Is there a threshold that triggers cortical arousals in obstructive sleep apnea

Abstract

Study objectives: To determine whether there is a consistent epiglottic pressure value that predicts respiratory arousal from sleep.

Methods: Thirty-one patients with obstructive sleep apnea underwent overnight polysomnography while instrumented with an epiglottic catheter to measure airway pressures. Nadir epiglottic pressures during respiration events (obstructive apneas/hypopneas) terminated with or without arousals were compared. The events were selected by two methods, (1) 20 events with/without arousals were randomly selected, and (2) Events were sampled in pairs (one terminated with arousal and one without arousal) to minimize the effect of sleep duration/stage on the measurement.

Results: A total of 1,317 respiratory events were analyzed. There was substantial variability in nadir epiglottic pressure within an individual and among different individuals. The average pressure of 20 randomly selected events with arousals was (-21.2 ± 11.2, ranged -6.68 to -63.34 cm H2O). The nadir epiglottic pressure during respiratory events in NREM stage 2 sleep terminated with arousals was more negative compared with those terminated without arousals using both sampling methods (-23.5 vs. -18.5 cm H2O, p = 0.007 and -20.3 vs. -16.3 cm H2O, p < 0.001).

Conclusions: There were very different levels of epiglottic pressures that preceded arousals within and among individuals. However, cortical arousals are associated with a level of more negative epiglottic pressure compared to events terminated without arousal, findings which support the concept of a respiratory arousal threshold.

Clinical trial registration: The study used existing data to study methodology (from clinical trial "The Impact of Arousal Threshold in Obstructive Sleep Apnea" https://ichgcp.net/clinical-trials-registry/NCT02264353) and it is not a clinical trial.

Keywords: arousal; epiglottic pressure; obstructive sleep apnea; respiratory arousal threshold.

© Sleep Research Society 2019. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Figures

Figure 1.

An example of determining the arousal threshold during polysomnogram (PSG). C3–A2, C4–A1: electroencephalograms; CHIN, chin electromyogram; Pnasal, nasal pressure; SaO2, arterial blood oxygen saturation; Therm, thermistor; Pepi, epiglottic pressure trace. The respiratory arousal threshold was taken as the delta pressure swing immediately prior to arousal (PA, the solid arrow); the magnitude of the first pressure swing during the respiratory events in the epiglottic pressure trace was also taken (PT, the hollow arrow); The interval from the first pressure swing to the breath with nadir epiglottic pressure (the interval between the hollow arrow and the solid arrow).

Figure 2.

Medians and quartiles of individual nadir epiglottic pressures that (1) precede arousals from sleep during respiratory events (dark gray bars) and (2) were reached during events terminated without arousals (white bars). The three reported surrogates of arousal threshold (AHI, nadir SpO2 and Fraction of events that were hypopneas) of each subject are listed below. In three subjects, there were few respiratory events terminated without cortical arousals. Thus the figure fails to show their medians and quartiles. The comparison of nadir epiglottic pressures during events terminated with/without arousals are demonstrated in the Results section and in the Supplementary Figure S1. Note the substantial overlap in the ranges of the epiglottic pressures for events that terminate with and without arousal (more individual data are listed in Supplementary Table S1). Note also the differences in pressures between individuals.

Figure 3.

Mean nadir epiglottic pressures during events terminated with and without arousals in each individual in NREM stage 2 sleep (n = 19, note that four patients had more negative mean nadir epiglottic pressures during apneas and hypopneas terminated without arousals than events with arousals).

Figure 4.

Mean nadir epiglottic pressures during events terminated with and without arousals in each individuals (n = 22, subjects had less than five available pairs of events were excluded); Note that all subjects had more negative nadir epiglottic pressure during events that terminated with arousals.

Figure 5.

An example of defining the negative epiglottic pressure at which arousals would be triggered by respiratory stimuli using a Kaplan–Meier survival analysis in a subject with arousal threshold of −63.3 cm H2O (traditional way of measurement). At the negative epiglottic pressure of −54.9, −69.5, and −72.2 cm H2O, 25%, 50%, and 75% of the events would be terminated with arousals. (More data of individual traditional arousal threshold and the negative epiglottic pressure at which 25%/50%/75% of arousal would occur using survival analysis are listed in Supplementary Table S3)

Figure 6.

The Bland–Altman difference plot for the individual traditional description of arousal threshold and using survival analysis. The Bland–Altman difference plot for the individual traditional description of arousal threshold and the negative epiglottic pressure at which 25% (A), 50% (B), 75% (C) of arousal would occur using survival analysis.