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Sleep-related hypoventilation syndromes

Sleep-related hypoventilation syndromes. Jean Louis Pépin, Maurice Dematteis, Claire Arnaud, Sandrine Launois, Renaud Tamisier and Patrick Lévy. Sleep laboratory, HP2 laboratory EA 3745 ERI 0017 INSERM, Grenoble, France. Content

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Sleep-related hypoventilation syndromes

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  1. Sleep-related hypoventilation syndromes Jean Louis Pépin, Maurice Dematteis, Claire Arnaud, Sandrine Launois, Renaud Tamisier and Patrick Lévy Sleep laboratory, HP2 laboratory EA 3745 ERI 0017 INSERM, Grenoble, France

  2. Content General mechanisms leading to hypoventilation during sleep Obesity hypoventilation syndrome Sleep hypoventilation in other restrictive chronic respiratory failure Needs for polysomnography in patients receiving NIV

  3. General mechanisms leading to hypoventilation during sleep In normal subjects during sleep Upper airway resistance increases Chemosensitivity is reduced and the wakefulness drive to breathe is lost, resulting in a fall in ventilation Functional residual capacity decrease (body position) Wake Stage 3-4 REM sleep PaCO2 mmHg

  4. Bourke et al., ERJ 2002 During rapid eye movement (REM) sleep, ribcage and accessory breathing muscles are suppressed, particularly during bursts of eye movements, and breathing is more irregular, rapid and shallow, with a further fall in ventilation REM sleep hypoventilation: mostfrequentabnormality

  5. Gonzalez et al, 2002

  6. Depending upon the underlying condition or disease All these mechanims can be or not involved Upper airway collapse favoured by Vital Capacity reduction and/or neuromuscular weakness Decreased Compliance of the respiratory system Diaphragmatic weakness VA/Q Impairment of ventilation perfusion mismatch Inadequate respiratory drive

  7. Obesity hypoventilation syndrome

  8. Obesity hypoventilation syndrome Definition • Severe obesity BMI > 30 kg/m2 and diurnal PaCO2 > 43 mmHg • In the absence of other known cause of hypoventilation Olson et al Am J Med 2005

  9. Obesity hypoventilation syndrome Prevalence • 1.2 % hospitalized patients (47/4332) • Prevalence increase with BMI 30% BMI > 35 kg/m2, 49% BMI > 50 kg/m2 Nowbar Am J Med 2004

  10. Obesity hypoventilation syndrome Clinical presentation Pèrez de Llano Chest 2005 Morbid obesity nearly constant associated sleep apnea hypersomnia

  11. Obesity hypoventilation syndrome Clinical presentation Pèrez de Llano Chest 2005 41/69 (59.4%) were initially referred for acute respiratory failure 10/69 (14.5%) Deaths

  12. Obesity hypoventilation syndrome The Use of Health-Care Resources is increased compared to simple obesity Berg Chest 2001

  13. Obesity hypoventilation syndrome Mortality 9% * 23% Nowbar Am J Med 2004

  14. Obesity hypoventilation syndrome Mechanisms of the disease Why do some obese hypoventilate during daytime and sleep? Upper airway collapse Respiratory control Increase work of breathing

  15. Obesity hypoventilation syndrome Mechanisms of the disease All obese have increase in work of breathing but those without OHS Increase their respiratory drive to compensate Janssens, Pépin, Guo EurRespir Mon 2008

  16. Obesity hypoventilation syndrome Sleep apnea is associated in 90% of cases

  17. Obesity hypoventilation syndrome Specific sleep apnea patterns during the night may explain daytime hypercapnia Berger KI JAP 2002; 93:917-24 Ayappa I AJRCCM 2002; 166:1112-5

  18. Obesity hypoventilation syndrome REM sleep hypoventilation Reduced ventilatory Drive Leptin resistance

  19. Obesity hypoventilation syndrome REM sleep hypoventilation Chouri Chest 2007

  20. REM REM REM REM Eveil

  21. Obesity hypoventilation syndrome REM sleep hypoventilation Decrease in CO2 ventilatory responses Chouri Chest 2007

  22. Obesity hypoventilation syndrome REM sleep hypoventilation OHS with REM hypoventilation more sleepy Chouri Chest 2007

  23. Olson Am J Med 2005 obesity Leptin insensitivity Increased work of breathing Insufficient post apnea ventilation Normal or diminished ventilatory drive Hypoventilation, Hypercapnia Severe sleep hypoxemia and sleep fragmentation OSAS Adequate post apnea hyperventilation Obesity Hypoventilation Syndrome OHS-OSAS hypercapnia Simple obesity Obesity + OSAS Hypercapnia Eucapnia Increased ventilatory drive Eucapnia

  24. Obesity hypoventilation syndrome Leptin resistance : lost of central effects of leptin C57BL/6J-Lepob obese mouses without circulating leptin O’Donnell Am J Respir Crit care Med 1999

  25. Obesity hypoventilation syndrome Obesity-Intermittent hypoxia-hypercapnia-Leptin resistance Preservation of peripheral actions of leptin such as increased sympathetic outflow and cytokine production Fantuzzi JACI 2005

  26. Obesity hypoventilation syndrome Obesity-Intermattent hypoxia-hypercapnia-Leptin resistance Preservation of peripheral actions of leptin such as increased sympathetic outflow and cytokine production Lau Am J Physiol 2005

  27. Obesity hypoventilation syndrome Clinical study Hypothesis: OHS patients exhibit a specific inflammatory response that may participate to additional cardiovascular morbidity Design : Recruitment Obese recruited from the general population by announcement Aim To compare inflammatory status and endothelial function, in OHS versus obese patients, matched for BMI, age and sex. Methods Sleep, blood gazes and endothelial function, measured by peripheral arterial tonometry (PAT) were analyzed in all included patients. Inflammatory (TNF, IL-6, IL-8, IL-10, Leptin, MCP-1, RANTES) and anti-inflammatory (adiponectin and IL1-RA) parameters were also determined.

  28. Pro-inflammatory status for Obese (ob) versus Obesity hypoventilation syndrome (OHS) patients

  29. Anti-inflammatory status for Obese (ob) versus Obesity hypoventilation syndrome (OHS) patients

  30. 250 200 r=0.54, p=0.002 RANTES, ng/ml 150 100 50 ob 0 4 5 6 7 8 PaCO2, kPa r=0.63 p=0.002 (ns) OHS PaCO2, kPa r=-0.38 p=0.02 r=-0.69 p=0.006 (ns)

  31. Obesity hypoventilation syndrome Therapeutic strategy What kind of ventilatory support should be use for treating respiratory failure? Effects of treatment on blood gazes and survival Efficacy of treatment on Ventilatory responses Sleep structure and hypersomnia Leptin

  32. Obesity hypoventilation syndrome What kind of ventilatory support should be use for treating respiratory failure? OHS with OSA but without REM sleep hypoventilation and moderate hypercapnia: CPAP

  33. Obesity hypoventilation syndrome What kind of ventilatory support should be use for treating respiratory failure? OHS with REM sleep hypoventilation and moderate hypercapnia: Bi-level NIV Bilevel non invasive ventilation 1) Inspiratory trigger 3) Inspiratory/expiratory cycling 2) Difference between inspiratory and expiratory pressure provide Vt

  34. Obesity hypoventilation syndrome the leading cause for long term home non invasive ventilation Janssens JP CHEST 2003

  35. Obesity hypoventilation syndrome What kind of ventilatory support should be use for treating respiratory failure? OHS with REM sleep hypoventilation and moderate hypercapnia: Bi-level NIV with AVAPS Storre Chest 2006 Average Volume-Assured Pressure Support

  36. Obesity hypoventilation syndrome Bi-level non invasive ventilation Efficacy on sleep structure Chouri Chest 2007

  37. Obesity hypoventilation syndrome Bi-level non invasive ventilation Efficacy on daytime sleepiness Chouri Chest 2007

  38. Obesity hypoventilation syndrome Bi-level non invasive ventilation Efficacy on mortality Perez de Lano CHEST 2005

  39. Obesity hypoventilation syndrome Bi-level non invasive ventilation Efficacy on mortality Janssens et al. CHEST 2003;123:67-79

  40. Obesity hypoventilation syndrome Bi-level non invasive ventilation Changes in levels of serum leptin: contradictory results Brendon Respiration 2004

  41. Obesity hypoventilation syndrome Needs to adapt ventilatory support with time course evolution? Pèrez de Llano Chest 2005

  42. Obesity hypoventilation syndrome Take home message Highly prevalent and easy to diagnose Specific metabolic and cardiovascular morbidity Polysomnography is needed to differentiate OSA and/or REM sleep hypoventilation Interest of ventilatory responses to CO2 NIV improves blood gazes, sleep, daytime sleepiness and mortality Changes in ventilatory support in the time course evolution of the disease Other treatments of obesity required

  43. Sleep-related hypoventilation in other restrictive diseases

  44. Reduced VC with or whithout Neuromuscular weakness Perrin et al., 2005 Sleep-disordered breathing usually precedes, and probably contributes to daytime ventilatory failure

  45. Neuromusculardisorders

  46. Upper airway dysfunction Parkinson disease ALS DMD Obstructive hypopneas misclassified as central too weak muscles Diaphragmatic weakness Duchenne muscular dystrophy ALS Myotonic dystrophy Hypercapnia more common than in others muscular diseases with a similar degree of muscle weakness Daytime hypersomnia +++ Cortical defect ?

  47. Kyphoscoliosis

  48. Upper airway obstruction Guilleminault, Chest 1981 REM sleep hypoventilation Loss of compensation of the accessory muscles Kyphoscoliosis caused by poliomyelitis Acquired blunting of drive

  49. Needs for polysomnography • In patients receiving NIV • Disappearance of all abnormal respiratory events? • Asynchrony between the patient and the ventilator? • Occurrence of mouth leaks which induce sleep fragmentation? Precisely determine the beneficial effects of NIV

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