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Methylene Blue Administration in Septic Shock: A Retrospective Cohort Study.
Shannon M Fernando1,2, Bram Rochwerg3,4, Karim Soliman1,2
1Department of Critical Care, Lakeridge Health, Oshawa, ON, Canada.
Critical Care Medicine
|October 31, 2025
Summary
Methylene blue (MB) use in septic shock is rare in the United States, with decreasing utilization over time. Further randomized trials are needed to confirm the efficacy and safety of MB in treating septic shock.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Epidemiology
Background:
- Septic shock is a life-threatening condition requiring prompt management.
- Methylene blue (MB) has been explored as a treatment for septic shock, but its utilization patterns and impact on outcomes are not well-defined.
- Understanding the epidemiology of MB use is crucial for guiding clinical practice and future research.
Purpose of the Study:
- To describe the current epidemiology of methylene blue (MB) use in adult patients with septic shock in the United States.
- To explore the association between the dose of MB administered and hospital outcomes, including mortality.
- To analyze trends in MB utilization over time.
Main Methods:
- Retrospective cohort study utilizing data from the Premier Healthcare Database (2008-2021).
- Inclusion of adult patients diagnosed with septic shock.
- Analysis of MB utilization and association with hospital mortality using multivariable regression models, including restricted cubic splines for dose-response assessment.
Main Results:
- Methylene blue (MB) was administered to only 0.5% of septic shock patients across 1100 centers.
- Hospitals utilizing MB were typically larger, urban teaching facilities, and patients receiving MB were younger and more likely to have had major surgery.
- MB use declined from 2008 to 2020, and a nonlinear association was observed between early MB dosing and hospital mortality.
Conclusions:
- Methylene blue (MB) use in septic shock is infrequent in the United States, exhibiting significant inter-hospital variability and a downward trend in utilization.
- The observed nonlinear association between MB dose and outcomes warrants further investigation.
- Randomized controlled trials are essential to definitively establish the efficacy and safety of methylene blue for septic shock treatment.
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