Evidence map›Paper›PMID 41377532›Full record

ArticleWorld journal of critical care medicine2025

Current and emerging therapeutic options for refractory septic shock: A systematic review.

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 1 more

Abstract read
In one paragraph

Article in World journal of critical care medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Flavio Eduardo NaculIntensive Care Department, Pró-Cardíaco Hospital - Rio de Janeiro, Pró-Cardíaco Hospital, Rio de Janeiro 22280-003, Brazil.
Murilo Borges BezerraIntensive Care Department, Hospital Israelita Albert Einstein, São Paulo 05652-000, Sao Paulo, Brazil.
Brenno Cardoso GomesIntegrated Sciences Service, Universidade Federal do Paraná, Curitiba 80060-240, Paraná, Brazil. brennogomes@ufpr.br.
Fábio Barlem HohmannIntensive Care Department, Hospital Israelita Albert Einstein, São Paulo 05652-000, Sao Paulo, Brazil.
Ricardo Esper TremlDepartment of Anesthesiology, Stanford Medical School, Palo Alto, CA 94304, United States.
Tulio CaldonazoDepartment of Cardiothoracic Surgery, Friedrich-Schiller-University, Jena 07743, Germany.
Arnaldo Alves da SilvaIntensive Care Department, Hospital Israelita Albert Einstein, São Paulo 05652-000, Sao Paulo, Brazil.
Rogerio H PassosIntensive Care Department, Adult ICU Hospital Israelita Albert Einstein, São Paulo 05652-000, Brazil.
Neymar Elias de OliveiraIntensive Care Department, Hospital de Base, Sao Jose do Rio Preto 15090-000, São Paulo, Brazil.
Grazielle Pangratz BedretchukIntensive Care Department, Complexo do Hospital do Trabalhador de Curitiba, Curitiba 81050000, Paraná, Brazil.
Joao Manoel SilvaHospital das Clínicas, Faculdade de Medicina da USP, Sao Paulo 01246903, São Paulo, Brazil.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRefractory septic shock is a critical and multifaceted condition that continues to pose significant challenges in critical care.

aimTo systematically review randomized trials on emerging interventions for refractory septic shock, assessing mortality, vasopressor use, intensive care unit (ICU) length of stay, and organ dysfunction.

methodsA systematic search was conducted in PubMed, EMBASE, Cochrane CENTRAL Library, and Web of Science for studies published between 2000 and 2024. Inclusion criteria encompassed randomized controlled trials (RCT) evaluating innovative therapies for refractory septic shock. Variables of interest: The primary outcome was all-cause mortality among patients treated with novel interventions. Secondary outcomes included length of stay in the ICU, total hospital length of stay, and use of vasoactive drugs. Methodological rigor was assessed using the Cochrane Risk of Bias tool.

resultsFrom 850 records, 24 RCTs met the inclusion criteria, evaluating therapies such as methylene blue, vasopressin, terlipressin, and combinations of hydrocortisone, vitamin C, and thiamine. Mortality rates ranged from 28.6% to 56.8%. Methylene blue reduced vasopressor dependency in patients requiring high norepinephrine doses by 1.0 vasopressor-free day, and terlipressin improved renal perfusion by 13.1%. Combination therapies enhanced secondary outcomes, including reductions in Sequential Organ Failure Assessment score. However, no single intervention consistently demonstrated significant survival benefits.

conclusionAdjunctive therapies for refractory septic shock may improve hemodynamics and organ function, however, they have not been shown to consistently reduce mortality. Larger trials are needed to confirm these findings. Multimodal approaches targeting inflammation are critical.

Indexed as

Adjunctive therapiesMortality outcomeRefractory septic shockSepsisVasopressors

Identifiers

PMID41377532
PMCPMC12687076

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.