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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., (© 2021. The Author(s).)