Combination therapy with medical gases (nitric oxide and molecular hydrogen): safety assessment

Inhaled nitric oxide (NO) and molecular hydrogen (iH₂) are actively studied nowadays. The therapeutic algorithms for their use in the various conditions are being developed, but the combined use of these medical gases (MG) has not been studied well enough.

The aim of the study was to assess the safety of iNO and iH₂ combination in healthy volunteers.

Methods. 10 healthy volunteers (4 males and 6 females), mean age 24.0 ± 1.3 years, were included in the open non-comparative prospective study. All volunteers received a single combined inhalation of NO and H₂ for 90 minutes. The NO concentration was 60 ppm and the H₂ concentration did not exceed 4% in the gas mixture. Changes in the vital signs, arterial blood gases, and hemodynamic parameters were evaluated. The hemodynamic parameters were investigated before and after inhalation using echocardiography (Vivid E9 General Electric, USA). We also assessed the microcirculation of the bulbar conjunctiva (“OKO” capillaroscope), the main functional lung parameters, and the diffusion lung capacity (GANSHORN PowerCube Body apparatus). The clinical side effects were recorded. After inhalation, the serum concentration of methemoglobin was evaluated.

Results. When comparing the results before and after MG inhalation, there was no negative impact on the vital signs, arterial blood gases (РaO₂, РaСO₂, SаO₂), the functional lung volumes (FEV₁, FVC, FEV₁ / FVC), the diffusion test parameters, main EchoCG hemodynamic data (ejection fraction, tricuspid annular plane systolic excursion (TAPSE), mean pulmonary artery pressure, left and right ventricular sizes) (p > 0,05). After inhalation, the microcirculatory parameters (the volume velocity in arterioles and venules and the arteriolar diameter) increased significantly (p < 0.05). We did not observe the increase in serum methemoglobin concentration (0.59 ± 0.11%). No clinical side effects were reported during the study.

Conclusions. Combined use of inhaled NO / H₂ is clinically safe, does not have any negative impact on hemodynamic parameters, functional lung volumes, and arterial blood gases. The improvement of the microcirculation was noted after a single inhalation. This new method can be recommended for further studies of the therapeutic effect in various conditions.

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