Physiologic, Metabolic, and Protein Redox Effects of Methylene Blue in a Porcine Hemorrhage Model

BACKGROUND: Methylene blue (MB) has established benefit in vasodilatory shock, and a potential role in hemorrhagic shock. Some evidence suggests that MB could lower anesthetic requirements. The aim of this study was to investigate the effect of MB on volatile anesthetic requirements (primary), metabolic markers (secondary), and protein redox modifications (tertiary) in a porcine hemorrhage model. METHODS: This was a randomized 2 x 2 factorial animal study conducted at a tertiary medical center in 2019-2020. Forty swine were randomized to the following experimental interventions: hemorrhage (0 v. 30 mL/kg, at t = 0 min) and MB (0 v. 2 mg/kg, at t = 20 min). End-tidal isoflurane, blood pressure, and arterial blood gas parameters were recorded at prespecified intervals. Skeletal muscle was used for redox analyses. Group differences were investigated with mixed effects and one-way analyses of variance. RESULTS: There was no effect of MB on volatile requirements or metabolic markers (all P > 0.05). Hemorrhage was associated with 2.4 mg/dL higher lactate (95% CI, 1.4 to 3.4) and 23 mmHg lower mean arterial pressure (95% CI, 11 to 34). Hemorrhage was also associated with increased protein carbonyl levels (P < 0.001) that were non-significantly attenuated by MB (P = 0.130), and increased protein S-nitrosylation (P < 0.001) that was significantly attenuated by MB (P < 0.001). CONCLUSIONS: MB does not have a significant effect on volatile anesthetic requirements or systemic physiologic and metabolic responses during hemorrhagic shock. However, MB significantly attenuates protein S-nitrosylation and partially attenuates protein carbonyl accumulation.