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      Lung Protection Strategies during Cardiopulmonary Bypass Affect the Composition of Blood Electrolytes and Metabolites—A Randomized Controlled Trial

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          Abstract

          Cardiac surgery with cardiopulmonary bypass (CPB) causes an acute lung ischemia-reperfusion injury, which can develop to pulmonary dysfunction postoperatively. This sub-study of the Pulmonary Protection Trial aimed to elucidate changes in arterial blood gas analyses, inflammatory protein interleukin-6, and metabolites of 90 chronic obstructive pulmonary disease patients following two lung protective regimens of pulmonary artery perfusion with either hypothermic histidine-tryptophan-ketoglutarate (HTK) solution or normothermic oxygenated blood during CPB, compared to the standard CPB with no pulmonary perfusion. Blood was collected at six time points before, during, and up to 20 h post-CPB. Blood gas analysis, enzyme-linked immunosorbent assay, and nuclear magnetic resonance spectroscopy were used, and multivariate and univariate statistical analyses were performed. All patients had decreased gas exchange, augmented inflammation, and metabolite alteration during and after CPB. While no difference was observed between patients receiving oxygenated blood and standard CPB, patients receiving HTK solution had an excess of metabolites involved in energy production and detoxification of reactive oxygen species. Also, patients receiving HTK suffered a transient isotonic hyponatremia that resolved within 20 h post-CPB. Additional studies are needed to further elucidate how to diminish lung ischemia-reperfusion injury during CPB, and thereby, reduce the risk of developing severe postoperative pulmonary dysfunction.

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          Most cited references62

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          Modified Spin-Echo Method for Measuring Nuclear Relaxation Times

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            Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients.

            To assess risk factors for mortality in cardiac surgical adult patients as part of a study to develop a European System for Cardiac Operative Risk Evaluation (EuroSCORE). From September to November 1995, information on risk factors and mortality was collected for 19030 consecutive adult patients undergoing cardiac surgery under cardiopulmonary bypass in 128 surgical centres in eight European states. Data were collected for 68 preoperative and 29 operative risk factors proven or believed to influence hospital mortality. The relationship between risk factors and outcome was assessed by univariate and logistic regression analysis. Mean age (+/- standard deviation) was 62.5+/-10.7 (range 17-94 years) and 28% were female. Mean body mass index was 26.3+/-3.9. The incidence of common risk factors was as follows: hypertension 43.6%, diabetes 16.7%, extracardiac arteriopathy 2.9%, chronic renal failure 3.5%, chronic pulmonary disease 3.9%, previous cardiac surgery 7.3% and impaired left ventricular function 31.4%. Isolated coronary surgery accounted for 63.6% of all procedures, and 29.8% of patients had valve operations. Overall hospital mortality was 4.8%. Coronary surgery mortality was 3.4% In the absence of any identifiable risk factors, mortality was 0.4% for coronary surgery, 1% for mitral valve surgery, 1.1% for aortic valve surgery and 0% for atrial septal defect repair. The following risk factors were associated with increased mortality: age (P = 0.001), female gender (P = 0.001), serum creatinine (P = 0.001), extracardiac arteriopathy (P = 0.001), chronic airway disease (P = 0.006), severe neurological dysfunction (P = 0.001), previous cardiac surgery (P = 0.001), recent myocardial infarction (P = 0.001), left ventricular ejection fraction (P = 0.001), chronic congestive cardiac failure (P = 0.001), pulmonary hypertension (P = 0.001), active endocarditis (P = 0.001), unstable angina (P = 0.001), procedure urgency (P = 0.001), critical preoperative condition (P = 0.001) ventricular septal rupture (P = 0.002), noncoronary surgery (P = 0.001), thoracic aortic surgery (P = 0.001). A number of risk factors contribute to cardiac surgical mortality in Europe. This information can be used to develop a risk stratification system for the prediction of hospital mortality and the assessment of quality of care.
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              Pulmonary dysfunction after cardiac surgery.

              Postoperative lung injury is one of the most frequent complications of cardiac surgery that impacts significantly on health-care expenditures and largely has been believed to result from the use of cardiopulmonary bypass (CPB). However, recent comparative studies between conventional and off-pump coronary artery bypass grafting have indicated that CPB itself may not be the major contributor to the development of postoperative pulmonary dysfunction. In our study, we review the associated physiologic, biochemical, and histologic changes, with particular reference to the current understanding of underlying mechanisms. Intraoperative modifications aiming at limiting lung injury are discussed. The potential benefits of maintaining ventilation and pulmonary artery perfusion during CPB warrant further investigation.
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                Author and article information

                Journal
                J Clin Med
                J Clin Med
                jcm
                Journal of Clinical Medicine
                MDPI
                2077-0383
                21 November 2018
                November 2018
                : 7
                : 11
                : 462
                Affiliations
                [1 ]Department of Cardiothoracic Anesthesiology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark; hanne.berg.ravn@ 123456regionh.dk
                [2 ]Department of Anesthesia and Intensive Care, Aalborg University Hospital, 9000 Aalborg, Denmark; bodil.steen.rasmussen@ 123456rn.dk (B.S.R.); mhanifa@ 123456dcm.aau.dk (M.A.H.)
                [3 ]Department of Clinical Medicine, School of Medicine and Health, Aalborg University, 9000 Aalborg, Denmark
                [4 ]Department of Biomedical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark; mortentl@ 123456sund.ku.dk
                [5 ]Department of Chemistry and Bioscience, Aalborg University, 9220 Aalborg, Denmark; rw@ 123456bio.aau.dk
                Author notes
                [* ]Correspondence: katrine.buggeskov@ 123456gmail.com (K.B.B.); rm@ 123456rn.dk (R.G.M.); Tel.: +45-35454141 (K.B.B.); +45-97661787 (R.G.M.)
                [†]

                These authors have contributed equally to the study.

                Author information
                https://orcid.org/0000-0003-2332-2312
                https://orcid.org/0000-0003-2190-145X
                https://orcid.org/0000-0002-2711-1259
                https://orcid.org/0000-0001-6942-5056
                https://orcid.org/0000-0003-4702-5195
                Article
                jcm-07-00462
                10.3390/jcm7110462
                6262287
                30469433
                f5249a56-ae01-4bd6-8bb6-7a8ead7c9bb2
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 05 November 2018
                : 19 November 2018
                Categories
                Article

                copd,ischemia-reperfusion,cpb,lung protection,pulmonary perfusion,htk,oxygenated blood,metabolites,randomized controlled trial

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