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

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.

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 ), time with oxygen saturation <90% (t _<90), apnoea-hypopnoea index (AHI) and sleep apnoea severity.

In 20 patients with PVD (55% women, nine with pulmonary arterial hypertension, 11 with distal chronic thromboembolic pulmonary hypertension; mean±sd nocturnal S _pO 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 +2.3% (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 ≥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.

Acetazolamide given for 5 weeks reduces nocturnal hypoxaemia in PVD to a clinically relevant level and reduces the proportion of patients with obstructive sleep apnoea.