SPECIAL ISSUE 2: INVITED ARTICLE

Central Sleep Apnea Syndrome

Rushika Shah1, Abha Pandey2

International Journal of Head and Neck Surgery (2019): 10.5005/jp-journals-10001-1367

Case Description 1
Pulmonary Medicine, Guru Nanak Hospital, Mumbai, Maharashtra,
A 68 years male with BMI- 26 kg/m2, known case of cerebrovascular India
2
accident 4 years ago, congestive heart failure with low left Department of Respiratory Diseases, Lilavati Hospital and Research
ventricular ejection fraction (LVEF) of 25% requiring diuretics since Centre, Mumbai, Maharashtra, India
2 years. He had complaints of excessive daytime somnolence, Corresponding Author: Rushika Shah, Pulmonary Medicine, Guru Nanak
unrefreshing sleep and snoring during night. PSG showed evident Hospital, Mumbai, Maharashtra, India, e-mail: dr_rushika85@gmail.com
central apneas with AHI – 32/hr and lowest SpO2 – 88%. It also How to cite this article: Shah R, Pandey A. Central Sleep Apnea
showed Cheyn–Stokes breathing pattern. Syndrome. Int J Head Neck Surg 2019;10(2):34–38.
Sleep apneas have received increasing recognition since the Source of support: Nil
last few years due to spread of awareness and its association with Conflict of interest: None
various comorbidities. Unlike obstructive sleep apnea (OSA), central
sleep apneas (CSAs) are not as widely studied with evident lacuna in
literature. CSA includes a variety of sleep related breathing disorders CSB also known as crescendo-decrescendo pattern of breathing is
characterized by diminished or absent respiratory efforts in addition defined as waxing and waning in ventilation. This disorder is most
to cessation of airflow for at least 10 seconds. This is in contrast to commonly observed in patients with congestive heart failure (CHF)
obstructive apneas, wherein the respiratory effort is preserved and and left ventricular systolic dysfunction. Apneas or hypopneas
is rather paradoxical. CSA usually occurs in association with OSA or occur at the nadir of the characteristic crescendo-decrescendo
due to underlying medical ailments. ventilatory pattern and are most common during initial lighter
sleep (stages 1 and 2). The cycle time of this pattern of unstable
ventilation (typically 60 to 90s) is much longer than other forms
Definition of CSA, due to prolonged circulation time in patients with CHF.
Central sleep apnea syndrome (CSAS) is defined as presence of Arousal typically occurs mid-cycle at the peak of ventilatory effort
CSA i.e period of absent airflow due to lack of respiratory efforts rather than at the cessation of apnea.5 Recurrent events of apnea,
alongwith symptoms of snoring, excessive daytime sleepiness, hypoxia, arousal and re-oxygenation in HF patients with CSA have
morning headaches, restless sleep or insomnia.1 CSA has been pathological consequences including sympathetic nervous system
classified in various ways either based on status of ventilation activation, oxidative stress, systemic inflammation, and endothelial
(hypercapnea or eucapnea) or based on causative etiology by dysfunction. However, there has not been robust evidence to
International Classification of Sleep Disorders-32. The following support this but understanding of physiology definitely advocates
criteria based on Apnea-Hypopnea index is used to grade CSA the same.
where majority of events should be central.
• Mild CSA: AHI: 5 – 15/hr Treatment Emergent Central Sleep Apnea
• Moderate CSA: AHI: 15 – 30/hr Treatment emergent CSA (TECSA) is defined as emergence of CSA
• Severe CSA: AHI >30/hr (i.e central apnea index > 5/hour) in patients with established OSA
while they are initiated on PAP therapy, which was not present
P at h o p hys i o lo g y at the time of diagnosis. Prevalence of TECSA varies from 5.0 to
Various mechanisms have been postulated for the occurrence of 20.3%.6 Common risk factors identified for this entity have been
CSAS. However, pathophysiology can be best explained under two male gender, advancing age, high baseline AHI, presence of heart
broad headings, i.e CSA with hyperventilation or hypoventilation failure or ischemic heart disease, high baseline arousal index, high
(Fig. 1 and Flowchart 1). CPAP pressure and low BMI.7
Mechanism of TECSA is not well understood. Several hypotheses
Central Sleep Apnea and Heart Failure have been proposed as yet. It is a type of CSA only where cessation
Central Sleep Apnea (CSA) in heart failure (HF) needs special of breathing occurs when persistent CO2 washout leads to PCO2
attention as it is found to be present in approximately 30–50% of levels below the apnea threshold due to any reason like relief of
patients with HF with reduced LVEF and in 18–30% of patients with upper airway obstruction, frequent awakening due to poor sleep
preserved LVEF.4 quality and significant mouth leak. Treatment is observation only
Cheyne–Stokes breathing (CSB) is a peculiar accompaniment for initial 3 months as most of TECSA events resolve in this period.
of patients with CSA especially those with associated heart failure. For those who persist with TECSA after 3 months, assisted servo

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.
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 Central Sleep Apnea Syndrome

Figs 1A and B: Comparison of events in obstructive and central sleep apnea on polysomnography. (A) Central event; (B) Obstructive events

ventilation (ASV) mode is preferred. All such patients should be Risk Factors for CSA
checked for mouth leaks and over titration of PAP. Also, in a few • Age: Adults >65 years
repeat PAP titration may be needed to optimize the PAP levels.8 • Gender: Males > Females
• Heart failure: Males >60 years, atrial fibrillation, daytime PaCO2
C l i n i c a l P r e s e n tat i o n <38 mm of Hg
Patients with CSA commonly present with poor sleep quality, • Stroke: acute events and usually self-limiting
insomnia, excessive daytime sleepiness, poor concentration, • Miscellaneous: acromegaly, renal failure
• Medications: opioids
paroxysmal nocturnal dyspnea, morning headaches, nocturnal
angina, witnessed pauses in breathing, nocturnal arrhythmias,
moodiness, reduced libido and impotence. Findings of associated D i ag n o s i s
medical conditions should be elicited like pedal edema and raised Any patient with the presence of daytime sleepiness with presence
JVP due to heart failure and asymmetric weakness due to stroke, of any risk factor or >1 symptom or sign of CSA should be subjected
etc. The clinical characteristics vary slightly between hypercapnic to a full night, attended, in-lab polysomnography which is the gold
and nonhypercapnic central sleep apnea (Tables 1 to 3). standard for diagnosis of CSA. Essentially, level 1 polysomnography

International Journal of Head and Neck Surgery (Theme: Obstructive Sleeep Apnea), Volume 10 Issue 2 (April-June 2019) 35
 Central Sleep Apnea Syndrome

Flowchart 1: Schematic diagram of events leading to central sleep apnea3

Table 1: Classification of central sleep apnea1

Hypercapnic (PCO2 >45) Nonhypercapnic (PCO2 ≤45)
Central alveolar hypoventilation a. Secondary
a. Secondary Congestive heart failure (CHF)
Brainstem tumors Brain lesions
Bulbar polio Renal failure
Encephalitis Acromegaly
b. Primary Cerebrovascular disease
Respiratory neuromyopathy Atrial fibrillation
Neuromyopathies High altitude periodic breathing
Myotonic dystrophy Opioid related
Muscular dystrophy Complex sleep apnea
Myasthenia gravis b. Primary
Amyotrophic lateral sclerosis Idiopathic central sleep apnea
Postpolio syndrome
Diaphragm paralysis

Table 2: Pathophysiology and consequences of CSAS

Hyperventilation Hypoventilation
Posthypocapnia response to restore CO2 • Removal of wakefulness stimulus to breathe
• Compromised neuromuscular ventilator control
Seen in CHF, high altitude CSA, primary CSAS, etc Seen in CNS disorders like encephalitis, neuromuscular disorders, kyphoscoliosis,
etc.
Leads to Leads to
• Hypocapnia in awake or sleep state • Severely reduced ventilatory output
• Sleep state instability • Insufficient alveolar ventilation
• Chronic hyperventilation state • Chronic hypoventilation state
CHF, chronic heart failure; CNS, central nervous system

is required to diagnose a CSA as it can detect respiratory effort and Diagnostic criteria varies as per the type of CSA like CSA
airflow limitation. As a general rule, patients with glaring cardiac, associated with Cheyne–Stokes breathing, high altitude or primary
neurological comorbidities and also those who are on codeine CSA. Importantly, all patients should have symptoms of EDS,
preparations for considerable period of time, complete overnight nocturnal awakening, snoring, witnessed apneas or insomnia with
polysomnography should be opted than a limited channel study polysomnography showing ≥ 5 central apnea (CA) and /or central
as they are much more predisposed for central events. hypopnea (CH) in an hour of sleep; the number of CA and/or CH is

36 International Journal of Head and Neck Surgery (Theme: Obstructive Sleeep Apnea), Volume 10 Issue 2 (April-June 2019)
 Central Sleep Apnea Syndrome

Table 3: Clinical characteristics of patients with central sleep apnea1

Characteristic Hypercapnic Nonhypercapnic
Sex distribution Equal Predominantly male
History of respiratory failure Frequent Not reported
Peripheral edema and cor pulmonale Frequent Not reported
Polycythemia Frequent Not reported
Muscle weakness Frequent Not reported
Morning headaches Common Uncommon
Snoring Common Frequent
Nasal obstruction Uncommon Common
Hypertension Uncommon Common
Nocturnal choking Uncommon Common
Nocturnal awakenings and insomnia Uncommon Common
Excessive daytime sleepiness Frequent Frequent
Restless sleep Common Common

>50% of the total no of apneas and hypopneas. Along with these Assisted Servo-Ventilation
features supportive of accompanying etiology should be present. Ideal mode of ventilation for CSA would the one which adapts to
Disorder is not better explained by another current sleep disorder, the breathing rate and tidal volume of a patient and matches it at
medical or neurological disorder, medication use or substance the end of minute ventilation. ASV mode supplies a small sustained
use disorder. Also, congenital central alveolar hypoventilation or positive air pressure. It senses an event of CSA and appropriately
Ondine’s curse should be ruled out. delivers the tidal volume at a preset respiratory rate (set in the
In our case patient is elderly male, with underlying risk factors device). The goal of assisted servo-ventilation (ASV) is to maintain
for CSA like heart failure and cerebrovascular accident in past. a precise ventilation with tight control of PaCO2 by avoiding
PSG showed evident central apnea events with Cheyne–Stokes ventilatory overshoot and undershoot which in turn dampens
breathing, classical of CSA. periodic breathing cycle. It has been found to improve LVEF, quality
of life and overall sleep quality. ASV mode is indicated in patients
Differential Diagnosis with associated HF and preserved EF>45%.
Obstructive sleep apnea periodic limb movement disorder, Rotating
Shift Workers, Narcolepsy, respiratory diseases such as COPD, ILD, Pharmacologic Therapy
asthma, neuromuscular disorder should be ruled out. As an alternative to CPAP therapy when patients are not benefitting
or tolerating the same, pharmacological therapy can be tried. It
T r e at m e n t includes drugs like acetazolamide and theophylline. Acetazolamide
Goals of therapy in CSA are mainly directed to achieve a normal acts by causing metabolic acidosis which stimulates the respiratory
sleeping pattern thus reducing the daytime sleepiness and centre thus abolishing the resultant apneas. It has found some
improving the quality of life. Patients with mild-to-moderate CSA benefit in patients with hyperventilation related CSA. Theophylline
with minimal symptoms can be put on management of underlying has been found to have some benefit in patients with CSA
etiology. If CSA persists despite the best management, CSA specific associated with CSB due to heart failure. It acts as a respiratory
therapy like positive airway pressure therapy should be initiated. stimulant and can reduce the AHI. However, both these drugs carry
However, in patients with severe CSA, positive airway pressure side effects and hence should be used in the right patient type with
therapy should be initiated parallel to management of underlying caution. Recently, zolpidem and triazolam have been considered
etiology. as an option for treatment of primary CSAS, if the patient does not
have any underlying risk factors for respiratory depression.
Positive Airway Pressure Therapy
Adjuvant Therapy
Continuous Positive Airway Pressure (CPAP)
Oxygen therapy can be used as a salvage therapy if patient doesn’t
Initial small trials in CSA patients showed that CPAP could improve tolerate CPAP at all especially in those with associated heart failure.
the ejection fraction of heart and the quality of life. This method of Bicarbonate buffers during night hour dialysis can be used in CSA
treatment was associated with reduction in AHI, nocturnal urinary patients with accompanying renal failure.
frequency, daytime plasma norepinephrine levels and ventricular
ectopic beats.
P o i n ts to Remember
Bilevel PAP Therapy • CSA is an impor tant accompaniment of OSA , of ten
Bilevel PAP therapy along with maintaining a pneumatic splint underdiagnosed
improves alveolar ventilation. Role of bilevel PAP therapy is in • CSA should be suspected in patients with suggestive symptoms
those CSA patients who are not tolerating CPAP well, have evident and underlying neurological disorders, heart failure, long-term
hypoventilation pattern persistent despite CPAP therapy. Back up opioids usage and those with OSA on PAP therapy.
rate should always be set to avoid any incipient periodic breathing. • Diagnosis of CSA warrants a supervised level I polysomnography

International Journal of Head and Neck Surgery (Theme: Obstructive Sleeep Apnea), Volume 10 Issue 2 (April-June 2019) 37
 Central Sleep Apnea Syndrome

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