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      The additional use of methylene blue has a decatecholaminisation effect on cardiac vasoplegic syndrome after cardiac surgery

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          Abstract

          Background

          Postoperative vasoplegia with minimal responsiveness to vasopressors is common after cardiac surgery. Called cardiac vasoplegic syndrome (CVS), it is caused by multiple factors. Treating CVS involves a high dose of fluids and catecholamines, however high doses of catecholamines and fluids are associated with serious side effects. There is evidence that new therapeutic strategies can lead to a reduction in norepinephrine doses and mortality in CVS. Specifically, the use of non-adrenergic vasopressors such as methylene blue (MB) can be beneficial.

          Methods

          We retrospectively analyzed the electronic records of 8716 adult cardiac surgery patients from November 2008 to December 2016. Medication, hemodynamic and outcome parameter data were analyzed for CVS until discharge. We determined CVS according to the following parameters: a postoperative onset of ≤24 h, a reduced mean arterial pressure (MAP) of < 70 mmHg, a dose of norepinephrine ≥0.8 mg*h − 1 and a continuously increasing need for catecholamine, without ventricular dysfunction.

          Results

          We identified 513 patients with CVS. Perioperative risk factors were higher in patients treated with methylene blue (MB). Before MB administration patients had a significantly higher dose of norepinephrine, and MAP increased after MB administration. Norepinephrine could be reduced after MB administration and MAP remained stable at the same level even after the reduction of norepinephrine.

          Conclusions

          CVS patients have a severe systemic disease accompanied by significant operative stress and a high catecholamine requirement. The administration of MB in addition to standard treatment for CVS in the first 24 h was accompanied by an increase in MAP followed by a decrease in vasopressor requirement, indicating that early MB administration can be beneficial.

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          Most cited references29

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          Vasopressin versus Norepinephrine in Patients with Vasoplegic Shock after Cardiac Surgery: The VANCS Randomized Controlled Trial.

          Vasoplegic syndrome is a common complication after cardiac surgery and impacts negatively on patient outcomes. The objective of this study was to evaluate whether vasopressin is superior to norepinephrine in reducing postoperative complications in patients with vasoplegic syndrome.
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            Systemic inflammatory response syndrome after cardiac operations.

            A systemic inflammatory response after open heart operation may be responsible for hyperdynamic circulatory instability and organ dysfunction. To what extent mediator release is involved needs to be clarified. Ten patients with postoperative hyperdynamic circulatory dysregulation (group I) requiring application of alpha-constrictors and 10 patients with routine cardiac procedures and stable postoperative hemodynamic indices (group II) were analyzed for mediator release and metabolic and hemodynamic changes until the third postoperative day. Group I patients showed a significantly increased cardiac index and decreased systemic vascular resistance after bypass (cardiac index, group I: 5.2 +/- 1.2 L.min-1.m-2, group II: 2.5 +/- 1.6 L.min-1.m-2; systemic vascular resistance, group I: 495 +/- 204 dyne.s. cm-5, group II: 1,356 +/- 466 dyne.s.cm-5) and at 3 hours (cardiac index, group I: 4.4 +/- 0.8 L.min-1.m-2, group II: 2.9 +/- 0.6 L.min-1.m-2; systemic vascular resistance, group I: 567 +/- 211 dyne.s.cm-5, group II: 1,053 +/- 273 dyne.s.cm-5). Significantly higher serum levels of interleukin-6 were assessed in group I (postbypass, group I: 6,812 +/- 9,293 pg/mL, group II: 295 +/- 303 pg/mL; 3 hours, group I: 3,474 +/- 5,594 pg/mL, group II: 286 +/- 296 pg/mL). Concentrations of elastase, tumor necrosis factor, soluble tumor necrosis factor receptor, and interleukin-8 were elevated in group I (not significant). Early postoperative levels of soluble E-selectin and soluble intercellular adhesion molecule were also higher in group I (not significant). Continuously increased levels of endotoxin could be detected in only 3 of 10 patients in group I. Severe lactic acidosis (> or = 5 mmol/L) occurred in group I only. Postoperative hyperdynamic instability after open heart operations appears to be associated with a certain pattern of mediator release. In particular, interleukin-6 appears to be involved in circulatory dysregulation and metabolic derangement.
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              Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery.

              The discovery of nitric oxide as mediator in cardiac postoperative vasoplegia encourages the use of inhibitory drugs such as methylene blue. This drug has been used with favorable results in isolated cases. The purpose of this article is to analyze the incidence of the postoperative vasoplegic syndrome, to consider its prognosis, and to evaluate the effect of intravenous methylene blue on mortality. Cardiac surgery patients were consecutively included. Vasoplegic syndrome was defined by the presence of the following five criteria: (1) hypotension, (2) low filling pressures, (3) high or normal cardiac index, (4) low peripheral resistance, and (5) vasopressor requirements. Those with vasoplegia were randomized to receive 1.5 mg/Kg of methylene blue or a placebo. A p value less than 0.05 was considered significant. Six hundred thirty eight cardiac surgery patients were consecutively included in this study. Fifty-six of these patients fulfilled vasoplegia criteria (8.8%) resulting in higher mortality (10.7% or 6 of 56 patients vs 3.6% or 21 of 582 patients; p value = 0.02). Those treated with methylene blue showed morbidity and mortality reductions (0% versus 21.4% or 6 of 28 patients; p value = 0.01). The duration of the vasoplegic syndrome was shorter in those patients treated with the drug, lasting less than 6 hours in all patients. Patients in the control group showed a slower recovery, lasting more than 48 hours in 8 patients (p value = 0.0007). Vasoplegic postoperative syndrome was seen in 8.8% of all patients. Outcome in patients with vasoplegia was worse with increased morbidity and mortality. The use of methylene blue reduced the high mortality in this population.

                Author and article information

                Contributors
                walter.petermichl@ukr.de
                Journal
                J Cardiothorac Surg
                J Cardiothorac Surg
                Journal of Cardiothoracic Surgery
                BioMed Central (London )
                1749-8090
                28 July 2021
                28 July 2021
                2021
                : 16
                : 205
                Affiliations
                [1 ]GRID grid.7727.5, ISNI 0000 0001 2190 5763, Department of Anesthesiology, , University of Regensburg, ; Franz-Josef-Strauß-Allee 11, 93053 Regensburg, Germany
                [2 ]Department of Anesthesiology, Aschaffenburg-Alzenau Hospital, Am Hasenkopf 1, 63739 Aschaffenburg, Germany
                Author information
                http://orcid.org/0000-0002-9430-6208
                Article
                1579
                10.1186/s13019-021-01579-8
                8320154
                34321019
                b7e760f0-f142-4e9e-be22-bc204319c3b8
                © The Author(s) 2021

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 26 August 2020
                : 9 July 2021
                Funding
                Funded by: Universität Regensburg (3161)
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2021

                Surgery
                methylene blue,cardiac vasoplegic syndrome,cardiac surgery,decatecholaminisation
                Surgery
                methylene blue, cardiac vasoplegic syndrome, cardiac surgery, decatecholaminisation

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