain extent.

Project description:IntroductionModulating the stress response and perioperative factors can have a paramount impact on the neurodevelopmental outcome of infants who undergo cardiac surgery utilizing cardiopulmonary bypass.Materials and methodsIn this single center prospective follow-up study, we evaluated the impact of three different anesthetic techniques on the neurodevelopmental outcomes of 19 children who previously underwent congenital cardiac surgery within their 1(st) year of life. Cases were done from May 2011 to December 2013. Children were assessed using the Stanford-Binet Intelligence Scales (5(th) edition). Multiple regression analysis was used to test different parental and perioperative factors that could significantly predict the different neurodevelopmental outcomes in the entire cohort of patients.ResultsWhen comparing the three groups regarding the major cognitive scores, a high-dose fentanyl (HDF) patients scored significantly higher than the low-dose fentanyl (LDF) + dexmedetomidine (DEX) (LDF + DEX) group in the quantitative reasoning scores (106 ± 22 vs. 82 ± 15 P = 0.046). The bispectral index (BIS) value at the end of surgery for the -LDF group was significantly higher than that in LDF + DEX group (P = 0.011). For the entire cohort, a strong correlation was seen between the standard verbal intelligence quotient (IQ) score and the baseline adrenocorticotropic hormone level, the interleukin-6 level at the end of surgery and the BIS value at the end of the procedure with an R(2) value of 0.67 and P < 0.04. There was an inverse correlation between the cardiac Intensive Care Unit length of stay and the full-scale IQ score (R = 0.4675 and P 0.027).ConclusionsPatients in the HDF group demonstrated overall higher neurodevelopmental scores, although it did not reach statistical significance except in fluid reasoning scores. Our results may point to a possible correlation between blunting the stress response and improvement of the neurodevelopmental outcome.

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A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass.

Publications

A prospective cohort study of dynamic cell-free DNA elevation during cardiac surgery with cardiopulmonary bypass.

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