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      After Thirty Years, We Still Cannot Understand Why Methylene Blue is not a Reference to Treat Vasoplegic Syndrome in Cardiac Surgery

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          Abstract

          Vasoplegic syndrome (VS) comprises a constellation of concurrent signs and symptoms: hypotension, high cardiac index, low systemic vascular resistance, low filling pressures, the tendency to occur diffuse bleeding, and sustained hypotension. All of these parameters may persist even despite the use of high doses of vasoconstrictor amines. VS arises from vasoplegic endothelial dysfunction with excessive release of nitric oxide by polymorphonuclear leukocytes mediated by the nitric oxide synthase’s inducible form and is associated with systemic inflammatory reaction and high morbimortality. The achievements regarding the treatment of VS with methylene blue (MB) are a valuable Brazilian contribution to cardiac surgery. The present text review was designed to deliver the accumulated knowledge in the past ten years of employing MB to treat VS after cardiac surgery. Considering that we have already published two papers describing acquired experiences and concepts after 15 and 20 years, now, as we achieve the 30-year mark, we compose a trilogy.

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          Twenty years of vasoplegic syndrome treatment in heart surgery. Methylene blue revised

          Objective This study was conducted to reassess the concepts established over the past 20 years, in particular in the last 5 years, about the use of methylene blue in the treatment of vasoplegic syndrome in cardiac surgery. Methods A wide literature review was carried out using the data extracted from: MEDLINE, SCOPUS and ISI WEB OF SCIENCE. Results The reassessed and reaffirmed concepts were 1) MB is safe in the recommended doses (the lethal dose is 40 mg/kg); 2) MB does not cause endothelial dysfunction; 3) The MB effect appears in cases of NO up-regulation; 4) MB is not a vasoconstrictor, by blocking the cGMP pathway it releases the cAMP pathway, facilitating the norepinephrine vasoconstrictor effect; 5) The most used dosage is 2 mg/kg as IV bolus, followed by the same continuous infusion because plasma concentrations sharply decrease in the first 40 minutes; and 6) There is a possible "window of opportunity" for MB's effectiveness. In the last five years, major challenges were: 1) Observations about side effects; 2) The need for prophylactic and therapeutic guidelines, and; 3) The need for the establishment of the MB therapeutic window in humans. Conclusion MB action to treat vasoplegic syndrome is time-dependent. Therefore, the great challenge is the need, for the establishment the MB therapeutic window in humans. This would be the first step towards a systematic guideline to be followed by possible multicenter studies.
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            Methylene blue for vasoplegic syndrome treatment in heart surgery: fifteen years of questions, answers, doubts and certainties.

            There is strong evidence that methylene blue (MB), an inhibitor of guanylate cyclase, is an excellent therapeutic option for vasoplegic syndrome (VS) treatment in heart surgery. The aim of this article is to review the MB's therapeutic function in the vasoplegic syndrome treatment. Fifteen years of literature review. 1) Heparin and ACE inhibitors are risk factors; 2) In the recommended doses it is safe (the lethal dose is 40 mg/kg); 3) The use of MB does not cause endothelial dysfunction; 4) The MB effect appears in cases of nitric oxide (NO) up-regulation; 5) MB is not a vasoconstrictor, by blocking of the GMPc system it releases the AMPc system, facilitating the norepinephrine vasoconstrictor effect; 6) The most used dosage is 2 mg/kg as IV bolus followed by the same continuous infusion because plasmatic concentrations strongly decays in the first 40 minutes; 7) There is a possible 'window of opportunity' for the MB's effectiveness. Although there are no definitive multicentric studies, the MB used to treat heart surgery VS, at the present time, is the best, safest and cheapest option, being a Brazilian contribution for the heart surgery.
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              Vasoplegic syndrome: a new dilemma.

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                Author and article information

                Contributors
                Role: MD, PhD
                Role: MD
                Role: MD
                Role: MD, PhD
                Role: MD
                Role: MD, PhD
                Journal
                Braz J Cardiovasc Surg
                Braz J Cardiovasc Surg
                rbccv
                Brazilian Journal of Cardiovascular Surgery
                Sociedade Brasileira de Cirurgia Cardiovascular
                0102-7638
                1678-9741
                May-Jun 2021
                May-Jun 2021
                : 36
                : 3
                : 406-411
                Affiliations
                [1 ] Department of Surgery & Anatomy, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
                [2 ] Faculdade de Medicina de Marília, Marília, São Paulo, Brazil.
                Author notes
                Correspondence Address: Paulo Roberto B. Evora, https://orcid.org/0000-0001-9631-946X, Rua Rui Barbosa, 367, Ap. 15, Ribeirão Preto, SP, Brazil - Zip Code: 14015-120. E-mail: prbevora@ 123456gmail.com
                Author information
                https://orcid.org/0000-0001-9631-946X
                Article
                10.21470/1678-9741-2021-0955
                8357386
                34387976
                0a247205-58c0-4524-be60-defcad3ed833

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 January 2021
                : 28 February 2021
                Categories
                Special Article

                vasoplegia,cardiac surgical procedures,methylene blue,nitric oxide,neutrophils,hypotension

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