Introduction Vasoplegic syndrome (VS) is a severe complication after cardiac surgery with cardiopulmonary bypass (CPB), characterised by vasodilation, hypotension and vasopressor dependence. Endothelial dysfunction, dysregulated nitric oxide signalling, inflammation and glycocalyx injury may contribute. Combining flow-mediated dilation (FMD), sublingual side-stream dark-field (SDF) imaging and biomarkers may improve postoperative vascular phenotyping. The primary objective is to compare allometrically corrected brachial artery FMD between patients with VS and patients without VS 48 hours after CPB weaning.

Methods and analysis This prospective, single-centre observational cohort study will enrol 124 adults aged 18–80 years undergoing cardiac surgery with CPB (62 VS and 62 non-VS). VS is defined clinically as norepinephrine bitartrate ≥0.05 µg/kg/min for at least 4 hours to maintain mean arterial pressure ≥65 mm Hg after CPB weaning, following haemodynamic optimisation and exclusion of a predominant low-cardiac-output phenotype or another cause of shock. FMD, SDF imaging and biomarkers will be assessed at 4–8 and 48 hours after CPB weaning. The primary comparison will use multiple linear regression for corrected FMD at 48 hours with prespecified covariate adjustment. Secondary and exploratory analyses will assess SDF-derived parameters, biomarkers and associations across modalities.

Ethics and dissemination The protocol was approved by the Comité de Protection des Personnes Sud-Méditerranée III (CPP Sud-Méditerranée III; 2023-A02079-36). For this non-interventional routine-care study, French law requires prior oral and written information and absence of opposition rather than written consent; absence of opposition will be documented. Results will be published in peer-reviewed journals and presented at scientific conferences.