CCM:脓毒性休克中亚甲蓝的应用：一项回顾性队列研究

Abstract

Objectives: To describe the epidemiology of methylene blue (MB) use in septic shock and explore the association between MB dose and hospital outcomes.描述美国脓毒性休克患者中使用亚甲蓝（MB）的流行病学情况，并探究亚甲蓝使用剂量与住院结局之间的关联。

Design: Retrospective cohort study.回顾性队列研究。

Setting: United States.美国

Patients: Eight hundred fifty-nine thousand eight hundred sixty-eight adult (≥ 18 yr) patients from 1100 centers with a diagnosis of septic shock (sepsis with vasopressor administration), discharged from Premier Healthcare Database hospitals in the United States from 2008 to 2021.来自美国1100家医疗中心的859,868例成年（≥18岁）脓毒性休克（即使用血管活性药物治疗的脓毒症）患者，这些患者于2008 – 2021年从美国Premier医疗保健数据库所属医院出院。

Interventions: None.无

Measurements and main results: We included patients who received MB at any point during hospitalization (to describe utilization), then separately focused on those who received MB within the first 3 hospital days (to examine association of dose with outcomes). The primary outcome was hospital mortality. We used mixed-effects multivariable regression models to evaluate the MB use and the association between MB dose (modeled as a five-knot restricted cubic spline) and outcomes. Among patients with septic shock, 4082 patients (0.5%) from 663 hospitals received at least one dose of MB. Patients receiving MB tended to be younger and received major surgery. Hospitals in which MB was administered were larger urban teaching hospitals. After multivariable adjustment, use of MB was lower in 2016-2020 than in 2008. Of 2507 patients (61.4%) who received MB within the first 3 days of hospitalization, 375 (15.0%) died in hospital. Our spline analysis suggests a nonlinear association between MB dosing and outcomes among patients receiving MB early in their hospitalization.

测量指标与主要结果：我们纳入了住院期间任何时段接受亚甲蓝治疗的患者（以描述其使用情况），随后单独重点关注住院前3天内接受亚甲蓝治疗的患者（以探究剂量与结局的关联）。主要结局指标为住院死亡率。我们采用混合效应多变量回归模型，评估亚甲蓝的使用情况以及亚甲蓝剂量（以五节点限制性立方样条模型进行建模）与结局之间的关联。在脓毒性休克患者中，共有来自663家医院的4082例患者（占0.5%）至少接受过一剂亚甲蓝治疗。接受亚甲蓝治疗的患者往往更年轻，且曾接受过重大手术。实施亚甲蓝治疗的医院多为规模较大的城市教学医院。经多变量调整后显示，2016-2020年间亚甲蓝的使用率较2008年有所下降。在住院前3天内接受亚甲蓝治疗的2507例患者（占61.4%）中，有375例（占15.0%）于住院期间死亡。我们的样条分析结果表明，对于住院早期接受亚甲蓝治疗的患者，其亚甲蓝用药剂量与临床结局之间存在非线性关联。

Conclusions: Use of MB in septic shock is rare in the United States, but with substantial inter-hospital variability and decreased use over time through 2020. Randomized evidence is required to evaluate the efficacy and safety of MB.在美国，脓毒性休克患者中使用亚甲蓝的情况较为罕见，但不同医院之间存在显著差异，且截至2020年其使用率呈下降趋势。需要开展随机对照研究来评估亚甲蓝的有效性和安全性。