1. Adaptive Servo-Ventilation Cases Geoffrey S Gilmartin, MD Beth Israel Deaconess Medical Center Harvard Medical School Boston, MA

2. Outline Case Based Case Based Ventilatory Control During NREM Sleep Ventilatory Control During NREM Sleep Conceptual framework Conceptual framework Specific components Specific components Lessons Learned Lessons Learned Cases Cases Snapshots Snapshots Literature Literature Conclusions Conclusions

3. Case #1 SH SH 37 yo male 37 yo male Arnold Chiari malformation, spinal stenosis, syringomyelia Arnold Chiari malformation, spinal stenosis, syringomyelia Shunt failure in cervical region Shunt failure in cervical region Herniation, quadriplegia, PEG and Trach Herniation, quadriplegia, PEG and Trach Snoring converted to witnessed apneas Snoring converted to witnessed apneas EDS and extended sleep times EDS and extended sleep times

4. Case #1 Previous PSG Previous PSG Failed CPAP/BI-level titration Failed CPAP/BI-level titration Residual disease Residual disease 624 central and 121 obstructive events 624 central and 121 obstructive events CPAP=7, BI-level=11/7 with RDI-22 CPAP=7, BI-level=11/7 with RDI-22 Treated at home and intolerant Treated at home and intolerant Current treatment with O2 2 lpm Current treatment with O2 2 lpm Referred for evaluation Referred for evaluation

5. Case #1

10. Sleep Disordered Breathing Obstructive Sleep Apnea Obstructive Sleep Apnea CPAP CPAP Cardiovascular, metabolic risk Cardiovascular, metabolic risk Central Sleep Apnea Central Sleep Apnea Cheyne-Stokes Respiration Cheyne-Stokes Respiration Complex Sleep Apnea Complex Sleep Apnea Mixed Sleep Apnea Mixed Sleep Apnea

11. Cheyne Stokes Respiration

12. The System NREM Loss of wakefulness drive Ventilatory Pattern Generator Medulla (pH) Carotid Body (PCO2, PO2) Upper Motor Neuron Lower Motor Neuron Respiratory Muscle/Chest Wall Adapted From: Malhotra, Berry and White, “Central Sleep Apnea”

13. CSDB-Treatment Body Position- Body Position- Ventilatory Reserves/Obstruction Ventilatory Reserves/Obstruction Sleep Consolidation- Sleep Consolidation- Ventilatory Overshoot/Sleep Wake Instability Ventilatory Overshoot/Sleep Wake Instability Supplemental O2- Supplemental O2- Stabilize Chemoreceptors Stabilize Chemoreceptors CPAP/BI-level Pressures- CPAP/BI-level Pressures- Plant Gain Plant Gain Stabilize Ventilation- “Adaptive Ventilation” Stabilize Ventilation- “Adaptive Ventilation” Stabilize Plant Gain Stabilize Plant Gain

14. Adaptive Servo-Ventilation Determine Target Ventilation Determine Target Ventilation Monitors recent average minute ventilation (ie.~3 min window) Monitors recent average minute ventilation (ie.~3 min window) Calculates a target ventilation (ie. 90% of recent average ventilation) Calculates a target ventilation (ie. 90% of recent average ventilation) Ventilates to the Target Ventilates to the Target Algorithm monitors patient ventilation and compares it to the target ventilation Algorithm monitors patient ventilation and compares it to the target ventilation Adjusts pressure support up or down as needed to achieve target Adjusts pressure support up or down as needed to achieve target Back-up rate when needed Back-up rate when needed

15. End Expiratory Pressure EEP = CPAP level EEP = CPAP level Fixed Fixed May adjust to improve upper airway obstruction May adjust to improve upper airway obstruction EEP: manually titrate like CPAP to hold airway patent Time Pressure (cm H 2 0)

16. Pressure Support (PS) Pressure support = Pressure support = (Peak Inspiratory Pressure – End Expiratory Pressure) (Peak Inspiratory Pressure – End Expiratory Pressure) Pressure support varies between limits Pressure support varies between limits minPS minPS maxPS maxPS Can vary the range Can vary the range Device determines the level Device determines the level maxPS Time Pressure (cm H 2 0) minPS

17. Response The device “automatically” adjusts the magnitude of pressure support breath by breath to: Provide minimal support during hyperpnea or stable breathing Provide minimal support during hyperpnea or stable breathing Increase support during hypopnea or apnea Increase support during hypopnea or apnea Assumption is all is central Assumption is all is central Time Pressure (cm H 2 0) Central apnea Normal breathing effort

18. Cautions-Hypoventilation Chronic hypoventilation Chronic hypoventilation Moderate to severe COPD Moderate to severe COPD Chronically elevated PCO 2 on ABG (> 45 mm Hg) Chronically elevated PCO 2 on ABG (> 45 mm Hg) Restrictive thoracic or neuromuscular disease Restrictive thoracic or neuromuscular disease

19. Baseline Effort Flow SpO 2 Central even, no effort Desaturations after Central apneas One CSR/CSA cycle, ~1min

20. Support When Needed Effort Flow SpO 2 FG

21. Continued Adaptation Response to remaining events Effort Flow SpO 2 FG

22. Stability? Effort Flow SpO 2 FG

23. Variable Input = Stability?

24. 2001 Adaptive Pressure Support Servo- Ventilation Adaptive Pressure Support Servo- Ventilation Teschler H, et al. Teschler H, et al. AJRCCM, 164, 614-19, 2001 AJRCCM, 164, 614-19, 2001 Patients with CHF and CSR (3%, >15/hr) Patients with CHF and CSR (3%, >15/hr) Acute prospective randomized crossover Acute prospective randomized crossover 5 sequential nights 5 sequential nights N=16 N=16

25. Teschler, et al.

28. Single night (acute) study Single night (acute) study Did randomize order Did randomize order Covers standard interventions Covers standard interventions ASV performs well in this population, in the lab ASV performs well in this population, in the lab PCO2 results “reassuring” PCO2 results “reassuring”

29. Case #2 RA RA 67 yo male 67 yo male Asthma Asthma OSA-AHI=13, RDI=43, desats to 80% OSA-AHI=13, RDI=43, desats to 80% Failed CPAP/BIPAP Titration-AHI=14.7 Failed CPAP/BIPAP Titration-AHI=14.7 Adapt SV- EEP 5-7, PS 2-10 Adapt SV- EEP 5-7, PS 2-10 Perfection Perfection

35. Recent Data Adaptive Servoventilation Versus Noninvasive Positive Pressure Ventilation for Central, Mixed And Complex Sleep Apnea Syndromes Adaptive Servoventilation Versus Noninvasive Positive Pressure Ventilation for Central, Mixed And Complex Sleep Apnea Syndromes Morgenthaler T, et al. Morgenthaler T, et al. Sleep, 30(4), 2007 Sleep, 30(4), 2007 Multicenter, prospective randomized crossover design Multicenter, prospective randomized crossover design

36. Morgenthaler et al.

37. Morgenthaler, et al. DEFINITITIONS DEFINITITIONS CSA-CSR CSA-CSR CAI >5 events/hr CAI >5 events/hr CAI/AHI >50% CAI/AHI >50% CSR pattern CSR pattern SA-Mixed SA-Mixed AHI >5 AHI >5 >50% mixed apneas >50% mixed apneas Complex SAS Complex SAS AHI >5 (majority obstructive) AHI >5 (majority obstructive) CAI >5 or CSR during titration at best CPAP CAI >5 or CSR during titration at best CPAP

38. Morgenthaler et al.

39. Morgenthaler, et al.

41. Morgenthaler et. al. Small study Small study Definitions standard and important Definitions standard and important Bi-level alone poor Bi-level alone poor Exclusion criteria- Exclusion criteria- CPAP >10 CPAP >10 Hypoventilation Hypoventilation Unstable CHF Unstable CHF Beneficial, ? superior Beneficial, ? superior

42. Case #3 CH CH 83 yo male 83 yo male CAD-IMI, EF=55%, CRI CAD-IMI, EF=55%, CRI OSA-AHI=82.5, Sat Nadir 88% OSA-AHI=82.5, Sat Nadir 88% Failed BIPAP 13/8 with 2 lpm O2 Failed BIPAP 13/8 with 2 lpm O2 Concern for central sleep apnea Concern for central sleep apnea ASV titration-EEP 5-8, PS-3-10 ASV titration-EEP 5-8, PS-3-10 Disaster Disaster

50. Long Term Compliance with and effectiveness of adaptive servo-ventilation versus CPAP in the treatment of Cheyne-Stokes respiration in heart failure over a six month period Compliance with and effectiveness of adaptive servo-ventilation versus CPAP in the treatment of Cheyne-Stokes respiration in heart failure over a six month period Philippe C, et. al. Philippe C, et. al. Heart 92, 337-42, 2006 Heart 92, 337-42, 2006 Randomized, prospective trial (CSR) Randomized, prospective trial (CSR)

51. Background CPAP CPAP Improves CSR Improves CSR Decreases SNA Decreases SNA Improves ejection fraction Improves ejection fraction Improved combined mortality-cardiac transplantation rates Improved combined mortality-cardiac transplantation rates But, incomplete “in-lab” response But, incomplete “in-lab” response Relative benefit over time? Relative benefit over time?

52. Philippe, et al. Subjects- Subjects- N=25 N=25 18-80 yo 18-80 yo Stable CHF (EF <45%), newly diagnosed CSR Stable CHF (EF <45%), newly diagnosed CSR AHI >15, >80% central AHI >15, >80% central Design- Design- Randomized to Randomized to Best CPAP (mean=8) or Best CPAP (mean=8) or ASV-Default settings ASV-Default settings

53. Philippe, et al.

55. ESS ESS Non-significant decrease Non-significant decrease MWT MWT Non-significant increase Non-significant increase QOL QOL Improved Improved Greater in ASV Greater in ASV

56. Philippe, et al.

57. Patients with CSR and symptomatic CHF Patients with CSR and symptomatic CHF Reasonable compliance (> with ASV) Reasonable compliance (> with ASV) Improvement in Improvement in CSR severity CSR severity QOL (greater in ASV) QOL (greater in ASV) EF (ASV only) EF (ASV only) Hemodynamic tolerance Hemodynamic tolerance

58. Case #4 DB DB 79 yo male 79 yo male A-Fib, HTN, Spinal Stenosis, P-vera A-Fib, HTN, Spinal Stenosis, P-vera Sleep Apnea-AHI=42.1, Nadir-80% Sleep Apnea-AHI=42.1, Nadir-80% CPAP poorly tolerated CPAP poorly tolerated Adapt Titration EEP 5-8, PS 3-10 Adapt Titration EEP 5-8, PS 3-10 Synchrony? Synchrony?

62. Very Recent Data Effect of Flow-Triggered Adaptive Servo-Ventilation Compared with CPAP in Patients with Chronic Heart Failure with Coexisting OSA and Cheyne- Stokes Respiration Effect of Flow-Triggered Adaptive Servo-Ventilation Compared with CPAP in Patients with Chronic Heart Failure with Coexisting OSA and Cheyne- Stokes Respiration Kasai T, et. al. Kasai T, et. al. Circ Heart Fail. 2010:3:140-148 Circ Heart Fail. 2010:3:140-148 Randomized, prospective trial Randomized, prospective trial 31 Patients 31 Patients

63. Kasai et al Stable EF <50% Stable EF <50% Stable Class >/= II Heart Failure Stable Class >/= II Heart Failure AHI >15 AHI >15 Obstructive AHI >5 Obstructive AHI >5 Cheyne-Stokes Respiration Cheyne-Stokes Respiration Not previously treated Not previously treated Randomized to (titration) Randomized to (titration) CPAP (4-12) CPAP (4-12) HEART PAP (flow-triggered ASV) HEART PAP (flow-triggered ASV)

64. Kasai et al

68. ASV-Treatment We know We know Physiology Physiology Patients Patients Literature Literature In-lab In-lab Titration process-what to control Titration process-what to control When to abandon When to abandon If effective in lab, hope for long term If effective in lab, hope for long term