Depicting and defining sleep disturbed breathing associated with vagal nerve stimulation

Abstract

Background: Vagal nerve stimulators (VNS), which have been approved for management of refractory epilepsy and depression, induce unique disturbances of breathing during sleep (SDB_VNS) that are not captured well using standard criteria. The primary purpose of this retrospective study was to compare AASM definitions with alternative criteria to more accurately measure SDB_VNS We also sought to assess outcome variables that may be clinically relevant and response to positive airway pressure therapy.

Methods: We analyzed the electronic medical records and comprehensive polysomnography results of all adult subjects with active VNS for epilepsy who were referred to the sleep center for suspected sleep apnea (2015-2020). We compared standard AASM criteria for defining apneas/hypopnea index (AHI_AASM) with three novel scoring criteria for hypopnea according to degree of oxygen desaturation associated with VNS events: AHI_VNS0 (none required); AHI_VNS2 (2% required); and AHI_VNS3 (3% required).

Results: Twenty-six subjects were included in the final analysis with 35 PSGs (14 females/12 males). The mean age was 33.6 years and mean body mass index (BMI) of 32.2 kg/m². AHI_AASM measured ≥ 15/hour in 7 (26.9%) subjects versus 21 (80.8%) by AHI_VNS0; 15 (70.0%) by AHI_VNS2; and 5 (19.2%) by AHI_VNS3. Clinically significant hypoxemia was not present. The mean time SpO₂<89% was 7 (20.8) minutes. Oximetry tracings often showed a desaturation pattern that resembled a sawfish rather than sawtooth. Arousals specifically linked to VNS activation were not elevated (2.9/hour). The baseline AHI_VNS0 was 27.7/hour with a lowest AHI_VNS0 on PAP of 27.9/hr.

Conclusions: AASM scoring criteria significantly underestimated the degree of VNS induced respiratory disturbances. VNS events were not associated with increased arousals or significant hypoxemia. PAP therapy was an ineffective treatment in this population. This study adds to the increasing body of evidence of sleep disordered breathing related to VNS and questions the clinical significance of this finding.

Keywords: Obstructive sleep apnea; Polysomnography; Sawfish; Vagal nerve stimulator.