Metoprolol safe, eases lung inflammation in critically ill COVID-19 patients

Intravenous (IV) administration of the beta-blocker metoprolol safely reduces the exacerbation of lung in patients with COVID-19–related acute respiratory distress syndrome (ARDS), a study has shown. Reduced lung inflammation then leads to improvement in oxygenation and to fewer days on mechanical ventilation and of admission to intensive care unit (ICU).

“Metoprolol repurposing for the treatment of ARDS associated with COVID-19 is a safe and cheap intervention that can help to alleviate the massive personal and healthcare burden associated with the pandemic,” the researchers said.

Twenty COVID-19 patients with ARDS on invasive mechanical ventilation were randomly assigned to receive metoprolol (15 mg daily for 3 days) or no treatment (control). They all underwent bronchoalveolar lavage (BAL) before and after metoprolol/control.

The researchers then evaluated the safety of metoprolol administration by invasive haemodynamic and electrocardiogram monitoring and echocardiography.

Metoprolol administration showed no side effects. Neutrophil content in BAL did not differ between groups at baseline. However, patients on metoprolol had significantly fewer neutrophils in BAL on day 4 (median, 14.3 vs 397 neutrophils/µl; p=0.016). Metoprolol also decreased neutrophil extracellular traps content and other markers of lung inflammation. [J Am Clin Cardiol 2021;78:1001-1011]

After 3 days of metoprolol treatment, oxygenation (PaO₂:FiO₂) improved significantly (median, 130 vs 267 at baseline and day 4, respectively; p=0.003). Oxygenation did not change in control patients. Of note, patients in the metoprolol group 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).

“We previously demonstrated that metoprolol protects the heart during ongoing myocardial infarction by stunning neutrophils and abrogating exacerbated inflammation,” the researchers said. [Nat Commun 2017;8:14780; Eur Heart J 2020;41:4425-4440]

“The identification of this cardioprotective mechanism created an opportunity to repurpose metoprolol for other acute conditions in which exacerbated inflammation plays a role, as is the case for COVID-19–associated ARDS,” they added.

A previous retrospective study reported better vital prognosis among patients admitted with septic shock and previously on maintenance beta-blocker therapy than those who were not on beta-blockers before admission. [Crit Care 2019;23:298]

Moreover, small prospective clinical trials examined the benefits of IV beta-blockers in sepsis patients and found that such treatment offered a clinical benefit. [J Anaesthesiol Clin Pharmacol 2015;31:460-465; Crit Care 2008;12:R99; Crit Care Med 2013;41:2162-2168; JAMA 2013;310:1683-1691]

“COVID-19–associated ARDS is characterized by active neutrophil infiltration into the alveolar space, which perpetuates exacerbated inflammation, leading to a cytokine storm and hypoxaemia,” the researchers said. “Neutrophil infiltration is thus a major contributing factor to the poor prognosis of these patients.” [BMC Pulm Med 2020;20:301; Front Pharmacol 2020;11:572009]

“Mitigation of immune dysregulation is therefore a major therapeutic avenue for the treatment and prevention of severe COVID-19,” the researchers noted.