Effects of acetazolamide on sleep-disordered breathing in pulmonary vascular disease (RCT)

Abstract

Question addressedPatients with pulmonary vascular disease (PVD) often suffer from nocturnal hypoxemia, 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.MethodsIn a randomised controlled cross-over trial, patients with PVD were randomly assigned to acetazolamide 250 mg and placebo twice daily for five 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, time with oxygen saturation <90% (t<90), apnoea hypopnoea index (AHI), and sleep apnoea severity.ResultsIn 20 patients with PVD (55% women, 9 with pulmonary arterial hypertension, 11 with distal chronic thromboembolic pulmonary hypertension, mean nocturnal SpO2 88.8 (sd3.5)%, obstructive AHI 12.6 (12.3)), 5 weeks of acetazolamide resulted in a significant improvement in nocturnal oxygenation compared to placebo (mean nocturnal SpO2 +2.3 (95%CI 0.9 to 3.7) %, p=0.002; t<90 −18.8 (95%CI −35.7 to −1.9) %, p=0.030). Acetazolamide increased the proportion of patients with a mean nocturnal SpO2 ≥90% from 45% to 85%. The percent of patients with an AHI >5/h was reduced from 75% to 60%, and with an AHI >15/h from 30% to 15%. 2 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.