Use of almitrine in spontaneously breathing patients with COVID-19 treated with high-flow nasal cannula oxygen therapy and with persistent hypoxemia

Abstract

Background: Almitrine, a selective pulmonary vasoconstrictor in hypoxic area, improves oxygenation in mechanically ventilated patients with COVID-19 but its effects in spontaneously breathing patients with COVID-19 remain to be determined.

Methods: We prospectively studied the effects of almitrine (16 µg/kg/min over 30 min followed by continuous administration in responders only) in 62 patients (66% of male, 63 [53-69] years old) with COVID-19 treated with high-flow nasal cannula oxygen therapy (HFNO) and with persistent hypoxemia, defined as a PaO₂/FiO₂ ratio < 100 with FiO₂ > 80% after a single awake prone positioning session. Patients with an increase in PaO₂/FiO₂ ratio > 20% were considered as responders.

Results: Overall, almitrine increased the PaO₂/FiO₂ ratio by 50% (p < 0.01), decreased the partial arterial pressure of carbon dioxide by 7% (p = 0.01) whereas the respiratory rate remained unchanged and 46 (74%) patients were responders. No patient experienced right ventricular dysfunction or acute cor pulmonale. The proportion of responders was similar regardless of the CT-Scan radiological pattern: 71% for the pattern with predominant ground-glass opacities and 76% for the pattern with predominant consolidations (p = 0.65). Responders had lower intubation rate (33 vs. 88%, p < 0.01), higher ventilator-free days at 28-day (28 [20-28 ] vs. 19 [2-24] days, p < 0.01) and shorter ICU length of stay (5 [3-10] vs.12 [7-30] days, p < 0.01) than non-responders.

Conclusions: Almitrine could be an interesting therapy in spontaneously breathing patients with COVID-19 treated with HFNO and with persistent hypoxemia, given its effects on oxygenation without serious adverse effects regardless of the CT-Scan pattern, and potentially on intubation rate. These preliminary results need to be confirmed by further randomized studies.

Keywords: Acute respiratory distress syndrome; Awake prone positioning; COVID-19; Mechanical ventilation; Oxygenation.

Fig. 1

Flow chart of the study. HFNO: high-flow nasal cannula oxygen therapy, ICU: intensive care unit

Fig. 2

Effects of almitrine on respiratory and oxygenation variables (n = 62). The box shows the 25th and 75th percentiles, the line in the box the median and the whiskers the minimum and maximum values. Lines represent the individual changes (green lines for responders and orange lines for non-responders). FiO₂: inspired oxygen fraction; PaO₂: partial arterial pressure of oxygen, PaCO₂: partial arterial pressure of carbon dioxide

Fig. 3

Proportion of responders according to the different thoracic CT-Scan radiological patterns

Fig. 4

Cumulative incidence of intubation during the first week after almitrine administration in responders (red curve, n = 46) and non-responders (blue curve, n = 16) and proportion of patients receiving almitrine at each time point (blue bars)