Obstructive Sleep Apnea: A Physiological Approach Robert L. Owens, - PDF document

2/13/2018 Obstructive Sleep Apnea: A Physiological Approach Robert L. Owens, MD February 2018 Outline • Cause(s) of OSA • Can we measure the causes in an individual? • Is that useful? 1

2/13/2018 Thoracic pressure swings (↑LV a�erload) What happens when you fall asleep: normal Wake Sleep Ventilation Ventilatory Demand Time 2

2/13/2018 What happens when you fall asleep: normal or OSA Wake Sleep Ventilation Ventilatory Demand Ventilation ≠ Demand Because of poor anatomy Time What happens when you fall asleep: normal or OSA Hypoventilation leads to increased ventilatory Wake Sleep demand, which will activate upper airway Ventilation muscles to improve ventilation. Ventilatory But, muscle recruitment Demand and improvement in ventilation is variable. Good muscle response achieves acceptable ventilation Time 3

2/13/2018 What happens when you fall asleep: OSA Hypoventilation leads to increased ventilatory Wake Sleep demand, which will activate upper airway Ventilation muscles to improve ventilation. Ventilatory But, muscle recruitment Demand and improvement in ventilation is variable. Poor muscle response does not achieve acceptable ventilation Time What happens when you fall asleep: OSA Wake Sleep Arousal Arousal Threshold Ventilation Ventilatory Demand Poor muscle response does not achieve acceptable ventilation and the respiratory arousal threshold is crossed Time 4

2/13/2018 What happens when you fall asleep: OSA Wake Sleep Arousal Arousal Threshold Ventilation Loop gain Ventilatory Demand How quickly the ventilatory demand increases for a change in ventilation is the loop gain of the system Time What happens when you fall asleep: OSA Wake Sleep Arousal Arousal Threshold Ventilation Ventilatory Demand This patient has OSA – when they go to sleep they hypoventilate, and wake themselves up due to: Anatomy, upper airway muscles, arousal threshold, and loop gain Time 5

2/13/2018 Better muscles can prevent OSA Wake Sleep Arousal Threshold Ventilation Ventilatory Demand For same anatomy, better muscles can lead to stable flow limited breathing, no arousal Time ↑ arousal threshold may prevent OSA Wake Sleep Arousal Threshold Ventilation Ventilatory Demand Similarly, with same anatomy and muscle response, a higher arousal threshold may allow respiratory drive to increase enough to recruit muscles sufficiently to sustain ventilation. Time 6

2/13/2018 Decreased loop gain can help, too Wake Sleep Arousal Threshold Ventilation Ventilatory Demand Similarly, a lower loop gain may prevent ventilatory demand from rising above the arousal threshold. Time Pathogenesis of sleep apnea High loop gain Poor upper airway muscle response Small, collapsible Low arousal threshold upper airway Obstructive Sleep Apnea 7

2/13/2018 Outline • Cause(s) of OSA • It might be more than just a fat neck • Can we measure the causes in an individual? • Is that useful? Can we measure the response to hypoventilation during sleep? Wake Sleep Ventilation Ventilatory Demand Time 8

2/13/2018 Yes, by letting the airway collapse 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 0 5 CPAP 0 level ( cmH 2 O ) -5 -10 Measuring anatomy 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 0 8 6 Eupnea Ventilation 4 ( L/min ) 2 Anatomy 0 50 100 150 200 250 Time (seconds) With repeated drops, we can measure how much the upper airway is open at different pressures, or at atmospheric pressure (0cmH 2 O) 9

2/13/2018 Measuring muscle response 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 0 8 ? 6 Eupnea Ventilation 4 ( L/min ) UA muscle response 2 Passive UA 0 50 100 150 200 250 Time (seconds) With hypoventilation, ventilatory demand will increase an unknown amount, and some muscle recruitment will occur Measuring loop gain 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 Obstruction 0 removed, ventilation again 8 matches ventilatory drive 6 Eupnea Ventilation 4 ( L/min ) UA muscle response 2 Passive UA 0 50 100 150 200 250 Time (seconds) Return to holding pressure opens upper airway and reveals ventilatory demand 10

2/13/2018 Measuring loop gain 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 0 Ventilatory Drive 8 6 Eupnea Ventilation 4 ( L/min ) UA gain = muscle response/ventilation deficit 2 Passive UA 0 50 100 150 200 250 Time (seconds) With knowledge of the ventilatory drive, can calculate loop gain of the system, and upper airway gain Measuring loop gain 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 0 8 Ventilatory Drive 6 overshoot ventilation Eupnea Loop gain = Ventilation ventilation deficit 4 ( L/min ) UA gain = muscle response/ventilation deficit 2 Passive UA 0 50 100 150 200 250 Time (seconds) With knowledge of the ventilatory drive, can calculate loop gain of the system, and upper airway gain 11

2/13/2018 Measuring arousal threshold 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 0 Ventilatory Drive? 8 ? 6 Eupnea Ventilation 4 ( L/min ) X 2 Passive UA 0 50 100 150 200 250 Time (seconds) Some CPAP drops, the ventilation will be so low, that the ventilatory drive gets so high that you have an arousal. Measuring arousal threshold 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 0 Ventilatory Drive at arousal 8 6 √ = arousal threshold ventilatory drive Eupnea Loop gain = Ventilation √ ventilation deficit 4 ( L/min ) X 2 Passive UA 0 50 100 150 200 250 Time (seconds) Use loop gain to predict ventilatory drive at this point = AT 12

2/13/2018 Measuring the traits 15 CPAP Therapeutic pressure 10 level ( cmH 2 O ) 5 0 Ventilatory Drive 8 6 overshoot ventilation Eupnea Loop gain = Ventilation ventilation deficit 4 ( L/min ) UA muscle response 2 Passive UA 0 50 100 150 200 250 Time (seconds) Wellman JAP 2011 Automated methods to measure the traits! 13

2/13/2018 Outline • Cause(s) of OSA • It might be more than just a fat neck • Can we measure the causes in an individual? • Yes • Is that useful? N = 75 subjects 2013 14

2/13/2018 As expected, anatomy worse in those with OSA Worse Anatomy Better Anatomy AHI (OSA Severity) But no difference in muscle responsiveness… Controls OSA 15

2/13/2018 Or Loop Gain between controls and those with OSA And Arousal Threshold goes the wrong way?! Harder to wake up (Protective??) Controls OSA 16

2/13/2018 Pathogenesis of sleep apnea Poor pharyngeal muscle response High loop gain Small, collapsible Low arousal threshold upper airway So is this true? Is it just having a Obstructive Sleep Apnea fat neck? A new model that includes Effect Modification Upper airway Exposure passive anatomy Open Closed Effect modifiers No OSA Outcome OSA (High LG – CSA?) (Low AT – insomnia?) 17

2/13/2018 Non anatomical traits are important in some people Upper airway Exposure passive anatomy Vulnerable Anatomy Open Closed Effect Loop gain modifiers Arousal threshold Upper airway gain Outcome No OSA OSA Anatomy is important in everyone Always have OSA Worse Anatomy Vulnerable anatomy – could go either way Better Anatomy Never have OSA AHI (Apnea Severity) 18

2/13/2018 Loop gain is important if you have vulnerable anatomy LOW LG HIGH LG In this anatomically vulnerable group of patients, whether you have OSA is dependent on LG Muscle responsiveness is important if you have vulnerable anatomy Good muscles (no sleep apnea) Bad muscles (OSA) No difference in slope, until you get to vulnerable anatomy 19

2/13/2018 Non anatomical traits are important in some people Upper airway Exposure passive anatomy Vulnerable Anatomy Open Closed Effect Loop gain modifiers Arousal threshold Upper airway gain Outcome No OSA OSA Will always have OSA Probably should have OSA, but many could be treated without CPAP? Probably should not have OSA 20

2/13/2018 Outline • Cause(s) of OSA • It might be more than just a fat neck • Can we measure the causes in an individual? • Yes • Is that useful? • Potentially Physiology may help: • Understand the cause of OSA in an individual (or group of people) • Predict the improvement with non PAP anatomical therapy (e.g. surgery, oral appliance) • Choose a primary treatment for OSA? • Predict adherence to therapy? • Predict symptoms related to OSA? 21

2/13/2018 Why do different people have OSA? Why do different groups of people have OSA? 22

2/13/2018 Can physiology predict those who respond to oral appliances and surgery? Can physiology predict those who respond to oral appliances and surgery? 23

2/13/2018 Can physiology predict those who respond to oral appliances and surgery? Treatments to improve the non‐anatomical traits • Arousal Threshold • Sedative hypnotics (eszopiclone, trazodone) • ?Behavioral therapy + non CPAP Anatomy Improvements • Loop Gain • Oxygen Position Therapy • Acetazolamide Oral Appliance • Upper airway muscles • HGNS • Drugs? 24

2/13/2018 Targeting the problem Eckert Clin Sci 2011 Does low ArTH predict adherence? 25

2/13/2018 Does low ArTH predict adherence? Ye ERJ 2014 26