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Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Bronchoalveolar Fluid and Lung Tissue in Cardiac Surgery Patients.

ABSTRACT: Pulmonary dysfunction is among the most frequent complications to cardiac surgeries. Exposure of blood to the cardiopulmonary bypass (CPB) circuit with subsequent lung ischemia-reperfusion leads to the production of inflammatory mediators and increases in microvascular permeability. The study aimed to elucidate histological, cellular, and metabolite changes following two lung protective regimens during CPB with Histidine-Tryptophan-Ketoglutarate (HTK) enriched or warm oxygenated blood pulmonary perfusion compared to standard regimen with no pulmonary perfusion. A total of 90 patients undergoing CPB were randomized to receiving HTK, oxygenated blood or standard regimen. Of these, bronchoalveolar lavage fluid (BALF) and lung tissue biopsies were obtained before and after CPB from 47 and 25 patients, respectively. Histopathological scores, BALF cell counts and metabolite screening were assessed. Multivariate and univariate analyses were performed. Profound histological, cellular, and metabolic changes were identified in all patients after CPB. Histological and cellular changes were similar in the three groups; however, some metabolite profiles were different in the HTK patients. While all patients presented an increase in inflammatory cells, metabolic acidosis, protease activity and oxidative stress, HTK patients seemed to be protected against severe acidosis, excessive fatty acid oxidation, and inflammation during ischemia-reperfusion. Additional studies are needed to confirm these findings.

SUBMITTER: Maltesen RG

PROVIDER: S-EPMC6316472 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Bronchoalveolar Fluid and Lung Tissue in Cardiac Surgery Patients.

Maltesen Raluca G RG Buggeskov Katrine B KB Andersen Claus B CB Plovsing Ronni R Wimmer Reinhard R Ravn Hanne B HB Rasmussen Bodil S BS

Metabolites 20180921 4

Pulmonary dysfunction is among the most frequent complications to cardiac surgeries. Exposure of blood to the cardiopulmonary bypass (CPB) circuit with subsequent lung ischemia-reperfusion leads to the production of inflammatory mediators and increases in microvascular permeability. The study aimed to elucidate histological, cellular, and metabolite changes following two lung protective regimens during CPB with Histidine-Tryptophan-Ketoglutarate (HTK) enriched or warm oxygenated blood pulmonary ...[more]

PMID: 30241409

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Project description:Essentials Heparin-protamine balance (HPB) modulates bleeding after neonatal cardiopulmonary bypass (CPB). HPB was examined in 44 neonates undergoing CPB. Post-operative bleeding occurred in 36% and heparin rebound in 73%. Thrombin-initiated fibrin clot kinetic assay and partial thromboplastin time best assessed HPB.SummaryBackground Neonates undergoing cardiopulmonary bypass (CPB) are at risk of excessive bleeding. Blood is anticoagulated with heparin during CPB. Heparin activity is reversed with protamine at the end of CPB. Paradoxically, protamine also inhibits blood coagulation when it is dosed in excess of heparin. Objectives To evaluate heparin-protamine balance in neonates undergoing CPB by using research and clinical assays, and to determine its association with postoperative bleeding. Patients/Methods Neonates undergoing CPB in the first 30 days of life were studied. Blood samples were obtained during and after surgery. Heparin-protamine balance was assessed with calibrated automated thrombography, thrombin-initiated fibrin clot kinetic assay (TFCK), activated partial thromboplastin time (APTT), anti-FXa activity, and thromboelastometry. Excessive postoperative bleeding was determined by measurement of chest tube output or the development of cardiac tamponade. Results and Conclusions Of 44 neonates enrolled, 16 (36%) had excessive postoperative bleeding. The TFCK value was increased. By heparin in neonatal blood samples, but was only minimally altered by excess protamine. Therefore, it reliably measured heparin in samples containing a wide range of heparin and protamine concentrations. The APTT most closely correlated with TFCK results, whereas anti-FXa and thromboelastometry assays were less correlative. The TFCK and APTT assay also consistently detected postoperative heparin rebound, providing an important continued role for these long-established coagulation tests in the management of postoperative bleeding in neonates requiring cardiac surgical repair. None of the coagulation tests predicted the neonates who experienced postoperative bleeding, reflecting the multifactorial causes of bleeding in this population.

Project description:INTRODUCTION:Modulating 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 METHODS:In 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. RESULTS:When 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). CONCLUSIONS:Patients 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.

Project description:Cardiopulmonary bypass triggers systemic inflammation, resulting in lung injury, and frequently leads to prolonged mechanical ventilation. Biomarkers of systemic inflammation are required to predict the risk of such complications. We hypothesize that specific serum proteins can be used as biomarkers to predict the severity of lung injury following cardiac surgery.DesignRetrospective chart review study.SettingClinical variables were collected and used in conjuncture with unbiased proteomic analysis using mass spectrometry that was performed on frozen plasma samples from a study group (patients with mechanical ventilation > 48 hr post surgery) and a control group (patients with mechanical ventilation < 48 hr post surgery).SubjectsSubjects included were infants who underwent cardiac surgery with similar complexity (Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery 3 or 4) using cardiopulmonary bypass. Patients in both groups were matched for their weight, age, and duration of cardiopulmonary bypass.InterventionNone.Measurements and main resultsFour-hundred eighty-three proteins were identified (99% minimum confidence and two peptides minimum, protein false discovery rate 0.1%) on proteomic analysis of four control and four study patients at precardiopulmonary bypass, 0, and 48 hours postcardiopulmonary bypass samples. Thirty-six of 178 proteins were significantly different (≥ 1.5-fold; p < 0.05) at precardiopulmonary bypass (top increased: tenascin; top decreased: tetranectin), 18 of 140 proteins at 0 hour (top increased: hemoglobin beta; top decreased: C8 beta), and 25 of 166 proteins at 48 hours post surgery (top increased: proteoglycan 4; top decreased: galectin-3-binding protein). The top pathway involved cytoskeleton remodeling. Other pathways involved immune response and blood coagulation. Proteoglycan 4 was validated by enzyme-linked immunosorbent assay in a different set of samples (n = 20/group; mean ± sd: 128 ± 67 vs 195 ± 160 ng/mL) (p = 0.037).ConclusionsMultiple proteomic biomarkers were associated with worse respiratory outcomes. Precardiopulmonary bypass biomarkers might indicate risk factors (e.g., abnormalities of coagulation), whereas those identified at 0 hour and post cardiopulmonary bypass may reflect mechanisms of ongoing pathobiology.

Project description:BACKGROUND:There is no consensus on the ventilation management during cardiopulmonary bypass (CPB), and the anesthesiologists or the surgeons usually ventilate the lungs with different ventilation strategies or keep them static. Better outcomes are more likely to occur when the ventilation is administered during CPB according to the existing literatures. However, the use of high fraction of inspired oxygen (FiO2) is debatable in cardiac surgery. And the potential effects of strategies combining low tidal volume (VT) ventilation with different FiO2 during CPB on postoperative pulmonary complications (PPCs) are unclear. DESIGN:The VONTCPB trial is a single-center, prospective, double-blinded, randomized, controlled trial. We are going to recruit total 420 elective cardiac surgery patients with median sternotomy under CPB, who will be equally randomized into three different ventilation strategy groups: NoV, LOV and HOV. (1) The NoV group receives no mechanical ventilation during CPB; (2) the LOV group receives a low VT of 3-4?ml/kg of ideal body weight (IBW) with the respiratory rate (RR) of 10-12 acts/min, and the positive end-expiratory pressure (PEEP) of 5-8 cmH2O during CPB; the FiO2 is 30%; (3) the HOV group receives a low VT of 3-4?ml/kg of IBW with the RR of 10-12 acts/min, and the PEEP of 5-8 cmH2O during CPB; the FiO2 is 80%. The primary endpoints are the incidence of the composite of PPCs and the PPCs score. The secondary endpoints refer to the incidence of the oxygenation index (PaO2/FiO2 ratio) <?300?mmHg at three time points (the moment arriving in the ICU, 6 and 12?h after arrival in the ICU), the surgical incision healing grade, the intubation time, the stay of ICU, the length of hospital stay, and mortality at 30?days after the surgery. DISCUSSION:The VONTCPB trial is the first study to assess the effects of strategies combining low tidal volume (VT) ventilation with different FiO2 during CPB on patients' outcomes. TRIAL REGISTRATION:ChiCTR1800015261 . Registered on 20 March 2018.

Dataset Information

Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Bronchoalveolar Fluid and Lung Tissue in Cardiac Surgery Patients.

Publications

Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Bronchoalveolar Fluid and Lung Tissue in Cardiac Surgery Patients.

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