Methylene Blue in Septic Shock: Emerging Evidence, Clinical Applications, and Future Directions

Abstract

Septic shock remains a significant cause of mortality in intensive care units worldwide despite advances in management strategies. The pathophysiology involves profound circulatory and cellular abnormalities leading to vasoplegic shock. While norepinephrine remains the first-line vasopressor, there is growing interest in catecholamine-sparing agents to mitigate the adverse effects of adrenergic overstimulation. Methylene blue, with its inhibitory action on nitric oxide pathways, has emerged as a potential adjunctive therapy. This review examines the theoretical mechanisms, pharmacokinetics, clinical evidence, and practical considerations for methylene blue use in septic shock. While some promising results regarding reduced vasopressor requirements and length of stay are suggested, current evidence does not support methylene blue as a replacement for established second-line agents like vasopressin. Further large-scale randomized trials are needed to establish optimal dosing regimens, timing of administration, and specific patient populations who might benefit most from this intervention.

Keywords: catecholamine-sparing therapy; cyclic gmp pathway; methylene blue; nitric oxide inhibition; refractory septic shock; vasopressin comparison; vasopressor requirements.