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. 2020 Nov 4;10(1):151.
doi: 10.1186/s13613-020-00769-2.

Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome

François Bagate  1   2 , Samuel Tuffet  1   2 , Paul Masi  1   2 , François Perier  1   2 , Keyvan Razazi  1   2 , Nicolas de Prost  1   2 , Guillaume Carteaux  1   2 , Didier Payen  3 , Armand Mekontso Dessap  4   5   6
Affiliations

Rescue therapy with inhaled nitric oxide and almitrine in COVID-19 patients with severe acute respiratory distress syndrome

François Bagate et al. Ann Intensive Care. .

Abstract

Background: In COVID-19 patients with severe acute respiratory distress syndrome (ARDS), the relatively preserved respiratory system compliance despite severe hypoxemia, with specific pulmonary vascular dysfunction, suggests a possible hemodynamic mechanism for VA/Q mismatch, as hypoxic vasoconstriction alteration. This study aimed to evaluate the capacity of inhaled nitric oxide (iNO)-almitrine combination to restore oxygenation in severe COVID-19 ARDS (C-ARDS) patients.

Methods: We conducted a monocentric preliminary pilot study in intubated patients with severe C-ARDS. Respiratory mechanics was assessed after a prone session. Then, patients received iNO (10 ppm) alone and in association with almitrine (10 μg/kg/min) during 30 min in each step. Echocardiographic and blood gases measurements were performed at baseline, during iNO alone, and iNO-almitrine combination. The primary endpoint was the variation of oxygenation (PaO2/FiO2 ratio).

Results: Ten severe C-ARDS patients were assessed (7 males and 3 females), with a median age of 60 [52-72] years. Combination of iNO and almitrine outperformed iNO alone for oxygenation improvement. The median of PaO2/FiO2 ratio varied from 102 [89-134] mmHg at baseline, to 124 [108-146] mmHg after iNO (p = 0.13) and 180 [132-206] mmHg after iNO and almitrine (p < 0.01). We found no correlation between the increase in oxygenation caused by iNO-almitrine combination and that caused by proning.

Conclusion: In this pilot study of severe C-ARDS patients, iNO-almitrine combination was associated with rapid and significant improvement of oxygenation. These findings highlight the role of pulmonary vascular function in COVID-19 pathophysiology.

Keywords: ARDS; Almitrine; COVID-19; iNO.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Box and whiskers plots of the change in the ratio of oxygen partial pressure (PaO2) to fraction of inspired oxygen (FiO2) in arterial blood in prone position and supine position, before and after administering inhaled nitric oxide (iNO) and almitrine in patients with severe acute respiratory distress syndrome secondary to coronavirus disease 2019. *, #, and & denote a p value < 0.05 for paired Wilcoxon (with Benjamini–Hochberg correction) following Friedman test, as compared to supine (before prone), supine (after prone), and supine with iNO, respectively
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