Complex Sleep Apnea: Clinical Challenges Brian J. Bohner, M.D. Diplomate ABSM Fellow AASM CBTS Sept 14, 2012

Complex Sleep Apnea Clinical Challenges: Objectives Definition of Complex Sleep Apnea Causes of Central Apnea Developing on CPAP Therapy Natural History Diagnostic and Therapeutic Challenges

Case Study – T.Y.  54 Y.O. Male C/O: 1. Daytime Sleepiness/Fatigue Awakenings per Night 3. Snoring  PMH: 1. HTN 2. Lumbar Arthritis 3. No history or symptoms of CHF  Medications: 1. Celebrex 2. Metoprolol 3. No opiates  ROS: 1. Chronic nasal congestion  Exam: Wt = 199 lbs, (BMI = 27) Moderate nasal congestion  ESS (Epworth Sleepiness Scale): 16

Baseline Polysomnogram

Polysomnogram Results: Apnea Index = 21.3 Apnea + Hypopnea Index = 43.1 Total Sleep Time = 4.8 Hours O 2 Saturation Nadir = 84% Trial of Automatic CPAP: AHI min large leak.

CPAP Titration Study

CPAP Titration – Development of Central Events

Complex Sleep Apnea: Definition Complex Sleep Apnea is a form of sleep apnea in which central apneas persist or emerge (CAI >5) during attempts to treat obstructive events with nCPAP or Bilevel PAP.

Patient Characteristics 1. > 90% are Male (ref 14) 2. BMI is slightly less than average OSA patient (ref 16) 3. ? Higher incidence of ischemic heart disease or CHF (ref 15) 4. Slight predominance in atrial fibrillation, opiate use (ref 1 and 2) 5. ? Elevated nasal resistance (ref4)

Natural History of Complex Apnea Prevalence of syndrome- 5.7 to 20%. In 78%- 92% of pts, CAs resolve within months in CPAP adherent patients. Of pts without Com SA on initial CPAP titration, 4% developed it on 3 mo f/u !! Ref 1 and 2

Polysomnographic Characteristics  May have evidence of central events on baseline PSG (CAI >5) (ref 1)  Events more common in nREM sleep (ref 16)  Elevated Arousal Index (ref 16)  On F/U CPAP titration in 2-3 months, persistent CA more likely if severe OSA or CSA >5 (ref 1)

Clinical Impact of nCPAP in “Complex Apnea” 1.Residual or Worsening Symptoms (Fatigue, EDS, Depression) Secondary to Arousals/Disrupted Sleep 2.Higher Incidence of “CPAP Difficulty” (ref18) 3. ↑ Sympathetic Activity (ref 18)

A.Behavioral B.Metabolic 1.Chemoreceptors a.Carotid Bodies b.Medulla Eupnea Apnea Threshold CO2 Reserve Controls of Breathing: AWAKE Y axis = pCO2 o xxx o oo o

Controls of Breathing - Sleep 38 Apnea Threshold REM nREM 1.Loss of Behavioral Control 2.Narrow CO2 Reserve in nREM 3.Hypoxia Further Reduces pCO2 4.Metabolic Acidosis Widens CO2 Reserve Y axis = pCO2 CO2 Reserve Apnea Threshold CO2 Reserve 39 OoOo oo job

Controls of Breathing During Sleep - CHF 1. Pulmonary Afferent Receptors pCO2 Apnea Threshold 2. Loop Gain A. Increased Response to pCO2 B. Increased Lung to Peripheral Chemoreceptor Circulation Time xxx o ooo

Controls of Breathing During Sleep Effects of nCPAP/Bilevel PAP 1. Effect of Opening Airway - ↑ Minute Ventilation (Increases plant gain) 2. Fragmented Sleep with Arousal – (discomfort/ elevated nasal resistance) 3. PAP induced distention of stretch receptors (Hering Breuer inflation reflex) pCO2 Apnea Threshold CO2 Reserve

Diagnostic Challenges 1.Increasing number of patients not undergoing CPAP titration 2.Autotitrating PAP devices vary in ability to warn clinician of emerging central apnea 3.Failure to diagnose Complex Apnea may lead to poor compliance and abandonment of PAP therapy. 4.Overtitration may result in inappropriate dx.

Waveform Report So here is what’s going on

Therapy for Complex Apnea 1.Adaptive Servo Ventilation 2.nCPAP Close F/U, permissive flow limitation/ additional dead space 3.Supplemental 02 4.Medications benzodiazepines/ acetazolamide

Adaptive Servo Ventilation (ASV) Airway Pressure Device devised for Treatment of CSA/CSR as well as Complex Apnea Automatic Pressure Support (Dynamically Calculated) to result in Consistent Tidal Volume Automatic Backup Rate (Calculated) Multiple Studies show Effective Clinical Results in Treating Complex Apnea

Respironics BiPAP Auto SV Responds to Peak Flow and Adjusts Pressure Support Accordingly Manufacturers Suggestion for Settings: Set EPAP or EPAP min Set PS 2-15 Set IPAP max = 25 Rate = auto

Breath to Breath Pressure Support Backup Breath Stabilization of Breathing BiPAP Auto SV BiPAP Auto SV

Res Med ♠ VPAP Adapt SV ♠ Algorithm Directed at Measuring “Baseline” TV and Respiratory Rate ♠ Can Titrate for EPAP (EEP) or use “Default Setting” of 5 cm ♠ IPAP Suggestions: Set Min PS = 3 cm Set Max PS = 10 cm

The VPAP Adapt SV Response VPAP Adapt SV (ASV mode on) Airflow HYPOPNEA APNEA Adapt SV responds to apnea by increasing support ( Apnea converted to a hypopnea & breathing quickly normalized by VPAP Adapt SV)

CSA/CSR Returns Without Treatment VPAP Adapt SV Airflow ASV mode turned off (CSA/CSR rapidly returns) Off

Comparison VPAP Adapt ASV (n=35) Avg use 5.0 Change ESS -2.5 % nights > 4 h 67 CMS compliant % 34 BIPAP Auto ASV (n=41) Reference 3

Patient T.Y. On ASV

Therapeutic Challenges 1.Adaptive Servo Ventilation costly 2.nCPAP may eventually be adequate therapy. 3.Other therapies not well studied.

Conclusions/ Suggestions Clinicians caring for all OSA pts need proper training/ education given prevalence and natural history of Complex SA. Difficult to predict patients who will develop the syndrome. Prevalence of the syndrome highlights importance of CPAP titration study in OSA patients.

Conclusions/ Suggestions (cont) Treatment decision generally pertains to ? ASV vs close f/u on CPAP Insurance carriers may impact on these decisions Suggest confirming emergent CAs prior to ASV titration Consider 02 and pharmacologic agents Need to consider best therapy for pt, but sensitive to costs (CPAP titration/ ASV)

For More Info:

ReferencesReferences 1. Javaheri The prevalence and Natural History of Complex Sleep Apnea JCSM No 3, Hoffman The Appearance of Central Sleep Apnea after Treatment of Obstructive Sleep Apnea Chest Aug Kuzniar Comparison of two servo ventilator devices in the treatment of complex sleep apnea Sleep Medicine (2011) Nakazaki Continuous positive airway pressure intolerance associated with elevated nasal resistance is a possible mechanism of complex sleep apnea Sleep Breath (2012) 16:

ReferencesReferences 5Efficacy of adaptive servoventilation in treatment of complex and central sleep apnea syndromes. Chest Dec; 132 (6): PMID: [PubMed – indexed for MEDLINE] 6.CPAP should be used for central sleep apnea in congestive heart failure patients. J Clin Sleep Med Oct; 15;2 (4): PMID: [PubMed – indexed for MEDLINE] 7.Brown LK, Casey KR. Complex sleep apnea: the hedgehog and the fox. Curr Opin Pulm Med Nov; 13 (6): PMID: [PubMed – indexed for MEDLINE] 8.The significance and outcome of continuous positive airway pressure-related central sleep apnea during split-night sleep studies. Chest Jul; 132 (1): Epub 2007 May 2. PMID: [PubMed – indexed for MEDLINE]

ReferencesReferences 9. Chest Feb; 131 (2): Review PMID: [PubMed – indexed for MEDLINE] 10. Recognition and management of complex sleep-disordered breathing. Curr Opin Pulm Med Nov; 11 (6): Review. PMID: [PubMed – indexed for MEDLINE] 11. Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med Jan 15; 173 (2): Epub 2005 Oct 20. PMID: [PubMed – indexed for MEDLINE] 12. Kuzniar TJ, Golbin JM, Morgenthaler TI. Moving beyond empiric continuous positive airway pressure (CPAP) trials for central sleep apnea: a multi-modality titration study. Sleep Breath Dec; 11(4): PMID: [PubMed – in process]

ReferencesReferences 13. Kuzniar TJ, Pusalavidyasagar S, Gay PC, Morgenthaler TI. Natural course of complex sleep apnea – a retrospective study. Sleep Breath Sept 15; (Epub ahead of print) PMID: [PubMed – as supplied by publisher] 14. Lehman S, Antic NA, Thompson C, Catcheside PG, Mercer J, McEvoy RD. Central sleep apnea on commencement of continuous positive airway pressure in patients with a primary diagnosis of obstructive sleep apnea-hypopnea. J Clin Sleep Med Aug 15; 3 (5): PMID: [PubMed – indexed for MEDLINE] 15. Morgenthaler TI, Gay PC, Gordon N, Brown LK. Adaptive servoventilation versus noninvasive positive pressure ventilation for central, mixed, and complex sleep apnea syndromes. Sleep Apr 1; 30 (4): PMID: [PubMed – indexed for MEDLINE] 16 Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: is it a unique clinical syndrome? Sleep Sept; 7 (6): Epub 2006 Aug 23. PMID: [PubMed – indexed for MEDLINE]

ReferencesReferences 17.Papacostas SS, Myrianthopoulou P, Dietis A, Papathanasiou ES. Induction of central-type sleep apnea by vagus nerve stimulation. Electromyogr Clin Neurophysio Jan-Feb; 47 (1): PMID: [PubMed – indexed for MEDLINE] 18.Pusalavidyasagar SS, Olson EJ, Gay PC, Morgenthaler TI. Treatment of complex sleep apnea syndrome: a retrospective comparative review. Sleep Med Sept; 7 (6): Epub 2006 Aug 23. PMID: [PubMed – indexed for MEDLINE] 19.Thomas RJ. Effect of added dead space to positive airway pressure for treatment of complex sleep-disordered breathing. Sleep Med Mar; 6 (2): Epub 2005 Jan 25. PMID: [PubMed – indexed for MEDLINE] 20.Wang D, Teichtahl H, Drummer O, Goodman C, Cherry G, Cunnington D, Kronborgl Central sleep apnea in stable methadone maintenance treatment patients. Chest Sept; 128 (3): PMID: [PubMed – indexed for MEDLINE]