Use of Methylene Blue in Refractory Shock and Its Impact on Vasopressor Requirements

Introduction: Refractory shock has been defined as the requirement of high-dose vasopressors to attain hemodynamic targets and is associated with a high rate of mortality. Methylene blue is used by some providers as an adjunct to vasopressors for the treatment of refractory shock. Lack of established guidance has created a need to assess the benefit of adding this drug to standard vasopressor therapy. The objective of this project was to determine if treatment with methylene blue decreases vasopressor requirements in patients experiencing refractory shock.


Methods: This single-center, retrospective review assessed patients admitted to the Advocate Christ Medical Center medical intensive care unit (ICU) for the management of shock between August 1, 2022, and December 31, 2024. A report generated from the electronic health record was used to identify patients, and patients were evaluated for inclusion in this study if they were ≥ 18 years of age and received ≥ 2 concomitant vasopressors. Peri- or post-operative patients were excluded. Medication orders for methylene blue were used to identify patients in the intervention group, and an equal number of control patients were enrolled. The primary endpoint was vasopressor-free days (VFDs) at 28 days. Secondary endpoints included ICU and hospital length-of-stay (LOS), mortality at 28 days, and mortality within 4 hours. This study was approved by the Institutional Review Board.


Results: 77 patients were included (38 patients in the methylene blue group and 39 patients in the control group). Median VFDs at 28 days were 0.10 days for methylene blue versus 0.21 days for control (p=0.328). Median LOS was shorter in the methylene group than the control group at 7.33 days vs 9.98 days for hospital (p=0.474) and 2.78 days versus 3.52 days for ICU (p=0.276). Mortality at 28 days was 76.32% for methylene blue and 76.92% for control (p>0.99). 2 patients died within 4 hours of vasopressor initiation in the methylene blue group versus 0 patients in the control group (p=0.157).


Conclusions: Administration of methylene blue was not associated with increased vasopressor-free days compared to standard therapy. Further research regarding appropriate dosing and timing of initiation is necessary to determine the role in therapy of methylene blue for refractory shock.