CENTRAL SLEEP APNEA:

Treatment

Yüksel Peker MD, PhD

Sleep Medicine Unit, Skaraborg

HospitalSkövde, Sweden

Hypercapnic Central Sleep ApneaHypercapnic Central Sleep Apnea

• Alveolar hypoventilationAlveolar hypoventilation

• Central Neurological diseaseCentral Neurological disease– StrokeStroke

• Peripheral Neurological diseasePeripheral Neurological disease– Polyneuropathy ALSPolyneuropathy ALS– Mononeuropathy, phrenic diaphragmMononeuropathy, phrenic diaphragm

• Chest wall complianceChest wall compliance– Skeletal deformity, Congenital KyphoscoliosisSkeletal deformity, Congenital Kyphoscoliosis

• Abnormal Lung mechanicsAbnormal Lung mechanics– COPDCOPD

Hypercapnic Central Sleep Apnea: Hypercapnic Central Sleep Apnea: treatmenttreatment

• Optimise lung mechanics (bronchodilators)Optimise lung mechanics (bronchodilators)

• Avoid hypoventilation Avoid hypoventilation – positioning, CPAPpositioning, CPAP

• Removal of dead spaceRemoval of dead space– tracheostomytracheostomy

• Ventilatory stabilisationVentilatory stabilisation– Avoid respiratory depressants, sleep Avoid respiratory depressants, sleep

state manipulation (REM avoidance) state manipulation (REM avoidance) • BiPAPBiPAP

Normo- Hypocapnic Central Sleep ApneaNormo- Hypocapnic Central Sleep Apnea

• AltitudeAltitude

• Metabolic disorders, Acromegaly, Metabolic disorders, Acromegaly, Hypothyroidism, Renal failureHypothyroidism, Renal failure

• StrokeStroke

• Obesity / idiopathicObesity / idiopathic

• Congestive cardiac failureCongestive cardiac failure

• Treat underlying disease Treat underlying disease

• Respiratory stimulantsRespiratory stimulants

• OxygenOxygen

• CPAP / BiPAP /Adaptive servo-ventilation CPAP / BiPAP /Adaptive servo-ventilation (ASV)(ASV)

• AcetazolamideAcetazolamide

Normo- Hypocapnic Central Sleep Apnea:Normo- Hypocapnic Central Sleep Apnea:treatmenttreatment

Respiratory stimulantsRespiratory stimulants

• Theophylline +Theophylline +

• Medroxyprogesterone +Medroxyprogesterone +

• Oestrogen ?Oestrogen ?

• Acetazolamide +Acetazolamide +

• Opiate antagonists –Opiate antagonists –

• Nicotine – (causes sleep disruption)Nicotine – (causes sleep disruption)

• SSRI s (no effect)SSRI s (no effect)

AcetazolamideAcetazolamide

• Mild diuretic and respiratory stimulantMild diuretic and respiratory stimulant• Treatment of periodic breathing at high Treatment of periodic breathing at high

altitudealtitude

• Impact on central sleep apnea associated Impact on central sleep apnea associated with heart failure?with heart failure?

• 12 male patients with systolic heart failure 12 male patients with systolic heart failure and AHI >15 /hand AHI >15 /h

• Randomized, double-blind, cross-over Randomized, double-blind, cross-over protocolprotocol

• Acetazolamide or placebo, 1 h before Acetazolamide or placebo, 1 h before bedtime 6 nights with 2 wk wash-out bedtime 6 nights with 2 wk wash-out

Javaheri S. AJRCCM 2006 Jan 15; 173 (2) 234-237.

AcetazolamideAcetazolamide

• Baseline Baseline vsvs placebo placebo– No significant differencesNo significant differences

• Acetazolamide Acetazolamide vs vs placeboplacebo– Central apne index: 23 (21) Central apne index: 23 (21) vs vs 49 (28); p=0.00449 (28); p=0.004– Time spent < Sat. 90%: 6 (13) Time spent < Sat. 90%: 6 (13) vsvs 19 (32); p= 0.01) 19 (32); p= 0.01)– Improved sleep quality (p=0.003)Improved sleep quality (p=0.003)– Feeling rested on awakening (p=0.007)Feeling rested on awakening (p=0.007)– Improved daytime fatigue (p=0.02)Improved daytime fatigue (p=0.02)– Improved falling asleep daytime (p=0.002) Improved falling asleep daytime (p=0.002) – No significant changes regarding arterial blood gases, No significant changes regarding arterial blood gases,

pulmonary function tests and LVEFpulmonary function tests and LVEF

Javaheri S. AJRCCM 2006 Jan 15; 173 (2) 234-237.

CONCLUSIONSCONCLUSIONS: : AcetazolamideAcetazolamide

In patients with heart failure, administrationIn patients with heart failure, administrationof a single dose of acetazolamide before of a single dose of acetazolamide before sleep improves central apnea and relatedsleep improves central apnea and relateddaytime symtoms. daytime symtoms.

Javaheri S.

AJRCCM 2006 Jan 15; 173 (2) 234-237.

Oxygen: Short-termOxygen: Short-term

• 51 patients with stable CHF, mean age 79 (12) yrs51 patients with stable CHF, mean age 79 (12) yrs

• 38 had sleep apnea (75%)38 had sleep apnea (75%)

• 49% with CSA-CSR, 51% with OSA49% with CSA-CSR, 51% with OSA

• Oxygen 2 liter/min during 2 consecutive nightsOxygen 2 liter/min during 2 consecutive nights

• AHI and ODI declined in the patients with CSA-CSRAHI and ODI declined in the patients with CSA-CSR

• No significant changes in CHF patients with OSANo significant changes in CHF patients with OSA

Sakakibara M et al. J Cardiol

2005, Aug; 46 (2): 53-61

Oxygen: Long-term (1)Oxygen: Long-term (1)

• Impact of nocturnal oxygen during 3 monthsImpact of nocturnal oxygen during 3 months

• 22 patients with severe CHF, median age 71 yrs22 patients with severe CHF, median age 71 yrs

• PSG, echocardiography, 6 min walk test, PSG, echocardiography, 6 min walk test, questionnaires at baseline and after 3 monthsquestionnaires at baseline and after 3 months

• 41% of patients with CSA-CSR41% of patients with CSA-CSR

Broström A et al. J Cardiovasc Nurs

2005, Nov-Dec; 20 (6): 385-396

Oxygen: Long-term (2)Oxygen: Long-term (2)

• Improved functional capacity in all patients (p<0.01) and Improved functional capacity in all patients (p<0.01) and in patients with CSA-CSR (p<0.05).in patients with CSA-CSR (p<0.05).

• No improvement in cardiac function, objective sleep, No improvement in cardiac function, objective sleep, subjective sleep or CSA-CSR except for ODI (p<0.05)subjective sleep or CSA-CSR except for ODI (p<0.05)

• No improvement in quality of life measuresNo improvement in quality of life measures

• Long-term nocturnal oxygen treatment improves Long-term nocturnal oxygen treatment improves functional capacity in patients with severe CHF, with or functional capacity in patients with severe CHF, with or without CSA-CSR. without CSA-CSR.

Broström A et al. J Cardiovasc Nurs

2005, Nov-Dec; 20 (6): 385-396

Sin DD et al, Circulation 2000;102:61–66

Transplant free survival in CHF with and without CSR

Sin DD et al, Circulation 2000;102:61–66

CPAP in CHF

Sin DD et al, Circulation 2000;102:61–66

CPAP in CHF without CSR

Sin DD et al, Circulation 2000;102:61–66

CPAP in CHF with CSR

Patient CharacteristicsHF, LVEF <40%, CSA (AHI ≥ 15/hr)

Multicenter StudyRANDOMIZATION

n > 400

Control Group: Optimal Medical Therapy Alone, n > 200

Treatment Group: Optimal Medical Therapy + CPAP, n > 200

Primary outcome ♦ Combined rate of mortality and heart transplantation

Secondary Outcomes ♦ AHI, mean nocturnal SaO2

♦ LVEF♦ 6-minute walk distance♦ Atrial Natriuretic Peptide♦ Plasma Norepinephrine♦ Hospital admissions♦ Chronic Heart Failure Questionnaire Scores

Bradley TD et al., Can J Cardiol 2001;17:677

CANPAPCANPAP

CPAP for CSA and Heart FailureCPAP for CSA and Heart Failure

Bradley TD et al, N Engl J Med 2005; 353:2025-33Bradley TD et al, N Engl J Med 2005; 353:2025-33 • N=258 N=258 • CSR CHF stage III/IV LVEF ~24.5%CSR CHF stage III/IV LVEF ~24.5%• AHI ~40AHI ~40• CPAP use 3.6 hrs during 2 yrs follow-upCPAP use 3.6 hrs during 2 yrs follow-up

• Improved LVEF (2.2 %) Improved LVEF (2.2 %) • Distance walked in 6 min (20meters) Distance walked in 6 min (20meters) • Better oxygenationBetter oxygenation• Reduced NorepinephrineReduced Norepinephrine• AHI reduced to ~20AHI reduced to ~20

CPAP for CSA and Heart FailureCPAP for CSA and Heart Failure

• Trial stopped earlyTrial stopped early

• No difference in transplant free survivalNo difference in transplant free survival

• No change in Quality of lifeNo change in Quality of life

• Early deaths in CPAP groupEarly deaths in CPAP group

• CANPAP data do not support the use of CPAP CANPAP data do not support the use of CPAP to extend life in CHF with CSRto extend life in CHF with CSR

Bradley TD et al, N Engl J Med 2005; 353:2025-33Bradley TD et al, N Engl J Med 2005; 353:2025-33

Potential problems with CPAP in CSRPotential problems with CPAP in CSR

• Patient selection difficultPatient selection difficult

• Poor compliance to CPAPPoor compliance to CPAP

• Lack of experience in adjusting CPAPLack of experience in adjusting CPAP

• The time needed for optimal pressure can be The time needed for optimal pressure can be up to 4 weeksup to 4 weeks

• CPAP titration criteria still unclearCPAP titration criteria still unclear– Alleviation of the respiratory event is not Alleviation of the respiratory event is not

mandatorymandatory– The pressure never exceeds 10 cmH20The pressure never exceeds 10 cmH20

CPAP CPAP vs vs BiPAPBiPAP

• 18 patients 18 patients • LVEF <35% LVEF <35% • CSR AHI >15CSR AHI >15• Randomised crossover 2 week blocksRandomised crossover 2 week blocks

AHI pre/hrAHI pre/hr AHI CPAPAHI CPAP AHI BIPAPAHI BIPAP 26.7 (10.7)26.7 (10.7) 7.7 (5.6)7.7 (5.6) 6.5 (6.6)6.5 (6.6)

AI pre /hrAI pre /hr AI CPAPAI CPAP AI AI BIPAPBIPAP

31.131.1 15.715.7 16.416.4

• Both improved sleep quality, daytime fatigue and Both improved sleep quality, daytime fatigue and NYHA classNYHA class

Kohnlein et al, ERJ;2002;20;934-41Kohnlein et al, ERJ;2002;20;934-41

BiPAP for 3 monthsBiPAP for 3 months• 14 patients with CSR-CSA14 patients with CSR-CSA

• 7 received BiPAP, 7 only conventional medication7 received BiPAP, 7 only conventional medication

• BiPAP group BiPAP group vsvs baseline baseline– LVEF 36.3% LVEF 36.3% vsvs 46.0% (p=0.02) 46.0% (p=0.02)– BNP 993.6 pg/ml BNP 993.6 pg/ml vsvs 474.0 pg/ml (p=0.02) 474.0 pg/ml (p=0.02)– NYHA functional class 3.1 NYHA functional class 3.1 vsvs 2.1 (p=0.03) 2.1 (p=0.03)

• Control group Control group vsvs baseline baseline– No significant changesNo significant changes

• Conclusion:Conclusion: Treatment with BiPAP improved cardiac functions in CHF Treatment with BiPAP improved cardiac functions in CHF patients with CSR-CSA.patients with CSR-CSA.

Kasai T et al . Circ J 2005, Aug; 69 (8): 913-921

BiPAP: adverse effect on central apneas?BiPAP: adverse effect on central apneas?

• Retrospective analysis of all sleep studies during 2 yrsRetrospective analysis of all sleep studies during 2 yrs

• 95 patients treated with BiPAP95 patients treated with BiPAP

• 80 out of these 95 had been treated with CPAP as well.80 out of these 95 had been treated with CPAP as well.

• BiPAP was more likely to worsen than improve CSR BiPAP was more likely to worsen than improve CSR (p=0.002), non-CSR central apneas (p<0.001).(p=0.002), non-CSR central apneas (p<0.001).

• Higher BiPAP levels worsened central events in 28% of Higher BiPAP levels worsened central events in 28% of patients while 7% were improved.patients while 7% were improved.

Johnson KG, Johnson DC.

Chest 2005, Oct; 128 (4): 2141-2150

Adaptive pressure support servo-ventilation (ASV)Adaptive pressure support servo-ventilation (ASV)

• To provide the hydrostatic benefits of low levels of To provide the hydrostatic benefits of low levels of CPAP while directly suppressing CSA/CSR and CPAP while directly suppressing CSA/CSR and attendant sleep disturbance without causing attendant sleep disturbance without causing overventilation.overventilation.

• The adaptive servo-ventilator provides a baseline The adaptive servo-ventilator provides a baseline degree of ventilatory support (4 cmH20) and degree of ventilatory support (4 cmH20) and maximum support 10 cmH20 (automatically).maximum support 10 cmH20 (automatically).

• End-expiratory pressure 4-6 cmH20 with the End-expiratory pressure 4-6 cmH20 with the intention of eliminating any obstructive sleep apnea.intention of eliminating any obstructive sleep apnea.

ASV in CHF with CSRASV in CHF with CSR

Teschler et al AJRCCM, 2001; 164:614-619Teschler et al AJRCCM, 2001; 164:614-619

Acute Acute changeschanges

Teschler et al AJRCCM, 2001; 164:614-619Teschler et al AJRCCM, 2001; 164:614-619

One singel One singel night, night, respectivelyrespectively

Teschler et al AJRCCM, 2001; 164:614-619Teschler et al AJRCCM, 2001; 164:614-619

One singel One singel night, night, respectivelyrespectively

Adaptive Servo-Ventilation: effects on symptoms,BNP and catecholamines (1 month)

Pepperell et al, AJRCCM 2003;168:1109-1114

Adaptive Servo-Ventilation improves daytime Adaptive Servo-Ventilation improves daytime sleepinesssleepiness

Pepperell et al, AJRCCM 2003; 168:1109-1114

ASV ASV versus versus Nocturnal oxygen therapy; Nocturnal oxygen therapy;

2 yr follow up 2 yr follow up baselinebaseline 2yrs O2 2yrs O2 2yrsASV 2yrsASV

Patients (nr)Patients (nr) 2323 1212 1111 AHI (events/hr)AHI (events/hr) 3838 2222 8*8* Arousals (/hr)Arousals (/hr) 4242 3333 12*12* 6MWD (m)6MWD (m) 220220 265265 332*332* Ejection fraction (%)Ejection fraction (%) 2929 3232 37*,**37*,** Usage (hrs/day)Usage (hrs/day) 8.38.3 5.15.1

Days in hospitalDays in hospital 6161 8*8* Death (n)Death (n) 44 22

* p<0.05 baseline, ** p<0.05 O2

Vogt Ladner AJRCCM A836, 2003

Conclusions: CPAP in CHF with CSRConclusions: CPAP in CHF with CSR

– CPAP corrects CSR CPAP corrects CSR

– Allows PaCO2 to rise in CSRAllows PaCO2 to rise in CSR

– Reduces sympathetic activation and hyperventilation Reduces sympathetic activation and hyperventilation

– Reduces blood pressure and heart rateReduces blood pressure and heart rate

– Improves LVEFImproves LVEF

– No reduction in mortality rateNo reduction in mortality rate

– No impact on transplant free survivalNo impact on transplant free survival

• CANPAP data do not support the use of CPAP to extend life in CANPAP data do not support the use of CPAP to extend life in CHF with CSRCHF with CSR

Conclusions: BiPAP in CHF with CSRConclusions: BiPAP in CHF with CSR

– BiPAP corrects CSRBiPAP corrects CSR

– BiPAP reduces arousalsBiPAP reduces arousals

– Improves LVEF, NYHA, fatigueImproves LVEF, NYHA, fatigue

– No better than CPAP in small trialNo better than CPAP in small trial

– Might induce central apnéer due to hypocapnia secondary to overventilationMight induce central apnéer due to hypocapnia secondary to overventilation

– Probably to prefer in hypercapnic central apnéas in COPDProbably to prefer in hypercapnic central apnéas in COPD

Conclusions: Autoset CS ASV Conclusions: Autoset CS ASV in CHF with CSRin CHF with CSR

– Autoset CS ASV corrects CSRAutoset CS ASV corrects CSR

– Autoset CS ASV reduces arousalsAutoset CS ASV reduces arousals

– Reduces AHI and AI more than CPAPReduces AHI and AI more than CPAP

– Improves daytime sleepiness, BNP, Improves daytime sleepiness, BNP, catecholamines, hyperventilationcatecholamines, hyperventilation

– No difference in Quality of lifeNo difference in Quality of life• Larger comparative trials are needed with clinical endpoints Larger comparative trials are needed with clinical endpoints ie mortalityie mortality

Treatment of Cheyne-Stokes Treatment of Cheyne-Stokes Respiration and central apneas in Respiration and central apneas in

congestive heart failurecongestive heart failure

Do not forget to treat Do not forget to treat

CONGESTIVE HEART FAILURE!CONGESTIVE HEART FAILURE!

Do not forget to PREVENT Do not forget to PREVENT congestive heart failure:congestive heart failure:

Treat obstructive sleep apneas!Treat obstructive sleep apneas!