Acute upper airway responses to hypoglossal nerve stimulation during sleep in obstructive sleep apnea

Abstract

Rationale: Hypoglossal nerve stimulation (HGNS) recruits lingual muscles, reduces pharyngeal collapsibility, and treats sleep apnea.

Objectives: We hypothesized that graded increases in HGNS relieve pharyngeal obstruction progressively during sleep.

Methods: Responses were examined in 30 patients with sleep apnea who were implanted with an HGNS system. Current (milliampere) was increased stepwise during non-REM sleep. Frequency and pulse width were fixed. At each current level, stimulation was applied on alternating breaths, and responses in maximal inspiratory airflow (V(I)max) and inspiratory airflow limitation (IFL) were assessed. Pharyngeal responses to HGNS were characterized by the current levels at which V(I)max first increased and peaked (flow capture and peak flow thresholds), and by the V(I)max increase from flow capture to peak (ΔV(I)max).

Measurements and main results: HGNS produced linear increases in V(I)max from unstimulated levels at flow capture to peak flow thresholds (215 ± 21 to 509 ± 37 ml/s; mean ± SE; P < 0.001) with increasing current from 1.05 ± 0.09 to 1.46 ± 0.11 mA. V(I)max increased in all patients and IFL was abolished in 57% of patients (non-IFL subgroup). In the non-IFL compared with IFL subgroup, the flow response slope was greater (1241 ± 199 vs. 674 ± 166 ml/s/mA; P < 0.05) and the stimulation amplitude at peak flow was lower (1.23 ± 0.10 vs. 1.80 ± 0.20 mA; P < 0.05) without differences in peak flow.

Conclusions: HGNS produced marked dose-related increases in airflow without arousing patients from sleep. Increases in airflow were of sufficient magnitude to eliminate IFL in most patients and IFL and non-IFL subgroups achieved normal or near-normal levels of flow, suggesting potential HGNS efficacy across a broad range of sleep apnea severity.

Figures

Figure 1.

Representative polysomnographic recording examples of hypoglossal nerve stimulation (HGNS) response at low (1.7 mA, left panel), moderate (2 mA, middle panel), and high (2.5 mA, right panel) levels of stimulation in one patient. In each panel, two stimulated breaths are shown (stimulation marker signal at bottom and stimulus artifact in EMGSM), and are bracketed by adjacent unstimulated breaths during stable non-REM sleep. Unstimulated breaths displayed evidence of severe inspiratory airflow limitation as characterized by an early plateau in inspiratory flow at a low level and high frequency mid-inspiratory oscillations in airflow, consistent with snoring. During unstimulated breaths, maximal inspiratory airflow did not change across all stimulation levels, indicating that severe inspiratory flow limitation persisted across stimulation levels. In contrast, a graded response in maximal inspiratory airflow (downward direction) was observed with increasing levels of maximal inspiratory airflow as current was increased. Inspiratory airflow limitation persisted at low (left panel) and mid-levels (middle panel) of stimulation, but was abolished at the highest stimulation level applied (right panel). Note time lags of respiratory impedance signal (HGNS [Z]) and stimulus current marker signal (STIM) of approximately 400 ms and approximately 250 ms, respectively, relative to the airflow and ABD signals caused by signal processing and transmission from the implanted neurostimulation device. ABD = abdominal piezoelectric gauge; EMGSM = submental electromyogram; F4M1, C4M1, and O2M1 = electroencephalogram leads; FLOW = tidal airflow; HGNS (Z) = implanted respiratory impedance sensor; L. EOG = left electrooculogram; R. EOG = right electrooculogram; STIM = stimulation current marker signal.

Figure 2.

Inspiratory airflow (VImax) response to increasing hypoglossal nerve stimulation current amplitude during non-REM sleep for stimulated and unstimulated breaths in the patient illustrated in Figure 1. As stimulation current increased beyond the flow capture threshold, VImax increased linearly until the peak flow threshold was attained, at which point VImax plateaued as increasing stimulus current was applied. Note that inspiratory flow limitation persisted at intermediate current levels (closed circles). Further increases in current abolished inspiratory flow limitation (open circles).

Figure 3.

Baseline (unstimulated) and peak (stimulated) maximal inspiratory airflow (VImax) during non-REM sleep. Maximal inspiratory airflow (VImax) with stimulation OFF (mean baseline unstimulated breaths) and ON (at peak flow threshold) is represented for each patient and for the group as a whole (means ± SEM). A significant increase in VImax was observed for the group as a whole (P < 0.001). At the peak flow threshold, flow limitation was eliminated in 17 of 30 patients (open circles, stimulation ON), and persisted in the remaining 13 patients (solid circles, stimulation ON).

Figure 4.

Maximal inspiratory airflow (VImax) versus stimulation current (milliamperes) in groups with (solid circles) and without (open circles) inspiratory flow limitation at the peak flow threshold. The flow response slope in the non–flow-limited group was greater than that in the flow-limited subgroup (1241 ± 199 vs. 674 ± 167 ml/s/mA; n = 25; P < 0.05). Lower levels of stimulation current were required to achieve peak airflow in the non–flow-limited compared with flow-limited subgroup (1.23 ± 0.10 vs. 1.80 ± 0.20 mA; n = 25; P < 0.05), although peak inspiratory airflow did not differ between non–flow-limited and flow-limited subgroups (564 ± 58 vs. 438 ± 35 ml/s). Both groups attained normal or near normal levels during sleep of approximately 400 ml/s or greater (shaded region).