And miles to go before we sleep...
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Adult↗
Biomedical subjects
Carole L Marcus
Publications and source records attributed to Carole L Marcus.
Influence of airway pressure on genioglossus activity during sleep in normal children.
RATIONALE: Most children with obstructive sleep apnea are able to sustain stable breathing during portions of sleep, despite an anatomic predisposition toward airway collapse. This suggests that additional determinants of airway patency are active, such as neuromuscular compensation. OBJECTIVES/METHODS: Using a custom intraoral surface electrode to record pharyngeal dilator muscle activity (the genioglossus [EMGgg]), we evaluated the muscle, ventilatory, and arousal responses to negative-pressure challenges during sleep in 19 healthy control children. MEASUREMENTS AND MAIN RESULTS: In response to these challenges, we observed (1) marked variability in individual EMGgg responsiveness (peak EMGgg [mean+/-SD], 214+/-101% baseline), which was consistent within subjects; (2) a relationship between EMGgg activity and inspiratory flow and airway collapsibility; (3) reflex increases in flow (peak flow increase from challenge breaths 1-5 [mean+/-SD], 49+/-41% baseline) and respiratory rate often sufficient to sustain minute ventilation near baseline levels, without arousal; and (4) arousal threshold to be highest in stage 4, intermediate in stage 2, and lowest in REM sleep. CONCLUSIONS: Healthy children have wide variation in upper airway neuromuscular compensatory responses and arousal thresholds that could represent intermediate phenotypes affecting the expression of sleep apnea. Children with robust upper airway neuromuscular responsiveness, or a very high arousal threshold, may be able to sustain minute ventilation when challenged with negative airway pressure.
Adolescent↗
The toll of poverty: no respite even in sleep.
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Child↗
Ventilatory management of sleep-disordered breathing in children.
PURPOSE OF REVIEW: The purpose of this review is to summarize the current management of continuous positive airway pressure and noninvasive positive pressure ventilation in children with sleep-disordered breathing. RECENT FINDINGS: Although most children with sleep-disordered breathing respond to surgical treatment, the use of continuous positive airway pressure and noninvasive positive pressure ventilation in nonresponders has become common, with hundreds of cases reported in the literature, despite the fact that these devices are not approved by the Food and Drug Administration for use in children weighing under 30 kg. Studies show that continuous positive airway pressure and non-invasive positive pressure ventilation are safe and efficacious. Side-effects are minor, and include nasal symptoms and skin breakdown. Midfacial hypoplasia is an uncommon adverse event. Problems with triggering and cycling of noninvasive positive pressure ventilation remain an issue in small or weak children. As in adults, poor adherence is the major obstacle to successful continuous positive airway pressure or noninvasive positive pressure ventilation use. SUMMARY: Continuous positive airway pressure is a useful second-line treatment for children with sleep-disordered breathing. Strategies to improve adherence are needed. Equipment manufacturers should be encouraged to develop equipment that better meets children's needs.
Child↗
Upper airway collapsibility in anesthetized children.
We sought to establish the feasibility of measuring upper airway narrowing in spontaneously breathing, anesthetized children using dynamic application of negative airway pressure. A secondary aim was to compare differences in upper airway collapsibility after the administration of sevoflurane or halothane. Subjects were randomized to either drug for inhaled anesthetic induction. Each was adjusted to their 1 MAC value (0.9% for halothane and 2.5% for sevoflurane) and a blinded anesthesia provider held the facemask without performing manual airway opening maneuvers but with inclusion of an oral airway device. Inspiratory flows were measured during partial upper airway obstruction created by an adjustable negative pressure-generating vacuum motor inserted into the anesthesia circuit. Critical closing pressure of the pharynx (Pcrit) was obtained by plotting the peak inspiratory flow of the obstructed breaths against the corresponding negative pressure in the facemask and extrapolating to zero airflow using linear correlation. Fourteen children were enrolled, seven in each anesthetic group. Two children in the halothane group did not develop flow-limited airway obstruction despite negative pressures as low as -9 cm H2O. Pcrit for sevoflurane ranged from -6.7 to -11.6 (mean +/- sd, -9.8 +/- 1.9) cm H2O. Pcrit for halothane ranged from -8.1 to -33 (mean +/- sd, -19.4 +/- 9.3) cm H2O (sevoflurane versus halothane, P = 0.048). We conclude that when using dynamic application of negative airway pressure, halothane appears to cause less upper airway obstruction than sevoflurane at equipotent concentrations.
Airway Obstruction↗
Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury.
BACKGROUND: Childhood obstructive sleep apnea (OSA) is associated with neuropsychological deficits of memory, learning, and executive function. There is no evidence of neuronal brain injury in children with OSA. We hypothesized that childhood OSA is associated with neuropsychological performance dysfunction, and with neuronal metabolite alterations in the brain, indicative of neuronal injury in areas corresponding to neuropsychological function. METHODS AND FINDINGS: We conducted a cross-sectional study of 31 children (19 with OSA and 12 healthy controls, aged 6-16 y) group-matched by age, ethnicity, gender, and socioeconomic status. Participants underwent polysomnography and neuropsychological assessments. Proton magnetic resonance spectroscopic imaging was performed on a subset of children with OSA and on matched controls. Neuropsychological test scores and mean neuronal metabolite ratios of target brain areas were compared. Relative to controls, children with severe OSA had significant deficits in IQ and executive functions (verbal working memory and verbal fluency). Children with OSA demonstrated decreases of the mean neuronal metabolite ratio N-acetyl aspartate/choline in the left hippocampus (controls: 1.29, standard deviation [SD] 0.21; OSA: 0.91, SD 0.05; p = 0.001) and right frontal cortex (controls: 2.2, SD 0.4; OSA: 1.6, SD 0.4; p = 0.03). CONCLUSIONS: Childhood OSA is associated with deficits of IQ and executive function and also with possible neuronal injury in the hippocampus and frontal cortex. We speculate that untreated childhood OSA could permanently alter a developing child's cognitive potential.
Adolescent↗
Adherence to and effectiveness of positive airway pressure therapy in children with obstructive sleep apnea.
OBJECTIVES: Positive airway pressure therapy (PAP) is frequently used to treat children who have obstructive sleep apnea syndrome and do not respond to adenotonsillectomy. However, no studies have evaluated objectively adherence to PAP in children, and few studies have evaluated objectively the effectiveness of PAP. The objective of this study was to determine adherence and effectiveness of PAP (both continuous [CPAP] and bilevel [BPAP] pressure) in children with obstructive apnea. METHODS: A prospective, multicenter study was performed of children who were randomly assigned in a double-blind manner to 6 months of CPAP versus BPAP. Adherence was measured objectively using the equipment's computerized output. Effectiveness was evaluated using polysomnography. RESULTS: Twenty-nine children were studied. Approximately one third of children dropped out before 6 months. Of the 21 children for whom 6-month adherence data could be downloaded, the mean nightly use was 5.3 +/- 2.5 (SD) hours. Parental assessment of PAP use considerably overestimated actual use. PAP was highly effective, with a reduction in the apnea hypopnea index from 27 +/- 32 to 3 +/- 5/hour, and an improvement in arterial oxygen saturation nadir from 77 +/- 17% to 89 +/- 6%. Results were similar for children who received CPAP versus BPAP. Children also had a subjective improvement in daytime sleepiness. CONCLUSIONS: Both CPAP and BPAP are highly efficacious in pediatric obstructive apnea. However, treatment with PAP is associated with a high dropout rate, and even in the adherent children, nightly use is suboptimal considering the long sleep hours in children.
Adolescent↗
Sleep-disordered breathing, behavior, and cognition in children before and after adenotonsillectomy.
OBJECTIVES: Most children with sleep-disordered breathing (SDB) have mild-to-moderate forms, for which neurobehavioral complications are believed to be the most important adverse outcomes. To improve understanding of this morbidity, its long-term response to adenotonsillectomy, and its relationship to polysomnographic measures, we studied a series of children before and after clinically indicated adenotonsillectomy or unrelated surgical care. METHODS: We recorded sleep and assessed behavioral, cognitive, and psychiatric morbidity in 105 children 5.0 to 12.9 years old: 78 were scheduled for clinically indicated adenotonsillectomy, usually for suspected SDB, and 27 for unrelated surgical care. One year later, we repeated all assessments in 100 of these children. RESULTS: Subjects who had an adenotonsillectomy, in comparison to controls, were more hyperactive on well-validated parent rating scales, inattentive on cognitive testing, sleepy on the Multiple Sleep Latency Test, and likely to have attention-deficit/hyperactivity disorder (as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) as judged by a child psychiatrist. In contrast, 1 year later, the 2 groups showed no significant differences in the same measures. Subjects who had an adenotonsillectomy had improved substantially in all measures, and control subjects improved in none. However, polysomnographic assessment of baseline SDB and its subsequent amelioration did not clearly predict either baseline neurobehavioral morbidity or improvement in any area other than sleepiness. CONCLUSIONS: Children scheduled for adenotonsillectomy often have mild-to-moderate SDB and significant neurobehavioral morbidity, including hyperactivity, inattention, attention-deficit/hyperactivity disorder, and excessive daytime sleepiness, all of which tend to improve by 1 year after surgery. However, the lack of better correspondence between SDB measures and neurobehavioral outcomes suggests the need for better measures or improved understanding of underlying causal mechanisms.
Adenoidectomy↗
Subjective sleepiness and polysomnographic correlates in children scheduled for adenotonsillectomy vs other surgical care.
STUDY OBJECTIVE: To compare a validated subjective measure of childhood sleepiness to an objective determination, assess the frequency of problematic sleepiness among children with suspected sleep-disordered breathing (SDB), and examine what standard or investigational polysomnographic measures of SDB predict subjective sleepiness. DESIGN: Prospective, cross-sectional. SETTING: University-based sleep disorders laboratory. PARTICIPANTS: Washtenaw County Adenotonsillectomy Cohort. INTERVENTION: Polysomnography followed by Multiple Sleep Latency Tests (MSLTs) in 103 children aged 5 to 12 years old: 77 were scheduled for clinically indicated adenotonsillectomy, usually for suspected SDB, and 26 for unrelated surgical care. Parents completed the previously validated, 4-item Pediatric Sleep Questionnaire-Sleepiness Subscale (PSQ-SS). RESULTS: Thirty-three (43%) of the children scheduled for adenotonsillectomy had high PSQ-SS scores, in comparison with only 3 (12%) of the controls (p = .004). The PSQ-SS scores correlated inversely with mean sleep latencies on the MSLTs (rho = -0.23, p = .006). The obstructive apnea index, apnea-hypopnea index, and respiratory disturbance index (which included respiratory event-related arousals identified by esophageal pressure monitoring) each correlated similarly with PSQ-SS scores, as did investigational quantification of esophageal pressures and respiratory cycle-related electroencephalographic changes (each rho approximately 0.30, p < .02). A stepwise regression identified sigma-frequency respiratory cycle-related electroencephalographic changes as the strongest independent predictor of subjective sleepiness among all subjects and particularly among those without obstructive sleep apnea. CONCLUSIONS: Sleepiness is a frequent problem among children with suspected SDB. Subjective sleepiness (PSQ-SS) reflects MSLT results to a limited extent, as in adults. Standard polysomnographic measures of SDB predict subjective sleepiness, but respiratory cycle-related electroencephalographic changes may offer additional clinical utility.
Adenoidectomy↗
Childhood obesity, inflammation, and apnea: what is the future for our children?
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Adolescent↗
Acoustic arousal responses in children with obstructive sleep apnea.
Our objectives were to study the arousal responses to nonrespiratory (acoustic) stimuli in children with obstructive sleep apnea syndrome (OSAS). The acoustic arousal response was studied in children with OSAS due to adenotonsillar hypertrophy compared to normal, age-matched children. Acoustic stimuli were delivered incrementally from 30-100 dB during stage 2, slow wave sleep, and rapid eye movement (REM) sleep. The percentage of children who aroused in response to acoustic stimuli, and the arousal threshold (i.e., sound level at which arousal occurred), were compared between groups and sleep stages. The percentage of children who aroused was similar between children with OSAS and controls. The percentage of children who aroused was lower during slow wave sleep than REM sleep and stage 2 in both OSAS and controls. There were no statistically significant differences in acoustic arousal threshold between OSAS and control children. There was no difference in arousal response to moderate acoustic stimulation between children with OSAS and controls. These results contrast with previous data showing blunted arousal responses to hypercapnia and upper airway loading during sleep in children with OSAS, suggesting that children with OSAS have an arousal deficit specific to respiratory stimuli. However, further studies evaluating arousal to both respiratory and nonrespiratory stimuli in the same subjects are needed.
Acoustic Stimulation↗
Polysomnographic values in children 2-9 years old: additional data and review of the literature.
The establishment of normal pediatric polysomnographic parameters is important for both clinical and research interests. Our objectives were to describe respiratory events, paradoxical breathing, periodic limb movements, and sleep architecture of children at the age of peak incidence of obstructive sleep apnea syndrome. We performed a retrospective cross-sectional analysis of a prospective cohort study of 66 children, 2-9 years old, at the Sleep Disorders Center at the Children's Hospital of Philadelphia. Subjects screened by questionnaire underwent a standard polysomnogram. The percent of total sleep time spent in sleep stages 1, 2, 3, 4, and rapid eye movement (REM) were 4 +/- 3%, 44 +/- 10%, 10 +/- 6%, 22 +/- 8%, and 21 +/- 6%, respectively. The arousal and awakening index was 11.2 +/- 4.3/hr. Respiratory events included a central apnea index of 0.08 +/- 0.14/hr, obstructive apnea index of 0.01 +/- 0.03/hr, and obstructive hypopnea index of 0.3 +/- 0.5/hr. The baseline arterial oxygen saturation (SpO2) was 97 +/- 1%, with a nadir of 92 +/- 3%. The index of periodic limb movements in sleep (PLMS) was 1.3 +/- 2.2/hr. Paradoxical breathing appeared significantly more frequent with piezo crystal effort belts (40 +/- 24% of epochs) than with respiratory inductive plethysmography (1.5 +/- 3% of epochs). We describe the occurrence of hypopneas during sleep, arousals and awakenings, and PLMS. We illustrate how different technologies can vary the apparent amount of paradoxical breathing. We also confirm previous data on the frequency distribution of sleep stages, SpO2, and relative rarity of respiratory events in this age group.
Age Distribution↗
Upper airway dynamic responses in children with the obstructive sleep apnea syndrome.
Normal children have a smaller upper airway than adults, but, nevertheless, snore less and have less apnea. We have previously shown that normal children have an upper airway that is resistant to collapse during sleep. We hypothesized that this resistance to collapse is due to preservation of upper airway neuromotor responses during sleep. Furthermore, we hypothesized that upper airway responses would be diminished in children with the obstructive sleep apnea syndrome (OSAS). We therefore compared the upper airway pressure-flow relationship during sleep between children with OSAS and controls. Measurements were made by correlating maximal inspiratory airflow with the level of nasal pressure applied via a mask. Neuromotor upper airway activation was assessed by evaluating the upper airway response to 1) hypercapnia and 2) intermittent, acute negative pressure. We found that children with OSAS had no significant response to either hypercapnia or negative pressure during sleep, compared with the normal children. After treatment of OSAS by tonsillectomy and adenoidectomy, there was a trend for normalization of upper airway responses. We conclude that upper airway dynamic responses are decreased in children with OSAS but recover after treatment. We speculate that the pharyngeal airway neuromotor responses present in normal children are a compensatory response for a relatively narrow upper airway. Further, we speculate that this compensatory response is lacking in children with OSAS, most likely due to either habituation to chronic respiratory abnormalities during sleep or to mechanical damage to the upper airway.
Adenoidectomy↗
Reliability of scoring arousals in normal children and children with obstructive sleep apnea syndrome.
STUDY OBJECTIVES: Scoring of arousals in children is based on an extension of adult criteria, as defined by the American Sleep Disorders Association (ASDA). By this, a minimum duration of 3 seconds is required. A few recent studies utilized modified criteria for the study of children, with durations as short as 1 second. However, the validity and reliability of scoring these shorter arousals have never been verified. Based on studies in adults, we hypothesized that interscorer agreement for scoring arousals shorter than 3 seconds was poor. DESIGN: Retrospective review of polysomnograms by 2 experienced sleep practitioners who independently scored arousals according to the ASDA 3-second criteria and modified duration criteria of 1 and 2 seconds. SETTING: Academic hospital. PATIENTS OR PARTICIPANTS: 20 polysomnographic studies from children aged 3 to 8 years with mild to severe obstructive sleep apnea syndrome, and 16 polysomnographic studies from normal children. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The intraclass correlation coefficient for scoring ASDA arousals was 0.90 (95% confidence interval: 0.81-0.95), indicating excellent interscorer agreement. The intraclass correlation coefficient for scoring modified 1-second and 2-second arousals were 0.35 (95% confidence interval: 0.02-0.61) and 0.42 (95% confidence interval: 0.12-0.65) respectively, indicating poor to fair interscorer agreement. Furthermore, modified 1-second and 2-second arousals accounted for less than 15% of all arousals scored. CONCLUSIONS: We conclude that there is much poorer interscorer agreement for scoring arousals shorter than 3 seconds, when compared to the standard ASDA criteria. We propose that scoring of arousals in children should follow the standard ASDA criteria.
Arousal↗
Pathophysiology of upper airway obstruction: a developmental perspective.
The obstructive sleep apnea syndrome (OSAS) occurs in patients of all ages, from the premature infant to the elderly. Much remains unknown about the pathophysiology of the syndrome. However, research suggests that OSAS in all age groups is due to a combination of both anatomic airway narrowing and abnormal upper airway neuromotor tone. The anatomic predisposing factors for OSAS differ over the lifespan. However, a smaller upper airway is noted in all age groups and probably predisposes to airway collapse during sleep. Despite the known anatomic factors, such as craniofacial anomalies, obesity, and adenotonsillar hypertrophy, that contribute to OSAS throughout life, a clear anatomic factor cannot always be identified. This suggests that alterations in upper airway neuromotor tone also play an important role in the etiology of OSAS. Infants and children are less likely than adults to arouse in response to upper airway obstruction and do not compensate for prolonged increases in inspiratory resistive load. The overall ventilatory drive is probably normal in patients of all ages with OSAS. However, upper airway neuromotor tone and reflexes during sleep vary with age and are increased in normal infants and children compared to adults, perhaps as a compensatory response for their relatively narrow airway. This compensatory response appears to be blunted in children with OSAS. Further research is needed to fully understand the complexities of upper airway structure and function during both normal development and disease.
Adenoids↗
Developmental changes in upper airway dynamics.
Normal children have a less collapsible upper airway in response to subatmospheric pressure administration (P(NEG)) during sleep than normal adults do, and this upper airway response appears to be modulated by the central ventilatory drive. Children have a greater ventilatory drive than adults. We, therefore, hypothesized that children have increased neuromotor activation of their pharyngeal airway during sleep compared with adults. As infants have few obstructive apneas during sleep, we hypothesized that infants would have an upper airway that was resistant to collapse. We, therefore, compared the upper airway pressure-flow (V) relationship during sleep between normal infants, prepubertal children, and adults. We evaluated the upper airway response to 1). intermittent, acute P(NEG) (infants, children, and adults), and 2). hypercapnia (children and adults). We found that adults had a more collapsible upper airway during sleep than either infants or children. The children exhibited a vigorous response to both P(NEG) and hypercapnia during sleep (P < 0.01), whereas adults had no significant change. Infants had an airway that was resistant to collapse and showed a very rapid response to P(NEG). We conclude that the upper airway is resistant to collapse during sleep in infants and children. Normal children have preservation of upper airway responses to P(NEG) and hypercapnia during sleep, whereas responses are diminished in adults. Infants appear to have a different pattern of upper airway activation than older children. We speculate that the pharyngeal airway responses present in normal children are a compensatory response for a relatively narrow upper airway.
Adolescent↗
Evaluating the upper airway during wakefulness: what can it tell us about sleep?
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Child↗
Pediatric sleep medicine comes into its own.
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Child↗