Elevating blood pressure in neurogenic orthostatic hypotension: Investigating the efficacy and tolerability of rebreathing therapy

PURPOSE: ) alone. METHODS: In this exploratory sub-study, ten patients with nOH (F = 3; 69 ± 9 years) performed two sit-to-stand tests while breathing either room air or simulated rebreathing. Continuous blood pressure, heart rate, respiration, stroke volume, cardiac output, and systemic vascular resistance were recorded. Hemodynamics were averaged over the final minute of stand for each condition. Tolerability was defined as completing the full 5-minute stand without aborting due to breathing discomfort. RESULTS: Compared to room air, simulated rebreathing increased standing systolic blood pressure (p = 0.02), stroke volume (p = 0.03), cardiac output (p = 0.02), and reduced hypotensive time (p = 0.02). Hemodynamic responses and hypotensive time during simulated rebreathing did not differ from +CO₂ alone (all p > 0.1). Tolerability was lower with only 2/10 patients completing the simulated rebreathing protocol, primarily due to shortness of breath, whereas 9/10 completed +CO₂ alone (p = 0.014). CONCLUSIONS: Simulated rebreathing improves standing blood pressure in nOH but is poorly tolerated. High CO₂ alone appears equally effective and better tolerated. CO₂ delivery systems that elevate CO₂ while maintaining oxygen may offer a more feasible therapeutic strategy. CLINICAL TRIAL NO: NCT05295810 https://clinicaltrials.gov/study/NCT05295810.