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3/25/2019
1
Consequences of Pediatric Obstructive Sleep Apnea
(OSA)
Matt Dennis, MD
Sleep Medicine Physician‐Children’s Hospital & Medical Center Omaha
Pediatric Pulmonology Fellow‐University of Nebraska Medical Center
Conflict of Interest Disclosures
Consultant/
Speakers bureaus
No Disclosures
Research funding UNMC Department of Pediatrics – Objectively measuring the adequacy of the nasal pressure signal during pediatric polysomnography
Stock ownership/Corporate boards-employment
No Disclosures
Off-label uses No Disclosures
Objectives
• Describe basic sleep study terminology related to OSA
• Describe neurodevelopmental outcomes associated with pediatric OSA
• Describe cardiopulmonary outcomes associated with pediatric OSA
Basic Sleep Study Terminology
Pediatric Definitions per American Academy of Sleep Medicine (AASM) Scoring Manual:
• Oxygen desaturation: SpO2 decrease of ≥3% from baseline
• Oxygen desaturation index (ODI): number of desaturations averaged out over the total sleep time, reported as average number of events per hour
Berry 2018
Pediatric Definitions per AASM Scoring Manual (cont’d):
• Apnea: ≥90% reduction in airflow for 2 breaths
• Hypopnea: ≥30% reduction in airflow for 2 breaths that is associated with an arousal or oxygen desaturation
• Obstructive Apnea: apnea associated with the presence of respiratory effort (trying to breathe, but can’t get the air in)
• Obstructive Hypopnea: hypopnea associated with evidence of obstructed airflow (snoring, thoraco‐abdominal paradox, or blunted inspiratory airflow)
• Apnea hypopnea index (AHI): number of apneas and hypopneas averaged out over the total sleep time, reported as average number of events per hour
Berry 2018
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Outcomes
Kaditis 2016
Bradley 2009
Neurodevelopmental Outcomes
Tan 2017
The Childhood AdenotonsillectomyTrial (CHAT)• Inclusion criteria:
o 5‐9 years old
o OSA confirmed by in‐lab PSG at study center (OSA defined as oAHI ≥2, or oAI ≥1)
o Tonsil size ≥ 1+
o Deemed suitable candidate for AT by ENT surgeon
• Exclusion criteria:
o AHI >30 or oAI >20
o Hypoxemia (SpO2 <90% for ≥2% of TST)
o Craniofacial or airway abnormalities that would interfere with standard practice T&A
o Recurrent tonsillitis
o Clinically significant cardiac arrhythmia
o BMI z‐score >2.99
o Severe medical problems that could be exacerbated by delayed treatment of OSA
o Known chronic medical conditions likely to affect the airway, cognition, or behavior
o Current use of: ADHD medications, psychotropic medication, hypoglycemic agents or insulin, antihypertensives, growth hormone, anticonvulsants, anticoagulants, daily oral corticosteroids.
o Psychiatric or behavioral disorders likely to require initiation of new medication or treatment during the 7‐month study period
Redline 2011
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CHAT (cont’d)
• Subjects randomized to early AT (within 4wks of randomization) or watchful waiting
• Polysomnographic, cognitive, behavioral, sleep dysfunction, quality of life, and cardiometabolicparameters evaluated at baseline and at 7 months
Redline 2011 Marcus 2013
Marcus 2013
• Effect sizes calculated by Cohen’s d; relates the magnitude of group difference to the standard deviation:>0.20 ‐ 0.49 small effect size; 0.50 ‐ 0.79 medium effect size; ≥0.80 large effect size
Cardiovascular Outcomes
Tan 2017
Pulmonary Artery Pressures
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Yilmaz 2005
Pulmonary artery pressures before and after T&A
Naiboglu 2008
Pulmonary artery pressures before and after T&A
Impaired Cardiac Function
Figured created from text provided by Kasai 2012
Amin 2005 Amin 2005
Diastole
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Amin 2005
Systole
Kaditis 2010
Obstructive AHI: ≤2 >2, ≤5 >5
Kaditis 2010
Obstructive AHI: ≤2 >2, ≤5 >5
Kaditis 2016
European Respiratory Society Task Force on the diagnosis and management of obstructive sleep disordered breathing (SDB) in childhood.
Kaditis AG, et al. Obstructive sleep disordered breathing in 2‐ to 18‐year‐old children: diagnosis and management. Eur Respir J. 2016 Jan;47(1):69‐94.
Questions that Remain• Statistical support for the clinical consequences of OSA remains equivocal in a number of areas
• Improvement of clinical outcomes with treatment of underlying OSA
o Most recent studies focus on trying to answer this question (e.g. CHAT); suggest moderate improvement in a number of areas
• Risk stratification for clinical outcomes based on AHI level –just starting to get into this
• Risk stratification for clinical outcomes based on chronic duration of OSA
o If OSA is only present for a few years during childhood should we be concerned? Studies like CHAT suggest YES
o Stay tuned for follow‐up studies on CHAT participants 5, 10, and 20 years down the road
• Risk stratification for clinical outcome based on severity/duration of underlying OSA insults (i.e. intermittent hypoxemia, negative intrathoracic pressure, arousals)
What to do Now?
Tan 2017
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The Children’s Sleep Center Team
oGlennette White – Sleep Center Coordinator
oMegan Black – Supervisor Sleep Center & Neurodiagnostics
oDiane Workman, Sleep Clinic Nurse
The Children’s Sleep Center Team
oHeather Bohan, Respiratory Therapy
oDanielle Brazzle, Respiratory TherapyReferences
Amin RS, Kimball TR, Kalra M, Jeffries JL, Carroll JL, Bean JA, Witt SA, Glascock BJ, Daniels SR. Left ventricular function in children with sleep‐disordered breathing. Am J Cardiol. 2005 Mar 15;95(6):801‐4.
Amin R, Somers VK, McConnell K, Willging P, Myer C, Sherman M, McPhail G, MorgenthalA, Fenchel M, Bean J, Kimball T, Daniels S. Activity‐adjusted 24‐hour ambulatory blood pressure and cardiac remodeling in children with sleep disordered breathing. Hypertension. 2008 Jan;51(1):84‐91.
Bass JL, Corwin M, Gozal D, Moore C, Nishida H, Parker S, Schonwald A, Wilker RE, StehleS, Kinane TB. The effect of chronic or intermittent hypoxia on cognition in childhood: a review of the evidence. Pediatrics. 2004 Sep;114(3):805‐16.
Berry RB, Budhiraja R, Gottlieb DJ, et al. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. J Clin Sleep Med. 2012;8(5):597‐619.
Berry RB, Brooks R, Gamaldo CE, Harding SM, Lloyd RM, Quan SF; for the American Academy of Sleep Medicine. The AASM Manual for the Scoring of Sleep and Associated Events: Rules, Terminology and Technical Specifications. Version 2.4. Westchester, IL: American Academy of Sleep Medicine; 2018.
Bradley TD, Floras JS. Obstructive sleep apnoea and its cardiovascular consequences. Lancet. 2009 Jan 3;373(9657):82‐93.
Chervin RD, Ruzicka DL, Giordani BJ, Weatherly RA, Dillon JE, Hodges EK, Marcus CL, GuireKE. Sleep‐disordered breathing, behavior, and cognition in children before and after adenotonsillectomy. Pediatrics. 2006 Apr;117(4):e769‐78.
Garetz SL, Mitchell RB, Parker PD, Moore RH, Rosen CL, Giordani B, Muzumdar H, ParuthiS, Elden L, Willging P, Beebe DW, Marcus CL, Chervin RD, Redline S. Quality of life and obstructive sleep apnea symptoms after pediatric adenotonsillectomy. Pediatrics. 2015 Feb;135(2):e477‐86.
Hunter SJ, Gozal D, Smith DL, Philby MF, Kaylegian J, Kheirandish‐Gozal L. Effect of Sleep‐disordered Breathing Severity on Cognitive Performance Measures in a Large Community Cohort of Young School‐aged Children. Am J Respir Crit Care Med. 2016 Sep 15;194(6):739‐47.
Kaditis AG, Alonso Alvarez ML, Boudewyns A, Alexopoulos EI, Ersu R, Joosten K, LarramonaH, Miano S, Narang I, Trang H, Tsaoussoglou M, Vandenbussche N, Villa MP, Van Waardenburg D, Weber S, Verhulst S. Obstructive sleep disordered breathing in 2‐to 18‐year‐old children: diagnosis and management. Eur Respir J. 2016 Jan;47(1):69‐94.
Kaditis AG, Alexopoulos EI, Dalapascha M, Papageorgiou K, Kostadima E, Kaditis DG, Gourgoulianis K, Zakynthinos E. Cardiac systolic function in Greek children with obstructive sleep‐disordered breathing. Sleep Med. 2010 Apr;11(4):406‐12.
Kasai T. Sleep apnea and heart failure. J Cardiol. 2012 Aug;60(2):78‐85.
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Kohler M, Stradling JR. Mechanisms of vascular damage in obstructive sleep apnea. Nat Rev Cardiol. 2010 Dec;7(12):677‐85.
Marcus CL, Greene MG, Carroll JL. Blood pressure in children with obstructive sleep apnea. Am J Respir Crit Care Med. 1998 Apr;157(4 Pt 1):1098‐103.
Marcus CL, Moore RH, Rosen CL, Giordani B, Garetz SL, Taylor HG, Mitchell RB, Amin R, Katz ES, Arens R, Paruthi S, Muzumdar H, Gozal D, Thomas NH, Ware J, Beebe D, Snyder K, Elden L, Sprecher RC, Willging P, Jones D, Bent JP, Hoban T, Chervin RD, Ellenberg SS, Redline S; Childhood Adenotonsillectomy Trial (CHAT). A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med. 2013 Jun 20;368(25):2366‐76.
Melendres MC, Lutz JM, Rubin ED, Marcus CL. Daytime sleepiness and hyperactivity in children with suspected sleep‐disordered breathing. Pediatrics. 2004 Sep;114(3):768‐75.
Mitchell RB, Archer SM, Ishman SL, Rosenfeld RM, Coles S, Finestone SA, Friedman NR, Giordano T, Hildrew DM, Kim TW, Lloyd RM, Parikh SR, Shulman ST, Walner DL, Walsh SA, Nnacheta LC. Clinical Practice Guideline: Tonsillectomy in Children (Update). Otolaryngol Head Neck Surg. 2019 Feb;160(1_suppl):S1‐S42.
Naiboglu B, Deveci S, Duman D, Kaya KS, Toros S, Kinis V, Sürmeli M, Deveci I, Gokceer T. Effect of upper airway obstruction on pulmonary arterial pressure in children. Int J Pediatr Otorhinolaryngol. 2008 Sep;72(9):1425‐9.
Ng DK, Wong JC, Chan CH, Leung LC, Leung SY. Ambulatory blood pressure before and after adenotonsillectomy in children with obstructive sleep apnea. Sleep Med. 2010 Aug;11(7):721‐5.
Paruthi S, Buchanan P, Weng J, Chervin RD, Mitchell RB, Dore‐Stites D, Sadhwani A, Katz ES, Bent J, Rosen CL, Redline S, Marcus CL. Effect of Adenotonsillectomy on Parent‐Reported Sleepiness in Children with Obstructive Sleep Apnea. Sleep. 2016 Nov 1;39(11):2005‐2012.
Quante M, Wang R, Weng J, Rosen CL, Amin R, Garetz SL, Katz E, Paruthi S, Arens R, Muzumdar H, Marcus CL, Ellenberg S, Redline S; Childhood AdenotonsillectomyTrial (CHAT). The Effect of Adenotonsillectomy for Childhood Sleep Apnea on Cardiometabolic Measures. Sleep. 2015 Sep 1;38(9):1395‐403.
Redline S, Budhiraja R, Kapur V, Marcus CL, Mateika JH, Mehra R, Parthasarthy S, Somers VK, Strohl KP, Sulit LG, Gozal D, Wise MS, Quan SF. The scoring of respiratory events in sleep: reliability and validity. J Clin Sleep Med. 2007 Mar 15;3(2):169‐200.
Roland PS, Rosenfeld RM, Brooks LJ, Friedman NR, Jones J, Kim TW, Kuhar S, Mitchell RB, Seidman MD, Sheldon SH, Jones S, Robertson P; American Academy of Otolaryngology—Head and Neck Surgery Foundation. Clinical practice guideline: Polysomnography for sleep‐disordered breathing prior to tonsillectomy in children. Otolaryngol Head Neck Surg. 2011 Jul;145(1 Suppl):S1‐15.
Sedky K, Bennett DS, Carvalho KS. Attention deficit hyperactivity disorder and sleep disordered breathing in pediatric populations: a meta‐analysis. Sleep Med Rev. 2014 Aug;18(4):349‐56.
Shamsuzzaman A, Amin R. Chapter 30, Cardiovascular consequences of obstructive sleep apnea. In: Sheldon SH, Ferber R, Kryger MH, Gozal D. Principles and Practice of Pediatric Sleep Medicine. 2nd ed. London: Elsevier Saunders, 2014.
Tan HL, Alonso Alvarez ML, Tsaoussoglou M, Weber S, Kaditis AG. When and why to treat the child who snores? Pediatr Pulmonol. 2017 Mar;52(3):399‐412.
West JB, Luks AM. Chapter 6, Gas transport by the blood. In: West JB, Luks AM. West’s Respiratory Physiology. 10th ed. Philadelphia: Wolters Kluwer, 2016.
Yilmaz MD, Onrat E, Altuntaş A, Kaya D, Kahveci OK, Ozel O, Dereköy S, Celik A. The effects of tonsillectomy and adenoidectomy on pulmonary arterial pressure in children. Am J Otolaryngol. 2005 Jan‐Feb;26(1):18‐21.
Supplementary Slides
Updated Recommendations from American Academy of
Otolaryngology‐Head and Neck Surgery
Mitchell 2019
Current Guidelines
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Mitchell 2019
Current Guidelines
Mitchell 2019
Current Guidelines
Mitchell 2019 Roland 2011
Previous Guidelines
Roland 2011
Previous Guidelines
Pathophysiologic Consequences of OSA
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Bradley 2009 Figured created from text provided by Kasai 2012
Kohler 2010 Kohler 2010
Are oxygen desaturations of pathologic consequence if their nadir
is >90%?
What is the desaturation duration that is of pathologic consequence?
Reasons to Consider these Questions:
• I’ve suggested that intermittent hypoxemia is a driving insult behind the pathology associated with OSA – So, what is the definition of intermittent hypoxemia?
• Allows us to briefly discuss the methodology that has been used to generate the previous figures
• Helps us understand why clinical studies tend to focus on the AHI rather than the ODI
• Frequent clinical question – On our sleep studies we report desaturations that are often notrecorded, or deemed insignificant by home oximetry and standard inpatient monitoring
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West 2016
Studies on isolated intermittent hypoxemia:
• Most of these studies exposed animals to low FiO2 (<0.07) and did not monitor SpO2 or PaO2. Others used SpO2 desaturations with a wide delta and nadir <90%.
Studies on intermittent hypoxemia with obstructive events
• Several studies have demonstrated significant correlation between the AHI and OSA comorbidities regardless of whether a 3% or 4% oxygen desaturation was used to score hypopneas. These conclusions were reached despite not having a required SpO2 nadir.
• Potential interpretations include:• Oxygen desaturations with a small delta and SpO2 nadir >90% contribute significantly to the pathophysiology of OSA
• The unreported SpO2 nadirs in these studies were more significant than presumed, and are required to cause pathology
• Other obstructive phenomenon are driving the pathophysiology of OSA in these cases
Bass 2004; Berry 2012; Kohler 2010
Are oxygen desaturations of pathologic consequence if their nadir is >90%?
What is the desaturation duration that is of pathologic consequence?
• No uniform duration used in studies of isolated intermittent hypoxemia
o Duration of exposure to FiO2 <0.21 standardized, but duration of time with SpO2 drop not standardized
• Risk stratification for duration of desaturation not performed in studies of intermittent hypoxemia with obstructive events
• AASM Scoring Manual and guideline papers elude to the significance of short desaturations: “use pulse oximetry with a maximum acceptable signal averaging time of ≤ 3 seconds at a heart rate of 80 beats per minute.”
o Equates to ≤ 4 beat averaging time
Bass 2004; Berry 2018; Kohler 2010; Redline 2007
Moving Forward with Oxygen Desaturations
• Direct consequences of oxygen desaturations with a nadir >90% remain unclear
• Duration of oxygen desaturation required to cause pathology remains unclear
• The AASM has developed specific definitions for apneas and hypopneas, which have been consistently adopted by researchers
• The cut‐points that have been set for the apnea/hypopnea definitions may not be the natural line between normal and pathology, but they give us somewhere to start, particularly standardization amongst researchers
• In theory the AHI value takes into account all insults that are associated with obstructive apneas and hypopneas
For these reasons the clinical outcomes of OSA have been more clearly associated with AHI values, than ODI values
Neurodevelopmental Outcomes
Hunter 2016
Louisville & Chicago Cohort Study on Neurodevelopmental Outcomes
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Hunter 2016 Sedky 2014
Meta‐Analysis: ADHD symptoms and OSA
Chervin 2006
ADHD Symptoms Before & After T&A
• The Conners’ Parent Rating Scales‐Revised and Child Symptom Inventory‐4: Parent Checklist were used to generate the behavioral hyperactivity index
• The Integrated Visual and Auditory Continuous Performance Test and Children’s Memory Scale were used to generate the cognitive attention index
Triangles = T&A subjectsSquares = control subjects
Chervin 2006
Decreased Quality of Life
Excessive Daytime Sleepiness
Garetz 2015
• Effect sizes calculated by Cohen’s d; relates the magnitude of group difference to the standard deviation
• >0.20 to 0.49 small effect size; 0.50 to 0.79 medium effect size; and ≥0.80 large effect size
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Paruthi 2016
• Modified Epworth sleepiness scale (ESS) completed by parent/caregiver
o ESS > 10 equates to excessive sleep propensity
• Mean ESS score was significantly higher in S‐SDB group vs. control group (8.1 ± 4.9 vs 5.3 ± 3.9; P < 0.001)
Melendres 2004
• Mild OSAS: obstructive AI = 1‐4
• Moderate OSAS: obstructive AI = 5‐9
• Severe OSAS: obstructive AI ≥ 10
Melendres 2004
Elevated Blood Pressure
Marcus 1998 Amin 2008; Shamsuzzaman 2014
• Also, 6% of the healthy controls, 15% of the children with mild OSA, and 29% of the children with severe OSA had mean 24‐hour systolic blood pressures greater than the 95th percentile (P=0.01).
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Does treating OSA improve blood pressure?
To allow comparison between different age groups, blood pressure index (BPI) was calculated: BPI = measured mean BP/95th percentile pressure for sex, age and height.
Ng 2010 Ng 2010