Methylene blue therapy versus standard treatment for acute-phase septic shock: a pilot randomized controlled trial

Abstract

Purpose Methylene blue (MB) has been used to increase blood pressure in patients with septic shock by acting on guanylate cyclase and nitric oxide synthase (NOS). Objective To determine whether the administration of MB to patients in the initial phase of septic shock leads to a reduction in the use of vasopressors compared to that in the control group. Methods This was a 1:1 randomized clinical trial of two groups (methylene blue and control). We used MB after fluid replacement, vasopressors and antibiotic therapy. Patients received a loading dose of MB (3 mg/kg) and maintenance (0.5 mg/kg/h) for 48 hours. Vasopressor doses, laboratory test results, inflammatory and anti-inflammatory cytokine levels, and hemodynamic monitoring were recorded before the infusion of MB (T1) and after 20 minutes (T2), 2 hours (T3), 24 hours (T4), 48 hours after the infusion started (T5) and 24 hours after weaning (T6). Results Methylene blue therapy started within 72 hours of septic shock. The methylene blue group showed an immediate reduction in NOR dosage, earlier reduction in VAS dosage, and higher IL-10 levels compared to the control group. Integrative network analysis highlighted NO and IL-10's roles in coordinating correlations with "Hemodynamic Monitoring" in the control and methylene blue groups, respectively. Conclusion Early methylene blue (MB) administration alongside standard septic shock treatment reduces vasopressor doses, possibly involving nitric oxide (NO) mechanisms. A possible mechanism of action may involve modulation of inflammatory and anti-inflammatory mediators, enhancing immune response. However, larger and longer studies are needed for validation. Trial registration: Clinical registration: https://ensaiosclinicos.gov.br/rg/RBR-96584w4.