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Review
. 2025 Jun 17;17(6):e86224.
doi: 10.7759/cureus.86224. eCollection 2025 Jun.

Insights Into the Pathophysiology of Catecholamine-Refractory Shock: A Narrative Review

Ana Gonçalves  1 , Filipa Gonçalves Pereira  2 , Susana Fernandes  2   3 , João Gonçalves Pereira  1   2
Affiliations
Review

Insights Into the Pathophysiology of Catecholamine-Refractory Shock: A Narrative Review

Ana Gonçalves et al. Cureus. .

Abstract

Shock, characterized by severe hemodynamic failure and tissue hypoperfusion, is a life-threatening condition that requires immediate recognition and adequate treatment. Some patients exhibit a poor response to catecholamines, progressing to refractory shock, and have a high mortality risk. We aimed to review the characteristics of patients associated with the development of refractory shock and to evaluate proposed strategies for improving prognosis. Refractory shock remains poorly defined due to unclear pathophysiology. The failure of mitochondria to produce energy, neurohormonal dysregulation, adrenergic receptor desensitisation, and inflammatory vasodilation all contribute to this condition. Prompt recognition of at-risk patients is essential and may be supported by clinical signs, vasopressor load, and biomarkers such as lactate and base excess. Multimodal strategies, which combine vasopressors with complementary mechanisms, corticosteroids, and metabolic support, present a promising approach to enhance outcomes. Further research is required to refine shock phenotyping and guide personalised therapy.

Keywords: catecholamine-refractory shock; critical care; norepinephrine; septic shock; vasoplegia; vasopressin; vasopressor resistance.

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Conflict of interest statement

Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: JGP declare(s) a grant from Merck Sharp Dohme. Outside of this work. JGP declare(s) personal fees from Pfizer. JGP declare(s) personal fees from Biomerieux. JGP declare(s) personal fees from AOP. JGP declare(s) personal fees from Gilead. JGP declare(s) non-financial support from Grupo de Infeção e Desenvolvimento em Sépsis. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Figures

Figure 1
Figure 1. Pathophysiology of catecholamine-refractory shock
NO - Nitric oxide; iNOS - Inducible nitric oxide synthase Image credit: Authors
See this image and copyright information in PMC

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