{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T16:08:16Z","timestamp":1792858096389,"version":"4.5.0"},"reference-count":67,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T00:00:00Z","timestamp":1772582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Vasodilatory shock, primarily driven by sepsis, remains a leading cause of mortality in intensive care units (ICU), with mortality rates exceeding 90% in refractory cases. While norepinephrine is the first-line vasopressor, prolonged exposure to high doses of catecholamines is linked to severe adverse effects, including myocardial toxicity, arrhythmias, and immunodepression. Consequently, the concept of decatecholaminization, utilizing non-adrenergic vasopressors to reduce catecholamine burden, has emerged as a critical therapeutic strategy. This comprehensive review aims to define the current role of vasopressin and its analogues, terlipressin and selepressin, in managing patients with circulatory shock, evaluating their physiological rationale, clinical benefits, and adverse event profiles. The vasopressin system provides a multimodal approach to hemodynamic stability independent of \u03b1-adrenergic stimulation. Arginine vasopressin (AVP) acts on V1a receptors to induce vasoconstriction and improve glomerular filtration, and on V2 receptors for water reabsorption. Clinical trials indicate that while AVP may not reduce overall mortality, it significantly reduces the need for renal replacement therapy (RRT) and offers survival benefits in the less severe shock subgroup. Synthetic analogues like terlipressin offer a longer half-life but carry an increased risk of peripheral ischemia. Conversely, selepressin, a pure V1a agonist, was designed to mitigate fluid retention and edema, though recent trials have not yet demonstrated superior clinical outcomes over placebo. Modulation of the vasopressin system is a cornerstone of decatecholaminization in distributive and cardiogenic shock. Although a universal mortality benefit has not been established, these agents are crucial for protecting renal function, reducing catecholamine toxicity, and lowering the incidence of arrhythmias. Future strategies should focus on precision medicine, utilizing biomarkers like copeptin and artificial intelligence to optimize the timing and selection of multimodal vasopressor therapy.<\/jats:p>","DOI":"10.3390\/jcm15051953","type":"journal-article","created":{"date-parts":[[2026,3,4]],"date-time":"2026-03-04T13:11:36Z","timestamp":1772629896000},"page":"1953","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Modulation of the Vasopressin System in Distributive and Cardiogenic Shock: Theoretical Principles and Practical Applications"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7060-6938","authenticated-orcid":false,"given":"Alfredo","family":"Mauriello","sequence":"first","affiliation":[{"name":"S.C. Cardiology, Institute National Cancer, IRCCS, Fondazione \u201cG. Pascale\u201d, Via M. Semmola 52, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Correra","sequence":"additional","affiliation":[{"name":"Cardiology Department, Ospedali Riuniti University Hospital, Viale Pinto 1, 71122 Foggia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Chiara","family":"Maratea","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Disease, ASL Napoli 1 Centro, Via Comunale del Principe, 13\/a, 80145 Napoli, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2137-0188","authenticated-orcid":false,"given":"Valeria","family":"Cetoretta","sequence":"additional","affiliation":[{"name":"Cardiology and Arrhythmology Clinic, Marche Polytechnic University, University Hospital \u201cOspedali Riuniti\u201d, Via Conca 71, 60126 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-9397","authenticated-orcid":false,"given":"Francesco","family":"Giallauria","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, \u201cFederico II\u201d University of Naples, Via S. Pansini 5, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, \u201cFederico II\u201d University of Naples, Via S. 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