What is the Inspire procedure for treating obstructive sleep apnea (OSA) in patients who are intolerant to Continuous Positive Airway Pressure (CPAP) therapy?

Hypoglossal Nerve Stimulation (Inspire) for Obstructive Sleep Apnea

What is the Inspire Procedure?

Hypoglossal nerve stimulation (HNS), marketed as the Inspire device, is an FDA-approved implantable neurostimulation system that represents a highly effective second-line therapy for moderate-to-severe obstructive sleep apnea in patients who cannot tolerate CPAP. 1

The device consists of three components: an implanted pulse generator (similar to a cardiac pacemaker), a sensing lead that detects respiratory effort, and a stimulation lead attached to the hypoglossal nerve. 2 During sleep, the sensing lead monitors breathing patterns, and at end-expiration, the stimulation lead triggers the hypoglossal nerve to contract and stiffen the tongue, preventing airway collapse and maintaining upper airway patency. 2

Patient Selection Criteria

Strict eligibility criteria must be met for HNS candidacy, as only approximately 10% of screened patients typically qualify: 1

Mandatory Requirements:

• Age ≥18 years 1
• AHI between 15-65 events/hour (some guidelines specify 15-100, but the more conservative 15-65 range is preferred by VA/DOD and European guidelines) 1, 3
• BMI <32 kg/m² (European guidelines) or <40 kg/m² (some American guidelines, though <32 kg/m² predicts better outcomes) 1, 4
• Documented CPAP failure or intolerance after comprehensive optimization attempts including mask refitting, pressure adjustments, heated humidification, and behavioral interventions 1, 3
• Anatomical suitability confirmed by drug-induced sleep endoscopy (DISE) showing absence of complete concentric collapse at the soft palate level, as this pattern predicts HNS failure 1, 3

Additional Considerations:

• Polysomnography performed within 24 months 1
• No severe periodontal disease, cardiac/respiratory failure within past year, or obvious micrognathia 1
• Smoking cessation at least 1 month prior to surgery 1

Treatment Algorithm Position

CPAP remains the gold standard first-line treatment for moderate-to-severe OSA, and HNS should never be used as first-line therapy. 1, 3 The European Respiratory Society issued a conditional recommendation against HNS as first-line treatment but strongly supports its use as salvage therapy in appropriately selected CPAP-intolerant patients. 1

Hierarchical Treatment Approach:

1. First-line: CPAP with comprehensive optimization (mask types, pressure titration, heated humidification, behavioral support) 1, 3
2. Second-line (if CPAP fails): BiPAP trial if high pressures were the primary intolerance issue 1
3. Third-line: HNS for moderate-to-severe OSA meeting strict eligibility criteria 1, 3
4. Alternative considerations: Mandibular advancement devices are more appropriate for mild-to-moderate OSA (AHI <30) and represent a therapeutic step-down for moderate-to-severe disease 1, 3

Clinical Efficacy and Adherence

High-quality randomized controlled trial data, particularly the STAR trial, demonstrates significant improvements in AHI, quality of life measures, and Epworth Sleepiness Scale scores with HNS. 1 Long-term follow-up data (≥5 years) confirms sustained safety and efficacy. 1

Adherence to HNS is superior to CPAP, with patients using the device for a significant portion of nights, addressing one of the major limitations of PAP therapy. 1, 5 Quality of life improvements are substantial, with patients showing normalization of EuroQol utility indices comparable to the general population within 3 months of implantation. 6

Guideline Support

Multiple major guidelines endorse HNS for CPAP-intolerant patients:

• American Academy of Sleep Medicine (2021): Recommends HNS for moderate-to-severe OSA patients who are CPAP-intolerant when BMI <40 kg/m² and AHI 15-100 1
• Veterans Administration/Department of Defense (2020): Recommends evaluation for HNS for patients with AHI 15-65/h and BMI <32 kg/m² who cannot adhere to PAP therapy 1, 3
• European Respiratory Society (2021): Conditional recommendation for HNS as salvage treatment in symptomatic OSA patients who cannot be sufficiently treated with CPAP, with AHI <50 events/h and BMI <32 kg/m² 1

Critical Pitfalls to Avoid

Do not proceed with HNS without DISE confirmation of anatomical suitability, as complete concentric collapse at the soft palate level predicts failure. 1, 3 This anatomical assessment is non-negotiable and skipping it leads to poor outcomes.

Do not consider HNS in patients with AHI >65 events/hour, as success rates drop significantly in more severe disease, with multilevel surgery success falling from 100% in AHI <30 to 50% in AHI >50. 1

Do not delay definitive treatment with prolonged weight loss attempts when the patient has symptomatic moderate-to-severe OSA, though weight reduction should be pursued as adjunctive therapy. 1, 3

Do not cycle through additional PAP variants indefinitely after documented CPAP and BiPAP failure in appropriate candidates. 1

Mechanism and Physiological Rationale

OSA results from diminished neuromuscular activity of upper airway dilating muscles during sleep. 7 Stimulation of the genioglossus muscle (via the hypoglossal nerve) most effectively reduces airway resistance and critical closing pressure. 7 The Inspire device leverages this physiological principle by providing synchronized stimulation timed to the respiratory cycle, maintaining airway patency during the vulnerable inspiratory phase. 2

Contraindications and Alternatives

HNS is contraindicated in patients with:

• Central or mixed sleep apnea patterns
• BMI ≥32 kg/m² (European guidelines) or ≥40 kg/m² (American guidelines)
• Complete concentric collapse at soft palate level on DISE 1, 3
• Active cardiac or respiratory failure 1

For patients who don't meet HNS criteria, mandibular advancement devices should be considered for mild-to-moderate OSA (AHI <30), with 13 randomized controlled trials supporting their efficacy and equivalent patient-related outcomes to CPAP despite less AHI reduction. 3 Maxillomandibular advancement surgery can be considered for young patients without excessive BMI who refuse all other treatments, though this carries higher morbidity. 4