Determinants of ventilatory instability in obstructive sleep apnea: inherent or acquired?

Abstract

Study objectives: Certain respiratory control characteristics determine whether patients with collapsible upper airway develop stable or unstable breathing during sleep, thereby influencing the severity of obstructive apnea (OSA). These include arousal threshold (T(A)), response to transient hypoxia and hypercapnia (Dynamic Response) and the increase in respiratory drive required for arousal-free airway opening (T(ER)). We wished to determine whether these characteristics are inherent or are acquired during untreated OSA.

Design: T(A), Dynamic Response, and T(ER) were measured in patients with severe OSA before and after treatment with continuous positive airway pressure (CPAP). Changes observed after treatment were deemed to have been acquired during untreated OSA.

Setting: University-based sleep laboratory.

Patients: 15 patients with severe OSA.

Interventions: (1) 30-sec alterations in inspired gases during sleep on CPAP. (2) Brief dial-downs of CPAP (dial-downs) both during air breathing and when ventilation was increased to different levels.

Measurements and results: T(A): the increase in ventilation associated with a 50% probability of arousal (T(A)50). Dynamic Response: the increase in ventilation on the 5th breath following breathing 3% CO2 in 11% to 15% O2. T(ER): the increase in ventilation prior to dial-downs that was associated with an arousal-free airway opening during dial-down. CPAP therapy (10.5 +/- 4.3 months) resulted in marked reduction in Dynamic Response (131% +/- 95% to 52% +/- 34% baseline ventilation, P < 0.005), a decrease in T(A)50 (134% +/- 78% to 86% +/- 47% baseline ventilation, P < 0.05), and no change in T(ER).

Conclusions: T(ER) may be an inherent characteristic. Untreated OSA results in an increase in dynamic response to asphyxia and an increase in arousal threshold.

Figures

Figure 1

Polysomnographic recordings illustrating the basic experimental procedures. A) Patient breathing air. Airway pressure (PAW) was reduced during sleep from holding pressure (14 cm H2O) to the pressure that resulted in near complete obstruction (Dial-down; upgoing arrow). B) Ventilation was increased from a baseline of 6.7 L/min to 13.7 L/min prior to dial-down by breathing a CO2-enriched mixture starting 30 sec before Dial-down. Note that flow during Dial-down was unchanged from the level obtained during air Dial-down (downgoing arrow). C) Ventilation was increased to an even higher level (17.4 L/min) before Dial-down. Note that there is substantial flow during the dial-down (downgoing arrow) indicating that at this level of chemical drive the dilator muscles could effectively maintain an open airway at the same airway pressure that resulted in near obstruction at lower levels of chemical drive. DD, dial-down; EEG, electroencephalogram.

Figure 2

Kaplan-Meier plot in a single patient showing the probability of arousal not occurring at different levels of chemical drive. At baseline ventilation (≈5 L/min) the probability of no arousal is very high. At some ventilation level (TA0) the probability of avoiding arousal is zero. Arousal threshold is expressed as the increase in ventilation above baseline at which the probability of arousal is 50% (TA50). Note the reduction in TA0 and TA50 following CPAP therapy in this patient.

Figure 3

Method of determining Effective Recruitment Threshold (TER). A) Maximum flow observed during dial-downs (Dial-down V̇MAX) is plotted against minute ventilation in the last breath before dial-down. Individual data points are obtained from observations such as those shown in Figure 1. Below a certain ventilation, Dial-down V̇MAX does not increase as ventilation is increased. Above that level, Dial-down V̇MAX is higher than the level observed at baseline respiratory drive. The ventilation above which Dial-down V̇MAX is > mean + 2 SD of the values obtained during air dial-downs is identified. The difference between this value and baseline ventilation is TER. Note that in this patient, before CPAP therapy (panel A), it was possible to test for TER over a wide ventilation range because arousal threshold was high. TA0 represents the highest ventilation that could be reached without arousal. Following CPAP therapy (panel B), arousal threshold was considerably lower making it impossible to reach the pre-CPAP TER level. Accordingly, it is possible to state that TER did not decrease substantially, but not possible to determine whether it increased following CPAP therapy.

Figure 4

Effect of CPAP therapy on the dynamic (5th breath) ventilatory response to breathing 6% CO2 or 3% CO2 in mild hypoxia.

Figure 5

Change in arousal threshold following CPAP therapy. Arousal threshold is the increase in chemical drive (expressed as % baseline) that is associated with a 50% probability of arousal (TA50).

Figure 6

Estimated effect of untreated obstructive sleep apnea (OSA) on dynamic ventilatory response to asphyxia, and on arousal threshold, in individual patients. The effect of untreated OSA was assumed to be the opposite of the change observed following CPAP treatment. Ventilatory response to asphyxia is the increase in ventilation (expressed as % of baseline ventilation) during the 5th breath following a change in inspired gas from air to 3% CO2 in 15% or 11% O2. Arousal threshold is the increase in chemical drive (expressed as % baseline) that is associated with a 50% probability of arousal (TA50). Note the wide range of responses among patients and the lack of correlation between the 2 responses.