What is Complex Sleep Apnea Syndrome?

Complex Sleep Apnea Syndrome

Complex Sleep Apnea Syndrome (CompSAS) is a distinct form of sleep-disordered breathing characterized by the emergence or persistence of central apneas when obstructive sleep apnea is treated with continuous positive airway pressure (CPAP) therapy. This condition represents a hybrid disorder with features of both obstructive and central sleep apnea, requiring specialized diagnostic testing and targeted treatment approaches to improve patient outcomes and reduce cardiovascular mortality risk 1, 2.

Definition and Pathophysiology

CompSAS occurs when:

• Patients initially present with features of obstructive sleep apnea
• Upon treatment with CPAP to alleviate upper airway obstruction, central apneas emerge or persist
• These central events lead to continued sleep fragmentation and oxygen desaturations despite elimination of obstructive events

The primary pathophysiological mechanisms include:

• Ventilatory control instability with oscillations in PaCO2
• CPAP-related increased CO2 elimination
• Activation of airway and pulmonary stretch receptors
• Unstable chemosensitive ventilatory control 1, 2

Prevalence and Risk Factors

The prevalence of CompSAS ranges from 0.56% to 18% of patients diagnosed with sleep apnea 2. Risk factors include:

• Congestive heart failure
• Use of opioid medications
• History of stroke
• Underlying respiratory control abnormalities
• Higher respiratory controller gain (CO2 sensitivity) 3

Diagnosis

Polysomnography (PSG) is the standard diagnostic test for CompSAS 4. The diagnostic criteria include:

1. Initial presentation with obstructive sleep apnea
2. Emergence of central apneas (>5/hour) during CPAP titration
3. Central apneas comprising a significant proportion of respiratory events
4. Absence of other clear causes for central apneas such as narcotics or systolic heart failure

The diagnostic process should include:

• Comprehensive sleep evaluation
• Full-night diagnostic polysomnography or split-night protocol
• CPAP titration study to observe for emergence of central apneas 4

Clinical Presentation

Patients with CompSAS typically present with:

• Symptoms of obstructive sleep apnea (snoring, witnessed apneas, daytime sleepiness)
• Persistent sleep fragmentation despite CPAP therapy
• Continued daytime symptoms despite elimination of obstructive events
• Possible cardiovascular comorbidities 5

Treatment Options

Treatment approaches for CompSAS include:

First-line Treatment:

• Adaptive servo-ventilation (ASV) is the leading treatment for CompSAS, providing both a minimum pressure to maintain airway patency and precisely calculated ventilatory assistance to minimize respiratory instability 1, 6
  • ASV has been shown to dramatically improve AHI to a mean of 5 events/hour compared to baseline and CPAP (p<0.0001) 6
  • ASV also increases REM sleep compared to baseline and CPAP therapy 6

Alternative Treatments:

• Bilevel positive airway pressure (BPAP) in spontaneous-timed mode
• CPAP with supplemental oxygen
• CPAP with added dead space
• Permissive flow limitation
• Pharmacologic interventions 2

Treatment Considerations:

• In patients with heart failure, caution must be used with ASV based on findings from the SERVE-HF trial showing increased mortality in certain patients with heart failure with reduced ejection fraction and predominantly central sleep apnea 4
• For some patients, central apneas may resolve over time with continued CPAP use through adaptation 2

Prognosis and Follow-up

• The prognosis for CompSAS is generally similar to obstructive sleep apnea when properly treated
• In most patients, the central apnea component resolves during follow-up using CPAP therapy
• For those with persistent central apneas, alternative treatments like ASV show high success rates
• Regular follow-up with repeat polysomnography is recommended to assess treatment efficacy 2

Clinical Pitfalls and Caveats

1. Misdiagnosis: CompSAS can be misdiagnosed as treatment-resistant OSA if proper titration studies are not performed
2. Heart Failure Considerations: Use ASV with caution in patients with heart failure with reduced ejection fraction
3. Treatment Adherence: Ensure adequate adherence to therapy as treatment effectiveness depends on consistent use
4. Medication Effects: Always consider the impact of sedatives, opioids, and other medications that may contribute to central apneas
5. Comorbidity Management: Address underlying conditions like heart failure that may contribute to respiratory control instability

CompSAS represents an important clinical entity that requires proper identification and targeted treatment to improve sleep quality, daytime functioning, and potentially reduce cardiovascular risk in affected patients.