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

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.

Early effects of ventilatory rescue therapies on systemic and cerebral oxygenation in mechanically ventilated COVID-19 patients with acute respiratory distress syndrome: a prospective observational study

“…COVID-19 patients often present with severe hypoxemia not responsive to conventional treatment and at the same time are at high risk of neurological complications [ 17 , 36 ]. In this context, the role of rescue therapies generally used to improve oxygenation and outcomes in conventional severe ARDS [ 37 – 39 ] has not been completely elucidated in COVID-19 [ 14 , 40 – 43 ].…”

Ten things you need to know about intensive care unit management of mechanically ventilated patients with COVID-19

“…Inhaled nitric oxide (iNO) has been proposed as rescue therapy in cases of refractory hypoxemia related to COVID-19 pneumonia [ 44 ] in view of the presence of V′/Q′ mismatch with alterations in hypoxic vasoconstriction. However, preliminary reports have shown controversial results regarding the efficacy of iNO in cases of COVID-19 pneumonia.…”

Modeling NO Biotransport in Brain Using a Space-Fractional Reaction-Diffusion Equation

“…As mentioned in the section "Introduction" (see also Figure 1), a higher amount of Ang II is linked to the infection with the SARS-CoV-2 virus. The relationship among the SARS-CoV-2 virus infection, endotheliopathy, and NO was investigated in Akaberi et al (2020), Bagate et al (2020) and Goshua et al (2020). For instance, the blood test results of patients with COVID-19 that are presented in Goshua et al (2020) provide a biochemical proof of endotheliopathy presence.…”