Central Sleep Apnea Syndromes

6th Annual ConferenceNorthwest Ohio Southeast Michigan Sleep SocietyMay 1, 2009

Navin K Jain, MD

CENTRAL SLEEP APNEA

“ period of at least 10 seconds without airflow, during which no ventilatory effort is evident”

Normal Control of Breathing

Automatic / Metabolic Chemoreceptors (carotid body for hypoxia and carotid body and

medullary receptors for hypercapnia and H ion) Intrapulmonary receptors – vagus mediated Brainstem processes Keep ventilation regular and match to metabolic demands

Afferent Information from chest wall and respiratory muscles Behavioral / Volitional – under voluntary control Wakefulness stimulus – increased ventilation in awake state

(ventilation persist during wakefulness in absence of metabolic mechanisms)

Control of Breathing at Sleep/Wake Transition to Sleep

Loss of wakefulness stimulus and behavioral influences Muscle activity and chemoreceptor sensitivity is reduced

Apnea threshold Stable sleep changes – sleep specific CO2 set point Transition to Wake - important to restore gas

exchange; may cause central apnea: Arousal threshold Ventilatory Response to arousal

Control Of Breathing in Sleep Non REM Sleep

Metabolic Control – input from chemoreceptors and vagal intrapulmonary receptors (oxygen administration in hypoxic individuals reduces ventilation and may prolong apneas in some individuals; hypocapnic alkalosis also reduces ventilation)

Response of chemoreceptors are somewhat reduced in Non REM sleep but still well maintained and maintains rhythmic ventilation during sleep

REM Sleep – further reduction in responsiveness of chemoreceptors

Central Sleep Apnea

Lack of drive to breathe during sleep Lack of respiratory efforts during cessation of airflow Insufficient or absent ventilation leading to compromised gas

exchange May lead to frequent nighttime awakenings leading to excessive

daytime sleepiness and increased risk of adverse CV outcomes

Most patients have overlap of OSA and CSA CSA Syndrome is considered primary diagnosis when >50% of

apneas are scored as central in origin

CSA: Classification

Central Sleep Apnea High Altitude Periodic Breathing Idiopathic CSA Narcotic Induced Central Apnea

Cheyne Stokes Breathing (CSB) Obesity Hypoventilation Syndrome (OHS)

(Hypercapneic CSA) Complex Sleep Apnea

CSA Syndrome

Hypercapnic – impaired ventilatory output during wakefulness (worsens is sleep as wakefulness stimulus is removed) Impaired Central Drive Impaired Respiratory Motor Control

Nonhypercapnic Cheyne Stokes Breathing Idiopathic CSA

Hypercapnic CSA: Impaired Central Drive Lesions of brain stem – tumors, trauma

induced lesions Congenital Central Hypoventilation

Syndrome (Ondine’s curse) Long term use of Opioids – prolonged

periods of hypoventilation with marked hypoxemia and repetitive central apneas; dose dependent effects

Obesity Hypoventilation Syndrome (OHS)

CSA: Neurologic causes

Disorders of autonomic system Autonomic dysfunction - Shy Drager Syndrome Familial Dysautonomia Diabetes Mellitus

Damage to Brain Stem (respiratory centers) Post Polio syndrome Tumor, Infection, Hemorrhage, encephalitis

Interruption of Neural pathways from medullary respiratory centers to ventilatory muscles Cervical cordotomy

Chronic Opioid use

Becoming more common for chronic pain (even non malignant disorders)

Most experts believe – respiratory tolerance develops and respiratory depression is absent or mild

During wakefulness, chronic respiratory acidosis is absent or mild

While sleeping, 30-90% patients will have sleep apnea (central or obstructive) – may contribute to mortality

Obesity Hypoventilation Syndrome Obesity – BMI > 35 Alveolar Hypoventilation (PaCO2 >45 mm Hg) while awake Hypoventilation worsens during non-REM sleep and further

during REM sleep Other causes of hypoventilation have been ruled out

COPD, Interstitial Lung Disease Chest Wall Disease – Kyphoscoliosis Hypothyroidism Heart failure Diaphragm Paralysis

Hypercapnic CSA: Impaired Respiratory Motor Control Neuromuscular Disorders

Myasthenia Gravis ALS Post Polio Syndrome Myopathies

Chest wall syndromes Kyphoscoliosis

Nonhypercapnic CSA

CSB Idiopathic CSA

Cheyne-Stokes Breathing (CSB)

Cyclic crescendo-decrescendo respiratory effort and airflow during wakefulness and sleep, without upper airway obstruction

Idiopathic CSA

Do not show CSB / transition apnea with normocapnia

May occur as distinct events or repetitive cyclical pattern

Duration of cycle – usually 20-40 seconds; less severe O2 desaturations

Mainly in stage N1 and N2 sleep Arousals at termination of apnea May complain of insomnia or hypersomnia Usually have elevated hypercapnic ventilatory

response

High Altitude Periodic Breathing Most healthy individuals will have periodic

breathing on high altitude ascent provide ascent causes significant alveolar hypoxia

Factors affecting CSA severity Hypoxia

Any hypoxia tends to worsen CSA severity More severe hypoxia seen in OHS; mild in idiopathic CSA

and OHS Hypoxia may impair respiratory sensory feedback

Upper Airway Anatomy Narrow upper airway can collapse in central apnea (as it

depends on neuronal input) Treatment of OSA with PAP may cause hypocapnia in

patients and may cause treatment emergent CSA by causing hypercapnia (Complex Sleep Apnea)

Cheyne Stokes Breathing (CSB)

Cheyne-Stokes Breathing (CSB)

Cyclic crescendo-decrescendo respiratory effort and airflow during wakefulness and sleep, without upper airway obstruction

If decrescendo effort is accompanied by apnea during sleep, it is a type of central sleep apnea syndrome

Mainly seen is stage N1 and N2 sleep Cycle time – 60-90 seconds (longer than other forms of CSA);

correlation with severity of HF Arousal typically occurs mid cycle at peak of ventilatory effort Most commonly seen in patients with CHF and LV systolic dysfunction Often co-exist with OSA (together may be classified as Sleep

Disordered Breathing)

CSB: Pathogenesis

Uncertain Seen as series of events

Patients are hypocapnic to begin with, so to correct hypocapnia, respiratory center initiates an apnea; pCO2 begins to rise.

Duration from beginning of apnea until respiratory center detects increasing PaCO2 is prolonged due to increased circulatory time

When respiratory center terminates apnea, it is already hypercapnia

Hypercapnia causes hyperpnea which causes hypocapnia NET EFFECT – oscillation of ventilation between apnea and

hyperpnea Elimination of hypocapnia with inhaled CO2, CPAP or O2 can

attenuate CSB

Factors contributing to CSB

High ventilatory drive Minimal difference between apnea threshold

and sleeping eucapnic PaCO2 Long circulation time Impaired cerebrovascular reactivity to CO2 Increase pulmonary capillary wedge pressure

may stimulate J receptors in lung causing apnea and resultant hyperventilation

Sleep Disordered Breathing (SDB) in Heart Failure SDB may be seen in ~50% all patients with heart

failure and ~70% patients with heart failure who are referred to sleep laboratory

Can be seen among patients whose heart failure is optimally managed

CSB may be more common than OSA in patients with heart failure

CSB more common among men, elderly, atrial fibrillation, and hypocapnia

OSA more common among older individuals and increasing BMI

CSB: Effects

Intermittent hypoxia – increased sympathetic drive causing arhythmia and worsening of HF

Arousals – induce adrenergic surges Impair systolic and diastolic function Extremely negative intrapleural pressure with hyperpnea

increase ventricular transmural wall stress and afterload CSB in patients with heart failure is associated with higher

cardiac mortality Clinically

Poor sleep quality – sleepiness in daytime Symptoms of worsening heart failure – dyspnea, edema Paroxysmal nocturnal dyspnea (due to hyperpnea) Nocturnal angina, recurrent arrhythmia

CSB : Treatment

Management of CHF Supplemental Oxygen Acetazolamide Theophylline Pacemaker Heart Transplantation PAP therapy

Narcotic Induced CSA

Chronic Opioid use : CSA / CompSA

While sleeping, 30-90% patients on chronic opioids will have sleep apnea (central or obstructive) – may contribute to mortality

Acute uses – case report Chest 2008 (nightly dose) low AHI high sleep efficiency Disproportionate symptoms (excess daytime

sleepiness

CSA in Chronic Opioid Users

Develop combination of obstructive and central apnea events (pathogenesis – unknown) Central events mainly in Non REM sleep With PAP therapy, on CPAP obstructive events may be

corrected and central events persist When compared to age, gender, and BMI matched

controls, higher AHI is due to central events Dose relationship noted with AHI and dose of opioid

Central Apnea events Periods of apnea and hyperepnea (Biot’s respiration) Breaths at end of apnea are abrupt and not gradual Irregular; erratic pattern of respiratory rate and tidal volume

CSA in Chronic Opioid Users

Central Apnea events Periods of apnea and hyperepnea (Biot’s respiration) Breaths at end of apnea are abrupt and not gradual Irregular; erratic pattern of respiratory rate and tidal

volume

Biot’s Respiration

Narcotic Induced CSA: Treatment Minimize dose of Narcotics PAP therapy

CPAP – alone not effective Usually require APSSV

Obesity Hypoventilation Syndrome (OHS)

Pickwick Papers

Obesity Hypoventilation Syndrome Obesity – BMI > 35 Alveolar Hypoventilation (PaCO2 >45 mm Hg) Hypoventilation worsens during non-REM sleep and

further during REM sleep Other causes of hypoventilation have been ruled out

COPD, Interstitial Lung Disease Chest Wall Disease – Kyphoscoliosis Hypothyroidism Heart failure Diaphragm Paralysis

OHS: clinical features

Symptoms similar to OSA Loud snoring, periods of choking in sleep, excessive sleepiness in daytime,

fatigue Dyspnea on exertion BMI >35 kg/m2 May heave features of Right Heart Failure

Rales, hepatomegaly, edema Hypercapnia – PaCO2>45 mm Hg during wakefulness Hypoxic – PaO2 <70 mm Hg but have normal alveolar-arterial gradient

if no associated heart or lung disease Elevated hematocrit EKG, ECHO – features of RVH, Pulmonary HTN PFT – restrictive ventilatory defect Often have coexisting OSA

OHS: Pathogenesis

Obesity Related Physiologic abnormalities OSA Increased work of breathing – due to reduced lung compliance and

increased effort to move ribs and diaphragm Respiratory Muscle Impairment - Depressed Central Ventilatory Drive – reduced response to

chemostimuli – hypoxia and hypercapnia (it may be effect of OHS rather than cause)

V/Q mismatching – poor ventilation of lower lobes and increased perfusion to lower lobes

Diminished effects of neurohumoral modulators (leptin) due to reduce levels or resistance

Weight Loss alone can cause decrease in PaCO2 during wakefulness in these patients

OHS and sleep study

Oxygen desaturation during sleep Occur for longer periods than in patients who

have OSA alone Most patients have associated OSA AHI severity is not associated with likelihood

of coexisting OHS but severe oxygen desaturation is associated with coexisting OHS

OHS: Treatment

Weight Loss Respiratory Stimulants

Progesterone PAP therapy Oxygen Phlebotomy

Treatment Emergent CSA

Complex Sleep Apnea (CompSA)

Complex Sleep Apnea (CompSA)

Described by Morgenthaler; Sleep2006 29:1203-09

Treatment emergent central sleep apnea Persistence or emergence of central apneas

or hypopneas upon exposure to CPAP or an E0470 device when obstructive events have disappeared

Controversial – is it really a disease

CompSA: A Disease

Patients have anatomic and physiologic vulnerability causing OSA and a central breathing control instability

Seen more among men Less sleep maintenance insomnia complaint Higher likelihood of CHF or ischemic heart disease Is it transient or persist if treated with CPAP alone

CompSA: Not a Disease

Transient and disappear with CPAP therapy in most patients

Relief of upper airway obstruction may cause change in CO2 excretion (so PaCO2 falls below apnea threshold)

Over titration Activation of lung stretch receptors inhibits central

respiratory motor input Washout of CO2 from anatomic dead space

Increased transitions from sleep to wake as getting used to PAP – CPAP initiation may worsen sleep quality

BPAP Titration

BPAP - Timed

Adapt PS Servo Ventilation

PAP therapy

Continuous PAP (CPAP) Useful in OSA Useful in CSA with systolic heart failure

Bi-level PAP (BPAP) Bi-level PAP with timed mode (BPAP S/T) Adaptive Pressure Support Servo Ventilation

(APSSV) Used in patients with CSA, treatment emergent

CSA, CSB

APSSV

Expiratory Pressure is set to eliminate obstructive apneas

Inspiratory support (variable) above expiratory pressure – provided by breath-breath analysis

Back Up Rate – aborts any impending central apnea Some times may not work as well in patients with

chronic opioid therapy (may not regulate irregular breathing)

Diagnosis of CSA

No screening tool – like apnea link Main test - Polysomnogram