Mandibular distraction osteogenesis in very young patients to correct airway obstruction

The purpose of this study was to measure changes in the airway cross-sectional area of pediatric patients with micrognathia and obstructive airway symptoms after treatment by mandibular distraction. The measurements obtained were correlated with the clinical outcomes.Ten patients, ranging in age from 3 months to 8 years, underwent measurement and distraction. Eight patients were under 30 months of age. Six were diagnosed with Pierre Robin sequence, two with Treacher Collins syndrome, and two with Nager syndrome. All patients had retrognathia of greater than 8 mm and obstructive airway symptoms while awake that had resulted in tracheostomy (3), repeated apnea monitor triggering (5), or abnormal sleep study (2). Cephalometric analysis was performed pretreatment and posttreatment by distraction. The effective airway space was defined with the following boundaries: a horizontal line from the tip of the odontoid to the velum, the uvula tip to the tongue base along the shortest line, the tongue base down to the base of the epiglottis, and the horizontal line to the posterior pharynx. These lines were traced for each cephalogram, the outline was digitized, and the area was calculated by computer. An analysis of the square area change was done by paired t test. The range of distraction was 8 to 22 mm; the mean effective airway increase was 67.5 percent, with a range of 26 to 120 percent. Measurable airway increase occurred in all patients who underwent distraction, and all patients showed clinical improvement. Six patients with Pierre Robin sequence became asymptomatic, with normal sleep, feeding, and weight gain. Two patients with Nager syndrome and tracheostomies were decannulated and were asymptomatic postdistraction. One patient with Treacher Collins syndrome without tracheostomy became asymptomatic after mandibular distraction; one patient failed to distract because of premature consolidation and continued to require a cannula.Mandibular distraction seems to provide a consistent change in tongue base position that improves obstructive airway symptoms by increasing measured effective airway space. The potential for mandibular distraction exceeds the simple correction of malocclusion also by eliminating soft-tissue obstruction of the micrognathic airway. Airway improvement is independent of the syndrome diagnosed. Mandibular distraction osteogenesis may be useful to avoid or decannulate existing tracheostomy in infants with micrognathia.     

Craniofacial distraction with a modular internal distraction system: evolution of design and surgical techniques.

The present report summarizes the evolution of design for a modular internal distraction system that is applicable throughout the craniofacial region. Eleven patients (5 boys, 6 girls), whose ages ranged from 4 months to 10 years at the time of distraction, constitute the basis for this study. The clinical indications for distraction were exorbitism with corneal exposure (n = 1), obstructive sleep apnea (n = 4), tracheostomy decannulation (n = 1), severe maxillary hypoplasia with class III malocclusion (n = 3), severe vertical and sagittal maxillary deficiency with anophthalmia (n = 1), and relapse following frontoorbital advancement in a case of rare craniofacial clefting (n = 1). Twenty-two distraction devices were used in these 11 patients. Two initial prototypes were tested (prototype 1 = 8 devices; prototype 2 = 2 devices) until the modular internal distraction system (MIDS, Howmedica-Leibinger, Inc.) was developed (n = 12 devices). The craniofacial osteotomies used were Le Fort III (n = 4), monobloc (n = 3), mandibular (n = 3), Le Fort I (n = 2), and cranial (n = 1). The distraction distances ranged from 11 to 28 mm. One patient undergoing mandibular distraction developed transient swelling in the left mandibular region, which responded to antibiotics. There were no other complications. Depending on the age of the patient and the length of distraction, the distraction gap was allowed to consolidate from 6 weeks to 3 months. The devices were then removed on either an outpatient or a 23-hour-stay basis. The modular internal distraction system permits widespread application of easily customizable, buried distraction devices throughout the craniofacial region.     

Distraction osteogenesis in correction of micrognathia accompanying obstructive sleep apnea syndrome

To evaluate the effect of distraction osteogenesis in correction of micrognathia accompanying obstructive sleep apnea syndrome, a total of 28 patients with different severities of obstructive sleep apnea syndrome underwent mandibular distraction osteogenesis. A total of 51 distraction devices were placed for bilateral distraction in 23 patients and for unilateral distraction in five patients. The mean age of patients was 21.2 years (range, 3 to 60 years). Eleven patients had micrognathia accompanying obstructive sleep apnea syndrome secondary to bilateral temporomandibular joint ankylosis, and 10 patients had micrognathia accompanying obstructive sleep apnea syndrome secondary to unilateral temporomandibular joint ankylosis. Three patients had developmental micrognathia accompanying obstructive sleep apnea syndrome. The other four patients had micrognathia and concomitant obstructive sleep apnea syndrome induced by trauma, infection, or tumor resection. Each patient had been evaluated preoperatively and postoperatively with cephalometry and polysomnography. Mandible advancement ranged from 9 to 30 mm (average, 20.4 mm) and was successfully achieved after distraction. Fine new bone formed in the distraction gap when the distraction devices were removed 3 to 4 months after distraction was completed. No infection or other complications occurred in any patients. Complete curative effects were achieved in nine severe, six moderate, and eight mild obstructive sleep apnea syndrome patients after distraction, and the other five patients had been improved to the mild level. After distraction was completed, the posterior airway space was increased on average from 4.6 mm to 12.5 mm and the sella-nasion-point B angle was increased on average from 66 degrees to 75 degrees on cephalometric studies. The polysomnographic examination showed that the apnea hypopnea index was lowered on average from 58.0 to 3.15, and the lowest oxygen saturation was increased on average from 77 percent to 90.3 percent after distraction was completed. The follow-up period was 3 to 61 months (average, 18.1 months). The curative effect was stable and no relapse occurred. Therefore, the authors conclude that mandibular distraction osteogenesis is an effective method for correcting micrognathia accompanying obstructive sleep apnea syndrome. Compared with other current routine surgical procedures, it has many advantages, such as low risk, simple manipulation, high curative rate, low relapse rate, and stable result. It is presently the most effective method for the treatment of this difficult and complicated disorder.     

Diagnosis of obstructive sleep apnea syndrome]

Symptoms and signs in 12 patients with severe obstructive sleep apnea (OSA) syndrome have been presented. The most common symptoms were snoring , increased motor activity during sleep and excessive daytime somnolence. The factors predisposing to OSA syndrome were obesity and anatomic abnormalities of the upper airway structure. In some cases the signs of OSA syndrome included hypertension, right heart failure, chronic alveolar hypoventilation and polycythemia. Polysomnography showed sleep fragmentation and the prevalence of light sleep stages. Obstructive sleep apneas repeated 73 +/- 23 times per hour of sleep. The mean apnea duration was 19 +/- 8 s. The mean arterial oxygen saturation during apnea was 72 +/- 14%.     

Mandibular distraction in neonates: a strategy to avoid tracheostomy

Over the past 5 years, the authors developed an application of mandibular distraction osteogenesis to eliminate existing tracheostomy. That experience led the authors to attempt mandibular distraction osteogenesis in neonates as an alternative before tracheostomy. Success with this approach using supporting objective airway measurements has been reported previously. This report includes six neonates diagnosed with Pierre Robin sequence. Of the six, five neonates ranging in age from 6 to 26 days (mean, 14.5 days) were treated by the authors with mandibular distraction over a 22-month period. The sixth neonate was treated with tracheostomy, because of other airway abnormalities. Findings included retrognathia, glossoptosis, incomplete cleft palate, and airway obstruction in each patient. Birth weights ranged from 2.8 to 3.2 kg. All patients were unable to control their airway during feeding, as evidenced by repeated episodes of choking and obstruction. Resting oxygen saturations were in the 70 to 80 percent range in all patients, with further deterioration during attempted feeding. Bronchoscopy was performed in all patients under anesthesia before distraction. Recurrent near-complete and intermittent complete airway obstruction were present in all patients at the level of the tongue base. There was a consensus by a pediatric intensivist, a pediatric anesthesiologist, and a pediatric otolaryngologist in all cases. Each patient met all criteria requiring ventilation for life support. Tracheostomy would be required if mandibular distraction osteogenesis was not performed, or if it failed. Patients with other airway abnormalities were not considered for treatment. Maxillomandibular disharmony measured at the midline ranged from 8 to 15 mm (mean, 11.2 mm). Active distraction was performed at the rate of 1 to 2 mm a day, with a consolidation period of 4 weeks. Total time of treatment was less than 6 weeks in all cases. All patients were extubated by the completion of active distraction. Distraction distance ranged from 8 to 15 mm (mean, 12.4 mm). All patients were discharged to home on apnea monitors, the use of which was discontinued after 90 days with no further apneic events. Weight gains met or exceeded the average 500 g a month after distraction. Bronchoscopy at the time of distractor removal showed correction of airway obstruction at the tongue base. Radiographs showed bilateral ossification of the distraction sites. Tracheostomy was avoided in all cases selected for treatment by distraction. Patient follow-up range was 9 to 22 months. In selected Pierre Robin sequence patients with tongue base airway obstruction, mandibular distraction osteogenesis can successfully avoid the need for and the associated mortality and morbidity of indwelling tracheostomy.     

Variable site of airway narrowing among obstructive sleep apnea patients

The purpose of this was to determine whether the site of physiological narrowing within the upper airway was uniform or differed among patients with obstructive sleep apnea. Inspiratory pressures were measured with an esophageal balloon catheter and three catheters located at different sites along the upper airway: supralaryngeal airway, oropharynx, and nasopharynx. Peak inspiratory pressure differences between catheters allowed assessment of pressure gradients across three airway segments: lungs-larynx-retroepiglottal airway (esophageal-supralaryngeal pressure), hypopharynx (supralaryngeal-oropharynx pressure), and transpalatal airway (oropharynx-nasopharynx pressure). In five patients, hypopharyngeal obstruction was present, and in four patients no hypopharyngeal obstruction existed. In these four patients the site of obstruction was located at the level of the palate. In a given subject, the site of obstruction was the same during repeated measurements. The presence or absence of hypopharyngeal narrowing during sleep was not predictable from gradients measured across different segments of the upper airway during wakefulness. We conclude that the site of physiological upper airway obstruction varies among patients with obstructive sleep apnea and is not predictable from pressure measured during wakefulness. We speculate that uvulopalatopharyngoplasty may not relieve obstructive apneas in patients with hypopharyngeal obstruction.     

Mandibular distraction osteogenesis in Pierre Robin sequence: application of a new internal single-stage resorbable device

Pierre Robin sequence may result in physiologically significant obstructive apnea in the neonatal and infant period. This may be life threatening and is most often treated by tracheostomy. To avoid tracheostomy or allow for early decannulation in severely affected infants and children, the authors have developed a new class of neonatal and infant mandibular bone distraction devices. These devices require a single operative procedure for placement and no operative removal is necessary. Fifteen infants (aged 7 days to 11 months; mean age, 3 months) and five children (aged 2 to 8 years; mean age, 5.5 years), 10 boys and 10 girls, with severe obstructive apnea and Pierre Robin sequence were treated with the mandibular infant devices over a 24-month period. Tracheostomy was avoided in 14 patients, whereas five of six patients who had previous tracheostomy were decannulated after mandibular distraction. The final tracheostomy status in one patient will be determined after surgery for gastroesophageal reflux. There were no major complications and no structural device failures.     

To distract or not to distract: an algorithm for airway management in isolated Pierre Robin sequence

Approaches advocated for treatment of airway obstruction among neonates with Pierre Robin sequence include positioning, tongue-lip adhesion, mandibular distraction, and tracheostomy, with no established guidelines regarding which modality is appropriate for a specific patient. This report proposes an algorithm for the management of neonatal upper airway obstruction among patients with isolated Pierre Robin sequence. Data for 21 patients with isolated Pierre Robin sequence who were treated by one surgeon during a 9-year period were reviewed. Eighteen patients presented during the first 1 week of life and three patients presented late, between 12 and 33 months of age. Follow-up periods ranged from 9 to 70 months (median, 33 months). Successful airway management was achieved with positioning alone for 10 patients, with tongue-lip adhesion for seven of nine patients, with tracheostomy for two patients, and with mandibular distraction for three patients. Changes in the maxillary-mandibular discrepancy were significant with natural mandibular growth during the first 1 year of life (p < 0.0001). Oromotor studies performed 3 months or more after tongue-lip adhesion reversal (n = 9) demonstrated no appreciable deficits in tongue function, relative to other children with cleft lips/palates. A multidisciplinary team should evaluate all patients with isolated Pierre Robin sequence, to fully assess the maxillary-mandibular relationship, anatomically define the site of airway obstruction, and identify feeding difficulties. Patients should be evaluated for episodes of desaturation occurring spontaneously, during feeding, or during sleeping. Patients with desaturation should be further evaluated with double endoscopy (nasoendoscopy and bronchoscopy). If the airway obstruction is localized to the tongue base alone and cannot be controlled with positioning, then tongue-lip adhesion is the initial treatment of choice, because such patients demonstrate significant mandibular growth during the first 1 year of life. Mandibular distraction among neonates is reserved for failures of tongue-lip adhesion in which isolated tongue-base airway obstruction is documented. Neither of the patients who experienced failure of tongue-lip adhesion in this series would have been a candidate for distraction with the algorithm presented. Avoiding routine neonatal distraction serves to avoid facial scarring, nerve and tooth bud injury, and potential disturbances of intrinsic mandibular growth. Patients with persistent respiratory difficulties beyond age 9 months require reevaluation for multiple sites of airway obstruction. Mandibular distraction may be one of several modalities required to avoid tracheostomy for such patients.     

Site and mechanics of spontaneous, sleep-associated obstructive apnea in infants.

To examine the mechanics of infantile obstructive sleep apnea (OSA), airway pressures were measured using a triple-lumen catheter in 19 infants (age 1-36 wk), with concurrent overnight polysomnography. Catheter placement was guided by correlations between measurements of magnetic resonance images and body weight of 70 infants. The level of spontaneous obstruction was palatal in 52% and retroglossal in 48% of all events. Palatal obstruction predominated in infants treated for OSA (80% of events), compared with 38.6% from infants with infrequent events (P = 0.02). During obstructive events, successive respiratory efforts increased in amplitude (mean intrathoracic pressures -11.4, -15.0, and -20.4 cmH(2)O; ANOVA, P < 0.05), with arousal after only 29% of the obstructive and mixed apneas. The soft palate is commonly involved in the upper airway obstruction of infants suffering OSA. Postterm, infant responses to upper airway obstruction are intermediate between those of preterm infants and older children, with infrequent termination by arousal but no persisting "upper airway resistance" and respiratory efforts exceeding baseline during the event.     

Dynamic interaction between the tongue and soft palate during obstructive apnea in anesthetized patients with sleep-disordered breathing.

Little is known about the mechanisms of persistence of obstructive apnea. Structurally, the dorsum of the tongue locates anterior to the soft palate. On the basis of the observation of posterior displacement of the tongue during obstructive apnea, we hypothesized that the dorsum of the tongue pushes the anterior wall of the soft palate posteriorly during inspiratory efforts, maintaining closure at the retropalatal airway. To test this hypothesis, we measured the pressure between dorsum of the tongue and anterior wall of the soft palate (PT&P) during experimentally induced obstructive apneas in anesthetized patients with sleep-disordered breathing. P(T&P) changes during the obstruction significantly depended on collapsibility of the retroglossal airway. Progressive increase in the P(T&P) during obstructive apnea was observed only in patients with highly collapsible retroglossal airways. Significant increase in the P(T&P) during inspiratory effort in accordance with positive deflection pattern of P(T&P) tracing was evident in the patients with highly collapsible retroglossal airways. The results indicate significant dynamic interaction between the tongue and soft palate during both obstructive apnea and each inspiratory effort, possibly maintaining closure at the retropalatal airway.     

Effect of distraction osteogenesis of the mandible on upper airway volume and resistance in children with micrognathia

Children with craniofacial anomalies often have compromise of the upper airway, a condition with potential for morbidity and mortality. In children with microretrognathia, the diminutive size and retruded position of the mandible reduces the size of the oropharynx, thereby predisposing to glossoptosis and airway obstruction. Although several authors have reported successful use of mandibular distraction osteogenesis to alleviate this type of upper airway obstruction, the physiologic relationship between changes in mandibular shape, size, and position and upper airway dynamics remains undefined. The purpose of this study was to develop methodologies to quantitatively evaluate upper airway dynamics in children with micrognathia both before and after mandibular distraction osteogenesis. The patient population consisted of four children with micrognathia who had successfully undergone upper airway stabilization by bilateral mandibular distraction osteogenesis. The data used were digitally archived computed tomographic scan data from high-resolution, thin-slice head computed tomographic scans obtained before and after mandibular distraction. Upper airway evaluation was performed in two ways: static and dynamic. Static analysis consisted of computer quantification of predistraction and postdistraction mandibular and upper airway volumes using Analyze imaging software. Dynamic analysis consisted of fabrication of rigid stereolithographic hollow cast models of the upper airway produced from computed tomographic scan data. Models were used for characterization of upper airway resistance and flow patterns as related to respiration. After distraction osteogenesis, mandibular total volume increased 32, 32, 18, and 25 percent (mean, 27 percent) and upper airway volume increased by 20, 31, 23, and 71 percent (mean, 37 percent). A significant decrease in flow resistance, both inspiratory and expiratory, was observed in the patient with the greatest upper airway volume increase (71 percent) after distraction. After distraction, the inspiratory resistance was diminished by 51 percent and the expiratory resistance diminished by 85 percent. However, the three patients with more modest upper airway volume increases of 20 to 31 percent demonstrated no statistically significant change in flow resistance after distraction. Results of this study support the conclusion that distraction osteogenesis of the micrognathic mandible increases the volume of the upper airway, roughly paralleling the increase in mandibular volume. In the biomechanical airway model studied, upper airway volume expansion has been shown to be able to decrease the flow resistance over the length of the airway, presumably secondary to an increase in the average cross-sectional area. The artificial rigidity of the stereolithographic "airway" compared with the elasticity of the human upper airway may account for the insensitivity of this model to smaller but clinically significant airway changes.     

Mandibular distraction in temporomandibular joint ankylosis

Condylar damage during childhood can produce ankylosis and alteration of the mandibular growth. In case of unilateral ankylosis occurring in early childhood, a mandibular hypoplasia of the affected side may develop. The patients have limitation of mouth opening, facial asymmetry, and chin deviation toward the affected side. The aims of this study are to show the use of distraction osteogenesis in mandibular hypoplasia associated with ankylosis and to present our experience with a new therapeutic option for the treatment of mandibular hypoplasia with unilateral ankylosis in the childhood consisting of the association of arthroplasty to treat the ankylosis and mandibular distraction to correct the facial asymmetry, both accomplished in the same surgical procedure. From November of 1996 to November of 1997, three male patients aged 2, 7, and 13 years with mandibular hypoplasia and ankylosis were treated by distraction osteogenesis. An arthroplasty consisting of the resection of the ankylotic block and interposition of a temporalis muscle flap, plus coronoidectomy was done in two of them and mandibular distraction was done in all three patients. Articular functional rehabilitation began on the first postoperative day. Mandibular distraction began on the fifth postoperative day with a rate of 1 mm per day, ending when the facial symmetry was achieved. From the first postoperative day, an increase in the mouth opening was achieved; this increase continued until ending the distraction. The average duration of distraction was 22 days. Average duration of consolidation was 6 weeks. Oral opening increased from 10 mm to 35 mm in the 7-year-old patient, from 9 mm to 27 mm in the 2-year-old patient, and from 14 mm to 38 mm in the 13-year-old patient. To date, oral opening and facial symmetry persist. Osseous mandibular distraction together with arthroplasty offers an excellent new alternative for treatment of patients with mandibular hypoplasia and associated ankylosis, with minimal morbidity and complications.     

Effect of cleft palate repair and pharyngeal flap surgery on upper airway obstruction during sleep

The effect of von Langenbeck palatoplasty and pharyngeal flap surgery on upper airway obstruction during sleep was studied by obtaining polysomnographic sleep studies on 10 patients undergoing each procedure at 1 to 2 days prior to surgery, 2 to 3 days postoperatively, and approximately 3 months postoperatively. The effects of von Langenbeck palatoplasty on sleep-related upper airway obstruction were usually minimal and clinically insignificant, whereas severe obstructive sleep apnea was present in all but one of the patients undergoing pharyngeal flap surgery at 2 to 3 days postoperatively. In most patients the upper airway obstruction was resolved at the 3-month postoperative sleep study. These data suggest that palatoplasty carries with it a very slight risk of upper airway obstruction, whereas pharyngeal flap surgery has as a very frequent concomitant the occurrence of severe obstructive sleep apnea in the immediate postoperative period.     

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.     

Removal of mandibular tooth follicles before distraction osteogenesis

Distraction osteogenesis is an innovative technique that has transformed the treatment of craniofacial malformations in young children. Bone generation obviates the need for graft material, which is in short supply in young patients, thus making possible surgical procedures on the craniofacial skeleton in young children. Sufficient mandibular volume is required for the osteotomy and placement of the device screws and/or pins. To have adequate bone stock and to facilitate distraction, the authors preoperatively examined all patients radiographically and selected those with tooth follicles that precluded successful osteotomy and pin placement for planned mandibular distraction. This report is of the first 13 children, aged 9 months to 6 years, who underwent predistraction enucleation. The osteotomy and device placement were performed successfully at least 4 months after enucleation. The described procedure has minimal morbidity and has resulted in successful subsequent distraction. The advantages, disadvantages, and cost-benefit issues are discussed.     

Distraction osteogenesis of the craniofacial skeleton

In summary, distraction osteogenesis is a safe and effective means of achieving bone lengthening. These techniques were originally applied to the long bones of the extremities; over the past 10 years they have been effectively applied to the bones of the craniofacial skeleton. The new bone regenerate that is observed after distraction osteogenesis is stable, and relapse rates after skeletal advancement are believed to be lower than with conventional osteotomy and bone graft techniques. There is considerable variability in distraction protocols employed in clinical practice, including differences in the types of devices used and in the rate, rhythm, latency, and period of consolidation for distraction osteogenesis. The greatest application for distraction osteogenesis in the craniofacial skeleton has been with mandible lengthening, for which there is presently a 10-year clinical experience. Midfacial advancement is a newer application of distraction osteogenesis, for which clinical experience has been accrued over the past 5 years. This latter experience indicates that distraction osteogenesis is a viable treatment option for lengthening of the hypoplastic mandible and midface. These techniques have advantages over conventional means of bone graft and rigid fixation because of the quality of the bone regenerate, the decrease in the long-term relapse rate of the advanced bone segments in both the mandible and the midface, and the simultaneous soft-tissue elongation that accompanies the distraction process. Distraction osteogenesis is particularly applicable to the correction of severe deformities of the mandible and midface in children with developmental hypoplasia and syndromic craniosynostosis. However, growth is an added variable in this patient population. The amount of overcorrection in lengthening of the hypoplastic bone required to compensate for continued growth discrepancy of the adjacent facial bones is difficult to predict. Therefore, the families of these patients should be informed that many children will require repeated operations at a later age as they reach skeletal maturity.     

Peripheral vascular resistance increases after termination of obstructive apneas.

The mechanisms by which obstructive apneas produce intermittent surges in arterial pressure remain poorly defined. To determine whether termination of obstructive apneas produce peripheral vasoconstriction, we assessed forearm blood flow during and after obstructive events in sleeping patients experiencing spontaneous upper airway obstructions. In all subjects, heart rate was monitored with an electrocardiogram and blood pressure was monitored continuously with digital plethysmography. In 10 patients (protocol 1), we used forearm plethysmography to assess forearm blood flow, from which we calculated forearm vascular resistance by performing venous occlusions during and after obstructive episodes. In an additional four subjects, we used simultaneous Doppler and B-mode images of the brachial artery to measure blood velocity and arterial diameter, from which we calculated brachial flow continuously during spontaneous apneas (protocol 2). In protocol 1, forearm vascular resistance increased 71% after apnea termination (29.3 +/- 15.4 to 49.8 +/- 26.5 resistance units, P < 0.05) with all patients showing an increase in resistance. In protocol 2, brachial resistance increased at apnea termination in all subjects (219.8 +/- 22.2 to 358.3 +/- 46.1 mmHg x l(-1) x min; P = 0.01). We conclude that termination of obstructive apneas is associated with peripheral vasoconstriction.     

Upper airway neuromuscular compensation during sleep is defective in obstructive sleep apnea

Obstructive sleep apnea is the result of repeated episodes of upper airway obstruction during sleep. Recent evidence indicates that alterations in upper airway anatomy and disturbances in neuromuscular control both play a role in the pathogenesis of obstructive sleep apnea. We hypothesized that subjects without sleep apnea are more capable of mounting vigorous neuromuscular responses to upper airway obstruction than subjects with sleep apnea. To address this hypothesis we lowered nasal pressure to induce upper airway obstruction to the verge of periodic obstructive hypopneas (cycling threshold). Ten patients with obstructive sleep apnea and nine weight-, age-, and sex-matched controls were studied during sleep. Responses in genioglossal electromyography (EMG(GG)) activity (tonic, peak phasic, and phasic EMG(GG)), maximal inspiratory airflow (V(I)max), and pharyngeal transmural pressure (P(TM)) were assessed during similar degrees of sustained conditions of upper airway obstruction and compared with those obtained at a similar nasal pressure under transient conditions. Control compared with sleep apnea subjects demonstrated greater EMG(GG), V(I)max, and P(TM) responses at comparable levels of mechanical and ventilatory stimuli at the cycling threshold, during sustained compared with transient periods of upper airway obstruction. Furthermore, the increases in EMG(GG) activity in control compared with sleep apnea subjects were observed in the tonic but not the phasic component of the EMG response. We conclude that sustained periods of upper airway obstruction induce greater increases in tonic EMG(GG), V(I)max, and P(TM) in control subjects. Our findings suggest that neuromuscular responses protect individuals without sleep apnea from developing upper airway obstruction during sleep.     

Effects of aortic nerve on hemodynamic response to obstructive apnea in sedated pigs.

In this study we test the hypothesis that aortic nerve traffic is responsible for the pressor response to periodic apneas. In nine intubated, sedated chronically instrumented pigs, periodic obstructive apneas were caused by occlusion of the endotracheal tube for 30 s, followed by spontaneous breathing for 30 s. This was done under control (C) conditions, after section of the aortic nerve (ANS), and after bilateral cervical vagotomy (Vagot). Blood-gas tensions and airway pressure changed similarly under all conditions: PO(2) decreased to 50-60 Torr, PCO(2) increased to approximately 55 Torr, and airway pressure decreased by 40-50 mmHg during apnea. With C, mean arterial pressure (MAP) increased from 111 +/- 4 mmHg at baseline to 120 +/- 5 mmHg at late apnea (P < 0.01). After ANS and Vagot, there was no change in MAP with apneas compared with baseline. Relative to baseline, cardiac output and stroke volume decreased with C but not with ANS or Vagot during apneas. Increased MAP was due to increased systemic vascular resistance. Heart rate behaved similarly with C and ANS, being greater at early interapnea than late apnea. With Vagot, heart rate increased throughout the apnea-interapnea cycle relative to baseline. We conclude that, in sedated pigs, aortic nerve traffic mediates the increase in MAP and systemic vascular resistance observed during periodic apneas. Increase in MAP is responsible for decreased cardiac output and stroke volume. Additional vagal reflexes, most likely parasympathetic efferents, are responsible for interacting with sympathetic excitatory influences in modulating heart rate.