Diagnosis of Obstructive Sleep Apnea

Diagnosis of Obstructive Sleep Apnea Eliot S. Katz and Carole L. Marcus

INTRODUCTION Sleep-disordered breathing (SDB) is a common and serious cause of morbidity during childhood. This chapter is concerned with diagnosing the spectrum of obstructive SDB, ranging from the frank, intermittent occlusion seen in obstructive sleep apnea syndrome (OSAS), to persistent, primary snoring (PS). OSAS is characterized by recurrent episodes of partial or complete airway obstruction resulting in hypoxemia, hypercapnia, and/or respiratory arousal (Figure 28-1). The sleep fragmentation and gas exchange abnormalities observed with OSAS may produce serious cardiovascular and neurobehavioral impairment. The upper airway resistance syndrome (UARS) is characterized by brief, repetitive respiratory effortrelated arousals (RERA) during sleep in the absence of overt apnea, hypopnea, or gas exchange abnormalities.1 It has been linked to significant cognitive and behavioral sequelae in children including learning disabilities, attention deficit, hyperactivity, and aggressive behavior.2 Obstructive hypoventilation (OH) features prolonged increased upper airway resistance accompanied by gas exchange abnormalities, but not frank apnea or hypopnea.3 Children with PS may have increased respiratory effort, but lack identifiable arousals, including respiratory-effort-related, EEG and subcortical arousals.4 Though PS has been traditionally defined as a benign condition, without polysomnographic abnormalities,5 recent evidence suggests that the increased respiratory effort in PS per se may be associated with untoward neurobehavioral consequences.6–9 Habitual snoring has been reported in 3–12% of the general pediatric population, although only 1–3% will have OSAS.10–12 Early recognition of SDB is important insofar as treatment with adenotonsillectomy or continuous positive airway pressure is effective. Establishing strict criteria for OSAS diagnosis and severity is the basis for optimizing the surgical and medical management of this condition.13 The diagnosis and management of pediatric OSAS continues to evolve as more precise measures of flow limitation and sleep fragmentation are introduced. Both the intermittent hypoxemia and sleep fragmentation characteristic of OSAS pose a risk to the vulnerable developing brain. The increased recognition of subtle neurocognitive impairments in children with SDB has forced clinicians to rethink the threshold level of disease requiring intervention. The optimal methodology and criteria for the diagnosis of OSAS in children has not been validated with outcomes data. Categorizing OSAS severity with threshold levels of the apnea–hypopnea index, gas exchange abnormalities, or sleep fragmentation have proven unsatisfactory, since they fail to account for the individual trait susceptibility to the neurocognitive, cardiovascular, and metabolic sequelae of OSAS. That

Chapter

28

 

is, the threshold amount of OSAS associated with adverse consequences varies widely among children. HISTORY AND PHYSICAL EXAMINATION The high incidence of OSAS in children mandates that screening inquiries about sleep disturbances should be a routine part of the primary care interview14 (Table 28.1). Particular attention should be given to conditions known to exacerbate SDB such as craniofacial abnormalities, neuromuscular weakness, and genetic conditions. A parent typically provides the clinical history, with the patient oblivious to their condition, other than sometimes the complaint of excessive daytime sleepiness. Nightly snoring is observed in most children with OSAS. However, snoring may be absent in the setting of craniofacial abnormalities in infants.15 A parental report of a snoring child is an accurate predictor of polysomnographic snoring, but not of OSAS.16 In addition, a population-based study using home-based polysomnography found that loud snoring one to two times per week during the last month was absent in at least 25% of children with documented OSAS.17 Snoring is often accompanied by labored breathing, hyperextension of the neck, and witnessed apneic pauses. Subjective reports of excessive daytime sleepiness are less common in young children with OSAS, although they are often present in adolescents. A recent study reported that only 7.5% of children with polysomnographically proven OSAS had a history of EDS.18 Using an objective measure of sleepiness, such as the multiple sleep latency test, reveals that only 13% of children with OSAS have a sleep latency <10 minutes.18 However, the incidence of objective sleepiness is higher in obese children with OSAS.19,20 Also, although not considered sleepy by adult standards, children with SDB may be relatively sleepier than normal children.21 Increasing BMI and apnea index (usually greater than 15–20 events/hour) have been independently correlated with shorter sleep latencies.18 The use of standardized screening questionnaires for OSAS has been disappointing. Brouillette et al. presented a questionnaire aimed at distinguishing children with OSAS from normal controls.22 However, subsequent application of this and other questionnaires to a population of snoring children demonstrated a wide-ranging positive predictive value, 48.3– 76.9%, and negative predictive value, 26.9–93%.22–25 Although children with OSAS are statistically more likely to have reported symptoms such as witnessed apnea, cyanosis, and/or labored breathing, no questionnaire has a sufficiently high positive predictive value and negative predictive value to be used as a primary diagnostic tool.25,26 Thus, the clinical history alone is insufficient to diagnose OSAS amongst a population 221

222    Principles and Practice of Pediatric Sleep Medicine BODY

RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS RS

C4A1 C3A2 O1C4 O2C3 ROC LOC CHIN EKG R-LEG L-LEG SNORE FLOW NAF THO ABD

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

98 98 98 98 98 98 98 98 98 98 98 98 98 98 98 98 98 98 97 97 97 97 97 97 97 98 98 98 98 98

SpO2 1:03:04

10"

20"

30" Raw data

40"

50"

60"

Figure 28-1  A 60-second epoch from a 16-year-old with snoring and excessive daytime sleepiness. Note flow limitation and reduction in the amplitude of the nasal pressure tracing leading to an EEG arousal. Inspiration is upward. Flow, thermistor; NAF, nasal pressure; Tho, thorax; Abd, abdomen; Body, body position; RS, right side; SpO2, pulse oximetry.

Box 28-1  Physical Examination in OSAS

Table 28.1  Clinical History in OSAS SLEEP

WAKEFULNESS

Snoring

Poor school performance

Witnessed apnea

Aggressive behavior

Choking noises

Hyperactivity

Increased work of breathing

Attention deficit disorder

Paradoxical breathing

Excessive daytime sleepiness

Enuresis

Morning headaches

Mouth breathing

Age-inappropriate napping

Restless sleep

Difficult to arouse from sleep

Diaphoresis

Depression

Hyperextended neck Frequent awakenings

General • Sleepiness • Obesity • Failure to thrive Head • Swollen mucous membranes • Deviated septum • Adenoidal facies • Infraorbital darkening • Elongated midface • Mouth-breathing • Tonsillar hypertrophy • High arched palate • Overjet

• Posterior buccal cross-bite • Crowded oropharynx • Macroglossia • Glossoptosis • Midfacial hypoplasia • Micrognathia/retrognathia • Increased neck circumference Cardiovascular • Hypertension • Loud P2 Extremities • Edema • Clubbing (rare)

Dry mouth

of snoring children. Questionnaires have also been developed that incorporate questions relating to the consequences of OSA, including hyperactivity and behavior. An affirmative response to at least one-third of these questions on the 22-question Pediatric Sleep Questionnaire had a sensitivity of 0.85 and a specificity of 0.87.27,28 Physical examination of children with OSAS is most often normal, with the exception of adenotonsillar hypertrophy or craniofacial abnormalities (Box 28-1). The majority of children with OSAS are of normal height and weight, although both obesity and failure to thrive may occur. Cardiovascular sequelae of SDB such as cor pulmonale and congestive heart failure are infrequently observed in current clinical practice, as heightened awareness has facilitated earlier diagnosis.

Although blood pressure is statistically elevated in children with OSAS, the wide range of normal makes this measurement a poor screening tool.29 The neurocognitive consequences of OSAS are non-specific, such as poor school performance,30 aggressive behavior, and hyperactivity.31 IMAGING AND LABORATORY EVALUATION The diagnosis of SDB is firmly established using polysomnography, and ancillary testing is rarely indicated. Further screening may be useful to facilitate the perioperative care and to exclude underlying conditions (Box 28-2). For example, concern regarding right ventricular dysfunction may

Diagnosis of Obstructive Sleep Apnea     223 Box 28-2  Ancillary Diagnostic Studies in OSAS

Box 28-3  Example of Polysomnogram Montage

Serum Markers • Hematocrit • Serum bicarbonate

Electroencephalography (C4-M1, O2-M1, F4-M1) Electromyogram (chin, both legs) Electrooculogram (right/left) Electrocardiogram Abdominal and thoracic excursion Oximetry (3 second averaging), pulse waveform End-tidal PCO2 (peak value, waveform) Flow: nasal pressure, oronasal thermistor Snore volume Body position sensor Esophageal pressure (in special circumstances) Video and audio taping

Imaging • Brain MRI • Anteroposterior and lateral neck radiograph • Upper airway CT/MRI (craniofacial) • Cine MRI • Dynamic fluoroscopy Sleep Monitoring • MSLT Miscellaneous • Echocardiogram • Neurocognitive testing • Electrocardiogram • Flow–volume loop

necessitate an EKG or echocardiogram. Occasionally, chronic intermittent hypoxemia may induce polycythemia, while persistent hypercarbia can elevate serum bicarbonate. Routine pulmonary function testing is not indicated in children suspected of having OSAS unless restrictive or obstructive lung disease is suspected. A fluttering pattern in the flow volume loop has been described in adults with OSAS.32 Magnetic resonance imaging (MRI) of the upper airway in children with OSAS compared to normal controls reveals a statistically smaller upper airway luminal volume and elongation of the soft palate, as well as enlarged tonsils and adenoids.33 However, there is considerable overlap between the groups, rendering MRI a poor screening tool. The measurement of the ratio of the width of the tonsil to the depth of the pharyngeal space on a lateral neck radiograph was reported to have a good sensitivity and specificity for distinguishing mild from moderate/severe OSAS in a small number of patients.34 Adenoidal enlargement measured by cephalometry was present in over 80% of children with OSAS but also in 42% with primary snoring.35 Though neck radiographs may be suggestive of adenoidal hypertrophy, direct visualization of the adenoids remains the diagnostic standard.36 Dynamic fluoroscopy under sedation may demonstrate glossoptosis, particularly in children with macroglossia, micrognathia, or neuromuscular weakness.37 Anatomical localization of the site of obstruction with cine MRI may alter the therapeutic approach in some children with residual OSAS following adenotonsillectomy or craniofacial anomalies.38 Other promising but understudied tools for identifying OSAS in children include nasal rhinometry39 and acoustic pharyngometry.40 Video/Audio Recordings Diagnosing OSAS using home audio recordings, in addition to a standard clinical history and physical examination, revealed a sensitivity of 71–92% and a specificity of 29–80%.41,42 Subtle forms of SDB are particularly difficult to evaluate using this technique. However, computer-aided processing of audio signals for regularity may improve predictive value.43 Frequency domain analysis of the snoring signal has also shown promise in distinguishing OSAS from PS.44 Video

recordings can also yield a noninvasive measure of movement and therefore arousal.45–47 Video is also a useful adjunct to a comprehensive polysomnogram to evaluate body and head positioning, paradoxing, snoring, and mouth breathing. Studies correlating video scoring systems to standard poly­ somnography have been encouraging.47 Future research will be necessary to validate the utility of a particular domiciliary video/audio study in a population with a well-characterized symptomatology. Overnight Polysomnography Polysomnography represents the gold standard for establishing the presence and severity of SDB in children, and can be performed in children of all ages. An expert consensus panel from the American Academy of Pediatrics has recommended overnight polysomnography as the diagnostic test of choice in evaluating children with suspected SBD.14 Guidelines for performing laboratory-based polysomnography in children have been established.48,49 The sleep laboratory should be a non-threatening environment that comfortably accommodates a parent during the study. Personnel with pediatric training should record, score, and interpret the study. The use of sedatives50 and sleep deprivation51 may worsen SDB, and is therefore not recommended. To the extent possible, sleep studies should conform to the child’s usual sleep period. Infants may reasonably be studied during the day, while adolescent studies should generally start later at night. The polysomnographic montage will vary with the patient’s suspected disorder (Box 28-3). Electroencephalogram Consensus guidelines for analyzing sleep architecture have been established in infants,48,52,53 children,48,52 and adults.48 Standard practice is to apply adult EEG criteria to children older than 2–3 months of age. Sleep staging establishes that an adequate amount of total sleep time (TST) and sufficient REM sleep was obtained on the night of the study, and demonstrates the presence or absence of sleep fragmentation. In addition to sleep staging, the EEG tracing is useful for scoring cortical arousals and detecting epileptiform discharges. By consensus, an electrocortical (EEG) arousal is defined in adults as an abrupt 3-second shift in EEG frequency.48 These criteria appear to be appropriate for use in children as well.54 However, visible EEG arousals are present in only 51% of obstructive events in children,55 complicating the diagnosis of

224    Principles and Practice of Pediatric Sleep Medicine UARS in children. Frequency domain analysis of the EEG tracing may further enhance the sensitivity of detecting respiratory events or arousal.56,57 Initial reports indicated that children with snoring58 or even severe OSAS may have normal sleep state distribution.59 However, a large cohort (n = 559) comparing normal children to children with OSAS revealed that OSAS patients have increases in slow-wave sleep (23.5 vs. 28.8% TST) and decreases in REM sleep (22.3 vs. 17.3% TST).60 Furthermore, these authors observed a decline in the spontaneous arousal index in OSAS patients versus controls (8.4 vs. 5.3), suggesting a homeostatic elevation in the arousal threshold.60 Arousal Arousal from sleep is a protective reflex mechanism that restores airway patency through dilator muscle activation. Both mechano- and chemoreceptors have a role in initiating the arousal response. Though arousals reverse the airway obstruction, they result in the untoward consequences of sleep fragmentation and sympathetic activation.61 Polysomnographically, arousal may be associated with EEG changes,57 increased airflow, elimination of airflow limitation, cessation of paradoxical breathing, tachycardia, movement,45 blood pressure elevation,62 and autonomic activation. In children, however, approximately 50% of obstructive events do not result in an EEG arousal.55 In infants, EEG arousals are even less common.55 Thus, depending on the EEG arousal index for the diagnosis of UARS is unreliable. Frequency domain analysis may reveal evidence of EEG arousal not readily visible, and may be a clinically useful tool in the future.56,57 Obstructive events that terminate with autonomic activation are termed subcortical arousals. Autonomic measures include heart rate variability,63 blood pressure elevations,62 pulse transit time,4 and peripheral arterial tonometry.64 The pulse transit time was reported to be a more sensitive measure of respiratory arousal compared to 3-second EEG arousals.4 As a screening tool for OSAS, the pulse transit time had a sensitivity of 81% and a specificity of 76%.65 Subcortical arousals alone have been demonstrated to result in neurocognitive impairment in adults.66 Measures of Respiratory Movements A variety of methodologies to categorize central and obstructive respiratory events is amenable to overnight polysomnography. Thoracic and abdominal excursion is measured most commonly with respiratory inductive plethysmography (RIP). The classification of central and obstructive apneas is achieved by determining whether respiratory efforts are present during intervals of reduced flow. Uncalibrated RIP tracings may also be used as an index of thoraco-abdominal asynchrony. The highly compliant chest wall in children results in asynchronous motion between the thoracic and abdominal tracings, termed paradoxical breathing. This disparity may be quantified using phase angle analysis that is independent of the relative contribution of the two compartments.67 Thoraco-abdominal asynchrony has been demonstrated in children with increased respiratory effort due to upper airway obstruction and OSAS.67,68 Paradoxical breathing is normally seen in infants due to the high compliance of their chest wall, particularly during REM sleep, but is rare after 3 years of age.69 Esophageal manometry (Pes) represents the gold standard for quantifying respiratory effort and permits the detection of

subtle, partially obstructive events that may produce sleep fragmentation.70 However, Pes monitoring is uncomfortable and may itself alter the frequency of respiratory events.71 The introduction of non-invasive, nasal pressure measurements has largely supplanted Pes in establishing the diagnosis of UARS (see Figure 28-1). Nevertheless, esophageal manometry peak amplitude and percent of time spent lower than −10 cmH2O has been reported to have a better correlation with behavioral outcomes than the traditional apnea–hypopnea index with or without respiratory-effort-related arousals.72 Current practice is to reserve Pes monitoring for rare cases of children with diagnostic uncertainty even after standard overnight polysomnography. Measures of Airflow Airflow can be quantitatively measured using an oronasal mask and pneumotachograph. However, mask breathing is uncomfortable and has been shown to alter respiratory mechanics. Practically speaking, this methodology is restricted to research settings and continuous positive airway pressure (CPAP) titration studies. Thermistors provide qualitative measures of oronasal airflow by measuring the temperature of expired air. Though thermistors accurately indicate complete cessation of flow, they are not an accurate measure of tidal volume and therefore hypopnea.73 Another drawback of the thermistor is its long time constant that obscures the nuance of the flow profile, making the evaluation of flow limitation impossible.73 Nasal cannula pressure recordings provide a minimally invasive, semi-quantitative measure of airflow.74,75 The resulting signal has been shown to be proportional to flow squared. Since nasal pressure measurements have a fast time constant, it is possible to detect flattening of the inspiratory nasal pressure signal, termed flow limitation, that occurs in a collapsible tube when flow becomes independent of driving pressure (Figure 28-2). Limitations of the nasal cannula pressure recordings include obstruction of the tubing with secretions, mouth breathing (especially in children with adenoidal hypertrophy), and the possible increase in nasal resistance due to obstruction of the nares. In children, the reported signal quality has varied in laboratory-based studies. Trang et al. reported an overall uninterpretable nasal cannula signal during only 4% of total sleep time.76 However, 17% of subjects had uninterpretable signals for more than 20% of total sleep time. In contrast, Serebrisky et al. reported adequate nasal cannula flow signals (>50% of total sleep time) during sleep in only 71.8% of patients.77 In a domiciliary study, the nasal cannula channel was not available overall for more than 50% of the night.78 Verginis et al. compared the combination of the thermistor and nasal pressure measurement with either modality alone and found the combination significantly lowered the scoring of false-negative and false-positive obstructive events.79 Airflow may be approximated using RIP by considering that lung volume can be approximated by a two-compartment model (thoracic and abdomen excursion). RIP may be calibrated using an isovolume maneuver or a statistical technique and used to derive a ‘sum’ channel proportional to tidal volume.80,81 Thus, the time derivative of the sum channel is proportional to flow. The RIP signal may therefore be analyzed for apnea, hypopnea, and flow limitation.82 Our current practice is to combine RIP, nasal cannula pressure,

Glottic pressure

Diagnosis of Obstructive Sleep Apnea     225

Normal contour Flattened contour

Cannula flow

Intermediate

0

5

10

15

20

Inspiratory flow Driving pressure

Inspiratory flow

Flow limitation Inspiratory flow

No flow limitation

25

Driving pressure

Driving pressure

Figure 28-2  Nasal cannula pressure tracing demonstrating that flow becomes independent of driving pressure during flow-limited breaths (Reproduced with permission from Hosselet JJ, Norman RG, Ayappa I, Rapoport DM. Detection of flow limitation with a nasal cannula/pressure transducer system. Am J Respir Crit Care Med. 1998;157:1461–1467).

capnometry, and an oronasal thermistor in our laboratorybased studies to ensure that a flow signal is likely to be available throughout the night. Gas Exchange Pulse oximetry, which is based on the absorption spectra of hemoglobin, is the standard polysomnographic measure of hypoxemia. The relationship between the arterial oxygen tension and the SpO2, the oxyhemoglobin curve, is sigmoidal. Patients with normal pulmonary function, whose baseline SpO2 is on the flat portion of the curve, require large changes in PaO2 to affect their SpO2. By contrast, patients with parenchymal lung disease may be operating on the steep portion of the oxyhemoglobin curve, thereby experiencing a profound decline in SpO2 with small decrements in PaO2. In sickle cell disease, the oxyhemoglobin curve is variably shifted, thus limiting the utility of SpO2 measurements in some patients.83 The adequacy of ventilation can be assessed non-invasively during sleep by sampling CO2 tension in respired air, termed capnography. Expired gas initially consists of dead space ventilation in the measuring apparatus as well as the physiologic dead space. In the setting of normal lungs, the terminal expired concentration of CO2 reaches a plateau and reflects alveolar gas. The concentration of CO2 in a given alveolus is predicated on the ventilation–perfusion relationship. In subjects with normal lung mechanics, end-tidal PCO2 (PETCO2) is approximately 2–5 mmHg below the arterial PaCO2 level.84 However, in diseases with uneven ventilation–perfusion or altered alveolar time constants, such as cystic fibrosis, the PETCO2 will not be an accurate measure of PaCO2. Also, the rapid respiratory rates characteristic of infants may not permit the alveolar CO2 to plateau, and therefore may underestimate the true CO2 value.85 The capnometry signal is prone to

artifact due to nasal secretions obstructing the sampling cannula. Morielli et al. reported that 27% of polysomnographic epochs in their laboratory had a poor PETCO2 waveform, stressing the importance of careful attention to technique.85 Transcutaneous CO2 (TcCO2) monitors might be valuable in patients in whom PETCO2 is not accurate, such as infants or patients with parenchymal lung disease.85 Though absolute values of TcCO2 are variable, the trend is proportional to the PaCO2 with a lag of several minutes. Sleep is normally associated with a 4–6 mmHg increase in TcCO2. Normative Polysomnographic Data Normative data for the EEG and respiratory parameters of sleeping children are shown in Table 28.2.59,60,86–88 In infants, longitudinal arterial oxygen saturation monitoring revealed a median SpO2 baseline of 98%, but the SpO2 was <90% during 0.51% of epochs.89 Marcus et al. presented the respiratory data of 50 normal, non-obese children between 1 and 18 years of age (mean 9.7 ± 4.6), using a thermistor and PETCO2 monitoring.88 Nine subjects had at least one obstructive apneic event. One ‘normal’ child had an apnea index of 3.1/h, though he had a sibling with OSAS. Including this outlier, an obstructive apnea index >1/h was determined to be statistically abnormal. However, the threshold level at which the apnea index becomes clinically significant has not been established. Only 15% of normal children had any hypopneas, with the mean hypopnea index being 0.1 ± 0.1 (range 0.1–0.7).90 Acebo et al. also reported that hypopneas were rare in older children and adolescents.87 Normative data using nasal pressure during sleep have not been presented in children. Experience from our laboratory indicates that hypopneas and respiratoryeffort-related arousals occur infrequently in normal young children (<1.5/hour).

226    Principles and Practice of Pediatric Sleep Medicine Table 28.2  Polysomnographic Data in Normal 5–10-year-old Children SLEEP

RESPIRATORY

EEG arousal index, n/h

Obstructive apnea Index, n/h TST

0.0 ± 2 0.1

Obstructive hypopnea Index, n/h TST

0.1 ± 2 0.1

Central apneas with desaturation n/hr TST

0.0 ± 2 0.1

26 ± 2 8

Duration of Hypoventilation (PETCO2 ≥45 mmHg), %TST

1.6 ± 2 0.8

19 ± 2 6

Peak PETCO2, mmHg

46 ± 2 3

SpO2 Nadir, %

95 ± 2 1

7 ± 2 2

Sleep efficiency, %

84 ± 2 13

Stage 1, %TST

5 ± 2 3

Stage 2, %TST Slow wave sleep, %TST

51 ± 2 9

REM sleep, %TST REM cycles, n

4 ± 2 1 47,48,70,72

Data, Mean ± 2 SD; see references

Normative data for esophageal manometry (ΔPes) from 10 normal subjects in our laboratory, aged 2–11 years, showed that control subjects had a mean ΔPes of −8 ± 2 cmH2O (range −6 to −12), a peak ΔPes of −12 ± 3 cmH2O (range −9 to −19 cmH2O), and had a ΔPes ≥−10 cmH2O for 8 ± 12% of breaths (range 3–61%).4 Other investigators have considered ΔPes swings of −8 to −14 cmH2O as normal,91 and suggested that normal children spend ≤10% of the night with inspiratory esophageal pressure swings ≤−10 cmH2O.70 However, our data showed that two control patients spent 21% and 61% of the night with a ΔPes ≤−10 cmH2O. Thus, normative data from non-snoring controls reveal considerable variability in respiratory effort. ΔPes is lower in normal infants, 5–6 cmH2O.92 Domiciliary and Nap Studies Attended overnight polysomnography in a designated pediatric sleep laboratory represents the gold standard for the diagnosis of SDB in children.49 However, such comprehensive testing is expensive, labor-intensive, and not widely available. Recognizing that only 10–20% of children who snore will have OSAS10,11 has prompted considerable interest in limited, nap or unattended domiciliary studies. Choosing the most appropriate evaluation is predicated on understanding the relative risks of OSAS and its treatments. Testing is indicated to determine the presence and severity of SDB, the type of treatment, the perioperative care, and necessary follow-up. Polysomnography during a daytime nap may underesti­ mate the degree of SDB.93,94 REM sleep often does not occur during naps. Furthermore, obstructive respiratory events worsen as sleep progresses.59 Thus, although the positive predictive value of an abnormal nap study is 100%, the negative predictive value is only 20%.93,94 Home study devices may range in complexity from oximetry alone95,96 to multi-channel recordings.97 Ambulatory studies may be used to evaluate oxygenation in infants with chronic lung disease, cystic fibrosis, restrictive lung diseases, and neuromuscular conditions. Jacob et al. compared laboratory and domiciliary studies in a population of symptomatic children with adenotonsillar hypertrophy.98 The multi-channel monitor used in that study included saturation, waveform, electrocardiogram, RIP, and video recording, and therefore cannot be compared to commercially available ambulatory systems.98 Similar indices of apnea–hypopnea, desaturation and arousal were observed during attended laboratory-based polysomnograms and domiciliary studies.98 Goodwin et al. performed a home-based

study that was set up by a technician and then was completed unattended, with an excellent success rate of 91%.99 Similarly, Rosen et al. performed 850 abbreviated home studies with 94% yielding technically satisfactory data.17 A subset of 55 children also underwent laboratory-based polysomnography and the sensitivity and specificity of the home study to detect OSAS as defined by an AHI >5/hour on the laboratory study were 88% and 98%, respectively.17 Overall, the utility of ambulatory studies depends on the age group and channels acquired. Documenting oximeters should include an algorithm for artifact reduction such as a plethysmograph waveform or heart rate detected by the oximeter. The oximetry channel alone has been compared to full polysomnography in a population of snoring children with adenotonsillar hypertrophy suspected to have SDB with adenotonsillar hypertrophy.100 One study reported that oximetry demonstrated an excellent positive predictive value, 97%, but a poor negative predictive ability, 53%.100 By contrast, Kirk reported that overnight oximetry alone has a poor correlation with laboratory-based polysomnography.101 Many children with SDB and clinically significant respiratory-effort-related arousals will not demonstrate oxygen desaturation.1,70 Similar observations have been made regarding the limitations of using oximetry as a screening tool for adult OSAS.95,96 Oximetry is inadequate to diagnose a considerable percentage of pediatric SDB in which arousal or hypoventilation, rather than hypoxemia, predominate.101 Night-to-Night Polysomnographic Variability A single overnight polysomnogram is a well-recognized diagnostic tool used to determine the presence and severity of OSAS in symptomatic children.49 However, in adults an adaptation effect of the sleep laboratory environment, termed the ‘first night effect,’ has been reported to disrupt sleep architecture102 and perhaps underestimate respiratory disturbance.103,104 There are several pediatric studies that have documented the excellent consistency in the diagnosis of OSAS from night to night.102,105–107 In children, the clinical diagnosis of either OSAS or primary snoring remained the same in two polysomnogram studies 1–4 weeks apart.105 Although the overall classification of subjects was unchanged, there were minimal changes in OSAS severity between nights. This supports the view that a single polysomnographic night is sufficient for the diagnosis of OSAS in otherwise normal, snoring children with adenotonsillar hypertrophy. No nightto-night systematic bias has been observed in any of the mean

Diagnosis of Obstructive Sleep Apnea     227 intersubject respiratory parameters.102,105 The intrasubject respiratory parameters, however, demonstrated considerable variability, particularly in children with severe disease. The variability in respiratory parameters could not be accounted for by changes in body position or percentage REM time. Among the sleep variables, a first night effect including increased wakefulness and a reduction of REM sleep was observed as the result of adaptation to the sleep laboratory environment.102 Circumstances in which a single study night may not be sufficient include studies with inadequate REM time, technical limitations in acquiring key channels, or if the parents report that the particular study night did not reflect a typical night’s sleep. However, studies primarily performed to assess sleep architecture (usually only in a research context) require adaptation nights in the sleep laboratory. Diagnostic and Event Classification The optimal definition for respiratory events and clinical classification has not been established in children. There are few clinical studies evaluating the relative merit of specific event definitions in relation to clinical outcomes. The polysomnographic criteria for event scoring and clinical diagnosis, based on our clinical experience, are summarized in Tables 28.3 and

28.4. However, well-designed outcomes studies are desperately needed to validate these criteria. Additional abnormal breathing patterns, including tachypnea and increased respiratory effort have been described in children with OSAS.108 Normative data for respiratory-effort-related arousals and flow limitation are scant in children, but these events appear to be uncommon. Nevertheless, the clinical classification of symptomatic children cannot be exclusively based on the apnea–hypopnea index alone. Consideration of the AHI, flow limitation, SpO2, PETCO2, work of breathing, and arousal indices, in conjunction with the clinical picture, also contribute to the diagnosis of OSAS. Thus, diagnostic interpretation of pediatric PSG will continue to require consideration of all respiratory parameters. Special Considerations in Infants The pathophysiology of OSAS in infants frequently differs from that observed in older children, with infants having a higher likelihood of congenital anomalies of the upper airway including larngomalacia, choanal atresia, laryngeal webs, and pyriform aperature stenosis, in addition to gastroesophageal reflux, hypotonia and other issues.109 Therefore, direct endoscopic visualization of the upper airway is a helpful part of the

Table 28.3  Respiratory Pattern Scoring Obstructive Apnea

Reduction of oronasal thermal airflow by ≥90% lasting at least 2 missed breaths with persistent respiratory effort

Hypopnea

Fall in the nasal pressure amplitude >50% for at least a 2-breath duration with persistent respiratory effort accompanied by a desaturation ≥3%, awakening, or arousal

Respiratory effort-related arousal

Discernible fall in the amplitude of the nasal pressure signal <50% of baseline or flattening of the signal contour lasting at least 2 breaths duration. Evidence of increased work of breathing, snoring or elevation of CO2

Flow limitation

Flattening of the inspiratory limb of nasal pressure channel

Snoring

Coarse, low-pitched inspiratory sound

Hypoventilation

End-tidal or transcutaneous CO2 >50 mmHg for >25% TST

Central Apnea

Absence of oronasal airflow for ≥20 seconds duration without respiratory effort. Alternatively, the event lasts at least 2 missed breaths duration and is associated with arousal, awakening or ≥3% desaturation

Periodic breathing

Succession of >3 central apneas of >3-second duration separated by <20 seconds of normal breathing

Mixed apneas

Reduction of oronasal thermal airflow by ≥90% lasting at least 2 missed breaths. Absent respiratory effort during the initial portion only

Table 28.4  Diagnostic Classification and Severity of SDB (ONE OR MORE OF THE FOLLOWING) APNEA INDEX (Events/h)

SpO2 NADIR (%)

PETCO2 PEAK (Torr)

PETCO2 > 50 Torr (%TST)

AROUSALS (Events/h)

Primary Snoring

≤1

>92

<53

<10%

EEG <11

Upper Airway Resistance Syndrome

≤1

>92

<53

<10%

RERA >1 EEG >11

Mild OSAS

1–4

86–91

>53

10–24%

EEG >11

Moderate OSAS

5–10

76–85

>60

25–49%

EEG >11

Severe OSAS

10

≤75

>65

≥50%

EEG >11

Arterial oxygen saturation, SpO2; End tidal Pco2, PETCO2; EEG, electrocortical; RERA, respiratory effort related arousal; Total sleep time, TST

228    Principles and Practice of Pediatric Sleep Medicine diagnostic work-up to establish nasal size, adenoidal volume, laryngeal stability/anatomy, mucosal swelling, and vocal cord function. Infants with OSA may not snore,15 and many snoring infants do not have OSA.110 Therefore polysomnography should be performed to confirm the diagnosis and establish the severity. Polysomnographically, normative data are different in infants with respect to REM sleep percentage, respiratory rate, oximetry, and the arousal index compared to older children.109 A few scored obstructive apneas and hypopneas may be observed in otherwise normal infants.

Clinical Pearls • Obstructive sleep-disordered breathing in children includes non-apneic and non-hypopneic patterns including sustained increased respiratory effort and respiratory- effort-related arousals. • The threshold level of OSAS severity that necessitates treatment varies widely among children. • Subjective reports of sleepiness are most often not present in pre-pubescent children with OSAS. • Direct endoscopic visualization of the airway is an essential part of the work-up in infants with OSAS.

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