Relation between arousability and outcome of upper airway stimulation in the Stimulation for Apnea Reduction (STAR) Trial

Abstract

Study objectives: Upper airway stimulation (UAS) is an innovative surgical treatment for obstructive sleep apnea; however, the treatment failure rate is approximately 22%. Easy arousability may limit the tolerability of stimulation and, by extension, its effectiveness. The odds ratio product (ORP) is a continuous electroencephalographic metric of arousal propensity (range: 0 [deep sleep] to 2.5 [full wakefulness]), and its rate of decline after arousal (ORP-9) is a risk factor for susceptibility to arousal in the presence of frequent arousal stimuli. We hypothesized that individuals with deeper sleep (low average ORP and low ORP-9) are more likely to respond to UAS.

Methods: ORP and ORP-9 were calculated from 126 baseline polysomnograms of participants in the STAR Trial. These values were compared between responders and nonresponders. Adjusted linear modeling was performed to determine the association between ORP-derived variables and treatment response.

Results: No differences were found between responders and nonresponders in unadjusted comparisons of ORP-derived variables. On linear regression modeling, significant correlation was found between non-rapid eye movement ORP and reduction in apnea-hypopnea index (P = .004).

Conclusions: No significant difference in ORP was noted between responders and nonresponders to UAS therapy; however, contrary to our initial hypothesis, linear regression modeling trended toward a positive relationship between ORP and UAS response, suggesting that those who have lighter sleep are more likely to respond to therapy; however, these results are only exploratory, and future larger prospective studies are needed to confirm this relationship.

Clinical trial registration: Registry: ClinicalTrials.gov; Name: STAR Trial; Identifier: NCT01161420.

Keywords: ORP; OSA; UAS; arousal; hypoglossal nerve stimulation.

Conflict of interest statement

All authors have seen and approved the manuscript. This material is based on work supported by the Sleep Research Society. The STAR trial, ClinicalTrials.gov no. NCT01161420, was funded by Inspire Medical Systems. M.Y. developed, and has a patent on, the ORP Technology. The technology has been licensed to Cerebra Health in Winnipeg. He is a shareholder and receives royalties and consultation fees from Cerebra Health.

© 2021 American Academy of Sleep Medicine.

Figures

Figure 1. Comparison of total apnea-hypopnea index (AHI) change and average ORPNREM values.

Comparison of total AHI change (negative values indicating reduction of AHI) and average ORPNREM values showing a weak but significantly positive correlation between increasing ORP and greater AHI reduction (r = .40, P = .004). Participants are stratified by whether they were considered responders (closed circles) or nonresponders (open circles) based on the Sher criteria. The dotted vertical line shows participants with NREM ORP > 1.25 that had a 100% response rate. NREM = non-rapid eye movement; ORP = odds ratio product.