CENTRAL SLEEP APNEA SYNDROME PATHOPHYSIOLOGY

1. CENTRAL SLEEP APNEA SYNDROME PATHOPHYSIOLOGY Oya İTİL Dokuz Eylül Medical Faculty,Dept.of Chest Diseases, İZMİR

2. CENTRAL APNEA • Absence of both respiratory effort and air flow during sleep

3. CENTRAL SLEEP APNEA SYNDROME • The clinical picture is characterized by: • AHI > 5 • > 50 % of apneas-hypopneas central • Frequent arousals and sleep fragmentation • Excessive daytime sleepiness

4. CENTRAL SLEEP APNEA SYNDROME • Primary central sleep apnea syndrome • Other central sleep apneas due to medical conditions • Cheyne Stokes breathing • Periodic breathing due to high altitude • Central sleep apnea due to a medical problem

5. Central sleep apnea syndrome related with drug addiction • Other sleep-disordered breathing syndromes due to drug addiction • İnfant primary sleep apnea

6. CLINICAL CLASSIFICATION HYPERCAPNIC Central Alveolar Hypoventilation Primary Secondary Ancephalitis Cervical chordotomy Brainstem infarct Brainstem tumours Bulbar polyomyelitis Respiratory Muscle Weakness Neuromyopathies Myotonic dystrophy Muscular dystrophy Myastenia Gravis A. Lateral Sclerosis Asid maltase deficiency Postpolio syndrome Diaphragm paralysis

7. NON-HYPERCAPNİC Cheyne-Stokes Breathing Congestive heart failure Brain lesions Renal failure High altitude İdiopathic central sleep apnea

8. Hypercapnic CSAS • Both daytime and nocturnal hypercapnia • Chronic pathology in the control or mechanic of respiration ( in the respiratory muscles ) • This type of CSAS have been classified in ‘‘Hypoventilation Syndromes’’according to the new classification.

9. Non – hypercapnic CSAS • Absence of daytime hypercapnia • Disorder in the control of respiration • İmbalance in chemorereflexes of respiration or in reflex inhibition of respiratory center

10. During transition to sleep ( awake pCO2 is lower than pCO2 during sleep and there is no response to respiratory effort) • When respiratory control system is dominant ( idiopathic central apnea ) • When respiratory control system is combined with the increase in circulation time ( Cheyne-Stokes respiration ) • When there is a defect in the control mechanisms of pCO2 ( hypercapnic respiratory failure ) central apneas can be seen

11. CONTROL OF RESPIRATION • Metabolic (automatic) control system • Behavioral control system • Wakefullness stimulus system

12. Metabolic (automatic) control system • Chemoreceptors, intrapulmonary vagal receptors, central nervous system receptors transporting peripheral signals of respiration to the brain

13. Carotid body functions in hypoxia while both carotid body and medullary chemoreceptors take role in hypercapnia. • This control system determines the amount and the frequency of the breath.

15. Behavioral control system • This system is an automatic state for actions without thinking like eating or speaking. • The origin of the neural stimulus to start the system is probably located in the frontal lobe.

16. Wakefullness stimulus system • It’s a tonic stimulus produced as a result of a decrease in the respiratory stimulants in the brain or sensorial mechanisms other than respiration like sighing although this is not been clarified exactly.

17. RESPİRATORY CONTROL SYSTEM Behavioral control system Waking neuralAutomatic CO2, drivecontrol system O2 N. Respiratory Vagus Muscles

18. During wakefullness while respiration is primarily controlled by metabolic and behavioral system waking neural drive is also active.

19. During sleeping • PaO2 3- 10 mm Hg decreases • PaCO2 4- 8 mm Hg increases • PH 0.01- 0.06 Ü decreases • SaO2 % 1-3 decreases • VE 1-2 lt / min

20. During sleep, particularly non-REM sleep, respiration is controlled by only ‘‘metabolic control system’’ (primarily with afferent chemoreceptors and vagal intrapulmonary receptors).

21. While response to hypoxia and hypercapnia diminishes in N-REM, this unresponsiveness increases more in REM sleep.

22. The most important factor in the regulation of respiration in sleep arterial PCO2 • A minimal increase in PCO2 causes a respiratory response while a change in PO2 within normal ranges doesn’t lead a respiratory response.

24. Small drops in PCO2 (approximately 3 – 6 mm Hg) at sleep can result in the development of apnea or hypoventilation. • Each person has his specific own apnea threshold value at which PCO2 drops.

25. Periodic breathing which develops as the result of chronic hypoxemia has been shown to end with increasing the PCO2 (over the threshold value) . • Now it’s clear that periodic breathing not only develops from hypoxemia but also from hypocapnia.

26. Another hypothesis is ; the development of vagal stimulus as the result of the increase in tidal volume (hyperventilation), act of apneic threshold and the appearance of central apneas. • The development of central apneas along with periodic breathing during sleep at high altitude clarifies the pathogenesis.

27. Central Apneas Developed As a Result of the Respiratory Control Disorder

28. Central Apneas Occurring During Transition To Sleep • During sleep, breathing becomes dependent on the metabolic control system and the primary stimulant of respiration is arterial PCO2. During the transition from wakefullness to the initial stages of sleep, respiration becomes irregular and PCO2 threshold value is reached and apnea develops, the patient awakens and this state continues till sleep becomes regular.

29. Then, metabolic control system becomes active. • In non hypercapnic CSAS, frequent central apneas appear during transition from wakefullness to sleep . For this reason, AHI is highest inN-REM stage I .

30. In patients with respiratory failure, behavioral control system becomes active in wakefullness. • However, since metabolic control system is also defective during transition to sleep in these patients, behavioral control system still continues to be active.

31. In patients with chronic hypercapnia in wakefullness, a few central apneas in REM, hypoventilasyon is dominant • In persons with a minimal or absent PCO2 sensitivity central apneas are frequent during sleep

32. These persons are with “Central Alveolar Hypoventilation” (Ondine’s curse) and “Obesity Hypoventilation” (Pickwick).

33. Hypoxemia and hypercapnia worsen more during sleep, central and obstructive apneas are seen together.

34. İdiopathic (Primary) Central Sleep Apnea • Persons with wakefullness hypercapnia who respond to even minimal hypercapnia (0.6 ± 0.2 L/dak/mmHg) during sleep, • Persons with low PCO2 levels in wakefullness who respond to higher hypercapnias (2.9 ± 0.4 L/dak/mmHg) during sleep (idiopathic central sleep apnea).

35. Hyperventilation and subsequent hypocapnia with arousal has been shown to develop in patients with idiopathic central sleep apnea. • Apneas of patients with idiopathic central apnea, end with a sharp-deep breath (the difference from Cheyne Stokes breathing).

36. Respiratory failure is not seen in non – hypercapnic type. • Symptoms are partly like the symptoms of patients with obstructive sleep apnea.

37. Daytime sleepiness appears less in patients with pure idiopathic central apnea in comparison with obstructive sleep apnea.

38. More frequent complaints of patients with central apneas are ‘insomnia’ ‘ tired awakening ’ and ‘frequent awakening at night’. Part of the awakenings are defined as shortness of breath or need for air. • Body weight is usually normal (different from obstructive sleep apnea )

39. No direct relation of the number and the duration of central apneas with the clinical picture has been shown.

40. Oxygen saturation drops more in obstructive apneas compared with central apneas. • The reason; 1) Longer apnea duration 2) Lower lung volume due to obesity 3) The continuation of the respiratory effort in spite of apnea.

41. Hemodynamic alterations have not been studied much in central apnea. • Pulmonary and systemic blood pressure have been reported to increase during central apnea.

42. Repeated , idiopathic central apneas develop in primary CSAS .With the action of respiratory muscles, respiration comes back suddenly and the apnea ends. No daytime hypercapnia is observed.

43. OTHER CENTRAL SLEEP APNEA SYNDROMES

44. Cheyne Stokes Breathing • In patients with congestive heart failure Cheyne Stokes Breathing (CSB) occurs in sleep and wakefullness. • Quality of sleep is disturbed particularly because of arousals which develop during hyperpneic breathing.

45. Persons with left heart failure and CSB have been reported to live shorter than persons with left heart failure without this type of breathing problem.

47. Delayed circulation time as well as increased PCO2 sensitivity have been detected. • Although CSB is frequently observed during sleep , it can appear during wakefullness in severe cases.

48. CSB can also be seen particularly in cerebrovascular disorders and renal failure. • CSB is typically observed in non – REM sleep.

49. Diagnostic criteriae according to AASM: 1) Absence of CHF or cerebrovascular disease 2) The appearance of respiratory pattern as creshendo-decreshendo type in minimum 3 subsequent respiratory cycli

50. Periyodik Solunum • “Mountain Disease” • lt’s observed in many people after climbing higher than 7600 meters.