亚甲蓝——脓毒症休克的“魔法锦囊”?

Methylene blue:“Magic bullet”for refractory septic shock?

血管活性药物是脓毒症休克的治疗基石。近年来,联合应用不同升压机制的非儿茶酚胺类药物成为脓毒症休克的研究热点,以期减少大剂量、长时程使用去甲肾上腺素(NE)相关的不良反应。然而,升压素类、血管紧张素(AT)Ⅱ价格昂贵,且大多未在国内上市;糖皮质激素联合代谢疗法由于廉价且易获得,备受瞩目,但研究结论存在争议;最新的多中心研究表明大剂量维生素C与脓毒症休克患者的死亡风险增加有关。不同于上述血管活性药物通过激活升压信号通路发挥作用,亚甲蓝的升压机制是抑制一氧化氮(NO)介导的扩血管作用。在小样本临床研究中,亚甲蓝作为顽固性休克患者的“魔法锦囊”,可以显著升高血压,甚至逆转患者的临床结局。亚甲蓝费用低廉,各基层医院均可获得,具有良好的应用前景。本文概述非儿茶酚胺类升压药物在脓毒症休克中的应用现状,并着重介绍亚甲蓝升压的作用机制、循证证据及前景展望,以期促进升压药物,尤其是亚甲蓝的合理使用。

The optimal start-up timing and reasonable combination of vasoactive drugs has recently been hot spots in the research field of septic shock.The latest Surviving Sepsis Campaign strongly recommend norepinephrine(NE)as first-line agent over other vasopressors.However,NE-related side effects such as immunosuppression and arrhythmia have gotten more and more attentions.High dose of NE has been demonstrated to be independent risk factors associated with mortality of septic shock.Many multicenter,randomized controlled studies have shown that the combination of non-catecholamine vasopressors significantly spared the usage of NE,enhanced blood pressure,and might improve survival outcome.Methylene blue(MB),which has unique mechanism to raise pressure,has often been used as“magic bullet”for refractory vasoplegia shock.But the effectiveness of MB was confined to small sample studies and case reports.MB has promising clinical value due to its low-cost and easy-access even in grassroots hospitals.This review summarizes the combination regimen of non-catecholamines vasopressors in septic shock,and the mechanism,status and prospect of MB,in order to promote agreements on indication,timing,dose and duration of MB administration.