亚甲蓝用于脓毒性休克的最佳给药策略探讨：单次推注还是持续输注？

Discussion on the Optimal Administration Strategy of Methylene Blue for Septic Shock: Bolus Injection versus Continuous Infusion?

摘要: 亚甲蓝可以抑制诱导型一氧化氮合酶(iNOS)和可溶性鸟苷酸环化酶(sGC)，从而在NO-sGC-cGMP通路上产生独特的血管加压作用，因此可以成为脓毒性休克多模态治疗的一个新的选择。但是不同的给药途径会直接影响到疗效。目前文献中主要使用的有三种策略，即一次推注、持续输注和推注联合持续输注。单次推注起效快但是升压效果一般只能维持2~3小时，适合于挽救性治疗；持续输注可以保持更好的血流动力学；推注联合持续输注既能迅速起效又能使血压稳定，有研究表明该方法可降低患者的28天死亡率，但此类研究存在选择偏倚和混杂因素，结论还需要前瞻性随机对照试验验证。本文对这三种策略的药代动力学基础以及临床证据进行梳理，比较了各自的优势与不足，分析了影响策略选择的因素，在已有证据的基础上给出了临床意见及未来的走向，希望可以给亚甲蓝的合理使用提供一些参照。

Abstract: Methylene blue can inhibit inducible nitric oxide synthase (iNOS) and soluble guanylyl cyclase (sGC), thereby producing a unique vasopressor effect via the NO-sGC-cGMP pathway and thus representing a novel option for multimodal therapy of septic shock. However, different routes of administration directly affect its efficacy. Three main strategies are currently used in the literature: single bolus injection, continuous infusion, and bolus combined with continuous infusion. A single bolus has a rapid onset, but its vasopressor effect generally lasts only 2~3 hours, making it suitable for rescue therapy; continuous infusion provides better hemodynamic stability; and bolus combined with continuous infusion can achieve both rapid onset and stable blood pressure. Some studies have shown that this combined approach may reduce 28-day mortality, but these studies are subject to selection bias and confounding factors, and the conclusions require validation by prospective randomized controlled trials. This article reviews the pharmacokinetic basis and clinical evidence for these three strategies, compares their respective advantages and disadvantages, analyzes factors influencing the choice of strategy, and provides clinical recommendations and future directions based on existing evidence, with the aim of offering some references for the rational use of methylene blue.