One of the most frequently encountered hemodynamic disturbances in ICUs is vasoplegic shock, a severe form of distributive shock characterized by profound vasodilation and loss of vascular tone. Although no universally accepted definition exists, vasoplegia is described as markedly reduced systemic vascular resistance (SVR) leading to severe hypotension despite normal or increased cardiac output. The imbalance between vascular tone and circulatory demand compromises effective tissue perfusion and can contribute to progressive organ dysfunction.1
The true prevalence of vasoplegic shock across ICU populations is difficult to determine. However, its clinical impact is most apparent in conditions like septic shock and post-cardiopulmonary bypass (CPB) vasoplegia. In these settings, reported mortality rates range from approximately 25% to 50%.2 Early recognition is therefore critical, as prompt therapeutic interventions aimed at restoring vascular tone can improve hemodynamic stability and patient outcomes.
Pathophysiology
Vasoplegic shock represents a final common pathway of vascular failure resulting from several overlapping mechanisms that impair vascular smooth muscle tone. First, inflammatory signaling—particularly in sepsis and systemic inflammatory states—stimulates inducible nitric oxide synthase, producing excess nitric oxide that increases cyclic guanosine monophosphate within vascular smooth muscle cells and promotes vasodilation. Second, endogenous vasopressin stores become depleted during prolonged hemodynamic stress, removing an important mediator of vascular tone. Third, ATP-sensitive potassium channel activation causes membrane hyperpolarization in smooth muscle cells, blocking calcium entry and impairing contraction. Impaired angiotensin II availability and progressive adrenergic receptor desensitization further diminishes vascular responsiveness, leaving patients refractory to multiple vasopressor classes.
Clinical recognition
Vasoplegic shock is characterized by profound hypotension despite preserved or elevated cardiac output and adequate treatment of sepsis. Hemodynamically, patients typically exhibit a cardiac index greater than 2.2 L/min/m² with markedly reduced SVR, often below 800 dyn·s/cm⁵. The syndrome most commonly develops in the setting of sepsis, cardiac surgery involving CPB, liver failure, anaphylaxis, or prolonged systemic inflammation. Early recognition can be challenging because the initial focus is on treatment of underlying condition and blood pressure management. In patients with persistent hypotension despite adequate preload and preserved cardiac output, vasoplegia should be actively considered rather than approached as a diagnosis of exclusion.
Management
Management focuses on restoring vascular tone while limiting fluid overload and catecholamine toxicity. Initial resuscitation should emphasize judicious IV fluids guided by dynamic measures of fluid responsiveness. In many patients—particularly those post-CPB, with cirrhosis, or with sepsis—vasodilation predominates over hypovolemia; once preload is optimized, early vasopressor initiation is appropriate.
Norepinephrine remains first-line therapy because of its potent α-adrenergic vasoconstrictive effects with modest chronotropic activity. Vasopressin is typically added early (eg, when norepinephrine reaches 0.2 to 0.3 µg/kg/min) to address relative vasopressin deficiency and reduce catecholamine exposure.
In the VASST trial, vasopressin demonstrated catecholamine-sparing effects with a signal toward benefit in less severe shock.3 The VANISH trial reported no difference in kidney failure-free days compared with norepinephrine, although fewer patients receiving vasopressin required renal replacement therapy.4 Together, these findings support early adjunctive vasopressin in distributive phenotypes.
Corticosteroids should be considered in patients with persistent vasopressor dependence despite adequate resuscitation. In the ADRENAL trial, hydrocortisone 200 mg/day accelerated shock resolution, while the APROCCHSS trial showed improved survival with hydrocortisone plus fludrocortisone in septic shock.5–6
For catecholamine-refractory vasoplegia, nonadrenergic agents are increasingly used. Methylene blue (2 mg/kg) inhibits nitric oxide-mediated vasodilation via guanylate cyclase blockade and is particularly useful in post-CPB vasoplegia. Hydroxocobalamin (5 g) scavenges nitric oxide and hydrogen sulfide and can produce rapid mean arterial pressure (MAP) augmentation; it is especially helpful when methylene blue is contraindicated (eg, serotonergic drug exposure). Clinicians should anticipate chromaturia and laboratory interference.
Angiotensin II, initiated at 20 ng/kg/min and titrated to effect, restores vascular tone through renin-angiotensin-aldosterone system activation. In the ATHOS-3 trial, angiotensin II significantly increased MAP in patients requiring high-dose vasopressors, supporting its role in refractory shock.7
In selected patients with persistent shock and evolving organ dysfunction despite maximal therapy, veno-arterial ECMO may serve as a bridge, particularly in mixed vasoplegic-cardiogenic states. A practical, stepwise approach—optimize preload, initiate norepinephrine, add vasopressin, consider corticosteroids, then escalate to nonadrenergic agents—remains the cornerstone of management.
Early recognition and structured escalation of therapy are essential in vasoplegic shock, as prompt restoration of vascular tone remains critical to reversing shock and improving patient outcomes.
References
1. Lambden S, Creagh-Brown BC, Hunt J, Summers C, Forni LG. Definitions and pathophysiology of vasoplegic shock. Crit Care. 2018;22(1):174. doi:10.1186/s13054-018-2102-1
2. Mistry RN, Winearls JE. Management of vasoplegic shock. BJA Educ. 2025;25(2):65-73. doi:10.1016/j.bjae.2024.10.004
3. Russell JA, Walley KR, Singer J, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358(9):877-887. doi:10.1056/NEJMoa067373
4. Gordon AC, Mason AJ, Thirunavukkarasu N, et al. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the vanish randomized clinical trial. JAMA. 2016;316(5):509-518. doi:10.1001/jama.2016.10485
5. Venkatesh B, Finfer S, Cohen J, et al. Adjunctive glucocorticoid therapy in patients with septic shock. N Engl J Med. 2018;378(9):797-808. doi:10.1056/NEJMoa1705835
6. Annane D, Renault A, Brun-Buisson C, et al. Hydrocortisone plus fludrocortisone for adults with septic shock. N Engl J Med. 2018;378(9):809-818. doi:10.1056/NEJMoa1705716
7. Khanna A, English SW, Wang XS, et al. Angiotensin II for the treatment of vasodilatory shock. N Engl J Med. 2017;377(5):419-430. doi:10.1056/NEJMoa1704154
