Altered K-complex morphology during sustained inspiratory airflow limitation is associated with next-day lapses in vigilance in obstructive sleep apnea

Study Objectives Determine if changes in K-complexes associated with sustained inspiratory airflow limitation (SIFL) during N2 sleep are associated with next-day vigilance and objective sleepiness. Methods Data from thirty subjects with moderate-to-severe obstructive sleep apnea who completed three in-lab polysomnograms: diagnostic, on therapeutic continuous positive airway pressure (CPAP), and on suboptimal CPAP (4 cmH2O below optimal titrated CPAP level) were analyzed. Four 20-min psychomotor vigilance tests (PVT) were performed after each PSG, every 2 h. Changes in the proportion of spontaneous K-complexes and spectral characteristics surrounding K-complexes were evaluated for K-complexes associated with both delta (∆SWAK), alpha (∆αK) frequencies. Results Suboptimal CPAP induced SIFL (14.7 (20.9) vs 2.9 (9.2); %total sleep time, p < 0.001) with a small increase in apnea–hypopnea index (AHI3A: 6.5 (7.7) vs 1.9 (2.3); p < 0.01) versus optimal CPAP. K-complex density (num./min of stage N2) was higher on suboptimal CPAP (0.97 ± 0.7 vs 0.65±0.5, #/min, mean ± SD, p < 0.01) above and beyond the effect of age, sex, AHI3A, and duration of SIFL. A decrease in ∆SWAK with suboptimal CPAP was associated with increased PVT lapses and explained 17% of additional variance in PVT lapses. Within-night during suboptimal CPAP K-complexes appeared to alternate between promoting sleep and as arousal surrogates. Electroencephalographic changes were not associated with objective sleepiness. Conclusions Sustained inspiratory airflow limitation is associated with altered K-complex morphology including the increased occurrence of K-complexes with bursts of alpha as arousal surrogates. These findings suggest that sustained inspiratory flow limitation may be associated with nonvisible sleep fragmentation and contribute to increased lapses in vigilance.

Mouth-opening Increases Upper-airway Collapsibility without Changing Resistance during Midazolam Sedation

Sedative doses of anesthetic agents affect upper-airway function. Oral-maxillofacial surgery is frequently performed on sedated patients whose mouths must be as open as possible if the procedures are to be accomplished successfully. We examined upper-airway pressure-flow relationships in closed mouths, mouths opened moderately, and mouths opened maximally to test the hypothesis that mouth-opening compromises upper-airway patency during midazolam sedation. From these relationships, upper-airway critical pressure (Pcrit) and upstream resistance (Rua) were derived. Maximal mouth-opening increased Pcrit to −3.6 ± 2.9 cm H2O compared with −8.7 ± 2.8 (p = 0.002) for closed mouths and −7.2 ± 4.1 (p = 0.038) for mouths opened moderately. In contrast, Rua was similar in all three conditions (18.4 ± 6.6 vs. 17.7 ± 7.6 vs. 21.5 ± 11.6 cm H2O/L/sec). Moreover, maximum mouth-opening produced an inspiratory airflow limitation at atmosphere that was eliminated when nasal pressure was adjusted to 4.3 ± 2.7 cm H2O. We conclude that maximal mouth-opening increases upper-airway collapsibility, which contributes to upper-airway obstruction at atmosphere during midazolam sedation.

Effect of alae nasi activation on maximal nasal inspiratory airflow in humans

The upper airway is a complicated structure that is usually widely patent during inspiration. However, on inspiration during certain physiological and pathophysiological states, the nares, pharynx, and larynx may collapse. Collapse at these locations occurs when the transmural pressure (Ptm) at a flow-limiting site (FLS) falls below a critical level (Ptm′). On airway collapse, inspiratory airflow is limited to a maximal level (V˙i max) determined by (−Ptm′)/Rus, where Rus is the resistance upstream to the FLS. The airflow dynamics of the upper airway are affected by the activity of its associated muscles. In this study, we examine the modulation ofV˙i maxby muscle activity in the nasal airway under conditions of inspiratory airflow limitation. Each of six subjects performed sniffs through one patent nostril (pretreated with an alpha agonist) while flaring the nostril at varying levels of dilator muscle (alae nasi) EMG activity (EMGan). For each sniff, we located the nasal FLS with an airway catheter and determinedV˙i max, Ptm′, and Rus. Activation of the alae nasi from the lowest to the highest values of EMGan increasedV˙i maxfrom 422 ± 156 to 753 ± 291 ml/s ( P < 0.01) and decreased Ptm′ from −3.6 ± 3.0 to −6.0 ± 4.7 cmH2O ( P < 0.05). Activation of the alae nasi had no consistent effect on Rus.V˙i maxwas positively correlated with EMGan, and Ptm′ was negatively correlated with EMGan in all subjects. Our findings demonstrate that alae nasi activation increasesV˙i maxthrough the nasal airway by decreasing airway collapsibility.

Electrical stimulation of the lingual musculature in obstructive sleep apnea

The influence of lingual muscle activity on airflow dynamics in the upper airway was examined in nine patients with obstructive sleep apnea. Muscles that retract the tongue (hyoglossus and styloglossus) and protrude the tongue (genioglossus) were selectively stimulated electrically during sleep with fine wire electrodes placed intramuscularly transorally. We confirmed that stimulation with 50 Hz and 40-microseconds pulse duration did not elicit changes in electroencephalographic patterns or heart rate or alter airflow after the stimulation burst had ceased. The highest stimulus intensity that did not arouse patients from sleep was then utilized to examine the effect of lingual muscle recruitment on airflow dynamics during steady-state periods of inspiratory airflow limitation. When applying a stimulus burst during single inspirations, maximal inspiratory airflow decreased by 239 +/- 177 ml/s (P < 0.05) during retractor stimulation, whereas maximal inspiratory airflow increased by 217 +/- 93 ml/s during protrusor stimulation (P < 0.001) compared with breaths immediately before and after the stimulated breath. When consecutive inspirations were stimulated repeatedly, protrusor stimulation decreased the frequency of obstructive breathing episodes in four patients breathing at 3.9 +/- 3.4 (SD) cmH2O nasal pressure. The findings suggest that stimulation of the lingual muscles can increase or decrease airflow depending on the specific muscles stimulated without arousing patients from sleep.

Tracheal and neck position influence upper airway airflow dynamics by altering airway length

Upper airway obstruction during sleep is characterized by inspiratory airflow limitation and reductions in maximal inspiratory airflow (VImax). To determine how mechanical factors modulate VImax, we analyzed pressure-flow relationships obtained in the isolated upper airway of paralyzed cats. VImax and its determinants, the pharyngeal critical pressure (Pcrit) and the nasal resistance (Rn) upstream to the flow-limiting site (FLS), were measured as caudal tracheal displacement, neck position, and airway length were systematically varied. As the proximal tracheal stump was displaced caudally, graded increases in VImax from 145.3 +/- 90.8 (SD) to 285.9 +/- 117.5 ml/s (P < 0.02) and decreases in Pcrit from -3.0 +/- 3.0 to -9.5 +/- 3.4 cmH2O (P < 0.002) were seen without any significant change in Rn. During neck flexion, significant decreases in VImax from 192.1 +/- 68.5 to 87.2 +/- 48.4 ml/s (P = 0.001), increases in Pcrit from -5.3 +/- 2.03 cmH2O to -1.6 +/- 1.4 cmH2O (P < 0.001), and decreases in Rn from 29.7 +/- 12.2 cmH2O.l-1.s to 16.2 +/- 8.9 cmH2O.l-1.s (P < 0.001) were noted compared with the neutral or extended neck position. Relative to the neutral airway length, upper airway length was found to decrease by 1.15 +/- 0.14 cm during neck flexion and to lengthen by 0.45 +/- 0.12 cm during neck extension. When tracheal displacement and neck position were altered, VImax and Rn correlated directly and Pcrit correlated inversely with airway length (P < 0.001). We conclude that alterations in airflow mechanics with caudal tracheal displacement and changes in neck positions are primarily due to alterations in airway length.

Effect of positive nasal pressure on upper airway pressure-flow relationships

To determine the influence of changes in nasal pressure (Pn) on airflow mechanics in the upper airway, we examined the effect of elevations in Pn on upper airway resistance and critical pressure (Pcrit) during stage I/II sleep in six patients with obstructive sleep apnea. When Pn was elevated above a Pcrit, periodic occlusions of the upper airway were eliminated and inspiratory airflow limitation was demonstrated by the finding that inspiratory airflow (VI) became maximal (VImax) and independent of fluctuations in hypopharyngeal pressure (Php) when Php fell below a specific Php (Php′). As Pn was elevated, VI vs. Php demonstrated 1) marked decreases in early and late inspiratory resistances from 75.9 +/- 34.7 and 54.6 +/- 19.0 to 8.0 +/- 1.7 and 7.6 +/- 1.6 cmH2O.l-1.s (P less than 0.05), respectively, and 2) increases in early and late inspiratory Php′ to levels that exceeded Pcrit by 3.0 +/- 0.6 and 3.1 +/- 0.7 cmH2O, respectively, at the highest level of Pn applied (P less than 0.01). This latter finding suggests that elevations in Pn result in increases in Pcrit. We suggest that elevations in Pn produce distinct alterations in upper airway resistance and collapsibility, which may influence oppositely the level of airflow through the upper airway during sleep.