Mechanisms of breathing instability in patients with obstructive sleep apnea

Abstract

The response to chemical stimuli (chemical responsiveness) and the increases in respiratory drive required for arousal (arousal threshold) and for opening the airway without arousal (effective recruitment threshold) are important determinants of ventilatory instability and, hence, severity of obstructive apnea. We measured these variables in 21 obstructive apnea patients (apnea-hypopnea index 91 ± 24 h−1) while on continuous-positive-airway pressure. During sleep, pressure was intermittently reduced (dial down) to induce severe hypopneas. Dial downs were done on room air and following ≈30 s of breathing hypercapneic and/or hypoxic mixtures, which induced a range of ventilatory stimulation before dial down. Ventilation just before dial down and flow during dial down were measured. Chemical responsiveness, estimated as the percent increase in ventilation during the 5th breath following administration of 6% CO2 combined with ≈4% desaturation, was large (187 ± 117%). Arousal threshold, estimated as the percent increase in ventilation associated with a 50% probability of arousal, ranged from 40% to >268% and was <120% in 12/21 patients, indicating that in many patients arousal occurs with modest changes in chemical drive. Effective recruitment threshold, estimated as percent increase in pre-dial-down ventilation associated with a significant increase in dial-down flow, ranged from zero to >174% and was <110% in 12/21 patients, indicating that in many patients reflex dilatation occurs with modest increases in drive. The two thresholds were not correlated. In most OSA patients, airway patency may be maintained with only modest increases in chemical drive, but instability results because of a low arousal threshold and a brisk increase in drive following brief reduction in alveolar ventilation.