Effect of oxygen in obstructive sleep apnea: role of loop gain

Abstract

We compared the effect of oxygen on the apnea-hypopnea index (AHI) in six obstructive sleep apnea patients with a relatively high loop gain (LG) and six with a low LG. LG is a measure of ventilatory control stability. In the high LG group (unstable ventilatory control system), oxygen reduced the LG from 0.69+/-0.18 to 0.34+/-0.04 (p<0.001) and lowered the AHI by 53+/-33% (p=0.04 compared to the percent reduction in the low LG group). In the low LG group (stable ventilatory control system), oxygen had no effect on LG (0.24+/-0.04 on room air, 0.29+/-0.07 on oxygen, p=0.73) and very little effect on AHI (8+/-27% reduction with oxygen). These data suggest that ventilatory instability is an important mechanism causing obstructive sleep apnea in some patients (those with a relatively high LG), since lowering LG with oxygen in these patients significantly reduces AHI.

Figure 1

LG is the ventilatory response to disturbance ratio. A. Example of a LG of 0.72. The ventilatory control system is disturbed with a transient reduction in ventilation (a). This produces a response (b) in the opposite direction that is 72 % as large as the disturbance. The next response (c) will also be 72 % as large as (b), etc. Thus, a LG of 0.72 produces transient fluctuations in ventilation, but ventilation eventually returns to baseline. B. A LG of 1 will produce a response that is equal in magnitude to the disturbance. Ventilation, therefore, oscillates without returning to baseline. The system in B is highly unstable. The closer LG is to zero, the smaller the fluctuations in ventilation, and thus the more stable the system.

Figure 2

Percent reduction in AHI in the high and low LG groups. Oxygen reduced the AHI from 63 ± 34 episodes/hr to 34 ± 30 episodes/hr in the high LG group (53 ± 33 % reduction) and from 44 ± 34 episodes/hr to 37 ± 28 episodes/hr in the low LG group (8 ± 27 % reduction).–, Mean value for each group.

Figure 3

Effect of oxygen on the length and type (central or mixed) of respiratory events. Diagrams on the left are the high LG group, and diagrams on the right are the low LG group. A. Supplemental oxygen prolonged apneas and hypopneas more in the high LG group than the low LG group. B. There was a non-significant decrease in the percentage of central and mixed events. –, Mean value for each group.

Figure 4

Effect of oxygen on LG. Oxygen significantly reduced the LG in subjects with a high LG but had little effect in the low LG group.–, Mean value for each group.

Figure 5

Stabilization of the ventilatory pattern with oxygen. Three-minute tracings of tidal volume (VT, liters) and oxygen saturation ( ${\mathrm{Sa}}_{{\mathrm{o}}_2}$) are shown for four high LG subjects who had LG measurements on and off oxygen. Figures on the left are room air breathing at the PAV level associated with periodic breathing. Figures on the right are oxygen breathing at the same, or slightly higher, PAV level as the corresponding figure on the left, i.e., the subject’s LG is amplified to the same extent in both tracings. Subject A and D breathed more regularly when oxygen was administered. The respiratory rate was substantially slower in subject A (right figure). Subject B and C continued to exhibit variability during oxygen breathing, but the variations were non-periodic.

Figure 6

Simulated obstructive hypopnea in a “high” LG OSA patient breathing room air (A) and supplemental oxygen (B and C). In all three tracings, the hypopnea was simulated by reducing ventilation (solid line) to 2 L/min for several seconds. Ventilatory drive (dotted line) is plotted on the same axes as ventilation. During the obstructive event, ventilatory drive increases until, after 20–30 seconds, the airway opens and ventilation increases to match the ventilatory demand, i.e., the solid line “catches up” with the dotted line. The arrowhead in each diagram marks the nadir ventilatory drive at which the airway is most susceptible to collapse. A. The LG is 0.57 and there is a 23 second obstructive hypopnea. These are similar to the values we observed in the high LG group. Note that, following the hypopnea, there is a large overshoot that leads to an undershoot to 0.67 L/min (arrowhead). Such a reduction in ventilatory drive to the upper airway muscles would likely cause obstruction in a susceptible person. B. The situation is different when LG has been lowered to 0.17 by supplemental oxygen. Here, the hypopnea lasts 29 seconds (similar to the increase in hypopnea length that we observed). Despite the longer event, there is only a small overshoot and virtually no undershoot. Thus, the airway would likely remain stable at this LG level. C. Even if the LG could only be lowered to 0.29 with oxygen, a prolonged (29 second) hypopnea would produce an undershoot in ventilatory drive of 2.9 L/min (arrowhead), which is still significantly greater than the nadir of 0.67 L/min above.