Amir Hadanny*, Finci Shachar, Catalogna Merav, Abu Hamed Ramzia, Korin Calanit, Levi Gabriella, Adler-Vallach Katya, Tarasula Natalya, Mahagna Hamad, Wang Zemer, Lang Erez, Zemel Yonatan, Bechor Yair, Rahimi-Levene Naomi, Shapira Yonatan, Gorelik Oleg, Tzur Irma, Ilgiyaev Eduard, Mizrachi Avi, Shiloach Eli, Maor Yasmin, Levtzion-Korach Osnat and Efrati Shai
Rationale: The hallmarks of pulmonary derangement due to severe COVID-19 disease include hypoxemia and a dysregulated and excessive immune response, i.e. a "cytokine storm". Several case series reported on the beneficial effect of Hyperbaric Oxygen Therapy (HBOT) on COVID-19 patients.
Objective: The aim of the study was to evaluate the effects of HBOT on COVID-19 patients.
Design: Randomized controlled design.
Setting: Single medical center with primary level care.
Participants: Thirty-one severe COVID-19 inpatients, suffering from respiratory insufficiency (saturation lower than 94% on room air or PaO2/FiO2<300 mmHg in addition to at least one risk factor) in addition to at least one other risk factor, were randomized between May-October 2020 to HBOT or a control arms in a 2:1 ratio. Patients underwent baseline evaluations which included symptoms questionnaire, vital signs, and blood tests.
Interventions: The HBOT arm patients underwent total of eight HBOT twice daily 1-hour sessions. The evaluation was repeated on day 5, the day after the last HBOT session.
Original primary endpoint was changed from arterial blood gas oxygenation to oxygen saturation, 5 days after enrollment. Secondary endpoints included vital signs, NEWS severity score, blood inflammatory markers, x-ray changes and outcomes.
Results: One day following the last HBOT session, there was a significant increase in room air saturation in the HBOT patients from 89.75 ± 2.67 to 93.78 ± 3.49, p<0.0014, compared to a non-significant decline in the control group from 90.44 ± 2.40 to 87.71 ± 7.86, p=0.356. HBOT group NEWS severity score improved from 5.94 ± 1.18 to 2.60 ± 2.10, p=0.001, while there was non-significant worsening in the control group 5.11 ± 1.36 to 5.71 ± 1.89, p=0.253. The respiratory rate decreased from 28.6 ± 5.5 to 20.1 ± 5.2 in the HBOT group (p<0.0001), compared to a non-significant increase in the control group from 25.1 ± 5.3 to 29.8 ± 6.7 (p=0.19). There was a significant decrease in CRP and LDH in the HBOT group compared to the control group and a significantly higher proportion developed COVID-19 IgG antibodies compared to the control group.
In the HBOT group, two patients experienced mild middle ear barotrauma and one patient suffered a myocardial infarction.
Conclusion: This study demonstrates, for the first time in a randomized clinical trial, that HBOT is a therapeutic modality that can improve oxygenation, attenuate inflammation, and improve the clinical status of severely-ill COVID-19 patients. Although underpowered, our study suggests the suggested HBOT protocol may be deployed safely with low rate of side effects. Larger scale studies are needed to evaluate the effect on inpatient mortality.
Published Date: 2022-03-10; Received Date: 2022-02-10