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Current and emerging therapeutic options for refractory septic shock: A systematic review
Flavio Eduardo Nacul1, Murilo Borges Bezerra2, Brenno Cardoso Gomes3
1Intensive Care Department, Pró-Cardíaco Hospital - Rio de Janeiro, Pró-Cardíaco Hospital, Rio de Janeiro 22280-003, Brazil.
World Journal of Critical Care Medicine
|December 11, 2025
Summary
Emerging therapies for refractory septic shock may improve hemodynamics but do not consistently reduce mortality. Multimodal approaches targeting inflammation are critical for better patient outcomes.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Clinical Trials
Background:
- Refractory septic shock presents significant challenges in critical care settings.
- Existing treatments for refractory septic shock have limitations.
Purpose of the Study:
- To systematically review randomized controlled trials (RCTs) of emerging interventions for refractory septic shock.
- To assess the impact of novel therapies on mortality, vasopressor use, ICU length of stay, and organ dysfunction.
Main Methods:
- Systematic literature search of major databases (PubMed, EMBASE, Cochrane, Web of Science) from 2000-2024.
- Inclusion of RCTs evaluating innovative therapies for refractory septic shock.
- Assessment of primary outcome (all-cause mortality) and secondary outcomes (ICU/hospital length of stay, vasoactive drug use) using Cochrane Risk of Bias tool.
Main Results:
- 24 RCTs evaluated therapies including methylene blue, vasopressin, terlipressin, and combination therapies (hydrocortisone, vitamin C, thiamine).
- Mortality rates varied widely (28.6%-56.8%). Methylene blue improved vasopressor-free days, and terlipressin enhanced renal perfusion.
- While some interventions improved organ function (e.g., SOFA score), no single therapy demonstrated consistent survival benefits.
Conclusions:
- Adjunctive therapies may improve hemodynamic stability and organ function in refractory septic shock.
- Current evidence does not consistently show reduced mortality with novel interventions.
- Larger trials and multimodal strategies targeting inflammation are necessary to improve outcomes.
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