Background

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.

Objectives

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.

Methods

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.

Results

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 (PaO₂:FiO₂) 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).

Conclusions

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.

中文翻译：

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美托洛尔在 COVID-19 重症患者中的应用

背景

严重的 2019 年冠状病毒病 (COVID-19) 可发展为急性呼吸窘迫综合征 (ARDS)，其中包括活化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塞环境中加重的炎症。

目标

本研究的目的是评估美托洛尔对 COVID-19 相关 ARDS 患者肺泡炎症和呼吸功能的影响。

方法

共有 20 名接受有创机械通气的 ARDS 的 COVID-19 患者被随机分配到美托洛尔（每天 15 毫克，持续 3 天）或对照组（不治疗）。所有患者在美托洛尔/对照之前和之后都接受了支气管肺泡灌洗 (BAL)。通过有创血流动力学和心电图监测以及超声心动图评估美托洛尔给药的安全性。

结果

美托洛尔给药没有副作用。在基线时，BAL 中的中性粒细胞含量在各组之间没有差异。相反，随机分配至美托洛尔的患者在第 4 天 BAL 中的中性粒细胞显着减少（中位数：14.3 中性粒细胞/μl [Q1、Q3：4.63、265 中性粒细胞/μl] 与中位数：397 中性粒细胞/μl [Q1、Q3：222、1,346 中性粒细胞/µl] 分别在美托洛尔和对照组中；P = 0.016)。美托洛尔还降低了中性粒细胞胞外陷阱含量和其他肺部炎症标志物。美托洛尔治疗 3 天后氧合（PaO ₂ :FiO ₂）显着改善（中位数：130 [Q1、Q3：110、162] 对比中位数：267 [Q1、Q3：199、298] 在基线和第 4 天；P =0.003），而对照组保持不变。美托洛尔治疗组的有创机械通气天数少于对照组（15.5 ± 7.6 vs 21.9 ± 12.6 天；P = 0.17）。

结论

在这项初步试验中，对 COVID-19 相关 ARDS 患者静脉注射美托洛尔是安全的，可减少肺部炎症的恶化并改善氧合。将美托洛尔重新用于与 COVID-19 相关的 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。