Effects of acetazolamide on sleep disordered breathing in pulmonary vascular disease: a randomised controlled trial

Background: Patients with pulmonary vascular disease (PVD) often suffer from nocturnal hypoxaemia, but also from sleep apnoea. Short-term use of acetazolamide increases ventilation due to metabolic acidosis and also reduces loop gain. We investigated whether prolonged use of acetazolamide improves sleep disordered breathing in PVD. Methods: In a randomised controlled crossover trial, patients with PVD were randomly assigned to acetazolamide 250 mg and placebo twice daily for 5 weeks. Patients underwent respiratory polygraphy at baseline and at the end of each intervention phase. Outcomes of interest were the effect of acetazolamide on mean nocturnal oxygen saturation (S$_{pO_{2}}$), time with oxygen saturation <90% (t$_{<90}$), apnoea–hypopnoea index (AHI) and sleep apnoea severity. Results: In 20 patients with PVD (55% women, nine with pulmonary arterial hypertension, 11 with distal chronic thromboembolic pulmonary hypertension; mean±sdnocturnal S$_{pO_{2}}$ 88.8±3.5%, obstructive AHI 12.6±12.3 events·h$^{−1}$), 5 weeks of acetazolamide resulted in a significant improvement in nocturnal oxygenation compared to placebo (mean nocturnal S$_{pO_{2}}$ +2.3% (95% CI 1.3–3.3%); p<0.001 and t $_{<90}$−18.8% (95% CI −29.6– −8.0%); p=0.001). Acetazolamide increased the proportion of patients with mean nocturnal S $_{pO_{2}}$ ≥90% from 45% to 85%. The percentage of patients with AHI >5 events·h$^{−1}$ was reduced from 75% to 60% and with AHI >15 events·h$^{−1}$ from 30% to 15%. Two patients discontinued the study because of mild side-effects.ConclusionsAcetazolamide given for 5 weeks reduces nocturnal hypoxaemia in PVD to a clinically relevant level and reduces the proportion of patients with obstructive sleep apnoea.