SLEEP IN PATIENTS WITH CHRONIC RESPIRATORY DISEASES – A Wake Up Call for Chest Physicians

1. SLEEP IN PATIENTS WITH CHRONIC RESPIRATORY DISEASES – A Wake Up Call for Chest Physicians DR. J.C.SURI MD, DTCD, DNB, FNCCP Consultant, Professor & Head Dept. of Pulmonary, Critical Care & Sleep Medicine Vardhman Mahavir Medical College & Safdarjang Hospital, New Delhi

2. PHYSIOLOGY OF BREATHING Respiratory center is under the influence of • Behavioral inputs from cortical centers via reticular activating system • Chemical inputs from chemoreceptors responding to PaO2, PaCO2 and pH • Mechanoreceptors in the airway, lungs and chest wall Phillipson EA Am Rev Respir Dis 1978;118:909-939

3. THE CENTRAL CONTROL OF BREATHING Wakefulness (neural) Chemical (Hypoxic & Hypercapnic) Sensory afferent (Mechano receptors) Reticular formation Respective network Rhythm Generator Pattern Generator Motor Output Upper airways Diaphragm Intercostal muscle Accessory muscles Thorsten Schafer. Sleep Apnea. Prog Respir Res. Basel, Karger, 2006, vol 35 pp21-28

4. Effect of Sleep on Ventilation • Decreased neural output (i.e. drive to breath) • Hypotonia of intercostal and accessory muscles during REM Sleep • Shift of ventilatory burden exclusively on the diaphragm • Increased upper airway resistance • Decreased responsiveness to hypoxemia and hypercapnia (i.e. chemosensitivity) • Presence of SDB or OHS may further worsen ventilation

5. SPECIAL EFFECTS OF REM SLEEP ON ACCESSORY & POSTURAL MUSCLES • REM sleep causes • Widespread cortical and medullary neuronal activity • Postural & accessory muscle atonia (including upper airway) • Intermittent disruption of diaphragm EMG activity. • The ventilatory consequences are • Greater dependence on diaphragmatic contraction • Both VT and f are more variable than in NREM • A more collapsible upper airway

6. REM HYPOVENTILATION IN COPD Fletcher. JAP 1983;54:632-9

7. SLEEP-DISORDERED BREATHING SECONDARY TO POST-POLIO SYNDROME AND KYPHOSCOLIOSIS C3/A2 O2/A1 ROC/A1 Muscle artifact in the LOC and ROC channels LOC/A2 Stage 2 Stage 2 Stage 2 Chin EMG Right Anterior Tibialis Left Anterior Tibialis ECG Nasal/oral Airflow Respiratory Effort – Chest Respiratory Effort – Abdomen • 100% • - 50% • - 0% SaO2 = 88% Oximetry

8. HYPOVENTILATION IN REM SLEEP CAUSED BY LOSS OF ACCESSORY MUSCLE USE IN POST-POLIO PATIENT C3/A2 O2/A1 ROC/A1 LOC/A2 Stage REM Stage 1 Stage REM Chin EMG Right Anterior Tibialis Phasic twitches in leg EMG Left Anterior Tibialis ECG Nasal/oral Airflow Respiratory Effort – Chest Respiratory Effort – Abdomen • 100% • - 50% • - 0% SaO2 = 70% Oximetry

9. Effect of Sleep on Respiratory Muscles

10. Airway Resistance • Upper airway resistance increases during sleep compared to wakefulness • Marked loss of tonic activity in tongue, pharyngeal, laryngeal and intercostal muscles in REM Hudgel DW, Martin RJ. J Applied Physiol 1984:56:133-137 • Lower airway patency may be compromised . Nocturnal broncho-contriction seen in 50% asthmatics compared to 8% normal subjects Hetzel MR, Clark TJH. Thorax 1980;35:732-738

11. RESISTANCE AND VENTILATION DURING SLEEP J Appl Physiol 1996;81:282-289

12. Mouth occlusion pressure (P 0.1) in five adults patients after Added Resistance • Ventilatory compensation to resistive loading occurs during NREM, but whether this compensation is as marked as during wakefulness is not clear • During REM, ventilatory compensation is markedly reduced Wakefulness & NREM before and after addition of inspiratory resistance of 17 cm H2O/L/s Iber C J Appl Physiol 1982;52:607-614

13. Hypoxic Ventilatory Response to Sleep In adult men the hypoxic ventilatory response in NREM sleep is 2/3rd that in wakefulness, falling to 1/3rd of level of wakefulness during REM In adult women: no change in hypoxic response between wakefulness & NREM but response in REM is ½ that in other stages Douglas NJ Clin Chest Med 1985;6:563

14. Hypercapnic Ventilatory Response • Hypercapnic ventilatory response in adults drops during NREM to about ½ the level in wakefulness and falls further during REM to about 1/3 the level of wakefulness • Gender differences may exist Douglas NJ Clin Chest Med 1985;6:563

15. Effect of Sleep Disorders • Obstructive Sleep Apnea Syndrome • Sleep related Obesity Hypoventilation Syndrome • Both produce respiratory failure in sleep

16. EFFECTS OF SLEEP ON RESPIRATION Sleep Cortical Inputs Respiratory Center sensitivity Chemoreceptor & Mechanoreceptor sensitivity Respiratory Muscle contractility Lung mechanics: Airflow resistance FRC V/Q relationships Hypoventilation Hypoxemia Hypercapnia

17. Increase in pCo2 by 2-8 mmHg Decrease in pO2 by 3-10 mmHg or 2% decrease in SaO2 The drop in pO2 , Sao2 and rise in pCO2 is much more in patients of chronic resp. diseases Disruption of sleep architecture. CLINICAL SEQUELAE OF HYPOVENTILATION AND DECREASED CHEMOSENSITIVITY

18. No significant harmful effect in healthy individuals because of typical shape of the ODC curve. Effect of sleep related hypoventilation in health and disease • Significant hypoxia and hypercapnia develops in patients with chronic lung disease. • Baseline values of low PO2 and high PCO2 • Significant use of accessory muscles during wakefulness. • Instability of the upper airways

19. PATHOGENESIS OF DIURNAL RESPIRATORY FAILURE Sleep Nocturnal Hypoventilation Po2 pCo2 Elevated pCo2 Frequent Arousal Bicarbonate retention from the kidney Sleep Disruption Daytime Hypersomnolence Poor quality of sleep Normalization of pH Multiple episodes of micro & macro sleep Sleep deprivation Decreased respiratory drive Decreased Ventilatory Drive to Co2 Hypoventilation Diurnal respiratory failure

20. CONSEQUENCES OF SLEEP RELATED HYPOXEMIA IN PATIENTS WITH RESPIRATORY DISEASES • Symptoms of disrupted sleep • Poor sleep • Restlessness during sleep • Tiredness during awakening, but no sleepiness • Morning headaches

21. Effect of Nocturnal NIV • Prevents nocturnal hypoventilation • Promotes HCO3 secretion from kidneys • Normalizes sleep • Reduces daytime hypersomnolence • Improves chemosensitivity • Respiratory muscle rest

22. SLEEP AND CHRONIC CHRONIC RESPIRATORY DISEASES • COPD • ASTHMA • NEUROMUSCULAR DISORDERS • DPLDs

23. Sleep and Ventilation in COPD • Loss of enhanced awake central neural drive during sleep • Changes in chemo responsiveness to CO2 is accentuated in COPD patients • Hypoventilation mainly in REM sleep • Altered V/Q mismatch • Increased upper airway resistance

24. OXYGEN SATURATION DURING SLEEP IN A PATIENT WITH COPD Douglas et al. 1979; lancet, I,1-4

25. Sleep Disordered Breathing and COPD Co-existing sleep apnoea (overlap syndrome) in severe COPD may very from 10-20% More than 10% of OSA patients have undiagnosed COPD Chaouat A, Weitzenbaum E, Kreiger J Am J Respir Crit Care Med 1995; 151:82-86 Bradley TD J Am J Respir Crit care Med 1986; 134:920-924

26. Predictors of nocturnal desaturation in COPD patients • Nonobese patients with moderate to severe COPD with a H/O progressive decline in ABGs. • Hypercapnic patients with severe chronic bronchitis • Patients who experience oxyHb desaturation during exercise • Nocturnal O2 desaturation is associated with increased likelihood of CRF

27. INDICATIONS FOR EVALUATION OF SDB IN COPD • Moderate to severe daytime hypoxemia • Continued clinical deterioration despite the use of oxygen therapy • Pulmonary and systemic hypertension • Heart failure • Symptoms suggestive of SDB in patients who experience worsening hypercapnic failure despite stable spirometry

28. Diagnostic Approach  • Polysomnography • Oximetry • Portable devices 

29. Treatment of COPD • Optimize medical management • Oxygen Therapy • Nocturnal NIV plus Oxygen Therapy

30. Effect of nocturnal NIV on Chronic Stable COPD meta-analysis Meta-analysis of 4 RCTs Peter J. Wijkstra. Chest 2003;124;337-343

31. Effect of nocturnal NIV on Chronic Stable COPD – Multicenter trial • Reduction in hospitalization • Improvement in dyspnea • Better health related quality of life • Reduction in health care cost Sturani et al Eur Respir J 2002;20:529-38

32. Short-Term Effect of Controlled Instead of Assisted NIV in COPD Dellweg et al. RESPIRATORY CARE • DECEMBER 2007 VOL 52 NO 12

33. Short-Term Effect of Controlled Instead of Assisted NIV in COPD Dellweg. Et al RESPIRATORY CARE • DECEMBER 2007 VOL 52 NO 12

34. Short-Term Effect of Controlled Instead of Assisted NIV in COPD Dellweg et al. RESPIRATORY CARE • DECEMBER 2007 VOL 52 NO 12

35. Weight Gain in Cachetic COPD Patients Receiving Noninvasive Positive-Pressure Ventilation Change in body mass index after 6 months and 12 months of noninvasive positive-pressure ventilation, compared to baseline values. * p 0.05. † p 0.01 Budweiser et al. RESPIRATORY CARE • FEBRUARY 2006 VOL 51 NO 2

36. High-intensity Non-Invasive Positive Pressure Ventilation for stable Hypercapnic COPD IPAP (cmH2O) 28.0 ± 5.4 17(min) 42(max) EPAP) (cmH2O) 4.6 ± 1.3 2(min) 9(max) Windisch et al Int. J. Med. Sci. 2009, 6

37. Conclusions High-intensity NPPV is better tolerated by patients with severe chronic hypercapnic COPD and has been shown to be superior to the conventional and widely-used form of low-intensity NPPV in controlling nocturnal hypoventilation. High-intensity NPPV therefore offers a new promising therapeutic option for these patients. Nocturnal mean6SD arterial carbon dioxide tension (Paco2) at baseline and at follow-up visits Dreher et al. Thorax 2010;65:303e308

38. NIV in pulmonary rehabilitation of COPD patients Conclusion: nocturnal NIPPV is feasible and enhances the effects of pulmonary rehabilitation in advanced stage COPD. Thomas Ko¨hnlein et al. Respiratory Medicine (2009) 103, 1329e1336

39. Effect of NIV on stable COPD (Comparison of Costs) Enrico M. Clini. Respiration 2009;77:44–50

40. Impact of sleep on patients with neuromuscular or chest wall disease

41. Specific diseases • The history of a particular disease may also be helpful in some cases. • Patients with polio who had initial involvement of respiratory, trunk, or bulbar muscles, particularly with associated scoliosis or vocal cord paralysis, are more likely to develop abnormalities of gas exchange during sleep. • Kyphoscoliosis, even in the absence of neuromuscular disease, is associated with nocturnal hypoventilation and obstructive sleep apnea.

42. Indications for a nighttime sleep study in patients with neuromuscular and chest wall disease • Symptoms of sleep disordered breathing • Arterial blood gases showing hypoventilation (PaCO2 >45 mmHg) • FVC <50 percent predicted • Severely reduced Pimax • Unexplained cor pulmonale

43. There are no randomised-controlled trials concerning the outcome of noninvasive ventilation in these conditions, but studies have shown an improved quality of life, physical activity and haemodynamics, normalisation of blood gases and slight improvement in other physiological measures, such as the vital capacity and maximal mouth pressures. Survival in chest wall disorders is 90% at 1 yr and 80% at 5 yrs, and similar figures have been obtained in nonprogressive neuromuscular conditions. If, however, the underlying disorder is deteriorating, particularly if it involves the bulbar muscles, it may limit survival despite the provision of adequate noninvasive ventilatory support. Shneerson et al. Eur Respir J 2002; 20: 480–487

44. Kyphoscoliotic Ventilatory Insufficiency Effects of Long-term Nocturnal NIV Blood Gas Levels and Lung Function Breathing Pattern and Respiratory Muscle Strength* Cruz Gonzalez. Chest 2003;124;857-862

45. CONCLUSIONS • Lung diseases can present with a vast array of sleep related breathing abnormalities and symptoms • Sleep induced hypoventilation is the common cause of worsening failure • If night-time symptoms are present or suspected, overnight PSG with the determination of optimal treatment in a laboratory setting are recommended • Treatment of the underlying lung disease is an important first step • Nocturnal NIV can significantly improve daytime symptoms and ABGs

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