What are the American Academy of Sleep Medicine (AASM) guidelines for treating mixed sleep apnea?

AASM Guidelines for Mixed Sleep Apnea

Critical Clarification: Mixed Sleep Apnea vs. Complex Sleep Apnea

The AASM 2019 PAP guideline explicitly excludes patients with "concurrent forms of obstructive and central sleep apnea" from its recommendations, stating these patients require separate management protocols addressed in other AASM guidelines. 1

Mixed sleep apnea refers to two distinct clinical entities that require different treatment approaches:

1. Mixed Apnea Events (Individual Respiratory Events)

Mixed apneas—individual respiratory events with both central and obstructive components—are conventionally scored together with obstructive events in calculating the apnea-hypopnea index (AHI). 2

• Standard scoring may underestimate the central component of disease, particularly in patients who later develop treatment-emergent central sleep apnea (complex sleep apnea). 2
• Patients with mixed apnea index ≥5/hour have a 17.9% risk of developing complex sleep apnea during CPAP titration. 2
• Begin with standard CPAP therapy as first-line treatment, as mixed apneas are managed within the obstructive sleep apnea treatment paradigm. 1, 3

2. Complex Sleep Apnea Syndrome (CompSAS/Treatment-Emergent Central Sleep Apnea)

Complex sleep apnea—the emergence or persistence of central apneas during PAP therapy—requires a fundamentally different treatment algorithm than pure obstructive sleep apnea. 4, 5

Treatment Algorithm for Complex Sleep Apnea

Step 1: Initial Assessment and CPAP Trial

Start with standard CPAP therapy as first-line treatment, as some patients with complex sleep apnea respond adequately to CPAP alone. 4, 5

• CPAP should be initiated using either auto-adjusting PAP (APAP) at home or in-laboratory titration for patients without significant comorbidities. 1
• Educational interventions must be provided at initiation (strong recommendation). 1
• Monitor for persistence of central apneas during the first few weeks of therapy. 4, 6

Step 2: Cardiac Risk Stratification (MANDATORY)

Before advancing to any therapy beyond CPAP, obtain ejection fraction assessment to determine cardiac contraindications. 4, 5

• If ejection fraction ≤45%: Adaptive servoventilation (ASV) is absolutely contraindicated due to increased all-cause and cardiovascular mortality. 4, 5
• Alternative options for heart failure with reduced ejection fraction include: standard CPAP, low-flow supplemental oxygen (conditional recommendation), or bilevel PAP with backup rate (BPAP-ST). 4, 5
• If ejection fraction >45%: ASV may be considered if CPAP fails, but requires close monitoring. 4, 5

Step 3: Advanced PAP Modality Selection

For patients without cardiac contraindications who fail CPAP, adaptive servoventilation (ASV) is the preferred therapy for complex sleep apnea. 4, 5

• ASV provides breath-by-breath dynamic adjustment of inspiratory pressure support using a three-minute moving average to target 90% of recent minute ventilation. 4
• ASV is suggested over no ASV for treatment-emergent central sleep apnea (conditional recommendation, low certainty). 5
• Bilevel PAP with backup rate (BPAP-ST) is the second-line option, superior to standard BPAP without backup rate but less effective than ASV. 4, 5
• BPAP without backup rate is suggested against for treatment-emergent central sleep apnea (conditional recommendation, very low certainty). 5

Step 4: Pharmacologic Adjuncts

Oral acetazolamide is suggested as an adjunctive therapy for treatment-emergent central sleep apnea (conditional recommendation, low certainty). 5

• Acetazolamide can be used in combination with PAP therapy or as monotherapy in selected cases. 5
• Low-flow oxygen is suggested for patients with heart failure (conditional recommendation, low certainty). 5

Step 5: Titration Protocol

In-laboratory polysomnography titration is strongly preferred over empiric home initiation for complex sleep apnea. 4

For ASV titration:

• Adjust EPAP to eliminate obstructive events. 4
• Set minimum and maximum pressure support values. 4
• Configure backup rate algorithm. 4

For BPAP-ST titration:

• Adjust EPAP to eliminate obstructive events. 4
• Increase pressure support if tidal volume remains low. 4
• Increase backup rate in 1-2 breaths/minute increments. 4

Common Pitfalls and Clinical Pearls

The most critical error is initiating ASV without cardiac assessment—this can increase mortality in patients with heart failure and reduced ejection fraction. 4, 5

• Treatment-emergent central apneas can occur during PAP titration; consider down-titration of pressure or switching to ASV. 6
• Patients with respiratory comorbidities (obesity hypoventilation syndrome, COPD), chronic opiate use, or neuromuscular disease require in-laboratory titration rather than home APAP initiation. 1, 6
• Mandatory close monitoring is required for all patients on ASV, particularly those with any degree of heart failure. 4
• Objective monitoring of efficacy and usage data is essential following therapy initiation. 4, 6
• Regular reassessment of cardiac function in patients with heart disease is necessary. 4

Evidence Quality Considerations

The AASM's 2025 central sleep apnea guideline represents the most authoritative source for complex sleep apnea management, based on systematic review using GRADE methodology. 5

The cardiac contraindication for ASV is based on high-quality evidence showing clear harm outweighing benefits in the heart failure with reduced ejection fraction population. 4

Most recommendations for complex sleep apnea are conditional with low to very low certainty of evidence, reflecting the heterogeneity of this condition and limited high-quality trials. 5