What is mixed (complex) sleep apnea, how is it diagnosed with overnight polysomnography, and what is the initial treatment approach?

Mixed (Complex) Sleep Apnea: Definition, Diagnosis, and Treatment

Definition

Mixed sleep apnea, also called complex sleep apnea syndrome (CompSAS), is characterized by the presence of both obstructive and central apneic events, with central apneas either predominating at baseline or emerging/persisting when obstructive events are treated with CPAP therapy. 1, 2

• A mixed apnea event contains both a central component (absent respiratory effort) followed by an obstructive component (continued respiratory effort against a closed airway), typically with at least one obstructed breath at the end of what would otherwise be a central apnea 1
• CompSAS specifically refers to patients who develop or continue to have ≥5 central apneas per hour after obstructive events are eliminated with PAP therapy, without clear causes like heart failure or opioid use 3, 2
• The prevalence ranges from 0.56% to 18% of patients undergoing sleep studies, with no clear predictive characteristics compared to pure obstructive sleep apnea 2

Polysomnographic Diagnosis

Overnight polysomnography is mandatory to diagnose mixed/complex sleep apnea, as it requires direct measurement of respiratory effort to distinguish central from obstructive components. 4

Key Diagnostic Features on PSG:

• Mixed apneas show initial absence of respiratory effort (central component) followed by resumed effort against an obstructed airway (obstructive component) 1
• Rib cage and abdominal movement monitoring is essential—absent initially, then present but paradoxical during the obstructive phase 1, 4
• Airflow cessation lasting ≥10 seconds with this characteristic biphasic respiratory effort pattern 1
• The apnea-hypopnea index (AHI) must be ≥5 events/hour for diagnosis 1, 4

Diagnostic Pitfall:

• Standard scoring conventionally groups mixed apneas with obstructive events, which may underestimate the central component and miss underlying central sleep apnea or risk for developing CompSAS 5
• Recent evidence suggests that scoring the central and obstructive portions of mixed apneas separately may better predict which patients will develop complex sleep apnea requiring advanced PAP therapy 5
• Patients with a mixed apnea index ≥5/hour who have their central components properly quantified are more likely to develop CompSAS during CPAP titration 5

Breathing Pattern Characteristics:

• Patients with mixed apnea-dominant sleep apnea show greater breath-to-breath variability during wakefulness compared to pure obstructive sleep apnea, similar to patterns seen in central sleep apnea 6
• This suggests underlying ventilatory control instability, with oscillations in PaCO2 driving the central component 6, 2

Initial Treatment Approach

The first-line treatment for mixed/complex sleep apnea is a trial of standard CPAP therapy, as the central component resolves in most patients over time with continued use. 2

Treatment Algorithm:

Step 1: Initial CPAP Trial

• Start with standard CPAP at the pressure needed to eliminate obstructive events 2
• In many patients, central apneas abate over time (weeks to months) as adaptation to CPAP occurs 7, 2
• Monitor for resolution of central events before escalating therapy 2

Step 2: If Central Apneas Persist (AHI remains >5/hour with central events)

• Adaptive servoventilation (ASV) is the most effective treatment, reducing AHI to <10 events/hour in the majority of patients 3
• ASV dramatically improved AHI from a median of 31 events/hour on CPAP to 5 events/hour, with 64% of patients achieving AHI <10/hour 3
• ASV also increased REM sleep percentage compared to baseline and CPAP (18% vs 12% and 10%, respectively) 3

Step 3: Alternative PAP Modalities if ASV Unavailable or Not Tolerated

• Bilevel PAP in spontaneous-timed mode (with backup rate) can improve AHI to approximately 15 events/hour 3, 7
• Avoid bilevel PAP in spontaneous mode without backup rate, as it may worsen central apneas (median AHI 75 events/hour vs 48 at baseline) 3

Critical Contraindication:

• ASV is absolutely contraindicated in patients with heart failure and reduced ejection fraction due to increased mortality risk 4
• Before initiating ASV, exclude heart failure as the underlying cause of central apneas 4

Treatment Considerations:

• CPAP adherence is significantly poorer in mixed apnea-dominant patients compared to pure obstructive sleep apnea, likely related to underlying differences in respiratory control 6
• This poor adherence may necessitate earlier escalation to ASV or other advanced PAP modalities 6
• Supplemental oxygen, added dead space, or CO2 supplementation have anecdotal support but insufficient data for routine recommendation 7

Exclude Secondary Causes Before Attributing to Primary CompSAS:

• Review medication list for opioids or sedative-hypnotics that can cause central apneas 4, 2
• Evaluate for heart failure, atrial fibrillation, renal failure, and neurological disorders 4
• Consider brain MRI if ≥5 central apneas/hour persist without clear etiology, to evaluate for brainstem or cerebellar lesions affecting respiratory control 8