Methylene blue versus hydroxocobalamin for septic shock: a real-world comparative effectiveness study using TriNetX
Joshua Pei Le1, Navneet Gupta1, Sachin Singh2
1Medicine Institute, Allegheny Health Network, Pittsburgh, Pennsylvania, USA.
Proceedings (Baylor University. Medical Center)
|August 7, 2026
Summary
Methylene blue (MB) and high-dose hydroxocobalamin (HC) are used for septic shock. MB showed similar early mortality but fewer complications like kidney injury and stroke compared to HC.
Area of Science:
- Critical Care Medicine
- Pharmacology
- Nephrology
Background:
- Septic shock treatment often requires adjunctive therapies for refractory vasodilation.
- Methylene blue (MB) and high-dose hydroxocobalamin (HC) show promise but lack comparative sepsis data.
- This study compares outcomes of MB versus HC in septic patients.
Purpose of the Study:
- To compare the efficacy and safety of methylene blue (MB) and high-dose hydroxocobalamin (HC) as adjunctive therapies in septic shock.
- To evaluate differences in mortality, acute kidney injury, and other secondary outcomes between MB and HC treatments.
Main Methods:
- Retrospective cohort study using the TriNetX US network (65 health systems).
- Included adults with sepsis, severe sepsis, or septic shock treated with MB or HC (2016-2025).
- Propensity score matching (1:1) balanced 91 covariates for 732 patients (366 MB, 366 HC).
Main Results:
- Overall mortality and acute kidney injury rates were similar between MB and HC groups.
- High-dose hydroxocobalamin (HC) was linked to increased continuous renal replacement therapy (CRRT) initiation at 3-7 days and 7 days (P < 0.001).
- Stroke and prolonged vasopressor use were more frequent with HC during days 3-7, but not by day 7.
Conclusions:
- Methylene blue (MB) and HC showed similar early mortality in septic shock.
- MB was associated with lower rates of CRRT initiation, stroke, and prolonged vasopressor use compared to HC.
- MB may be a more favorable adjunctive therapy, warranting prospective validation.
