Beyond catecholamine escalation: Receptor desensitization and endogenous vasopressor failure, and extracorporeal circuit biocompatibility after cardiopulmonary bypass-A narrative review.

BACKGROUND: Vasoplegic syndrome following cardiopulmonary bypass (CPB) is a major cause of postoperative circulatory failure in cardiac surgery and is associated with increased morbidity and mortality. Traditionally, vasoplegia has been attributed to systemic inflammation, endothelial dysfunction, excessive nitric oxide production, and pathological vasodilation. However, these mechanisms alone do not fully explain the marked variability in vasopressor responsiveness observed in clinical practice. Increasing evidence suggests that vasoplegia may result not only from depletion of endogenous vasopressors, but also from receptor desensitization and impaired intracellular signaling involving catecholamines, arginine vasopressin (AVP), and angiotensin II (Ang II). EVIDENCE SYNTHESIS: A narrative literature review was conducted using PubMed/MEDLINE, Scopus, and Web of Science, supplemented by citation tracking and manual cross-referencing. Literature was selected qualitatively according to its relevance to endogenous vasopressor physiology, GPCR signaling and desensitization, endothelial and glycocalyx dysfunction, extracorporeal circuit biocompatibility, and vasoplegic syndrome after cardiac surgery. Fifty-one publications representing the key clinical, experimental, translational, and physiological evidence informing these themes were included in the final narrative synthesis; this number represents the literature selected for qualitative discussion rather than the yield of a systematic-review screening process. RESULTS: The available evidence suggests that CPB profoundly alters endogenous vasopressor pathways through systemic inflammation, oxidative stress, endothelial activation, ischemia-reperfusion injury, and prolonged adrenergic stimulation. These mechanisms may contribute to depletion of endogenous vasopressors as well as receptor downregulation, desensitization, and uncoupling of intracellular signaling pathways. Alterations involving vasopressin V1/V2 receptors, β-adrenergic receptors, and the renin-angiotensin system may all participate in vasopressor refractoriness. Increased activation of the ACE2/Ang-(1-7) counter-regulatory axis may further promote vasodilatory pathways, particularly in patients with obesity, diabetes mellitus, and heart failure. Emerging evidence also suggests that multimodal vasopressor strategies, including vasopressin and Ang II supplementation, may be more effective than isolated catecholamine escalation in refractory vasoplegia. In severe cases, non-conventional therapies such as Methylene Blue may restore vascular tone independently of classic vasopressor receptor pathways. CONCLUSIONS: Vasoplegia after CPB may represent a complex endocrine and receptor-mediated disorder rather than a purely vasodilatory state. The interaction between endogenous vasopressor depletion, receptor dysfunction, and altered intracellular signaling may explain the development of catecholamine-refractory shock after cardiac surgery. A better understanding of these mechanisms could support more individualized and physiologically guided vasopressor strategies aimed at preventing receptor exhaustion and improving hemodynamic management in cardiac surgical patients.