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 pO2 ), 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±sd nocturnal S pO2 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 pO2 +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 pO2 ≥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.

CONCLUSIONS

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.