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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Crit Care Med. Dec 9, 2025; 14(4): 111164
Published online Dec 9, 2025. doi: 10.5492/wjccm.v14.i4.111164
Published online Dec 9, 2025. doi: 10.5492/wjccm.v14.i4.111164
Current and emerging therapeutic options for refractory septic shock: A systematic review
Flavio Eduardo Nacul, Intensive Care Department, Pró-Cardíaco Hospital - Rio de Janeiro, Pró-Cardíaco Hospital, Rio de Janeiro 22280-003, Brazil
Murilo Borges Bezerra, Fábio Barlem Hohmann, Arnaldo Alves da Silva, Intensive Care Depart
Brenno Cardoso Gomes, Integrated Sciences Service, Universidade Federal do Paraná, Curitiba 80060-240, Paraná, Brazil
Ricardo Esper Treml, Department of Anesthesiology, Stanford Medical School, Palo Alto, CA 94304, United States
Tulio Caldonazo, Department of Cardiothoracic Surgery, Friedrich-Schiller-University, Jena 07743, Germany
Rogerio H Passos, Intensive Care Department, Adult ICU Hospital Israelita Albert Einstein, São Paulo 05652-000, Brazil
Rogerio H Passos, DaVita Tratamento Renal, Rio de Janeiro 22775-022, Brazil
Neymar Elias de Oliveira, Intensive Care Department, Hospital de Base, Sao Jose do Rio Preto 15090-000, São Paulo, Brazil
Grazielle Pangratz Bedretchuk, Intensive Care Department, Complexo do Hospital do Trabal
Joao Manoel Silva Jr, Hospital das Clínicas, Faculdade de Medicina da USP, Sao Paulo 01246903, São Paulo, Brazil
Author contributions: Hohmann FB and Caldonazo T contributed to conceptualization, methodology; de Oliveira NE contributed to data curation, writing- original draft preparation; Nacul FE, Treml RE, da Silva AA, and Passos RH contributed to software, validation, investigation, supervision; Gomes BC, Silva Jr JM, Bedretchuk GP, and Bezerra MB contributed to writing- reviewing and editing.
Conflict-of-interest statement: All authors declare that they have no conflict of interest to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Check-list.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Brenno Cardoso Gomes, MD, PhD, Integrated Sciences Service, Universidade Federal do Paraná, R. Padre Camargo, 280-Alto da Glória, Curitiba 80060-240, Brazil. brennogomes@ufpr.br
Received: July 7, 2025
Revised: August 5, 2025
Accepted: August 27, 2025
Published online: December 9, 2025
Processing time: 144 Days and 20.5 Hours
Revised: August 5, 2025
Accepted: August 27, 2025
Published online: December 9, 2025
Processing time: 144 Days and 20.5 Hours
Core Tip
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.