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Complex Sleep Apnea: And Other Treatment Challenges In Airway Pressure Therapy

Brian J. Bohner, M.D. Diplomate ABSM Fellow AASM Conference By The Sea September 17, 2009

Complex Sleep Apnea And Other Treatment Challenges In Airway Pressure Therapy:


Complex Sleep Apnea: Definition and Treatment Approaches Five Key Challenges in nCPAP Compliance 2009 CPAP Mask Awards

Case Study T.Y.

54 Y.O. Male C/O:

1. 2. 3.
Daytime Sleepiness/Fatigue 5-10 Awakenings per Night Snoring

1. 2. 3.
HTN Lumbar Arthritis No history or symptoms of CHF

1. 2. 3.
Celebrex Metoprolol HCTZ

Nocturnal Reflux


Wt = 199 lbs, (BMI = 27) Normal Nasal and Oropharyngeal Exam

ESS (Epworth Sleepiness Scale): 16

Baseline Polysomnogram

Polysomnogram Results:
Apnea Index = 21.3 Apnea + Hypopnea Index = 43.1 Total Sleep Time = 4.8 Hours O2 Saturation Nadir = 84%

Trial of Automatic CPAP:

Night to Night Variance in Selected Pressure 6 to 15 cms H2O

CPAP Titration Study

CPAP Titration Development of Central Events

Classifications of Sleep Disordered Breathing (SDB)

CSA/CSR < 5%
1. Paradoxical Response to CPAP Development of Central Apnea 2. Position Dependent SDBs 3. Sleep Stage Dependent SDBs

Undefined SDB ~15%

4. Time of Night Dependent SDBs

OSA ~ 85% 5. Mixed Apneas

Complex Sleep Apnea:


Complex Sleep Apnea is a form of sleep apnea in which central apneas persist or emerge during attempts to treat obstructive events with nCPAP.

Patient Characteristics
1. > 90% are Male (Ref 1, 2, 3) 2. BMI is slightly less than average OSA patient (Ref 2) 3. Higher incidence of Atrial Fibrillation and Opioid Use (Ref 4) 4. Prevalence of 5-15% in OSA Patients (Ref 1,2)
1. Lehman: Journal of Clinical Sleep Medicine; August 2007, p 462 466. 2. Morgenhaler: Sleep; September 2006, p 1203 1209. 3. Thomas: Sleep; December 2007, p 1756 1769. 4. Javaheri: JCSM; 2009, Volume 5

Polysomnographic Characteristics
May have Evidence of Central Events on
Baseline PSG (Ref

Events More Common in nREM sleep (Ref 3)

Elevated Arousal Index (Ref 3)

Decreased Central Events on Follow-up (Ref 1, 4)
References: 1. Dernaika: Chest; July 2007, p 81-87 2. Lehman: Journal of Clinical Sleep Medicine; August 2007, p 462 466. 3. Morgenhaler: Sleep; September 2006, p 1203 1209. 4. Javaheri: JCSM; 2009, Volume 5

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 (Ref 1)

3. Sympathetic Activity (Ref 2)

References: 1. Pusalavidyasagar: Sleep Medicine; September 2006, p 474-479 2. Yumino: Proc American Thoracic Society; February 2008, 226-236

Understanding Pathophysiology Of Complex Sleep Apnea

Controls of Breathing: AWAKE


A. Behavioral
o o

B. Metabolic
1. Chemoreceptors a. Carotid Bodies b. Medulla

Y axis = pCO2

CO2 Reserve

Apnea Threshold

Controls of Breathing - SLEEP

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 CO2 Reserve Reserve

Apnea Threshold
Apnea Threshold

Controls of Breathing During Sleep - CHF

ooo xxx xxx xxx oo 1. Pulmonary Afferent Receptors 2. Loop Gain A. Increased Response to pCO2 B. Increased Lung to Peripheral Chemoreceptor Circulation Time

Apnea Threshold

Controls of Breathing During Sleep

Effects of nCPAP/Bilevel PAP
Minute Ventilation (Worse with Bi-Level) 2. Fragmented Sleep with Arousal pCO2. 3. Impact of High Loop Gain 1. Effect of Opening Airway

CO2 Reserve

Apnea Threshold

Treatment Considerations in Complex Apnea

1. Increase CO2 Reserve Value
A. ? O2 B. ? Induce Acidemia C. Increase Dead Space

2. Reduce Loop Gain

A. Treat CHF B. ? Sedatives

3. Provide Back-Up
A. Backup Rate on Therapy

Treatment Options
1. nCPAP with Permissive Flow Limitation
nCPAP Disregarding Central Events



Supplemental O2 Medications
A. B. C. Acetazolamide Theophylline Benzodiazepines

5. 6.

Additional Dead Space to nCPAP Adaptive Servo Ventilation (ASV)

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

BiPAP Auto SV Responds to Peak Flow and Adjusts Pressure Support Accordingly Manufacturers Suggestion for Settings:

Set EPAP per Titration Study (Pressure Eliminating Last Obstructive Event) Set IPAP min = EPAP Set IPAP max = EPAP + 10 cm (25-30 cms) Set Rate = Auto

Res Med

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 = 15 cm

Patient T.Y. On ASV

Therapy for Complex Sleep Apnea Conclusions

1. Adaptive Servo Ventilation (ASV) 2. Nasal CPAP With Careful Follow-Up 3. Possible Role for Modalities such as:
A. B. C. O2 with nCPAP Sedative Trial Rebreathing Mask/Dead Space

1. To OSA Patient:
5%-10% will not appropriately respond to nCPAP Cost of Alternative Therapies may be Prohibitive

2. To Sleep Centers:
Responsibility to Identify such patients and offer Treatment Modifications

3. To Sleep Medicine Society:

Consider Consequences in Offering Home Studies (Non-Titrated) as well as Automated CPAP

Challenges In nCPAP Compliance

Nasal CPAP Problem #1

Interface Intolerance/Discomfort/Mask Removal:

Review Alternatives ? Sedative Trial

Nasal CPAP Problem #2


Less obtrusive interface Wake time desensitization

Nasal CPAP Problem #3

Pressure Intolerance:

Temporary Reduction
Expiratory Pressure Reduction

Sleep State Reduction

Auto-Titrating Systems

Bi-Level Pressure

Nasal CPAP Problem #4

Persistent Daytime Symptoms:
Confirm pressure setting Increase duration of use ? System/Mouth leak: Chin Strap
Consider Full Face Mask

Stimulant Therapy (Modafinil; Armodafinil)

Nasal CPAP Problem #5

Nasal/Oral Mucosal Problems: 1. Dryness
Nasal dryness Heated humidifier Oral dryness Treat mouth leak


Heated humidification Nasal steroids/Saline Rinse

For More Info:

1. Allam JS, Olson EJ, Gay PC, Morgenthaler TI. Efficacy of adaptive servoventilation in treatment of complex and central sleep apnea syndromes. Chest. 2007 Dec; 132 (6): 1839-1846. PMID: 18079219 [PubMed indexed for MEDLINE] Bradley TD. CPAP should be used for central sleep apnea in congestive heart failure patients. J Clin Sleep Med. 2006 Oct; 15;2 (4): 394-398. PMID: 17557465 [PubMed indexed for MEDLINE] Brown LK, Casey KR. Complex sleep apnea: the hedgehog and the fox. Curr Opin Pulm Med. 2007 Nov; 13 (6): 473-478. PMID: 17901751 [PubMed indexed for MEDLINE] Dernaika T, Tawk M, Nazir S, Younis W, Kinasewitz GT. The significance and outcome of continuous positive airway pressure-related central sleep apnea during split-night sleep studies. Chest. 2007 Jul; 132 (1): 81-87. Epub 2007 May 2. PMID: 17475636 [PubMed indexed for MEDLINE] Eckert DJ, Jordan AS, Merchia P, Malhotra A. Central sleep apnea: Pathophysiology and treatment. Chest. 2007 Feb; 131 (2): 595-607. Review PMID: 17296668 [PubMed indexed for MEDLINE]





6. Gay PC. Complex Sleep Apnea: It Really Is A Disease. Journal of Clinical Sleep Medicine. 2008; Vol 4. No.5 Gilmartin GS, Daly RW, Thomas RJ. Recognition and management of complex sleep-disordered breathing. Curr Opin Pulm Med. 2005 Nov; 11 (6): 485-493. Review. PMID: 16217173 [PubMed indexed for MEDLINE] Javaheri S. Acetazolamide improves central sleep apnea in heart failure: a double-blind, prospective study. Am J Respir Crit Care Med. 2006 Jan 15; 173 (2): 234-237. Epub 2005 Oct 20. PMID: 16239622 [PubMed indexed for MEDLINE] Javaheri, MD. The Prevalence and Natural History of Complex Sleep Apnea. Journal of Clinical Sleep Medicine. 2009; Vol 5. No3 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. 2007 Dec; 11(4): 259-266. PMID: 17541664 [PubMed in process]





11. Kuzniar TJ, Pusalavidyasagar S, Gay PC, Morgenthaler TI. Natural course of complex sleep apnea a retrospective study. Sleep Breath. 2007 Sept 15; (Epub ahead of print) PMID: 17874254 [PubMed as supplied by publisher] 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. 2007 Aug 15; 3 (5): 462-466. PMID: 17803008 [PubMed indexed for MEDLINE] Malhotra A. Complex Sleep Apnea: It Isnt Really A Disease. Journal of Clinical Sleep Apnea. 2008; Vol 4. No.5 Morgenthaler TI, Gay PC, Gordon N, Brown LK. Adaptive servoventilation versus noninvasive positive pressure ventilation for central, mixed, and complex sleep apnea syndromes. Sleep. 2007 Apr 1; 30 (4): 468-475. PMID: 17520791 [PubMed indexed for MEDLINE] Morgenthaler TI, Kagramanov V, Hanak V, Decker PA. Complex sleep apnea syndrome: is it a unique clinical syndrome? Sleep. 2006 Sept; 7 (6): 474-479. Epub 2006 Aug 23. PMID: 16931153 [PubMed indexed for MEDLINE]





16. Papacostas SS, Myrianthopoulou P, Dietis A, Papathanasiou ES. Induction of central-type sleep apnea by vagus nerve stimulation. Electromyogr Clin Neurophysio. 2007 Jan-Feb; 47 (1): 61-63. PMID: 17375884 [PubMed indexed for MEDLINE] Pusalavidyasagar SS, Olson EJ, Gay PC, Morgenthaler TI. Treatment of complex sleep apnea syndrome: a retrospective comparative review. Sleep Med. 2006 Sept; 7 (6): 474-479. Epub 2006 Aug 23. PMID: 16931153 [PubMed indexed for MEDLINE] Thomas RJ. Effect of added dead space to positive airway pressure for treatment of complex sleep-disordered breathing. Sleep Med. 2005 Mar; 6 (2): 177-178. Epub 2005 Jan 25. PMID: 15716223 [PubMed indexed for MEDLINE]




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