Acute Upper Airway Responses to Hypoglossal Nerve Stimulation during Sleep in Obstructive Sleep Apnea

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 VImax first increased and peaked (flow capture and peak flow thresholds), and by the V(I)max increase from flow capture to peak (Delta V(I)max). Measurements and Main Results: HGNS produced linear increases in VImax 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 +/- 0.11mA. 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.