Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain.
Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid, Spain; Cardiology Department, IIS-Fundación Jiménez Díaz University Hospital, Madrid, Spain.
J Am Coll Cardiol. 2021 Sep 7;78(10):1001-1011. doi: 10.1016/j.jacc.2021.07.003.
Severe coronavirus disease-2019 (COVID-19) can progress to an acute respiratory distress syndrome (ARDS), which involves alveolar infiltration by activated neutrophils. The beta-blocker metoprolol has been shown to ameliorate exacerbated inflammation in the myocardial infarction setting.
The purpose of this study was to evaluate the effects of metoprolol on alveolar inflammation and on respiratory function in patients with COVID-19-associated ARDS.
A total of 20 COVID-19 patients with ARDS on invasive mechanical ventilation were randomized to metoprolol (15 mg daily for 3 days) or control (no treatment). All patients underwent bronchoalveolar lavage (BAL) before and after metoprolol/control. The safety of metoprolol administration was evaluated by invasive hemodynamic and electrocardiogram monitoring and echocardiography.
Metoprolol administration was without side effects. At baseline, neutrophil content in BAL did not differ between groups. Conversely, patients randomized to metoprolol had significantly fewer neutrophils in BAL on day 4 (median: 14.3 neutrophils/µl [Q1, Q3: 4.63, 265 neutrophils/µl] vs median: 397 neutrophils/µl [Q1, Q3: 222, 1,346 neutrophils/µl] in the metoprolol and control groups, respectively; P = 0.016). Metoprolol also reduced neutrophil extracellular traps content and other markers of lung inflammation. Oxygenation (PaO:FiO) significantly improved after 3 days of metoprolol treatment (median: 130 [Q1, Q3: 110, 162] vs median: 267 [Q1, Q3: 199, 298] at baseline and day 4, respectively; P = 0.003), whereas it remained unchanged in control subjects. Metoprolol-treated patients spent fewer days on invasive mechanical ventilation than those in the control group (15.5 ± 7.6 vs 21.9 ± 12.6 days; P = 0.17).
In this pilot trial, intravenous metoprolol administration to patients with COVID-19-associated ARDS was safe, reduced exacerbated lung inflammation, and improved oxygenation. Repurposing metoprolol for COVID-19-associated ARDS appears to be a safe and inexpensive strategy that can alleviate the burden of the COVID-19 pandemic.
严重的 2019 年冠状病毒病（COVID-19）可进展为急性呼吸窘迫综合征（ARDS），其涉及被激活的中性粒细胞对肺泡的浸润。β受体阻滞剂美托洛尔已被证明可改善心肌梗死情况下的炎症加重。
本研究旨在评估美托洛尔对 COVID-19 相关 ARDS 患者肺泡炎症和呼吸功能的影响。
共纳入 20 例接受有创机械通气的 COVID-19 合并 ARDS 患者，随机分为美托洛尔组（每日 15mg，连续 3 天）或对照组（不治疗）。所有患者在接受美托洛尔/对照组治疗前后均接受支气管肺泡灌洗（BAL）。通过有创血流动力学和心电图监测及超声心动图评估美托洛尔给药的安全性。
美托洛尔给药无副作用。基线时，两组 BAL 中的中性粒细胞含量无差异。相反，接受美托洛尔治疗的患者在第 4 天 BAL 中的中性粒细胞明显减少（中位数：14.3 个/µl[Q1，Q3：4.63，265 个/µl] vs 中位数：397 个/µl[Q1，Q3：222，1346 个/µl]；P=0.016）。美托洛尔还降低了中性粒细胞胞外诱捕网（NET）的含量和其他肺炎症标志物。接受美托洛尔治疗 3 天后，氧合（PaO:FiO）显著改善（中位数：130[Q1，Q3：110，162] vs 中位数：267[Q1，Q3：199，298]；P=0.003），而对照组无变化。与对照组相比，接受美托洛尔治疗的患者接受有创机械通气的天数更少（15.5±7.6 天 vs 21.9±12.6 天；P=0.17）。
在这项初步试验中，COVID-19 相关 ARDS 患者静脉注射美托洛尔是安全的，可减轻过度的肺部炎症并改善氧合。美托洛尔治疗 COVID-19 相关 ARDS 似乎是一种安全且廉价的策略，可以减轻 COVID-19 大流行的负担。
