PDF(Pubmed)
Abstract：
(1) Background/Objectives: Dexmedetomidine is a sedative for patients receiving invasive mechanical ventilation (IMV) that previous single-site studies have found to be associated with improved survival in patients with COVID-19. The reported clinical benefits include dampened inflammatory response, reduced respiratory depression, reduced agitation and delirium, improved preservation of responsiveness and arousability, and improved hypoxic pulmonary vasoconstriction and ventilation-perfusion ratio. Whether improved mortality is evident in large, multi-site COVID-19 data is understudied. (2) Methods: The association between dexmedetomidine use and mortality in patients with COVID-19 receiving IMV was assessed. This retrospective multi-center cohort study utilized patient data in the United States from health systems participating in the National COVID Cohort Collaborative (N3C) from 1 January 2020 to 3 November 2022. The primary outcome was 28-day mortality rate from the initiation of IMV. Propensity score matching adjusted for differences between the group with and without dexmedetomidine use. Adjusted hazard ratios (aHRs) for 28-day mortality were calculated using multivariable Cox proportional hazards models with dexmedetomidine use as a time-varying covariate. (3) Results: Among the 16,357,749 patients screened, 3806 patients across 17 health systems met the study criteria. Mortality was lower with dexmedetomidine use (aHR, 0.81; 95% CI, 0.73-0.90; p < 0.001). On subgroup analysis, mortality was lower with earlier dexmedetomidine use-initiated within the median of 3.5 days from the start of IMV-(aHR, 0.67; 95% CI, 0.60-0.76; p < 0.001) as well as use prior to standard, widespread use of dexamethasone for patients on respiratory support (prior to 30 July 2020) (aHR, 0.54; 95% CI, 0.42-0.69; p < 0.001). In a secondary model that was restricted to 576 patients across six health system sites with available PaO2/FiO2 data, mortality was not lower with dexmedetomidine use (aHR 0.95, 95% CI, 0.72-1.25; p = 0.73); however, on subgroup analysis, mortality was lower with dexmedetomidine use initiated earlier than the median dexmedetomidine start time after IMV (aHR, 0.72; 95% CI, 0.53-0.98; p = 0.04) and use prior to 30 July 2020 (aHR, 0.22; 95% CI, 0.06-0.78; p = 0.02). (4) Conclusions: Dexmedetomidine use was associated with reduced mortality in patients with COVID-19 receiving IMV, particularly when initiated earlier, rather than later, during the course of IMV as well as use prior to the standard, widespread usage of dexamethasone during respiratory support. These particular findings might suggest that the associated mortality benefit with dexmedetomidine use is tied to immunomodulation. However, further research including a large randomized controlled trial is warranted to evaluate the potential mortality benefit of DEX use in COVID-19 and evaluate the physiologic changes influenced by DEX that may enhance survival.
摘要：
（1）背景/目的：右美托咪定是一种用于有创机械通气（IMV）患者的镇静剂，先前的单中心研究发现，右美托咪定与COVID-19患者的生存率改善有关。报道的临床益处包括抑制炎症反应，减少呼吸抑制，减少躁动和谵妄，改善反应性和唤醒性的保存，改善低氧性肺血管收缩和通气灌注比。死亡率的改善是否明显，多点COVID-19数据研究不足。(2)方法：评估接受IMV的COVID-19患者使用右美托咪定与死亡率之间的关系。这项回顾性多中心队列研究利用了2020年1月1日至2022年11月3日参加国家COVID队列合作（N3C）的美国卫生系统的患者数据。主要结局是从IMV开始的28天死亡率。倾向评分匹配调整了使用右美托咪定和不使用右美托咪定组之间的差异。使用多变量Cox比例风险模型计算28天死亡率的调整风险比（aHRs），使用右美托咪定作为时变协变量。(3)结果：在筛查的16,357,749名患者中，17个卫生系统的3806名患者符合研究标准。使用右美托咪定的死亡率较低(aHR，0.81；95%CI，0.73-0.90；p<0.001)。关于子群分析，在IMV开始后的中位数3.5天内，早期使用右美托咪定的死亡率较低(aHR，0.67；95%CI，0.60-0.76；p<0.001）以及在标准前使用，接受呼吸支持的患者广泛使用地塞米松(2020年7月30日之前)(AHR，0.54；95%CI，0.42-0.69；p<0.001)。在二级模型中，该模型仅限于六个卫生系统站点的576名患者，并具有可用的PaO2/FiO2数据，使用右美托咪定的死亡率并没有降低(aHR0.95,95%CI,0.72-1.25;p=0.73);然而,关于子群分析，使用右美托咪定的开始时间早于IMV后中位右美托咪定开始时间的死亡率较低(aHR,0.72；95%CI，0.53-0.98；p=0.04)，并在2020年7月30日之前使用(AHR，0.22；95%CI，0.06-0.78；p=0.02)。(4)结论：右美托咪定的使用与COVID-19接受IMV的患者死亡率降低相关。特别是在较早发起时，而不是以后，在IMV的过程中以及在标准之前使用，在呼吸支持期间广泛使用地塞米松。这些特殊的发现可能表明，使用右美托咪定的相关死亡率益处与免疫调节有关。然而,有必要进行进一步研究,包括一项大型随机对照试验,以评估COVID-19中使用DEX的潜在死亡率获益,并评估DEX对可能提高生存率的生理变化.
