Early Methylene Blue for Mortality Reduction in High-Dose VasoPREssor-Dependent Septic Shock (EMPRESS): protocol for...

Area of Science:

• Critical Care Medicine
• Pharmacology
• Clinical Trials

Background:

• Septic shock is a leading cause of death, often involving excessive vasodilation via the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) pathway.
• Methylene blue (MB) inhibits this pathway and has shown hemodynamic benefits, suggesting potential as an adjunctive therapy for septic shock.
• A specific, high-mortality subgroup of septic shock patients requires high-dose vasopressors due to severe vasoplegia, and lacks large-scale trial data on MB's efficacy.

Purpose of the Study:

• To evaluate the efficacy of early Methylene blue administration in reducing 28-day all-cause mortality.
• To assess the impact of MB on secondary outcomes including ICU-free days and vasopressor dependence.
• To provide evidence for MB's role as an adjunctive therapy in managing high-dose vasopressor-dependent septic shock.

Main Methods:

• A multicenter, open-label, blinded endpoint randomized controlled trial (RCT) involving 566 adult patients with septic shock.
• Patients requiring norepinephrine equivalent doses > 0.3 μg/kg/min within 24 hours of vasopressor initiation were randomized.
• Intervention group received MB (2 mg/kg loading dose, 0.25 mg/kg/h infusion) or placebo (5% dextrose) for up to 48 hours, stratified by SOFA score and study center.

Main Results:

• Primary endpoint: 28-day all-cause mortality.
• Secondary endpoints: ICU-free days, vasopressor-free days, ventilator-free days, in-hospital mortality, and SOFA score improvement.
• Data analysis will determine the effect of MB on these critical care outcomes.

Conclusions:

• This RCT aims to determine if early MB administration decreases mortality in septic shock patients with high-dose vasopressor requirements.
• Findings may influence clinical guidelines for managing severe septic shock.
• The study will clarify MB's potential benefit in a high-risk, vasoplegic patient population.