Obstructive Sleep Apnea Poor bedfellow Dessislava Ianakieva MD

Obstructive Sleep Apnea: Poor bedfellow Dessislava Ianakieva, MD Sleep Medicine Fellow 5/17/17

Objectives Understand the mechanism of sleep apnea Know factors that increase the incidence of sleep apnea in adults Understand the meaning of “AHI” Understand the effects of sleep apnea on the cardiovascular system Learn the basic treatments of sleep apnea. Understand the risk factors for and symptoms of pediatric sleep apnea. Understand basic treatments of pediatric sleep apnea.

Obstructive sleep apnea: The basics

Evaluating sleep disorders: Polysomnogram EEG EOG Nasal Et. CO 2 Nasal Oral Airflow Chin EMG (2) Microphone Sa. O 2 EKG Tech Observer Video Camera Respiratory Effort Leg EMG (2) Records behavior Essentials of Sleep Technology: Pediatrics. Westchester, IL. American Academy of Sleep Medicine, 2006

Polysomnogram

Obstructive Sleep Apnea Ø Complete or partial upper airway obstruction Ø Often results in reductions in oxygen saturation Ø Often terminated by brief arousals from sleep Ø Duration of each obstruction is at least 10 seconds

Respiratory Events: Definitions Hypopnea

EKG Exhale Airflow Inhale Thoracic effort Effort gradually increases Paradoxing Abd. effort SAO 2 Airway opens Airway obstructs Paradoxing Ends Blood oxygen levels reduce to >3% of baseline value Obstructive Apnea Event

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Normal hypnogram Hypnogram in OSA

Obstructive Sleep Apnea in Adults Estimated prevalence: ü 9% in women ü 24% in men

Physiologic changes in OSA Intermittent hypoxia Endothelial dysfunction Intermittent hypercapnia Systemic inflammation Increased negative intrathoracic pressure swings Hypercoagulability Increased arousals from sleep Left atrial enlargement Sleep fragmentation Myocardial ischemia Sympathetic nervous system activation Cardiac remodeling Metabolic dysregulation Impaired cardiac function Arrhythmia

Other consequences of untreated OSA Overall increase in mortality Excessive daytime sleepiness Motor vehicle accidents Mood disorders Decreased quality of life OSA: Sudden cardiac death peaks between 12 -6 AM Cardiovascular events occur in the early hours

Sleep Apnea and Sudden Death Respiratory depressants may block the arousal process Alcohol Benzodiazepines Barbiturates Opioids Avoid alcohol within 4 hours of bedtime

Symptoms of OSA Middle Age Pauses in breathing Snoring Nocturia Frequent nocturnal awakenings Morning headache Dry mouth Morning GERD Excessive daytime sleepiness Impaired cognition Older > 60 years Excessive daytime sleepiness Nocturia

Risk factors for OSA Male sex Older age (40 -70 years) Postmenopausal status BMI >35 Craniofacial and upper airway abnormalities Resistant hypertension PCOS

Diagnosis of OSA In-lab polysomnogram is the gold standard Home sleep apnea test- unattended Apnea Hypopnea Index (AHI)= respiratory events per hour of sleep Apnea (90%obstruction of flow) + hypopnea (30% flow limitation) Normal < 5 Mild: 5 -15 Moderate: 15 -30 Severe > 30

Screening questionnaire: STOP-BANG STOP-Bang score ≥ 3 Sensitivity - 89% to detect moderate to severe OSA - 93% to detect severe OSA Specificities - 30% for moderate to severe - 29% for severe OSA

Physical Exam Findings Mallampati Macroglossia Neck circumference Women > 16 in Men >17 in High arched palate Midface hypoplasia BMI > 35 Central obesity Retrognathia

OSA and cardiovascular disease Circulation. 2008; 118: 1080 -1111

OSA and Hypertension ü ↑ sympathetic nerve activity and catecholamine levels ü Repetitive hypoxemia and hypercapnia chemoreflex-mediated sympathetic activation and vasoconstriction ü At the termination of apneas: ↑ cardiac output and severe vasoconstriction BP can rise from 130/60 mm Hg awake to 220/130 mm Hg during apneas ü Diastolic nocturnal hypertension ü Loss of nocturnal dipping of blood pressure. From Somers VK, Dyken ME, Clary MP, et al. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995; 96: 1897 -1904. )

OSA And Incident Hypertension Sleep Heart Health Study (6424 patients) Ø Linear relationship between the severity of OSA and the risk of systemic hypertension Mild OSA (AHI 5 -15): Ø 2 fold increased risk Moderate to severe OSA (AHI >15): Ø 3 fold increased risk N Engl J Med 2000; 342: 1378.

OSA And Hypertension 71% of patients with resistant hypertension have OSA compared to 38% of patients with controlled hypertension. Increased risk of hypertension in patients with OSA who were not compliant with CPAP at 12 years of follow up.

OSA and Diabetes OSA is an independent risk factor for the development of T 2 DM 15%– 30% of patients with OSA have T 2 DM ↑ severity of OSA correlates to increased T 2 DM incidence and poor glycemic control Sleep Health Heart Study Mild OSA – Diabetes OR=1. 27 ( CI 0. 98– 1. 64) Moderate-to-severe OSA- Diabetes OR=1. 46 (95% CI 1. 09– 1. 97) OSA severity was associated with increased insulin resistance Nocturnal hypoxemia independently associated with glucose intolerance

Nature and Science of Sleep 2015: 7

Treatment options for OSA in adults

Indications for treatment AHI >5 events per hour of sleep plus one or more clinical or physiologic sequelae attributable to OSA. AHI ≥ 15 events per hour of sleep, even in the absence of symptoms Mission critical work (airline pilots, air traffic controllers, locomotive engineers, DOT drivers) with AHI between 5 and 15 events per hour of sleep, even if there are no clinical or physiological symptoms attributable to OSA. Treatment options: Positive airway pressure therapy Oral appliances Positional therapy Bariatric surgery Adenotonsillectomy

Positive airway pressure modalities

Continuous Positive Airway Pressure (CPAP) Best Treatment for Significant OSA • CPAP splints open the airway wherever the obstruction

Effect of OSA treatment on comorbid conditions

CPAP Treatment And Cardiovascular Events A prospective cohort study followed 1651 men for a mean of 10 years following polysomnography. Treatment with CPAP reduced incidence of fatal and non-fatal cardiovascular events Lancet. 2005; 365(9464): 1046. A prospective cohort study followed 449 patients with mild or moderate OSA (~6 years follow up) Treatment of OSA (Primarily CPAP) associated with reduction of likelihood of cardiovascular events Adjusted HR 0. 36 (95% CI 0. 21 -. 62) Am J Respir Crit Care Med. 2007; 176(12): 1274.

CPAP Treatment And Cardiovascular Events ü Reduction in AHI from 29 to 3. 7 events per hour ü No statistically significant effect on cardiovascular events ü Significant reduction in snoring and daytime sleepiness ü Improvement in health-related quality of life and mood CAVEAT: Ø Average CPAP use ~ 3. 3 hours per night Ø Excluded patients with excessive daytime sleepiness

CPAP treatment and hypertension CPAP treatment decreases in systolic blood pressure of 2. 5 to 3. 0 mm Hg Patients with uncontrolled hypertension are likely to gain the largest benefit (reduction in blood pressure) from CPAP improves blood pressure control more than nocturnal oxygen supplementation

CPAP and Resistant Hypertension RCT of of 117 patients assessed the effect of continuous positive airway pressure (CPAP) treatment on 24 -h urinary aldosterone excretion in patients with Resistant hypertension (RHT) and moderate/severe OSA. Decreased aldosterone excess in resistant hypertensive individuals with OSA Effect was observed with optimal use only (>6 hr of use per night) More pronounced in effect: non-dippers, not on spironolactone, less obese, lowest nocturnal oxygen saturation J Hypertens. 2017 Apr; 35(4): 837 -844

Positive Airway Pressure And Heart Failure Men with severe OSA (AHI >30 ) were 58 % more likely to develop heart failure Canadian Positive Airway Pressure (CANPAP) trial Sleep. 2015; 38(5): 677. Epub 2015 May 1 A meta-analysis (6 RCT) CPAP was associated with a 5% improvement in ejection fraction PLo. S One. 2013; 8(5): e 62298 Canadian Positive Airway Pressure (CANPAP) trial Greater reduction in AHI Improvements in mean nocturnal O 2 sat Improvement in left ventricular ejection fraction Improvement in 6 minute walk distance Circulation 2007; 115: 3173.

Positive Airway Pressure Therapy And Atrial Fibrillation Rate of recurrent AF after cardioversion: • Untreated OSA- 86% • Treated OSA 42% • Without OSA 53 % CPAP therapy effect on AF: Ø Reduces the structural and electrical remodeling of the left atrium due to OSA Ø Decreases serum markers of oxidative stress (cytokines and free radicals) Heart Rhythm. 2013 Mar; 10(3): 331 -7.

Continuous Positive Airway Pressure Therapy In OSA and Glycemic Control Clinically significant improvement in glycemic control Ø Amelioration of evening fasting glucose metabolism Ø Reduction in the dawn phenomenon Diabetes Obes Metab, 2016.

Oral appliance: Mandibular repositioning devises ü Indicated for mild-moderate OSA ü 50% reduction in the AHI Advancement to the maximum tolerable distance or 65% of the maximum protrusion ü Discontinuation rates of 14– 63% after 4 -5 years Med Oral Patol Oral Cir Bucal. 2015 Sep 1; 20(5): e 605 -15

Bariatric surgery and OSA Higher prevalence of OSA among the morbidly obese: 55% in women and 80% in men . 2 Remission of OSA (AHI < 5 events/h) at 1 year follow up: 66% RYGB patients vs 40% ILI patients Journal of Clinical Sleep Medicine, Vol. 9, No. 5, 201 v 50% reduction in AHI with 10%15% reduction in body weight

Pediatric Obstructive Sleep Apnea

Snoring in children 10% of children snore 1 -5 % have sleep disordered breathing Snoring > 3 times per week associated with increased risk of OSA Peak prevalence: 2 and 8 years of age Chronic nasal congestion Adenotonsillar hypertrophy

Diagnosis Of Sleep Apnea In Children Overnight oximetry specific but not sensitive In-lab polysomnogram- gold standard Pediatric obstructive apnea index Excluding central apnea and hypopnea Mild: 1 -5 Moderate: 5 -10 Severe: >10 Respiratory events are shorter (2 breaths) Smaller oxygen desaturations

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OSA Risk factors in children Tonsillar and adenoidal hypertrophy History of prematurity and multiple gestation Family history of OSA Craniofacial abnormalities Neuromuscular disorders Myelomeningocele History of low birth weight Family history of OSA Uncontrolled epilepsy Obesity

Syndromes associated with OSA Trisomy 21 (Down Syndrome) Prader-Willi Robin sequence Treacher Collins Beckwith-Wiedemann Achondroplasia Smith Magenis Turner Syndrome Strickler Syndrome Fetal Alcohol Syndrome Arnold-Chiari malformation

OSA symptoms in children Common signs and symptoms during sleep: Snoring Common signs and symptoms during wakefulness: v Poor school performance Pauses in breathing Chocking or gasping Increased work of breathing Enuresis v Aggressive behavior v Hyperactivity Excessive sweating v Excessive daytime sleepiness Hyperextended neck v Morning headaches Frequent awakenings v Failure to thrive Only 9 -13% exhibit daytime sleepiness

Physical exam findings Tonsillar hypertrophy Retrognathia Obligate mouth breathers Midface hypoplasia Dental crowding Macroglossia

Effects Of Untreated Pediatric OSA Failure to thrive Increased energy expenditure due to increased work of breathing Decreased nocturnal growth hormone secretion may be decreased in children with increased upper airway resistance Improvement in growth hormone secretion after adenotonsillectomy Cadiovascular effects in children with POAHI >5 Lower RV ejection fraction Increased LV diastolic dysfunction Remodeling with larger interventricular septal thickness index on echocardiogram Effects noted were independent of the effect of obesity

Effects Of Untreated Pediatric OSA Endothelial dysfunction Metabolic dysregulation Impaired glucose tolerance Hyperlipidemia NASH Impairment of neurocognitive development Poor school performance Behavioral problems

Grey matter volume reductions superior frontal, prefrontal, superior and lateral parietal cortices that control of cognition and mood

Adenoidal Facies

Treatment of OSA in Children Mild sleep apnea: Optimization of nasal passage patency Nasal steroid Leukotriene receptor antagonists Saline rinse Weight loss Orthodontia Moderate-severe sleep apnea: Tonsillectomy and Adenoidectomy Residual or severe sleep apnea: CPAP therapy Other surgical interventions Mandibular distraction

Effects of treatment of pediatric sleep apnea Improvement of: Behavior Attention span Quality of life Neurocognitive functioning Enuresis Parasomnias Restless sleep Reversal of associated cardiovascular sequelae Improvement in cardiac function Decrease in average heart rate and blood pressure Improvement in endothelial function

Adenotonsillectomy Success rate of adenotonsillectomy is 75%-85% Poor prognostic factors: Obesity Severe OSA pre-surgery with an POAHI of >20/hr Cildren aged >7 years High Mallampati score African-American ethnicity Craniofacial abnormalities (e. g. , Pierre Robin syndrome) Chromosomal abnormalities (e. g. , trisomy 21) Neuromuscular disease

Risk Factors For Complications Following Adenotonsillectomy Ø Increased severity of OSA with increased obesity Ø Evaluate for atlantoaxial instability and Ø Likely to require adjuvant surgical procedures Ø Severity and sites of airway obstruction Ø Likely to require adjuvant surgical procedures Ø At risk for significant hypoventilation Ø At risk for pulmonary and cardiac dysfunction Ø Increased adenoid and tonsil size Ø Increased risk for respiratory complications

Adenotonsillectomy The Childhood Adenotonsillectomy Trial (CHAT) Surgical treatment did not significantly improve attention or executive function as measured by neuropsychological testing Surgical treatment did: Reduce symptoms Improve behavior and quality of life Normalization of polysomnographic findings 79% vs. 46% n engl j med 368; 25 june 20, 2013

Mandibular Distraction Bilateral corticotomy of the mandible Insertion of either internal or external metal distractors Gradual distraction of the mandible while new bone fills in the gap Indicated in children with significant micrognathia and severe sleep apnea Paediatr Respir Rev. 2015 June ; 16(3): 189– 196.

CPAP Therapy In Children Indications: - Residual OSA after adenotonsillectomy - OSA related to obesity - Craniofacial abnormalities - Neuromuscular disorders - OSA without adenotonsillar hypertrophy - Preference for non-sugical treatment Mental age of 8 Weigh >30 kg Desensitization Regular evaluation for mask fit BOTTOM LINE: Elimination of symptoms, signs, and polysomnographic abnormalities in 90 %

Questions ? ? ?

References: Durán-Cantolla. J et al. Efficacy of mandibular advancement device in the treatment of obstructive sleep apnea syndrome: A randomized controlled crossover clinical trial. Med Oral Patol Oral Cir Bucal. 2015 Sep 1; 20(5) Marin JM et al. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 2005; 365(9464): 1046. Buchner NJ et al. Continuous positive airway pressure treatment of mild to moderate obstructive sleep apnea reduces cardiovascular risk. Am J Respir Crit Care Med. 2007; 176(12): 1274. Marie-Françoise Vecchierini et al. A custom-made mandibular repositioning device for obstructive sleep apnoea–hypopnoea syndrome: the ORCADES study. Sleep Medicine. Volume 19, March 2016, Pages 131– 140 Mc. Evoy RD et. Al. CPAP for Prevention of Cardiovascular Events in Obstructive Sleep Apnea. N Engl J Med. 2016; 375(10): 919. Epub 2016 Aug 28. Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000; 342: 1378. Tomas Konecny et al. Obstructive Sleep Apnea and Hypertension. 2014; 63: 203 -209. Marin JM et al. Association between treated and untreated obstructive sleep apnea and risk of hypertension. JAMA. 2012; 307(20): 2169. Kanagala R et al. Obstructive sleep apnea and the recurrence of atrial fibrillation. Circulation. 2003; 107(20): 2589. Epub 2003 May 12. Holmqvist F et al. Impact of obstructive sleep apnea and continuous positive airway pressure therapy on outcomes in patients with atrial fibrillation-Results from the Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF). Am Heart J. 2015 May; 169(5): 647 -654. e 2. Epub 2015 Feb 7. Hla KM et al. Coronary heart disease incidence in sleep disordered breathing: the Wisconsin Sleep Cohort Study. Sleep. 2015; 38(5): 677. Epub 2015 May 1. Mansfield DR et al. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J Respir Crit Care Med. 2004; 169(3): 361. Sun H et al. Impact of continuous positive airway pressure treatment on left ventricular ejection fraction in patients with obstructive sleep apnea: a meta-analysis of randomized controlled trials. PLo. S One. 2013; 8(5): e 62298. Epub 2013 May 1 Nieminen P et al. Growth and biochemical markers of growth in children with snoring and obstructive sleep apnea. Pediatrics. 2002; 109(4): e 55. Chan JY et al. Cardiac remodelling and dysfunction in children with obstructive sleep apnoea: a community based study. Thorax. 2009; 64(3): 233. Gozal D et al. Obstructive sleep apnea and endothelial function in school-aged nonobese children: effect of adenotonsillectomy. Circulation. 2007 Nov; 116(20): 2307 -14. Epub 2007 Oct 29. Marcus CL et al. A randomized trial of adenotonsillectomy for childhood sleep apnea. N Engl J Med. 2013; 368(25): 2366. Waters KA et al. Obstructive sleep apnea: the use of nasal CPAP in 80 children. Am J Respir Crit Care Med. 1995; 152(2): 780.