Intermittent hypoxia-hyperoxia therapy in patients with chronic disorders of consciousness after severe acquired brain injury: interim study results

Introduction. Chronic disorders of consciousness (DoC) after severe brain injury are observed in patients requiring prolonged intensive care treatment and rehabilitation. Given the high medication burden, safe non-pharmacological approaches to consciousness recovery remain clinically relevant. One such approach is intermittent hypoxia–hyperoxia therapy (IHHT).
The objective was to assess the effect of IHHT on the dynamics of consciousness recovery in patients with DoC after severe acquired brain injury.
Materials and methods. Interim results of a prospective study are presented. Patients with DoC were assigned to a control group (n = 25), receiving standard therapy, and a main group (n = 24), in which treatment was supplemented with a 15-day IHHT course. The primary endpoint was an increase in the total Coma Recovery Scale–Revised (CRS-R) score by ≥3 points by day 30. Changes in the total CRS-R score and subscales, as well as transitions between diagnostic levels of consciousness, were additionally analyzed.
Results. By day 30, a ≥3-point CRS-R increase was registered in 15/24 patients in the main group (62.5%) and 6/25 patients in the control group (24.0%); p = 0.009. The total CRS-R score by day 30 was higher in the main group: 16 [8.25; 22] versus 9 [6; 14] points; p = 0.022. CRS-R subscale analysis revealed significant between-group differences in auditory and visual functions, communication, and arousal. Improvement in the diagnostic level of consciousness was more frequent in the main group: 17/24 versus 7/25 patients; p = 0.004.
Conclusion. In patients with DoC, adding IHHT to complex therapy was associated with more pronounced CRS-R improvement and a higher diagnostic level of consciousness by day 30.

1. Belkin A. A., Aleksandrova E. V., Akhutina T. V. et al. Chronic Disorders of Consciousness: guidelines of the All-Russian public organization “Federation of Anesthesiologists and Reanimatologists”. Vestnik intensivnoy terapii imeni A. I. Saltanova, 2023, vol. 3, pp. 7–42. http://doi.org/10.21320/1818-474X-2023-3-7-42.

2. Ilyina A. A., Petrova M. V., Ilyin D. V. et al. Application of hypoxia-hyperoxia therapy in clinical practice: prospects for use in neurorehabilitation: literature review. Vestnik anesteziologii i reanimatologii, 2025, vol. 22, no. 6, pp. 128–137. (In Russ.). http://doi.org/10.24884/2078-5658-2025-22-6-128-137.

3. Parfenov A. L., Razzhivin V. P., Petrova M. V. Chronic critical illness: current aspects of the problem (review). Sovremennye tekhnologii v meditsine, 2022, vol. 14, no. 3, pp. 70–81. (In Russ.). http://doi.org/10.17691/stm2022.14.3.08.

4. Chen H., Ma D., Yue F. et al. The potential role of hypoxia-inducible factor-1 in the progression and therapy of central nervous system diseases. Current Neuropharmacology, 2022, vol. 20, no. 9, pp. 1651–1666. http://doi.org/10.2174/1570159X19666210708121514.

5. Monti M. M., Spivak N. M., Edlow B. L. et al. What is a minimal clinically important difference for clinical trials in patients with disorders of consciousness? A novel probabilistic approach. PLOS ONE, 2023, vol. 18, no. 8, pp. e0290290. http://doi.org/10.1371/journal.pone.0290290.

6. NobelPrize.org. The Nobel Prize in Physiology or Medicine. 2019. URL: https://www.nobelprize.org/prizes/medicine/2019/summary (accessed: 10.07.26).

7. Nyamukondiwa M., Koneva E. S., Achkasov E. E. et al. Exploring hypoxia-induced neuroprotection mechanisms in post-stroke recovery. Translational Stroke Research, 2025. http://doi.org/10.1007/s12975-025-01364-y.

8. Pavlov Y. G., Spiegelsberger F., Kotchoubey B. Predicting outcome in disorders of consciousness: A mega-analysis. Annals of Clinical and Translational Neurology, 2024, vol. 11, no. 6, pp. 1465–1477. http://doi.org/10.1002/acn3.52061.

9. Russell M. E., Hammond F. M., Murtaugh B. Prognosis and enhancement of recovery in disorders of consciousness. NeuroRehabilitation, 2024, vol. 54, no. 1, pp. 43–59. http://doi.org/10.3233/NRE-230148

10. Uzun A.-B., Iliescu M. G., Stanciu L.-E. et al. Effectiveness of intermittent hypoxia-hyperoxia therapy in different pathologies with possible metabolic implications. Metabolites, 2023, vol. 13, no. 2, pp. 181. http://doi.org/10.3390/metabo13020181.

11. Weaver J. A., Cogan A. M., Kozlowski A. J. et al. Interpreting change in disorders of consciousness using the coma recovery scale-revised. Journal of Neurotrauma, 2024, vol. 41, no. 15–16, pp. e1996–e2008. http://doi.org/10.1089/neu.2023.0567.