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

Division of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Respiratory Physiology & Neurobiology (Impact Factor: 1.97). 06/2008; 162(2):144-51. DOI: 10.1016/j.resp.2008.05.019
Source: PubMed


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.

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Available from: Atul Malhotra, Mar 02, 2015
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    • "LG is a frequency dependent variable and therefore increases as a function of the circulatory delay and other time dependent variables. A non-invasive method for measuring LG could allow diagnose the contribution of LG to disordered breathing and then potentially treat the condition by using for example, oxygen or acetazolamide (Edwards et al., 2012; Wellman et al., 2008) to lower LG. However, such clinical utility of LG has been limited thus far by the fact that measurements Fig. 1. "
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    ABSTRACT: Non-invasive assessment of ventilatory control stability or loop gain (which is a key contributor in a number of sleep-related breathing disorders) has proven to be cumbersome. We present a novel multivariate autoregressive model that we hypothesize will enable us to make time-varying measurements of loop gain using nothing more than spontaneous fluctuations in ventilation and CO2. The model is adaptive to changes in the feedback control loop and therefore can account for system non-stationarities (e.g. changes in sleep state) and it is resistant to artifacts by using a signal quality measure. We tested this method by assessing its ability to detect a known increase in loop gain induced by proportional assist ventilation (PAV). Subjects were studied during sleep while breathing on continuous positive airway pressure (CPAP) alone (to stabilize the airway) or on CPAP + PAV. We show that the method tracked the PAV-induced increase in loop gain, demonstrating its time-varying capabilities, and it remained accurate in the face of measurement related artifacts. The model was able to detect a statistically significant increase in loop gain from 0.14 ± 10 on CPAP alone to 0.21 ± 0.13 on CPAP + PAV (p < 0.05). Furthermore, our method correctly detected that the PAV-induced increase in loop gain was predominantly driven by an increase in controller gain. Taken together, these data provide compelling evidence for the validity of this technique.
    Respiratory Physiology & Neurobiology 09/2014; 201. DOI:10.1016/j.resp.2014.07.002 · 1.97 Impact Factor
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    • "However, studies that have manipulated loop gain in CPAP-treated OSA patients have consistently shown that lowering the 'intrinsic' loop gain is associated with an improvement in OSA severity, highlighting the importance of loop gain as a cause of OSA. For instance, administration of oxygen, which is known to lower loop gain via reductions in controller gain, led to marked improvement in OSA among those patients with elevated loop gain at baseline (Wellman et al. 2008; Chowdhuri et al. 2010). No such improvement was observed in patients with low loop gain, highlighting that the intrinsic elevation in loop gain (at baseline) was pathophysiologically important in some OSA patients. "
    The Journal of Physiology 07/2014; 592(14). DOI:10.1113/jphysiol.2014.271841 · 5.04 Impact Factor
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    • "Our finding that the reduction in LG was primarily driven by the reduction in plant gain confirms this notion. Supplemental oxygen has been shown to selectively reduce LG (measured using proportional assist ventilation) and AHI by approximately 50% in OSA patients with a high LG but has no effect in those with a low LG (Wellman et al. 2008 "
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    ABSTRACT: There is some evidence to suggest that acetazolamide may improve obstructive sleep apnoea (OSA).However, how acetazolamide affects the key traits causing OSA remains uncertain. We aimed to investigate the effect of acetazolamide on the traits contributing to OSA and its severity. Acetazolamide (500 mg twice daily) was administered for 1 week to 13 OSA subjects. Pharyngeal anatomy/collapsibility, loop gain (LG), upper-airway muscle responsiveness (gain) and the arousal threshold were determined using multiple 3 min 'CPAP pressure drops': pharyngeal anatomy/collapsibility was quantified as the ventilation at CPAP=0. LG was defined as the ratio of the ventilatory overshoot to the preceding reduction in ventilation. Upper-airway gain was taken as the ratio of the increase in ventilation to the increase in ventilatory drive across the drop. Arousal threshold was quantified as the level of ventilatory drive associated with arousal. The apnoea-hypopnoea index (AHI)was assessed on separate nights using standard polysomnography. Acetazolamide reduced the median [interquartile range] LG (3.4 [2.4-5.4] versus 2.0 [1.4-3.5]; P <0.05) and NREM AHI (50 [36-57] versus 24 [13-42] events h-1; P <0.05), but did not significantly alter pharyngeal anatomy/collapsibility, upper-airway gain, or arousal threshold. There was a modest correlation between the percentage reduction in LG and the percentage reduction in AHI (r =0.660, P =0.05). Our findings suggest that acetazolamide can improve OSA, probably due to reductions in the sensitivity of the ventilatory control system. Identification of patients who may benefit from reductions in LG alone or in combination with other therapies to alter the remaining traits may facilitate pharmacological resolution of OSA in the future.
    The Journal of Physiology 01/2012; 590(Pt 5):1199-211. DOI:10.1113/jphysiol.2011.223925 · 5.04 Impact Factor
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