{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T16:11:20Z","timestamp":1786205480535,"version":"build-2736575974"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T00:00:00Z","timestamp":1664150400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"Background<\/jats:title>The role of methylene blue (MB) in patients with vasodilatory shock is unclear. The purpose of this systematic review and meta-analysis was to evaluate the efficacy and safety of MB in patients with vasodilatory shock.<\/jats:p><\/jats:sec>Methods<\/jats:title>We searched MEDLINE at PubMed, Embase, Web of Science, Cochrane, CNKI, CBM and Wanfang Medical databases for all observational and intervention studies comparing the effect of MB vs. control in vasodilatory shock patients. This study was performed in accordance with the PRISMA statement. There were no language restrictions for inclusion.<\/jats:p><\/jats:sec>Results<\/jats:title>A total of 15 studies with 832 patients were included. Pooled data demonstrated that administration of MB along with vasopressors significantly reduced mortality [odds ratio (OR) 0.54, 95% confidence interval (CI) 0.34 to 0.85,P<\/jats:italic>= 0.008;I<\/jats:italic>2<\/jats:sup>= 7%]. This benefit in mortality rate was also seen in a subgroup analysis including randomized controlled trials and quasi-randomized controlled trials. In addition, the vasopressor requirement was reduced in the MB group [mean difference (MD) \u22120.77, 95%CI \u22121.26 to \u22120.28,P<\/jats:italic>= 0.002;I<\/jats:italic>2<\/jats:sup>= 80%]. Regarding hemodynamics, MB increased the mean arterial pressure, heart rate and peripheral vascular resistance. In respect to organ function, MB was associated with a lower incidence of renal failure, while in regards to oxygen metabolism, it was linked to reduced lactate levels. MB had no effect on the other outcomes and no serious side effects.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Concomitant administration of MB and vasopressors improved hemodynamics, decreased vasopressor requirements, reduced lactate levels, and improved survival in patients with vasodilatory shock. However, further studies are required to confirm these findings.<\/jats:p><\/jats:sec>Systematic review registration<\/jats:title>Identifier: CRD42021281847.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.950596","type":"journal-article","created":{"date-parts":[[2022,9,26]],"date-time":"2022-09-26T05:43:06Z","timestamp":1664170986000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":28,"title":["Efficacy and safety of methylene blue in patients with vasodilatory shock: A systematic review and meta-analysis"],"prefix":"10.3389","volume":"9","author":[{"given":"Cong-Cong","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jia","family":"Zhai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Jie","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi-Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Jun","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2063","DOI":"10.1056\/NEJMc1312359","article-title":"Severe sepsis and septic shock","volume":"369","author":"Angus","year":"2013","journal-title":"N Engl J Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1016\/S0022-5223(94)70355-8","article-title":"Vasoplegic syndrome: a new dilemma","volume":"107","author":"Gomes","year":"1994","journal-title":"J Thorac Cardiovasc Surg."},{"key":"B3","doi-asserted-by":"publisher","first-page":"950","DOI":"10.1007\/s00134-012-2531-2","article-title":"Adverse cardiac events during catecholamine vasopressor therapy: a prospective observational study","volume":"38","author":"Schmittinger","year":"2012","journal-title":"Intens Care Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1177\/0885066609340519","article-title":"Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress","volume":"24","author":"Dunser","year":"2009","journal-title":"J Intensive Care Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1186\/s13613-022-01037-1","article-title":"Association between acute kidney injury and norepinephrine use following cardiac surgery: a retrospective propensity score-weighted analysis","volume":"12","author":"Huette","year":"2022","journal-title":"Ann Intensive Care."},{"key":"B6","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13613-019-0498-7","article-title":"Current use of vasopressors in septic shock","volume":"9","author":"Scheeren","year":"2019","journal-title":"Ann Intensive Care."},{"key":"B7","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1016\/j.jcrc.2020.02.011","article-title":"Clinical utility of midodrine and methylene blue as catecholamine-sparing agents in intensive care unit patients with shock","volume":"57","author":"Tchen","year":"2020","journal-title":"J Crit Care."},{"key":"B8","doi-asserted-by":"publisher","first-page":"3692","DOI":"10.1007\/s12325-020-01422-x","article-title":"Vasopressor-sparing action of methylene blue in severe sepsis and shock: a narrative review","volume":"37","author":"Puntillo","year":"2020","journal-title":"Adv Ther."},{"key":"B9","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1007\/s13181-013-0298-7","article-title":"Methylene blue for distributive shock: a potential new use of an old antidote","volume":"9","author":"Jang","year":"2013","journal-title":"J Med Toxicol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2271","DOI":"10.1097\/00003246-200210000-00015","article-title":"Does methylene blue administration to septic shock patients affect vascular permeability and blood volume?","volume":"30","author":"Donati","year":"2002","journal-title":"Crit Care Med."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1590\/S0100-879X1999001200009","article-title":"Blockade of the action of nitric oxide in human septic shock increases systemic vascular resistance and has detrimental effects on pulmonary function after a short infusion of methylene blue","volume":"32","author":"Weingartner","year":"1999","journal-title":"Brazil J Med Biol Res."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1860","DOI":"10.1097\/00003246-200110000-00002","article-title":"Infusion of methylene blue in human septic shock: a pilot, randomized, controlled study","volume":"29","author":"Kirov","year":"2001","journal-title":"Crit Care Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s12630-011-9458-x","article-title":"Prolonged methylene blue infusion in refractory septic shock: a case report","volume":"58","author":"Dumbarton","year":"2011","journal-title":"Canad J Anesth."},{"key":"B14","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1136\/pgmj.72.852.612","article-title":"Continuous infusion of methylene blue for septic shock","volume":"72","author":"Brown","year":"1996","journal-title":"Postgrad Med J."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-020-58828-4","article-title":"Methylene blue administration in patients with refractory distributive shock-a retrospective study","volume":"10","author":"Porizka","year":"2020","journal-title":"Sci Rep-UK."},{"key":"B16","first-page":"79","article-title":"Application of methylene blue in septic shock","volume":"9","author":"Li","year":"2021","journal-title":"Diet Health."},{"key":"B17","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1053\/j.jvca.2021.05.042","article-title":"Hydroxocobalamin or methylene blue for vasoplegic syndrome in adult cardiothoracic surgery","volume":"36","author":"Kram","year":"2021","journal-title":"J Cardiothor Vasc Ann."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1053\/j.jvca.2020.01.033","article-title":"Hydroxocobalamin versus methylene blue for vasoplegic syndrome in cardiothoracic surgery: a retrospective cohort","volume":"34","author":"Furnish","year":"2020","journal-title":"J Cardiothor Vasc Ann."},{"key":"B19","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1378\/chest.2267413","article-title":"Methylene blue utilization for refractory septic shock in the setting of cirrhosis as a bridge to successful liver-kidney transplant: case report and review of the literature","volume":"148","author":"Kavanaugh","year":"2015","journal-title":"Chest."},{"key":"B20","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1007\/s13181-013-0333-8","article-title":"Methylene blue does not have to be considered only as rescue therapy for distributive shock","volume":"9","author":"Evora","year":"2013","journal-title":"J Med Toxicol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"e1000097","DOI":"10.1371\/journal.pmed.1000097","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"6","author":"Moher","year":"2009","journal-title":"PLoS Med"},{"key":"B22","first-page":"p. 389","volume-title":"Cochrane Handbook: Special Topics","author":"Higgins","year":"2011"},{"key":"B23","article-title":"The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analysis","author":"Wells","year":"2014","journal-title":"Symposium on Systematic Reviews: Beyond the Basics"},{"key":"B24","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1177\/0310057X0203000606","article-title":"The influence of methylene blue infusion on cytokine levels during severe sepsis","volume":"30","author":"Memis","year":"2002","journal-title":"Anaesth Intens Care."},{"key":"B25","doi-asserted-by":"publisher","first-page":"168","DOI":"10.4103\/ijccm.IJCCM_494_17","article-title":"Methylene blue for vasoplegic syndrome postcardiac surgery","volume":"22","author":"Habib","year":"2018","journal-title":"Indian J Crit Care Med."},{"key":"B26","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.athoracsur.2020.05.172","article-title":"Methylene blue does not improve vasoplegia after left ventricular assist device implantation","volume":"111","author":"Saha","year":"2020","journal-title":"Ann Thorac Surg."},{"key":"B27","first-page":"4","article-title":"Effect of methylene blue on oxygen metabolism in patients wIm septic shock","volume":"30","author":"Xiong","year":"2010","journal-title":"China J Anesthesiol."},{"key":"B28","first-page":"3","article-title":"Therapeutic effect of methylene blue on septic shock","volume":"30","author":"Zhang","year":"2016","journal-title":"Contin Med Educ."},{"key":"B29","first-page":"4","article-title":"Efficacy of continuous intravenous infusion of methylene blue in patients with septic shock","volume":"99","author":"Lu","year":"2019","journal-title":"Nat Med J China."},{"key":"B30","first-page":"4","article-title":"Efficacy analysis of methylene blue and norepinephrine in the treatment of va- soparalysis syndrome after cardiac surgery","volume":"7","author":"Zhang","year":"2021","journal-title":"World J Complex Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"824","DOI":"10.1097\/00000539-200204000-00009","article-title":"The effect of methylene blue on the hemodynamic changes during ischemia reperfusion injury in orthotopic liver transplantation","volume":"94","author":"Koelzow","year":"2002","journal-title":"Anesth Analg."},{"key":"B32","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1213\/01.ane.0000221261.25310.fe","article-title":"The hemodynamic effects of methylene blue when administered at the onset of cardiopulmonary bypass","volume":"103","author":"Maslow","year":"2006","journal-title":"Anesth Analg."},{"key":"B33","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1016\/S0003-4975(03)01510-8","article-title":"Methylene blue reduces mortality and morbidity in vasoplegic patients after cardiac surgery","volume":"77","author":"Levin","year":"2004","journal-title":"Ann Thorac Surg."},{"key":"B34","first-page":"4","article-title":"Effect of methylene blue in infective endocarditis patients undergoing cardiac valve replacement with cardiopulmonary bypass","volume":"35","author":"Ma","year":"2019","journal-title":"J Clin Anesthesiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1121","DOI":"10.3390\/jcm11041121","article-title":"Early Use of Methylene Blue in Vasoplegic Syndrome: A 10-Year Propensity Score-Matched Cohort Study","volume":"11","author":"Kofler","year":"2022","journal-title":"J Clin Med."},{"key":"B36","first-page":"3","article-title":"Impact study of methylene blue on adult septic shock hemodynamics","volume":"21","author":"Li","year":"2014","journal-title":"China Mod Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1177\/0218492321998523","article-title":"Methylene blue for vasoplegic syndrome in cardiopulmonary bypass surgery: A systematic review and meta-analysis","volume":"29","author":"Perdhana","year":"2021","journal-title":"Asian Cardiov Thoracic Ann."},{"key":"B38","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/S1441-2772(23)02187-7","article-title":"Methylene blue as a vasopressor: a meta-analysis of randomised trials","volume":"15","author":"Pasin","year":"2013","journal-title":"Critical Care Resuscit."},{"key":"B39","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1590\/S0102-76382009000400005","article-title":"Methylene blue for vasoplegic syndrome treatment in heart surgery. Fifteen years of questions, answers, doubts and certainties","volume":"24","author":"Evora","year":"2009","journal-title":"Brazil J Cardiov Surg."},{"key":"B40","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.niox.2010.01.006","article-title":"A dose-finding study of methylene blue to inhibit nitric oxide actions in the hemodynamics of human septic shock","volume":"22","author":"Juffermans","year":"2010","journal-title":"Nitric Oxide."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1007\/s00134-021-06506-y","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2021","volume":"47","author":"Evans","year":"2021","journal-title":"Intens Care Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s13054-019-2433-6","article-title":"Minimizing catecholamines and optimizing perfusion","volume":"23","author":"Backer","year":"2019","journal-title":"Crit Care."},{"key":"B43","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.athoracsur.2017.02.057","article-title":"Methylene blue for vasoplegic syndrome after cardiac operation: early administration improves survival","volume":"104","author":"Mehaffey","year":"2017","journal-title":"Ann Thorac Surg."},{"key":"B44","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1097\/ACO.0000000000000548","article-title":"Intraoperative vasoplegia: methylene blue to the rescue!","volume":"31","author":"Mccartney","year":"2018","journal-title":"Curr Opin Anaesthesiol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s13054-022-03911-7","article-title":"Vasopressor choice and timing in vasodilatory shock","volume":"26","author":"Wieruszewski","year":"2022","journal-title":"Crit Care."},{"key":"B46","first-page":"982","article-title":"Methylene blue in the treatment of vasodilatory shock: a meta-analysis","volume":"29","author":"Zhang","year":"2017","journal-title":"Chin Crit Care Med."},{"key":"B47","first-page":"5","article-title":"Correlation of arterial blood lactic acid level in patients with septic shock and mortality 28 days after entering the intensive care unit","volume":"23","author":"Zhang","year":"2021","journal-title":"J Chin Physic."},{"key":"B48","first-page":"455","article-title":"Methylene blue as an adjunct to treat vasoplegia in patients undergoing cardiac surgery requiring cardiopulmonary bypass: a literature review","volume":"86","author":"Arevalo","year":"2018","journal-title":"AANA J."},{"key":"B49","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1053\/j.jvca.2015.09.011","article-title":"The blue coma: the role of methylene blue in unexplained coma after cardiac surgery: a case series","volume":"30","author":"Martino","year":"2016","journal-title":"J Cardiothorac Vasc Anesth."},{"key":"B50","first-page":"5","article-title":"Use of methylene blue in vasoplegic syndrome","volume":"41","author":"Lv","year":"2020","journal-title":"Int J Anesthesiol Resuscit."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.950596\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T18:14:53Z","timestamp":1701108893000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2022.950596\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,26]]},"references-count":50,"alternative-id":["10.3389\/fmed.2022.950596"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2022.950596","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,26]]},"article-number":"950596"}}