Impact of acetazolamide and CPAP on cortical activity in obstructive sleep apnea patients

Abstract

Study objectives: 1) To investigate the impact of acetazolamide, a drug commonly prescribed for altitude sickness, on cortical oscillations in patients with obstructive sleep apnea syndrome (OSAS). 2) To examine alterations in the sleep EEG after short-term discontinuation of continuous positive airway pressure (CPAP) therapy.

Design: Data from two double-blind, placebo-controlled randomized cross-over design studies were analyzed.

Setting: Polysomnographic recordings in sleep laboratory at 490 m and at moderate altitudes in the Swiss Alps: 1630 or 1860 m and 2590 m.

Patients: Study 1: 39 OSAS patients. Study 2: 41 OSAS patients.

Interventions: Study 1: OSAS patients withdrawn from treatment with CPAP. Study 2: OSAS patients treated with autoCPAP. Treatment with acetazolamide (500-750 mg) or placebo at moderate altitudes.

Measurements and results: An evening dose of 500 mg acetazolamide reduced slow-wave activity (SWA; approximately 10%) and increased spindle activity (approximately 10%) during non-REM sleep. In addition, alpha activity during wake after lights out was increased. An evening dose of 250 mg did not affect these cortical oscillations. Discontinuation of CPAP therapy revealed a reduction in SWA (5-10%) and increase in beta activity (approximately 25%).

Conclusions: The higher evening dose of 500 mg acetazolamide showed the "spectral fingerprint" of Benzodiazepines, while 250 mg acetazolamide had no impact on cortical oscillations. However, both doses had beneficial effects on oxygen saturation and sleep quality.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Design of the two studies (Study 1 ; Study 2 [3]).

The n indicates the number of participants included in the present analyses. In both studies, patients underwent two 3-day sojourns at two moderate altitudes, once receiving acetazolamide and once receiving placebo with a 2 week washout period at baseline level (BL, 490 m). The first night at altitude (1860 m in study 1 and 1630 m in study 2) always served for acclimatization. The order of altitude exposure of the two study nights at lower (1860 m and 1630 m) and higher altitude (2590 m) and at baseline (BL, 490 m) were performed in a randomized cross-over design with regard to the order of altitude exposure. Patients in study 1 stopped CPAP treatment starting 3 nights before study periods at altitude and baseline. In total 5 study nights were analyzed in study 1 and 6 in study 2.

Figure 2. Non-REM sleep EEG power density spectra of study 1 (no CPAP treatment [16]): Moderate altitude compared to baseline.

A) Average spectra (n = 39) at moderate altitude (1860 m and 2590 m) of the acetazolamide (250 mg in the evening) and placebo condition are plotted relative to baseline sleep (490 m; line at 1). Frequency resolution: 0.2 Hz. B and C) F-values of the frequency bins with significant effect of factor Treatment and Altitude of mixed model ANOVA with factors Altitude, Treatment and Order of treatment. Bins, which showed a trend, are indicated with white bars. D) Average absolute non-REM sleep EEG power density spectra of the 5 nights.

Figure 3. Non-REM sleep EEG power density spectra of study 2 (with CPAP treatment [3]): Moderate altitude compared to baseline.

A) Average spectra (n = 41) at moderate altitude (1630 m and 2590 m) of the acetazolamide (500 mg in the evening) and placebo condition are plotted relative to baseline sleep (490 m; line at 1). Frequency resolution: 0.2 Hz. B and C) F-values of the frequency bins with significant effect of factor Treatment and Altitude of mixed model ANOVA with factors Altitude, Treatment and Order of treatment. Bins, which showed a trend, are indicated with white bars. D) Absolute non-REM sleep EEG power density spectra of the 5 nights.

Figure 4. Effect of acetazolamide on non-REM sleep EEG spectra compared to placebo at 1630 m and 2590 m (Study 2).

Non-REM sleep EEG power density spectra of the acetazolamide conditions (500 mg in the evening) at moderate altitude (1630 m and 2590 m) are plotted relative to the placebo conditions at the corresponding altitude (line at 1). Significant differences (p

Figure 5. Effect of acetazolamide on wake EEG spectra during the sleep episode.

In study 1 (A and B; ‘no CPAP treatment’; n = 30) 250 mg acetazolamide were administered in the evening and in study 2 (C and D; ‘with CPAP treatment’; n = 33) 500 mg. Acetazolamide was compared to placebo at both altitudes. “▴” Increase in spectral power acetazolamide compared to placebo. “▾” Decrease in spectral power acetazolamide compared to placebo (p<0.05 paired t-test).

Figure 6. Impact of CPAP treatment on non-REM sleep EEG spectra at 490 m and at moderate altitudes.

A) Data of study 1. Non-REM sleep EEG power density spectra of 41 OSAS patients sleeping at 490 m ‘with CPAP’ (line at 1; AHI = 6.3 [1/h]) compared to sleeping during interrupted CPAP treatment (‘no CPAP’; AHI = 58.3 [1/h]). “▴” p<0.05 paired t-test comparing CPAP to ‘no CPAP’. B) Non-REM sleep EEG power density spectra of OSAS patients during ‘no CPAP’ (study 1, 1860 m placebo condition; n = 39) compared to ‘with CPAP’ (line at 1; study 2, 1630 m placebo condition; n = 41) and C) non-REM sleep EEG power density spectra of OSAS patients during ‘no CPAP’ (study 1, 2590 m placebo condition) compared to ‘with CPAP’ (line at 1; study 2, 2590 m placebo condition). “▴” p<0.05 unpaired t-test ‘with CPAP’ compared to ‘no CPAP’.