HIGH-RISK GROUPS FOR DEVELOPING OSAS

As mentioned above OSAS is associated with many pediatric conditions aside from adenotonsillar hypertro-phy. These conditions mainly fall into the categories of craniofacial and neurologic disorders affecting upper air-way anatomy and patency during sleep (Table 5-2). In addition, other conditions may be associated with high risk for OSAS and are discussed below.

Obesity

Obesity is a major risk factor in adults for developing OSAS, and an increased neck collar size is strongly asso-ciated with OSAS in this group⁷. In contrast, the major-ity of children with OSAS are not obese, many have normal weight, and failure to thrive is a common com-plication. However, there is evidence that obesity is a risk factor for the existence of OSAS in children.

Guilleminault et al.⁸reported that 10% of the 50 children who were diagnosed with OSAS were obese, and a simi-lar finding was reported by Brouillette et al.¹²who stud-ied 22 infants and children. A higher incidence of OSAS was reported when obese children were referred for evaluation of OSAS. Silvestri et al.²⁸found partial airway obstruction in 66% and complete airway obstruction in 59% of 32 obese children.

The above studies, however, were all performed on children who were referred for possible OSAS and there-fore the prevalence of sleep-disordered breathing may have been overestimated in this group. To evaluate more precisely the prevalence of OSAS in the general obese population, Marcus et al.²² studied 22 obese children and adolescents age 10 ± 5 years with an ideal body weight of 184 ± 36% and with no history of sleep-disor-dered breathing. They found that 10 children (46%) had abnormal polysomnography and in 6 children (27%) abnormalities were moderate to severe. Moreover, a pos-itive correlation between obesity and apnea index was found (r = 0.47, P < 0.05) as was an inverse relation

between obesity and oxygen saturation nadir (r= − 0.5, P< 0.01). Asymptomatic obese infants also have a higher incidence of obstructive apnea events compared with controls³², suggesting that OSAS is common in obese children of all ages.

Adenotonsillar hypertrophy is not always the cause for the development of OSAS in obese children^22,28. Several other reasons may contribute to OSAS in this group. Upper airway narrowing may result from deposi-tion of adipose tissue within the muscles and tissues sur-rounding the airway and increase pharyngeal resistance³³. Moreover, obese subjects were shown to have decreased chest wall compliance and displacement of the diaphragm while in the supine position. These physiologic alter-ations can result in decreased lung volumes and oxygen reserves during sleep and increase the risk for OSAS in this group.

Down Syndrome

Down syndrome (trisomy 21) is the most common genetic cause of developmental disability and mental retardation with an incidence of 1/660 live births.

Obstructive sleep apnea is common in this group and is noted in 30–60% of subjects^27,34,35. Anatomic factors related to the Down syndrome phenotype have been attributed to the causation of OSAS in this group. These include midfacial and mandibular hypoplasia, enlarged tongue, adenoid and tonsillar hypertrophy, laryngotra-cheal anomalies, and obesity³⁶. Reduced neuromuscular tone has also been suspected of having a role in the development of OSAS in these subjects.

Post-adenotonsillectomy

Postoperative respiratory compromise has been reported to occur in 16–27% of children with OSAS.

Particularly high-risk children include those younger than 3 years of age, those with severe OSAS, and those with additional complex medical conditions^24,25. A post-operative polysomnogram 2–3 months following surgery is recommended for patients with additional risk factors for OSAS, or those with a high apnea index, to ensure that additional treatment is not required.

Complications

The cumulative effects of OSAS have adverse sequelae on neurologic and cardiac function, and on growth.

Complications may be mild and reversible or become severe and progressive in untreated children. The various complications of childhood OSAS are the result of chronic nocturnal hypoxemia, acidosis, and sleep fragmentation.

Neurobehavioral and Neurocognitive Manifestations

Nocturnal hypoxemia and sleep fragmentation are considered the main causes for the neurobehavioral

sequelae of OSAS. In adults, EDS, decreased ability to perform everyday tasks, impairment in memory and attention, and reduction in general intellectual abilities have been reported16,29,37,38. Sleep fragmentation may lead to personality changes that are often first recog-nized by family members. These include irritability, anx-iety, aggression, and depression.

Excessive daytime sleepiness is less common in chil-dren with OSAS. However, there are some discrepancies in the prevalence of EDS reported in children with OSAS. Guilleminault et al.⁸ reported EDS in 84% of 50 children with OSAS, and in 70% of those cases symp-toms were noted by school teachers. However, Brouillette et al.⁹, in a controlled study, reported EDS in 33% of 23 children, and Frank et al.¹⁸reported EDS as a significant problem in only 9% of the 32 children they studied. Carroll et al.³⁹ reported a similarly low rate of EDS in a pediatric population. It is conceivable that fewer or shorter arousals and a more preserved sleep architec-ture seen in children with OSAS compared with adults with OSAS results in less daytime sleepiness^18,30. It is also possible that since EDS is a subjective complaint, it is underdiagnosed in young children who may take daytime naps routinely. The multiple sleep latency test (MSLT), in which patients are studied during four or five 20-minute naps after overnight polysomnography to determine how quickly a patient falls asleep, affords an objective measurement of sleepiness. Although widely used in adults, its applicability in children with OSAS has not been established; such studies could be useful to objec-tively assess prevalence and degree of EDS in children with OSAS.

Brouillette et al.¹² reported significant neurologic impairment related to OSAS in 7 of 22 children with OSAS.

In 5 children dysfunction was reversible with treatment and included EDS, behavioral disturbances, and mild developmental delay. However, 2 children, of whom one had a metabolic disorder, presented with permanent neurologic dysfunction related to asphyxia occurring dur-ing obstructive events. Delays in referral and diagnosis were noted in most of these children and were considered the cause for some of the above sequelae. In a second study⁹, 33% of children with OSAS had EDS and pathologic shyness/social withdrawal was noted in 22%, rates which were significantly more common than in controls. Other parental reports such as delays in development, morning headaches, hyperactivity, and bizarre behavior were not observed more frequently in these patients.

In another study Guilleminault et al.⁸reported abnor-mal behavior in 42% of children in elementary school, kindergarten, and in day care centers. The most com-mon behavioral abnormality described was hyperactiv-ity; however, asocial behavior and disciplinary problems were also noted. A small group of patients were reported

to have personality changes and bizarre withdrawn behavior suggestive in 2 children of psychosis.

Learning difficulties such as delayed language develop-ment and inadequate school performance are commonly reported, although only one report on neurocognitive function in children with OSAS has been published.

Rhodes et al.⁴⁰studied 14 obese patients of whom 5 had severe OSAS. The OSAS children demonstrated signifi-cantly lower scores for learning, memory, and vocabu-lary tests. Moreover, severity of OSAS measured by an apnea/hypopnea index, was found to be significantly and inversely correlated with the neurocognitive impair-ment. Recently, Gozal⁴¹ reported on the effects of ade-noid and tonsillar hyperplasia and sleep-disordered breathing on school performance. His study demon-strated that correction of these abnormalities resulted in improved school performance among first- and second-grade students. These findings, although preliminary, may explain reports of lower school performance and developmental delay in children with OSAS. However, it is still unknown whether the neurocognitive deficits result from chronic hypoxemia or sleep fragmentation and whether these deficits accumulate with time or are reversible. The extent to which recovery of functions is possible may depend on the age of onset of OSAS, severity, and chronicity of the disorder. More studies of this type are clearly required to define better the effect of OSAS on neurobehavioral/cognitive function.

Cardiovascular Complications

In adults with OSAS significant cardiovascular com-plications contribute to morbidity and mortality. These complications are associated with acute and/or chronic effects of hypoxemia, acidosis, and the hemodynamic effect of obstructive apnea on the cardiovascular system.

Acute cyclic changes in heart rate, blood pressure, intrathoracic pressures, and oxygen saturations may induce cardiac arrhythmia and various degrees of atri-oventricular blocks. Recent evidence suggests that adults with OSAS are at an increased risk for ischemic heart disease and cerebral infarction⁴².

In contrast to adults with OSAS, systemic hypertension is reported only anecdotally in children. However, pul-monary hypertension is the main cardiovascular complica-tion described in children with long-standing OSAS^12,43,44. In 1988 Tal et al.⁴⁴ performed cardiac evaluations in 27 children with OSAS between 9 months and 7.5 years of age. A radionuclide heart scan demonstrated a signifi-cant reduction in right ventricular ejection fraction in 10 (37%) of the children and normalization of heart func-tion after adenotonsillectomy. A more recent study of 28 children with OSAS has demonstrated hypertrophy involving both the right and the left ventricles and that the degree of left ventricular hypertrophy is related to

Sleep-Disordered Breathing in Children 85

the degree of severity of OSAS⁴⁵. In addition, cardiac arrythmias during obstructive events have been reported by some investigators^8,46,47.

Children with severe OSAS (SpO₂ < 70%, apnea index > 10/hour) should undergo cardiac evaluation prior to adenotonsillectomy. Preoperative and postoperative deaths have been observed in this group. Therefore, a careful cardiac evaluation including physical examina-tion, electrocardiogram, chest radiograph, and echocar-diogram should be performed to evaluate for any signs of congestive heart failure or perioperative risks. If these signs or abnormal laboratory findings are present, admis-sion to an intensive care unit for preoperative stabiliza-tion is indicated.

Growth Impairment

Growth impairment is one of the unique features of childhood OSAS. Early reports of children with severe OSAS almost always associated the two, especially when another complication such as cor pulmonale was present.

Later reports in the 1980s found failure to thrive in 27–56%

of the children with OSAS, while obesity in the same population was reported in about 10% of children^8,12.

Adenotonsillectomy in children with OSAS has a sig-nificant impact on growth. Brouillette et al.¹²found that relief of airway obstruction resulted in catch-up growth in all 6 children studied with failure to thrive. Moreover, Lind and Lundell⁴⁸ described a group of 14 children with OSAS in whom height and weight velocity were normal but significantly increased after adenotonsillec-tomy. These investigators hypothesized that abnormal release of growth hormone may alter growth in children with OSAS.

Poor caloric intake may also result in inadequate growth. Brouillette et al.⁹reported the presence of poor appetite, difficulty swallowing, and nausea and vomiting more frequently in children with OSAS compared with controls. Potsic et al.⁴⁹reported that 60% of children with OSAS were slow eaters and 37% had trouble swallowing.

Marcus et al.¹⁷ investigated the relation between growth, caloric intake, and energy expenditure during sleep before and after adenotonsillectomy in 14 children age 4 ± 1years with moderate OSAS. Diagnosis was based upon an apnea index of 6 ± 3, oxygen desaturation to 85 ± 5%, and an increase in PETCO₂during sleep. Caloric intake prior to intervention in these children was normal at 91 ± 30 kcal/kg/day, and remained the same after ade-notonsillectomy with resolution of OSAS in all.

However, energy expenditure during sleep dropped from 51 ± 6 kcal/kg/day prior to surgery to 46 ± 7 kcal/kg/day after surgery (P< 0.005). This finding was associated with a significant increase in weight in all children. These findings suggest that poor growth described in some children with OSAS may be secondary to an increased energy expenditure and increased work of breathing during sleep.

Evaluation Polysomnography

The gold standard for diagnosing childhood OSAS is polysomnography. This tool enables one to evaluate the breathing quality of the child in addition to objectively quantifying gas exchange, number of apneas and hypop-neas, and sleep architecture during the night. Studies should be scored and interpreted using age-appropriate criteria. The American Thoracic Society has published a consensus statement outlining the requirements for pediatric polysomnography³.

Screening Studies

Questionnaires, physical examination, lateral neck radiographs (Figure 5-4), and nocturnal audiotapes have been shown to have a low sensitivity and specificity for diagnosis³. Other screening tests, such as nocturnal video-taping, pulse oximetry, or nap polysomnograms, have lim-ited utility and have a high false-negative rate. Thus, they may be useful for initial testing if polysomnography is not readily available, but polysomnography is recommended if the studies are negative or if the patient has other significant medical conditions.

If suspicion of cor pulmonale from severe or long-standing OSAS exists, cardiologic evaluation is indicated.

An electrocardiogram may show evidence of right ven-tricular hypertrophy. Only after significant right ventric-ular hypertrophy has occurred will the chest radiograph show evidence of cardiomegaly. Echocardiography is a more sensitive technique and is indicated if more detailed information is needed or if there is suspicion of impaired cardiac function, or if congestive heart failure is present.

Treatment

Adenotonsillectomy should lead to complete resolu-tion of clinical symptoms and polysomnographic abnor-malities in most children with OSAS. However, it is important to note that OSAS results from abnormalities in the size and function of the upper airway structure as a whole, rather than from the absolute size of the ade-noid and tonsils.

Additional treatment modalities are available for those children who do not respond to adenotonsillectomy or those in whom adenotonsillectomy is not indicated. Non-invasive ventilatory support in the form of CPAP is com-monly used and is well tolerated in infants and older children^50,51. However, behavioral techniques or admis-sion to the hospital to acclimate the child to the use of this modality of treatment is necessary for it to be successful.

Uvulopharyngopalatoplasty has been successful in overcoming airway obstruction in children with oropha-ryngeal hypotonia, as in children with Down syndrome.

More involved craniofacial surgery such as maxillary and

mandibular advancement is appropriate for some children with craniofacial anomalies restricting the mid- and lower-face skeleton. Tracheostomy with or without ventilatory support should be considered as a short- or long-term treatment for severe cases when other modalities of ther-apy have failed. A weight management program should be offered to obese children with OSAS in conjunction with CPAP or non-invasive positive pressure ventilation (NPPV) therapy once evaluation and treatment for adenotonsillar hypertrophy has been completed.

The American Academy of Pediatrics has recently published guidelines for the evaluation and management of OSAS in children⁵². Recommendations include: (1) all children should be screened for snoring; (2) complex high-risk patients should be referred to a specialist;

(3) patients with cardiorespiratory failure cannot await elective evaluation; (4) diagnostic evaluation, ideally with polysomnography, is useful in discriminating between primary snoring and OSAS; (5) adenotonsillectomy is the first line of treatment for most children, and CPAP is an option for those who are not candidates for surgery or do not respond to surgery; (6) high-risk patients should be monitored as inpatients postoperatively; and (7) patients should be re-evaluated postoperatively to determine whether or not additional treatment is required.

Outcome

The natural history of children with OSAS is variable.

The course is most affected by the etiology of airway

obstruction, degree of obstruction, and chronicity of the disorder. The time elapsed from initial symptoms to diagnosis and management is a significant factor when assessing the outcome of children with long-standing OSAS. Nowadays, when OSAS is more commonly recog-nized by physicians as well as parents, delays in diagno-sis are seen less often. It is difficult to predict the exact outcome of each child with OSAS today. However, in severe cases, and if untreated, children can be expected to progress, as in the past, to develop cor pulmonale and congestive heart failure. Furthermore, they will encounter neurologic deficits that may extend to permanent brain damage due to asphyxia¹².

Only one study has evaluated long-term outcome after intervention. Guilleminault and colleagues⁵³ re-evalu-ated adolescents who had been successfully trere-evalu-ated with adenotonsillectomy during childhood. Thirteen percent of those evaluated had recurrence of OSAS. This study leads to the hypothesis that children at risk for OSAS, due to such factors as a small pharyngeal airway or decreased upper airway neuromuscular tone, develop OSAS when they reach the age of maximal adenotonsillar hyperpla-sia. The adenotonsillar hypertrophy results in an increased mechanical load on a marginal upper airway, thus precipitating OSAS.

It is important to mention that most complications described in the pediatric literature, including cor pul-monale, neurobehavioral, and growth impairments were reversible once patients were treated and relieved of airway obstruction. However, it is not known whether

Sleep-Disordered Breathing in Children 87

A B

Figure 5-4 (A) Lateral neck radiograph of a 2-year-old girl with severe OSAS demonstrating complete occlusion of the nasopharyngeal airway space (white arrow). (B) Lateral neck radiograph of a 4-year-old girl with mild OSAS demonstrating a narrowed nasopharyngeal airway space (NP).

A, adenoid; SP, soft palate.

neurocognitive deficits will also reverse with treatment.

The extent to which recovery of function is possible may depend on the age of onset of OSAS, severity, and chronicity of the disorder.

Some children may present with a mild form of OSAS or upper airway resistance syndrome. These children may have minimal findings by history, clinical examina-tion, and polysomnography. If there are no abnormali-ties in gas exchange during sleep, complications related to these changes are not expected. However, symptoms related to sleep fragmentation such as alteration in neu-robehavioral functions may persist and indicate need for treatment. When no abnormal neurobehavioral symp-toms exist, close observation of the child and sympsymp-toms is sufficient, since children may experience spontaneous resolution in mild cases.

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