Randomized crossover trial demonstrates that acetazolamide reduces sleep-disordered breathing in adults taking opioids, indicating therapeutic benefit via lowering plant gain.
Key Points
To determine whether oral acetazolamide mitigates opioid-associated sleep-disordered breathing by lowering plant gain or increasing cerebrovascular responsiveness to carbon dioxide.
Randomized crossover trial in 9 adults with opioid-associated sleep-disordered breathing assigned to oral acetazolamide or placebo for 6 days.
Assessed awake cerebrovascular responsiveness to hypercapnia on day 4, followed by noninvasive mechanical ventilation in NREM sleep to determine loop gain components and overnight polysomnography.
Acetazolamide reduced the apnea-hypopnea index (25.2 ± 8.3/hour vs. 32.2 ± 8.2/hour, p=0.03; 22% reduction) and central apnea-hypopnea index (0.9 ± 0.3/hour vs. 5.0 ± 1.1/hour, p=0.006; 82% reduction) compared to placebo.
Plant gain decreased significantly with acetazolamide compared to placebo (4.0 ± 0.7 vs. 6.6 ± 0.6 mmHg/L/min, p<0.001), driven by increased eupneic minute ventilation (10.0 ± 1.4 vs. 6.8 ± 0.5 L/min, p=0.04).
Controller gain and cerebrovascular responsiveness to carbon dioxide remained unchanged between the acetazolamide and placebo arms.