The Use of Methylene Blue in Adult Patients with Septic Shock: A Systematic Review and Meta-analysis

Abstract

Abstract Objectives Methylene blue exerts its vasopressor effects by inhibiting nitric oxide-mediated vasodilation. Recent studies have suggested the use of methylene blue as a rescue therapy for patients with septic shock. The primary aim was to investigate the effect of methylene blue on the mean arterial pressure among adult patients with septic shock. Methods The MEDLINE, EMBASE, and CENTRAL databases were searched from their inception until October 2023. Randomized clinical trials (RCTs) comparing methylene blue and placebo in adults with septic shock were included. Results Our systematic review included 5 studies (n = 257) for data analysis. Our pooled analysis revealed that compared with the placebo, methylene blue significantly increased the mean arterial pressure (MD: 1.34 mmHg, 95% CI: 0.15 to 2.53, ρ = 0.03; level of evidence: very low). Methylene blue was associated with a significantly lower mortality rate (OR: 0.49, 95% CI: 0.27 to 0.88; ρ = 0.02; level of evidence: low), reduced serum lactate levels (MD: -0.76 mmol/L, 95% Cl: -1.22 to -0.31; ρ = 0.0009; level of evidence: low), reduced length of hospital stay (MD: -1.94 days, 95% Cl: -3.79 to -0.08; ρ = 0.04; level of evidence: low), and increased PaO2/FiO2 (MD: 34.78, 95% CI: 8.94 to 60.61; ρ = 0.008; level of evidence: low). Conclusions This meta-analysis showed that methylene blue administration was associated with increased mean arterial pressure and PaO2/FiO2 and was associated with a reduced mortality rate, serum lactate levels, and duration of hospitalization. However, a substantial degree of heterogeneity and an inadequate number of studies with a low level of evidence warrant future adequately powered RCTs to affirm our results.