Methylene blue for septic shock in oncologic patients: A propensity score-matched cohort

Septic shock is associated with high mortality, yet evidence supporting adjunctive therapies remains limited. Methylene blue (MB) has been proposed as a rescue therapy targeting catecholamine-resistant vasodilation, but its impact on clinically meaningful outcomes is uncertain. Oncologic patients represent a clinically distinct subgroup with high disease severity and are underrepresented in prior studies. We evaluated the association between MB and outcomes in oncologic patients with septic shock requiring multiple vasopressors.

We conducted a retrospective cohort study using the TriNetX Research Network, including adult oncologic patients with septic shock between January 1, 2015, and December 31, 2025. Septic shock requiring multiple vasopressors was defined as septic shock requiring norepinephrine plus at least one additional vasopressor (vasopressin or epinephrine). MB recipients were matched 1:1 with non-recipients using propensity score matching. The primary outcome was 30-day all-cause mortality. Secondary outcomes included acute kidney injury (AKI), renal replacement therapy (RRT), invasive mechanical ventilation, and vasopressor escalation within 7 days.

Among 266 MB-treated patients and 10,163 controls, 262 balanced pairs were analyzed after matching. MB was associated with lower 30-day mortality (risk ratio [RR] 0.80, 95% CI 0.66-0.97). Favorable associations were observed for AKI and vasopressor escalation, whereas invasive mechanical ventilation did not differ between groups.

In oncologic patients with septic shock requiring multiple vasopressors, MB use was associated with lower 30-day mortality; however, within the limitations of this retrospective study, these findings should be interpreted cautiously. Prospective randomized trials are warranted to clarify the role of MB in this high-risk population.