Oxygen-Helium Gas Mixture «Heliox» for the Treatment of Respiratory Failure in Patients with New Coronavirus Infection Covid-19 (Randomized Single-Center Controlled Trial)

Introduction. Treatment of respiratory failure in pneumonia caused by coronavirus infection (COVID-19) is still an unsolved problem that requires a comprehensive approach and the development of new methods that expand the range of possibilities of modern therapy. There is evidence that the heated oxygenhelium mixture has a positive effect on gas exchange in the infiltration zone by improving both ventilation and diffusion.
AIM of study. To evaluate the effectiveness of the inclusion of a heated oxygen-helium mixture HELIOX (70% Helium/ 30% Oxygen) in the complex intensive care of respiratory failure of pneumonia caused by SARS-CoV-2 infection.
Material and methods. The study included 60 patients with confirmed viral pneumonia caused by COVID-19. The patients were randomized into two groups: group 1 (n=30) — patients who were treated with the standard COVID-19 treatment protocol with the heated oxygen-helium mixture HELIOX, and group 2 (control) (n=30) — patients who received standard therapy. Lethality was studied for 28 days, the time in days until a steady increase in SpO2>96% was achieved when breathing atmospheric air; the time until the patient is transferred from the intensive care unit (ICU) to the general department.
Results. Inhalation of the HELIOX mixture (70% Helium / 30% Oxygen) resulted in a faster recovery of the hemoglobin oxygen saturation index (SpO2). Starting from day 3, these differences became statistically significant. The time in days from inclusion in the study to a persistent increase in the degree of oxygen saturation of hemoglobin (SpO2>96%) when breathing atmospheric air in the group with inhalation of the HELIOX mixture was less — 8 (7; 10), compared to 10 (8;13) in the control group (p=0.006). In the group with inhaled HELIOX mixture, the median treatment time in the ICU was 8 (7; 9.5) days vs 13 (8; 17) days (p<0.001) in the comparison group.
Conclusions. Inhalation of the HELIOX mixture (70% Helium / 30% Oxygen) led to a faster recovery of the hemoglobin oxygen saturation index SpO2, which contributed to reduction in the duration of oxygen therapy and a decrease in mortality.

1. Grippo F, Grande E, Maraschini A, Navarra S, Pappagallo M, Marchetti S, et al. Evolution of Pathology Patterns in Persons Who Died From COVID-19 in Italy: A National Study Based on Death Certificates. Front Med. 2021;8:645543. PMID: 33829025 https://doi.org/10.3389/fmed.2021.645543

2. Qin W, Bai W, Liu K, Liu Y, Meng X, Zhang K, et al. Clinical Course and Risk Factors of Disease Deterioration in Critically Ill Patients with COVID-19. Hum Gene Ther. 2021;32(5–6):310-315. PMID: 33412996 https://doi.org/10.1089/hum.2020.255

3. Tsikala Vafea M, Zhang R, Kalligeros M, Mylona EK, Shehadeh F, Mylonakis E. Mortality in mechanically ventilated patients with COVID-19: a systematic review. Expert Rev Med Devices. 2021;18(5):457–471. PMID: 33836621 https://doi.org/10.1080/17434440.2021.1915764

4. Zaytsev AA, Chernov SA, Kryukov EV, Golukhova EZ, Rybka MM. Practical experience of managing patients with new coronavirus infection COVID-19 in hospital (preliminary results and guidelines). Lechaschi Vrach J. 2020;(6):74–79. https://doi.org/10.26295/OS.2020.41.94.014 (In Russ.).

5. Koronavirus v Rossii. Statistika zarazheniy koronavirusom v Rossii na segodnya. (in Russ.). Available at: https://coronavirus-monitor.info/country/russia/ [Accessed June 01, 2021]

6. Weekly Epidemiological Update on COVID-19 – 1 June 2021. Edition 42. URL: https://www.who.int/publications/m/item/weeklyepidemiological-update-on-covid-19---1-june-2021

7. Ahmad FB, Cisewski JA, Miniño A, Anderson RN. Provisional Mortality Data – United States, 2020. MMWR Morb Mortal Wkly Rep. 2021;70(14):519–522. PMID: 33830988 https://doi.org/10.15585/mmwr.mm7014e1

8. Challen R, Brooks-Pollock E, Read JM, Dyson L, Tsaneva-Atanasova K, Danon L. Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study. BMJ. 2021;372: n579. PMID: 33687922 https://doi.org/10.1136/bmj.n579

9. Faust JS, Krumholz HM, Du C, Mayes KD, Lin Z, Gilman C, et al. AllCause Excess Mortality and COVID-19-Related Mortality Among US Adults Aged 25–44 Years, March-July 2020. JAMA. 2021;325(8):785–787. PMID: 33325994 https://doi.org/10.1001/jama.2020.24243

10. Zaytsev AA, Chernov SA, Kryukov EV, Golukhova EZ, Rybka MM., et al. Practical experience of managing patients with new coronavirus infection COVID-19 in hospital (preliminary results and guidelines). Lechaschi Vrach Journal. 2020;(6):74–79. (In Russ.). https://doi.org/doi.org/10.26295/OS.2020.41.94.014

11. Liet JM, Ducruet T, Gupta V, Cambonie G. Heliox inhalation therapy for bronchiolitis in infants. Cochrane Database Syst Rev. 2015;(9):CD006915. PMID: 26384333 https://doi.org/10.1002/14651858.cd006915.pub3

12. Beurskens CJ, Aslami H, de Beer FM, Vroom MB, Preckel B, Horn J, et al. Heliox allows for lower minute volume ventilation in an animal model of ventilator-induced lung injury. PLoS One. 2013;8(10):e78159. PMID: 24205139 https://doi.org/10.1371/journal.pone.0078159

13. Beurskens CJ, Brevoord D, Lagrand WK, van den Bergh WM, Vroom MB, Preckel B, et al. Heliox Improves Carbon Dioxide Removal during Lung Protective Mechanical Ventilation.Crit Care Res Pract. 2014;2014:954814. PMID: 25548660 https://doi.org/10.1155/2014/954814

14. Krasnovsky AL, Grigoriyev SP, Loshkareva EO, Zolkina IV. The application of geliox in treatment of patients with broncho-pulmonary pathology. Medical Journal of the Russian Federation. 2012;18(5):46–51. (in Russ.)

15. Weber NC, Preckel B. Gaseous mediators: an updated review on the effects of helium beyond blowing up balloons. Intensive Care Med Exp. 2019;7(1):73. PMID: 31858285 https://doi.org/10.1186/s40635-019-0288-4

16. Beurskens CJ, Wösten-van Asperen RM, Preckel B, Juffermans NP. The potential of heliox as a therapy for acute respiratory distress syndrome in adults and children: a descriptive review. Respiration. 2015;89(2):166–174. PMID: 25662070 https://doi.org/10.1159/000369472

17. Krasnovsky AL, Grogoriev SP, Alekhin AI, Potapov VN. Application of Heated Oxygen-Helium Mixture for Combined Treatment of Community-Acquired Pneumonia. Clinical Medicine (Russian Journal). 2013;91(5):38–41. (In Russ.).

18. Hopster K, Duffee LR, Hopster-Iversen CCS, Driessen B. Efficacy of an alveolar recruitment maneuver for improving gas exchange and pulmonary mechanics in anesthetized horses ventilated with oxygen or a helium-oxygen mixture. Am J Vet Res. 2018;79(10):1021–1027. PMID: 30256141 https://doi.org/10.2460/ajvr.79.10.1021

19. Nawab US, Touch SM, Irwin-Sherman T, Blackson TJ, Greenspan JS, Zhu G, et al. Heliox attenuates lung inflammation and structural alterations in acute lung injury. Pediatr Pulmonol. 2005;40(6):524–532. PMID: 16193495 https://doi.org/10.1002/ppul.20304

20. Morgan SE, Vukin K, Mosakowski S, Solano P, Stanton L, Lester L, et al. Use of heliox delivered via high-flow nasal cannula to treat an infant with coronavirus-related respiratory infection and severe acute airflow obstruction. Respir Care. 2014;59(11):e166–e170. PMID: 25118308 https://doi.org/10.4187/respcare.02728

21. Kneyber MC, van Heerde M, Twisk JW, Plötz FB, Markhors DG. Heliox reduces respiratory system resistance in respiratory syncytial virus induced respiratory failure. Crit Care. 2009;13(3):R71. PMID: 19450268 https://doi.org/10.1186/cc7880

22. Seliem W, Sultan AM. Heliox delivered by high flow nasal cannula improves oxygenation in infants with respiratory syncytial virus acute bronchiolitis. J Pediatr (Rio J). 2018;94(1):56–61. PMID: 28506664 https://doi.org/10.1016/j.jped.2017.04.004