Effectiveness and tolerability of methylthioninium chloride (methylene blue) for the treatment of methemoglobinemia: twenty-four years of experience at a single poison center

Abstract

Introduction: Despite the widely accepted use of methylthioninium chloride (methylene blue) to treat methemoglobinemia, data regarding clinical outcomes are sparse. We sought to better elucidate the efficacy and tolerability of methylthioninium chloride.

Methods: We identified all cases reported to the New York City Poison Center from 2000 to 2024 in which methylthioninium chloride was administered for methemoglobinemia. We extracted clinical data from these cases, which we assessed using primarily descriptive statistics.

Results: A total of 185 cases were included. The median methemoglobin level was 29% (IQR: 19-42%). Implicated xenobiotics were most frequently volatile nitrites (41%), local anesthetics (15%), and dapsone (11%). The median methylthioninium chloride dose was 1 mg/kg (IQR: 1-2 mg/kg; range: 0.5-4 mg/kg). Multiple doses of methylthioninium chloride were administered in 11% of cases, with a median total dose of 2 mg/kg (IQR: 2-3 mg/kg), the majority of which were associated with volatile nitrites (n = 7) or dapsone (n = 6). Improvement after administration of methylthioninium chloride was reported in 98% of cases (95% CI: 96-100%). Adverse effects attributable to methylthioninium chloride were reported in nine cases (4.9%; 95% CI: 4.6-5.1%), including one instance of hemolysis. Glucose-6-phosphate dehydrogenase activity was found to be deficient in two of seven patients tested, only one of whom did not improve after methylthioninium chloride. Two deaths occurred in this series, both associated with sodium nitrite exposure.

Discussion: Most patients with methemoglobinemia improved after 1-2 mg/kg of methylthioninium chloride, supporting current treatment recommendations. Despite few instances of glucose-6-phosphate dehydrogenase activity testing, major adverse effects attributable to methylthioninium chloride were extremely rare. A relatively large proportion of cases receiving multiple doses were associated with dapsone exposure.

Conclusions: In this series, methylthioninium chloride was both efficacious and well tolerated in patients with methemoglobinemia, with a single dose of 1-2 mg/kg being sufficient to treat most patients.

Keywords: Methemoglobinemia; methylene blue; methylthioninium chloride; poisoning; treatment.