Effect of hypoxia-induced periodic breathing on upper airway obstruction during sleep

We studied the effect of hypoxia-induced unstable and periodic breathing on the incidence of obstructed breaths in nine subjects who varied widely in their increase in total pulmonary resistance (RL) during non-rapid-eye-movement (NREM) sleep. During normoxic NREM sleep, all subjects showed hypoventilation, augmented diaphragmatic electromyogram (EMGdi), and increased RL. This response varied: two subjects doubled their mean RL (range 6-9 cmH2O X l-1 X s); four moderate snorers increased RL four- to eightfold (RL = 16-48 cmH2O X l-1 X s); three heavy snorers showed high RL (31-89 cmH2O X l-1 X s) plus cyclical obstructive hypopnea as their predominant breathing pattern. In seven of nine subjects, hypoxia and coincident hypocapnia initially caused an irregular cyclical breathing pattern with obstructed breaths (RL greater than 50 cmH2O X l-1 X s). The incidence of obstructed breaths induced by unstable breathing was closely correlated with the level of RL experienced in the control condition of normoxic sleep (r = 0.91). The obstructed breaths had relatively high O2 saturation (90-96%) and markedly reduced EMGdi activity and peak flow rate (less than 0.2 l/s) compared with breaths immediately after the obstructed breaths, which showed lower O2 saturation (81-93%) and markedly augmented EMGdi and flow rates. After 3-6 cycles of obstructive hypopnea, periodic breathing occurred in most subjects. During periodic breathing in six of seven subjects, the incidence of obstructed or high-resistance breaths was decreased or eliminated since each central apneic period was followed by breath clusters characterized by very high EMGdi, very low RL, and high flow rates. The remaining subject showed a high incidence of obstructed breaths during all phases of normoxic and hypoxic sleep. These data show that hypoxia-induced instability in breathing pattern can cause obstructed breaths during sleep coincident with reduced motor output to inspiratory muscles. However, this obstruction is only manifested in subjects susceptible to upper airway atonicity and narrowing (such as snorers) and can be prevented in most cases if respiratory drive is permitted to reach sufficiently high levels (as during central apnea).     

Effects of upper airway anesthesia on pharyngeal patency during sleep

Pharyngeal patency depends, in part, on the tone and inspiratory activation of pharyngeal dilator muscles. To evaluate the influence of upper airway sensory feedback on pharyngeal muscle tone and thus pharyngeal patency, we measured pharyngeal airflow resistance and breathing pattern in 15 normal, supine subjects before and after topical lidocaine anesthesia of the pharynx and glottis. Studies were conducted during sleep and during quiet, relaxed wakefulness before sleep onset. Maximal flow-volume loops were also measured before and after anesthesia. During sleep, pharyngeal resistance at peak inspiratory flow increased by 63% after topical anesthesia (P less than 0.01). Resistance during expiration increased by 40% (P less than 0.01). Similar changes were observed during quiet wakefulness. However, upper airway anesthesia did not affect breathing pattern during sleep and did not alter awake flow-volume loops. These results indicate that pharyngeal patency during sleep is compromised when the upper airway is anesthetized and suggest that upper airway reflexes, which promote pharyngeal patency, exist in humans.     

Induction of periodic breathing during sleep causes upper airway obstruction in humans

To test the hypothesis that occlusive apneas result from sleep-induced periodic breathing in association with some degree of upper airway compromise, periodic breathing was induced during non-rapid-eye-movement (NREM) sleep by administering hypoxic gas mixtures with and without applied external inspiratory resistance (9 cmH2O X l-1 X s) in five normal male volunteers. In addition to standard polysomnography for sleep staging and respiratory pattern monitoring, esophageal pressure, tidal volume (VT), and airflow were measured via an esophageal catheter and pneumotachograph, respectively, with the latter attached to a tight-fitting face mask, allowing calculation of total pulmonary system resistance (Rp). During stage I/II NREM sleep minimal period breathing was evident in two of the subjects; however, in four subjects during hypoxia and/or relief from hypoxia, with and without added resistance, pronounced periodic breathing developed with waxing and waning of VT, sometimes with apneic phases. Resistive loading without hypoxia did not cause periodicity. At the nadir of periodic changes in VT, Rp was usually at its highest and there was a significant linear relationship between Rp and 1/VT, indicating the development of obstructive hypopneas. In one subject without added resistance and in the same subject and in another during resistive loading, upper airway obstruction at the nadir of the periodic fluctuations in VT was observed. We conclude that periodic breathing resulting in periodic diminution of upper airway muscle activity is associated with increased upper airway resistance that predisposes upper airways to collapse.     

Effect of upper airway negative pressure on inspiratory drive during sleep

To determine the effect of upper airway(UA) negative pressure and collapse during inspiration on regulation ofbreathing, we studied four unanesthetized female dogs duringwakefulness and sleep while they breathed via a fenestratedtracheostomy tube, which was sealed around the permanent trachealstoma. The snout was sealed with an airtight mask, thereby isolatingthe UA when the fenestration (Fen) was closed and exposing the UA tointrathoracic pressure changes, but not to flow changes, when Fen wasopen. During tracheal occlusion with Fen closed, inspiratory time(TI) increased duringwakefulness, non-rapid-eye-movement (NREM) sleep and rapid-eye-movement(REM) sleep (155 ± 8, 164 ± 11, and 161 ± 32%,respectively), reflecting the removal of inhibitory lung inflationreflexes. During tracheal occlusion with Fen open (vs. Fen closed):1) the UA remained patent;2)TI further increased duringwakefulness and NREM (215 ± 52 and 197 ± 28%, respectively) but nonsignificantly during REM sleep (196 ± 42%);3) mean rate of rise of diaphragmEMG (EMGdi/TI) and rate offall of tracheal pressure(Ptr/TI) were decreased,reflecting an additional inhibitory input from UA receptors; and4) bothEMGdi/TI andPtr/TI were decreasedproportionately more as inspiration proceeded, suggesting greaterreflex inhibition later in the effort. Similar inhibitory effects ofexposing the UA to negative pressure (via an open tracheal Fen) wereseen when an inspiratory resistive load was applied over severalbreaths during wakefulness and sleep. These inhibitory effectspersisted even in the face of rising chemical stimuli. This inhibitionof inspiratory motor output is alinear within an inspiration andreflects the activation of UA pressure-sensitive receptors by UAdistortion, with greater distortion possibly occurring later in theeffort.

     

The modified buccal musculomucosal flap method for cleft palate surgery

We have reported previously on a palatoplasty method, called the T-shaped musculomucosal buccal flap method, for the primary repair of a cleft palate. This method has been used on more than 90 patients, and satisfactory outcomes have resulted in terms of maxillar development, the prevention of fistulation, and verbal functions. However, 14.3 percent of these patients exhibited a velopharyngeal incompetence that showed no potential improvement through training. In the majority of these patients, the entire raw surface of the oral cavity side could not be covered with a buccal musculomucosal flap, and as a result, postoperative contraction of the soft palate occurred. Thus a new surgical method has proven effective in which both buccal musculomucosal flaps are used as an oral lining, the nasal mucosa having been extended by Z-plasty. We have performed 25 operations using this new method and have observed no postoperative contractions of the soft palate, notwithstanding two cases (8.0 percent) of postoperative fistulation.     

Three dimensional assessment of the pharyngeal airway in individuals with non-syndromic cleft lip and palate

Introduction

Children with cleft lip and palate (CLP) are known to have airway problems. Previous studies have shown that individuals with CLP have a 30% reduction in nasal airway size compared to non-cleft controls. No reports have been found on cross-sectional area and volume of the pharyngeal airway in clefts. Introduction of Cone-Beam CT (CBCT) and imaging software has facilitated generation of 3D images for assessment of the cross-sectional area and volume of the airway.

Objective

To assess the pharyngeal airway in individuals with CLP using CBCT by measuring volume and smallest cross-sectional areas and compare with 19 age- and sex-matched non-cleft controls.

Methods

Retrospective study of CBCT data of pre-adolescent individuals (N = 19, Mean age = 10.6, 7 females, 12 males, UCLP = 6, BCLP = 3) from the Center for Craniofacial Anomalies. Volumetric analysis was performed using image segmentation features in CB Works 3.0. Volume and smallest cross-sectional were studied in both groups. Seven measurements were repeated to verify reliability using Pearson correlation coefficient. Volume and cross-sectional area differences were analyzed using paired t-tests.

Results

The method was found to be reliable. Individuals with CLP did not exhibit smaller total airway volume and cross sectional area than non-CLP controls.

Conclusion

3D imaging using CBCT and CB Works is reliable for assessing airway volume. Previous studies have shown that the nasal airway is restricted in individuals with CLP. In our study, we found that the pharyngeal airway is not compromised in these individuals.     

Effect of Veau-Wardill-Kilner type of cleft palate repair on long-term midfacial growth

There is a common concern that the Veau-Wardill-Kilner type of cleft palate repair causes extensive denudation of the palate, resulting in inhibition of maxillary growth. The evidence for this belief is equivocal in the literature. The authors present some long-term results of this technique from a pure sample of nonsyndromic complete unilateral cleft lip and palate patients operated on by a single intermediate-volume cleft surgeon over a period of 25 years. Twenty-five patients, all born between 1977 and 1989, met the above inclusion criteria. Their age at the time of collection of study models and cephalograms was 9 to 17 years (average, 12 years). Midfacial growth was studied using 12-year dental models and lateral cephalograms taken before definitive orthodontic treatment. These were evaluated using the GOSLON Yardstick and digital cephalometric analysis. The final GOSLON results show that 72 percent of the patients had a good or satisfactory outcome, with a GOSLON score of 1, 2, or 3, and only 28 percent ended with a poor score of 4 or 5. The poor sensitivity of cephalometrics in discerning statistically significant differences was highlighted by the huge overlaps observed in the 95 percent confidence interval graph of mean sella-nasion-subspinale angle (S-N-A) values when comparing the results of the Eurocleft centers with those of the authors' center. The results suggest that satisfactory long-term midfacial growth can be obtained with Veau-Wardill-Kilner cleft palate repair.     

Effect of episodic hypoxia on upper airway mechanics in humans during NREM sleep.

We hypothesized that long-term facilitation (LTF) is due to decreased upper airway resistance (Rua). We studied 11 normal subjects during stable non-rapid eye movement sleep. We induced brief isocapnic hypoxia (inspired O(2) fraction = 8%) (3 min) followed by 5 min of room air. This sequence was repeated 10 times. Measurements were obtained during control, hypoxia, and at 20 min of recovery (R(20)) for ventilation, timing, and Rua. In addition, nine subjects were studied in a sham study with no hypoxic exposure. During the episodic hypoxia study, inspiratory minute ventilation (VI) increased from 7.1 +/- 1.8 l/min during the control period to 8.3 +/- 1.8 l/min at R(20) (117% of control; P < 0.05). Conversely, there was no change in diaphragmatic electromyogram (EMG(dia)) between control (16.1 +/- 6.9 arbitrary units) and R(20) (15.3 +/- 4.9 arbitrary units) (95% of control; P > 0.05). In contrast, increased VI was associated with decreased Rua from 10.7 +/- 7.5 cmH(2)O. l(-1). s during control to 8.2 +/- 4.4 cmH(2)O. l(-1). s at R(20) (77% of control; P < 0.05). No change was noted in VI, Rua, or EMG(dia) during the recovery period relative to control during the sham study. We conclude the following: 1) increased VI in the recovery period is indicative of LTF, 2) the lack of increased EMG(dia) suggests lack of LTF to the diaphragm, 3) reduced Rua suggests LTF of upper airway dilators, and 4) increased VI in the recovery period is due to "unloading" of the upper airway by LTF of upper airway dilators.     

Management and timing of cleft palate fistula repair

This study reviewed 199 cleft palate repairs resulting in 22 percent fistula formation. Of these, 49 percent were judged to be symptomatic. Of 44 fistulas, 21 required treatment, of which 14 had conventional type surgical closure with an overall success rate of 35 percent. Good surgical technique and good surgical judgment were felt to be important factors both in preventing postoperative fistula and in the success of their repair. Conventional methods of surgical repair of hard palate fistulas were seen to result in a very poor success rate. Orthodontic movement of maxillary segments was seen to contribute to late postoperative fistula formation. Therefore, orthodontic movement should be completed before undertaking surgical repair of anterior palatal fistulas. Finally, the success rate of anterior fistula repair has been dramatically improved by the addition of free periosteal grafts and cancellous bone grafts.     

Characteristics of the upper airway pressure-flow relationship during sleep

In examining the mechanical properties of the respiratory system during sleep in healthy humans, we observed that the inspiratory pressure-flow relationship of the upper airway was often flow limited and too curvilinear to be predicted by the Rohrer equation. The purposes of this study were 1) to describe a mathematical model that would better define the inspiratory pressure-flow relationship of the upper airway during sleep and 2) to identify the segment of airway responsible for the sleep-related flow limitation. We measured nasal and total supralaryngeal pressure and flow during wakefulness and stage 2 sleep in five healthy male subjects lying supine. A right rectangular hyperbolic equation, V = (alpha P)/(beta + P), where V is flow, P is pressure, alpha is an asymptote for peak flow, and beta is pressure at a flow of alpha/2, was used in its linear form, P/V = (beta/alpha) + (P/alpha). The goodness of fit of the new equation was compared with that for the linearized Rohrer equation P/V = K1 + K2V. During wakefulness the fit of the hyperbolic equation to the actual pressure-flow data was equivalent to or significantly better than that for the Rohrer equation. During sleep the fit of the hyperbolic equation was superior to that for the Rohrer equation. For the whole supralaryngeal airway during sleep, the correlation coefficient for the hyperbolic equation was 0.90 +/- 0.50, and for the Rohrer equation it was 0.49 +/- 0.25. The flow-limiting segment was located within the pharyngeal airway, not in the nose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuromechanical control of upper airway patency during sleep.

Obstructive sleep apnea is caused by pharyngeal occlusion due to alterations in upper airway mechanical properties and/or disturbances in neuromuscular control. The objective of the study was to determine the relative contribution of mechanical loads and dynamic neuromuscular responses to pharyngeal collapse during sleep. Sixteen obstructive sleep apnea patients and sixteen normal subjects were matched on age, sex, and body mass index. Pharyngeal collapsibility, defined by the critical pressure, was measured during sleep. The critical pressure was partitioned between its passive mechanical properties (passive critical pressure) and active dynamic responses to upper airway obstruction (active critical pressure). Compared with normal subjects, sleep apnea patients demonstrated elevated mechanical loads as demonstrated by higher passive critical pressures [-0.05 (SD 2.4) vs. -4.5 cmH2O (SD 3.0), P = 0.0003]. Dynamic responses were depressed in sleep apnea patients, as suggested by failure to lower their active critical pressures [-1.6 (SD 3.5) vs. -11.1 cmH2O (SD 5.3), P < 0.0001] in response to upper airway obstruction. Moreover, elevated mechanical loads placed some normal individuals at risk for sleep apnea. In this subset, dynamic responses to upper airway obstruction compensated for mechanical loads and maintained airway patency by lowering the active critical pressure. The present study suggests that increased mechanical loads and blunted neuromuscular responses are both required for the development of obstructive sleep apnea.