Comparative study between high and low dose methylene blue infusion in septic cancer patients: a randomized, blinded, controlled study.

Summary

In a double-blind RCT of 90 cancer patients with septic shock, adjunctive methylene blue (1 or 4 mg/kg bolus plus infusion) shortened time to vasopressor discontinuation, increased vasopressor-free days, and reduced norepinephrine dose versus placebo. The 4 mg/kg bolus showed a protective association with mortality.

Key Findings

• Methylene blue (1 or 4 mg/kg bolus + 72 h infusion) reduced time to vasopressor discontinuation versus placebo.
• Vasopressor-free days at 28 days increased and norepinephrine doses were lower with methylene blue.
• No significant difference between 1 mg/kg and 4 mg/kg for primary endpoints; safety acceptable with no significant adverse effects.
• The 4 mg/kg bolus was associated with lower mortality (HR 0.29, 95% CI 0.09-0.90) versus placebo.

Clinical Implications

Consider early adjunctive methylene blue for refractory vasoplegia in septic shock within clinical trials or protocols, especially where norepinephrine requirements remain high. Screen for contraindications (e.g., G6PD deficiency, serotonergic drugs) and monitor for interference with pulse oximetry.

Limitations

• Single-disease context (cancer patients) with modest sample size limits generalizability
• Mortality was a secondary outcome with borderline significance; trial not powered for survival

Future Directions

Conduct adequately powered multicenter RCTs across heterogeneous septic shock populations to confirm survival benefit, define optimal dosing, and refine patient selection (e.g., vasoplegic phenotype).