Publication Name	World Journal of Critical Care Medicine
Manuscript ID	111164
Country	Brazil

Category	Critical Care Medicine
Manuscript Type	Systematic Reviews
Article Title	Current and emerging therapeutic options for refractory septic shock: A systematic review
Manuscript Source	Unsolicited Manuscript
All Author List	Flavio Eduardo Nacul, Murilo Borges Bezerra, Brenno Cardoso Gomes, Fábio Barlem Hohmann, Ricardo Esper Treml, Tulio Caldonazo, Arnaldo Alves da Silva, Rogerio H Passos, Neymar Elias de Oliveira, Grazielle Pangratz Bedretchuk and Joao Manoel Silva Jr
Funding Agency and Grant Number
Corresponding Author	Brenno Cardoso Gomes, Integrated Sciences Service, Universidade Federal do Paraná, R. Padre Camargo, Curitiba 80060-240, Paraná, Brazil. brennogomes@ufpr.br
Key Words	Mortality outcome; Sepsis; Adjunctive therapies; Vasopressors; Refractory septic shock
Core Tip	This systematic review of 24 randomized controlled trials evaluates novel therapies for refractory septic shock, including methylene blue, vasopressin, terlipressin, and hydrocortisone-vitamin C-thiamine combinations. While these interventions improve hemodynamics and organ function, no consistent mortality reduction was observed. Methylene blue reduced vasopressor dependency, and terlipressin enhanced renal perfusion. Larger, standardized trials are needed to validate findings and guide multimodal treatment strategies.
Citation	Nacul FE, Bezerra MB, Gomes BC, Hohmann FB, Treml RE, Caldonazo T, da Silva AA, Passos RH, de Oliveira NE, Bedretchuk GP, Silva Jr JM. Current and emerging therapeutic options for refractory septic shock: A systematic review. World J Crit Care Med 2025; In press

Received	2025-07-07 10:41
Peer-Review Started	2025-07-07 10:41
To Make the First Decision
Return for Revision	2025-07-24 08:19
Revised	2025-08-05 21:25
Second Decision	2025-08-27 02:39
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2025-08-27 07:26
Articles in Press	2025-08-27 07:26
Publication Fee Transferred	2025-08-12 23:36
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	2220-3141(online)
Open Access	This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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