Methylene Blue Administration in Septic Shock: A Retrospective Cohort Study

Objectives: To describe the epidemiology of methylene blue (MB) use in septic shock and explore the association between MB dose and hospital outcomes. Design: Retrospective cohort study. Setting: United States. Patients: Eight hundred fifty-nine thousand eight hundred sixty-eight adult (≥ 18 yr) patients from 1100 centers with a diagnosis of septic shock (sepsis with vasopressor administration), discharged from Premier Healthcare Database hospitals in the United States from 2008 to 2021. Interventions: None. Measurements and Main Results: We included patients who received MB at any point during hospitalization (to describe utilization), then separately focused on those who received MB within the first 3 hospital days (to examine association of dose with outcomes). The primary outcome was hospital mortality. We used mixed-effects multivariable regression models to evaluate the MB use and the association between MB dose (modeled as a five-knot restricted cubic spline) and outcomes. Among patients with septic shock, 4082 patients (0.5%) from 663 hospitals received at least one dose of MB. Patients receiving MB tended to be younger and received major surgery. Hospitals in which MB was administered were larger urban teaching hospitals. After multivariable adjustment, use of MB was lower in 2016–2020 than in 2008. Of 2507 patients (61.4%) who received MB within the first 3 days of hospitalization, 375 (15.0%) died in hospital. Our spline analysis suggests a nonlinear association between MB dosing and outcomes among patients receiving MB early in their hospitalization. Conclusions: Use of MB in septic shock is rare in the United States, but with substantial inter-hospital variability and decreased use over time through 2020. Randomized evidence is required to evaluate the efficacy and safety of MB.