Hypoxemia Related to COVID-19 May Benefit From Almitrine Treatment

In patients with acute respiratory distress syndrome (ARDS) related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), treatment with almitrine 2 µg/kg/min was shown to be associated with an increased arterial oxygen partial pressure to fraction of inspired oxygen (PaO₂/FiO₂) ratio at 6 hours after administration, according to results of an analysis published in CHEST.

Recognizing that almitrine is used to decrease intrapulmonary shunt by enhancing hypoxic pulmonary vasoconstriction, thus improving gas exchange in individuals with ARDS, investigators sought to evaluate the association between the introduction of almitrine and improvement in oxygenation in patients with coronavirus disease 2019(COVID-19). They conducted a single center, retrospective, observational study was conducted in a 36-bed intensive care unit (ICU) at Hôpital Lariboisière in Paris, France, which was fully dedicated to patients with COVID-19.  

Medical records of all patients admitted to the ICU between March 14, 2020, and April 11, 2020, were reviewed. Study inclusion criteria were as follows: admission to the ICU for respiratory failure, a diagnosis of ARDS, laboratory-confirmed SARS-CoV-2 infection, and infusion of almitrine in the ICU. The primary study end point was the PaO₂/FiO₂ ratio between baseline and peak value in the 1- to 6-hour timeframe following the administration of almitrine. Secondary end points included the incidence of treatment failure at 24, 48, 72, and 96 hours, as well as safety. Treatment failure was defined as mortality or the requirement for additional rescue therapy. Safety data included an increase in right arterial pressure and lactate in the initial 6 hours, and peak values for liver function tests in the first 48 hours.

A total of 86 patients were admitted to the ICU during the study. Of the 20 patients who met inclusion criteria, 19 had complete data available and were evaluated. The median time from ICU admission was 4 days (range, 2-6 days). The average patient age was 63 years (range, 54-67 years). The average body mass index was 28 kg/m² (range, 26-32 kg/m²). At the time of almitrine administration, 79% (15 of 19) of the participants were receiving mechanical ventilation with neuromuscular blockade. Overall, 95% (18 of 19) of the patients received ≥1 session of prone positioning before almitrine infusion.

The median PaO₂/FiO₂ ratio increased significantly from 79 (range, 64-100) at baseline to 117 (range, 81-167) following the administration of almitrine (P =.001). The median arterial lactate concentration increased significantly from 1.2 mmol/L (range, 0.9-1.4 mmol/L) to 1.5 mmol/L (range, 1.1 to 1.7 mmol/L) following almitrine infusion (P =.002). Neither right arterial pressure nor liver tests (ie, alanine transaminase, alkaline phosphatase, and gamma glutamyl transpeptidase) changed significantly following almitrine infusion.

This was the first study to describe the therapeutic effects of almitrine in patients with COVID-19. The use of almitrine was linked to an increase in PaO₂/FiO₂ ratio following treatment with almitrine, even though this improvement in hypoxemia appeared to be heterogeneous among the participants. In spite of the increase in PaO₂/FiO₂ ratio, the majority of patients who were treated with almitrine either went on to require additional rescue interventions or died.

The investigators concluded that despite of the small sample size and the lack of a control group, results of this study demonstrated that enhancing hypoxic pulmonary vasoconstriction is a promising strategy for decreasing hypoxemia in patients with COVID-19. This might, in turn, prove beneficial for securing intra or interhospital transfers in those patients with the most severe disease, as well as for gaining precious time until a more invasive life support becomes available.

Disclosures: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Barthélémy R, Blot P-L, Tiepolo A, et al. Efficacy of almitrine in the treatment of hypoxemia in Sars-Cov-2 acute respiratory distress syndrome [published online June 5, 2020]. CHEST. doi:10.1016/j.chest.2020.05.573