Oxygen Has Potential Benefits as a Therapy for Pulmonary Arterial Hypertension

Treatment guidelines only recommend oxygen (O₂) therapy for patients with pulmonary arterial hypertension (PAH) if they develop hypoxemia, but a new review of evidence suggests the O₂ has potential therapeutic benefit for all patients.

There are 4 classes of drugs used to treat PAH and they all target mechanisms involved with vasodilation of pulmonary arterial vessels, plus some patients are given calcium channel blockers. Trials of these therapies have limited information on functional improvements and 20% of patients still experience PAH worsening or related hospitalization, according to researchers.

Only a minority of patients with PAH who develop severe hypoxemia are recommended to receive O₂ therapy based on 1 randomized controlled trial. “However, there are several lines of scientific and clinical evidence which raise questions about these guidelines and challenge the widespread clinical view related to them,” the authors wrote.

In a review published in European Journal of Preventive Cardiology, the investigators identified 9 studies of patients with PAH that examined the effect of acute O₂ exposure on pulmonary vascular responses.

In the 9 studies, there were 11 cohorts of patients, and in 10 of these, acute O₂ administration reduced mean pulmonary arterial pressure by 5% to 15%. O₂ administration had little effect on left atrial pressures or pulmonary capillary wedge pressures for the 6 cohorts that reported those measures. Among the 6 cohorts that reported systemic arterial pressures, O₂ had no significant effect on 5 cohorts and increased pressures slightly in 1 cohort.

“Overall, these data recorded for a broad spectrum of PAH patients show that O₂ consistently reduces blood pressure in pulmonary arteries with minimal pressure effects elsewhere in the pulmonary and systemic circulations,” the authors wrote.

Nine cohorts evaluated O₂ administration on cardiac output and pulmonary pressure gradient. For all cohorts, pulmonary pressure gradient decreased in response to O₂ administration. In 2 cohorts, the reductions were greater than O₂-induced reductions in cardiac output, and in 6 cohorts, pulmonary pressure gradient was reduced when cardiac output increased.

Only 1 study looked at the effect of O₂ administration on exercise, and it found this therapy increased patients’ peak power outputs by 17%, on average. In addition, O₂ administration increased endurance by 117%, on average.

“These results suggest that O₂ is a powerful physiological agent when performing exercise, although the underlying mechanisms are not clear…” the authors explained.

They also highlighted 5 studies—2 case reports, a nonrandomized clinical trial, and 2 randomized clinical trials—performed analyzing O₂ therapy in patients with PAH. In all studies, the therapy was administered at home and at night. The 4 studies that were performed close to sea level showed substantial benefit for all major outcomes, including survival rates after 2 to 5 years, pulmonary hemodynamics, echocardiographic measurements, and 6-minute walk distance. However, the 1 study performed at approximately 2240 meters above sea level showed no benefit.

“Overall, these studies provide evidence of therapeutic benefit of O₂ but do not provide clear insight into underlying mechanisms,” the authors wrote.

Although the review challenged assertions about the clinical effectiveness of O₂ therapy, the authors noted that there are pragmatic and technical challenges with this therapy. The costs associated with purchasing, maintaining, and running the necessary equipment can be too much for patients. The use of a mask or nasal cannula can cause issues, particularly in children and when there are upper respiratory tract infections. Finally, this therapy requires “commitment and scheduling.” If patients are not receiving nocturnal therapy, they will need to carry equipment out of the home during the day, which can be onerous.

Overall, the authors wrote that the need for more research into this subject has been apparent for decades.

“This evidence shows that O₂ is probably a more potent and beneficial agent than clinical guidelines would suggest, and a greater commitment is needed to establish just how effective it is,” they concluded.

Reference

Green S, Stuart D. Oxygen and pulmonary arterial hypertension: effects, mechanisms, and therapeutic benefits. Eur J Prev Cardiol. Published online August 18, 2020. doi:10.1093/eurjpc/zwaa001