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Diagnosis, Management and Pathophysiology of Central Sleep Apnea in Children ⇑ Anya T

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Diagnosis, Management and Pathophysiology of Central Sleep Apnea in Children ⇑ Anya T Paediatric Respiratory Reviews 30 (2019) 49–57 Contents lists available at ScienceDirect Paediatric Respiratory Reviews Review Diagnosis, management and pathophysiology of central sleep apnea in children ⇑ Anya T. McLaren a, Saadoun Bin-Hasan b, Indra Narang a,c, a Division of Respiratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G1X8, Canada b Department of Pediatrics, Division of Respiratory Medicine, Farwaniya Hospital, Kuwait c Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada Educational aims The reader will be able to: Identify the different types of pediatric central sleep apnea (CSA) Describe the clinical presentation of CSA in children Discuss the pathophysiology of CSA Understand the evaluation of CSA in the pediatric population article info summary Keywords: Central sleep apnea (CSA) is thought to occur in about 1–5% of healthy children. CSA occurs more com- Central sleep apnea monly in children with underlying disease and the presence of CSA may influence the course of their dis- Sleep disordered breathing ease. CSA can be classified based on the presence or absence of hypercapnia as well as the underlying Hypoventilation condition it is associated with. The management of CSA needs to be tailored to the patient and may Children include medication, non-invasive ventilation, and surgical intervention. Screening children at high risk will allow for earlier diagnosis and timely therapeutic interventions for this population. The review will highlight the pathophysiology, prevalence and diagnosis of CSA in children. An algorithm for the manage- ment of CSA in healthy children and children with underlying co-morbidities will be outlined. Ó 2018 Elsevier Ltd. All rights reserved. INTRODUCTION significant when the number of central apneas per hour (central apnea index, CAI) is 5/h [1]. CSA can occur in the presence or Central sleep apnea (CSA) is a sleep-related disorder occurring absence of hypoventilation, defined as a CO2 >50 mmHg for >25% when there is diminished or absent respiratory effort. CSA is often of the total sleep time in the pediatric population [2]. associated with arterial oxygen desaturation, arousals, frequent The International Classification of Sleep Disorders (ICSD)-2 rec- nocturnal awakenings and sleep fragmentation [1]. In the pediatric ognizes six different forms of central sleep apnea including pri- population, the AASM defines a central apnea as the absence of mary CSA and CSA due to other causes such as Cheyne-Stokes chest and/or abdominal movement associated with a cessation of breathing (CSB), medical conditions, drugs or substances, high- airflow of more than 20 s or lasting more than 2 baseline respira- altitude periodic breathing and infancy [1]. In the pediatric popu- tory cycles if it is associated with an arousal, an awakening or an lation, CSA occurs more commonly in association with underlying oxygen desaturation of at least 3% [2]. In adults, CSA is considered medical conditions. These conditions include anatomical brain and brainstem abnormalities (such as Arnold–Chiari Malformation, foramen magnum stenosis), neurogenetic conditions such as Pra- ⇑ Corresponding author at: Division of Respiratory Medicine, The Hospital for der–Willi syndrome, upper airway abnormalities (laryngomalacia), Sick Children, 555 University Avenue, Toronto, ON M5G1X8, Canada. prematurity, gastroesophageal reflux, obesity and hypothyroidism Fax: +1 4168136246. [3,4]. CSA can also occur in the context of other sleep disordered E-mail addresses: [email protected] (A.T. McLaren), Saadoun.binhasa- [email protected] (S. Bin-Hasan), [email protected] (I. Narang). breathing conditions such as OSA [5,6], emerge with the treatment https://doi.org/10.1016/j.prrv.2018.07.005 1526-0542/Ó 2018 Elsevier Ltd. All rights reserved. 50 Table 1 Central sleep apnea in healthy children and children with underlying conditions. Study Patient Population Methods Findings 2 N Age (years) BMI (kg/m ) Underlying Definitions OAHI CSA SpO2 condition Nadir (%) w/CA CA CSA CAI Range %Reported A.T. McLaren et al. / Paediatric Respiratory Reviews 30 (2019) 49–57 CSA Marcus et al., 1992 [14] 50 9.7 ± 4.6 18.6 ± 3.2 Healthy 10 s NA 0.1 ± 0.5 NR NR NA 89 Schluter et al., 2001 681 1–24 mo NA Healthy 3 s NA NR 1 mo:8.8/h NR NA NR 2 mo: 5.0/h Uliel et al., 2004 [19] 70 8.0 ± 4.6 NR Healthy 10 s OR dec SaO2 >4% or 92% NA 0.37 (SD NR) 0.4 (SD NR) NR NA 88 Traeger et al., 2005 [18] 66 6.6 ± 1.9 NR Healthy 20 s OR <20 s + dec SaO2 3% NA 0.01 ± 0.03 0.08 ± 0.14 0–6 NA 81 Montgomery et al., 2006 [16] 153 4.9 ± 0.69 16.7 ± 2.8 Healthy At least 2 breaths NA 0.03 ± 0.1 0.82 ± 0.73 0–3.6 NA NR 388 6.8 ± 0.48 17.1 ± 3.4 0.05 ± 0.11 0.45 ± 0.49 0–3.4 Verhulst et al., 2007 [17] 66 11.7 ± 2.6 NR Healthy 10 s OR dec SaO2 >3% NA 0.06 ± 0.16 0.85 ± 1.06 0–5.5 NA 82 Scholle et al., 2011 [15] 209 1–18 y NR Healthy At least 2 breaths NA **0.1–0.3 **0.4–2.8 0–6.9 NA NR Brockman et al., 2013 [12] 37 1 mo NA Healthy >20 s OR 2 breaths + dec SaO2 3% or HR changes NA 0.8/h 5.5/h 0.9–44.3 NA NR 3mo 0.8/h 4.1/h 1.2–27.3 White et al., 2016 [35] 17 2.4 ± 3.6 NR Ach NR >5/h 24.61 ± 23.63 3.32 ± 4.15 0–10.4 4.2 69 Waters et al., 1998 [23] 83 8.9 ± 5.6 NR ACM 20 s OR dec SaO2 4% 5/h NR NR NR 17 NR Kirk et al., 2000 [24] 73 1–>18 y NR ACM NR >5/h 17 (10.3–32.6) 16.6 (7.7–46.4) 34 67 ± 14 Amin et al., 2015 (22) 68 7.3 ± 4.0 (z-score) ACM AASM 5/h 1.9 (0.7–5.7) 2.4 (0.63–8.95) NR 18 NR Patel et al., 2015 [21] 52 8.3 ± 0.9 NR ACM 10 s 5/h NR NR NR 29 NR Cohen et al., 2014 [26] 44 1.9 (0.3, 15.6) (z-score) PWS AASM 5/h 4 (1.5–57) 10.6 (5–68.3) 5–68.3 14 52 Khayat et al., 2017 [27] 28 0.9 (0.5–1.1) 16 (14.3–16.8) PWS AASM 5/h 0.5 (0.2–33) 6.6 (2.6–12.1) 2.6–12.1 53 NR Al-Saleh et al., 2016 [36] 21 (10.7, 0.5–17.7) (z-score) DCM AASM 5/h 1.2 (0–26) 1.1 (0–17.6) 0–17.6 24 NR Values represented as mean ± standard deviation (where reported) or median (range or Interquartile range). All studies were retrospective. NR = not reported; NA = not applicable; dec = decreased. AASM: AASM Criteria for central apnea; Ach = achondroplasia; ACM = Arnold–Chiari malformation; PWS = Prader–Willi syndrome; DCM = Dilated cardiomyopathy; OAHI = obstructive apnea–hypopnea index; CAI-central apnea index A full overnight, laboratory PSG was used in all these studies except Brockman et al which used polygraphic recordings. CAI presented as mean ± SD, median (IQR) or range. ** In this study, the median CAI across the different age groups is reported as a range. Please refer to the study for more detail. A.T. McLaren et al. / Paediatric Respiratory Reviews 30 (2019) 49–57 51 of OSA [7] or hypoventilation disorders such as congenital central Central sleep apnea in children with underlying disorders hypoventilation syndrome (CCHS). CCHS is a rare genetic disorder of ventilatory control that is marked by alveolar hypoventilation The prevalence of CSA ranges between 4 and 6% in children [8]. CCHS is caused by a genetic defect in PHOX2B (paired-like [3,4]. Studies that have looked at CSA (using a cut-off of >5/h) in homeobox 2B gene). Mutations in this gene are known as polyala- children with underlying conditions is summarized in Table 1. nine repeat mutations (PARMs) or non-polyalanine repeat muta- In their retrospective chart review, Kritzinger et al. [3] reviewed tions (nPARMs) [8]. 969 children aged between 3 months to 13 years (median age 19 months) who underwent an overnight PSG. Of these, 52/969 (5.4%) patients had a CAI of >5/h. The commonest cause of CSA in Diagnosis of pediatric CSA patients who were not preterm was an underlying neurologic dis- order. In another retrospective study, Felix and colleagues [4],in A full-night in-laboratory polysomnography is the gold stan- their cohort of 441 patients found that 18/441 (4.1%) had a CAI dard diagnostic test for central apneas [2]. A finding of 5 central of >5/h. Neurosurgical disorders particularly Arnold–Chiari malfor- events per hour is considered clinically significant [3]. However, mations were the most common cause of CSA in their cohort and the minimum number of events required to cause a specific disor- occurred in four of the eighteen patients. Arnold–Chiari malforma- der or syndrome remains elusive and may be different in different tions are one of the most frequently reported neuroanatomical patient populations. As such, there is no threshold of the number of conditions with a frequency of CSA that ranges between 17 and central apneas associated with disease. Normative data are dis- cussed in more detail below. Table 2 Pediatric classification of central sleep apnea, adapted from [9].
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