Multimodal OSA Treatment: Nerve Stimulation, Surgery, Oral Appliances

Obstructive sleep apnea (OSA) is characterized by recurrent episodes of upper airway collapse during sleep, leading to intermittent hypoxia and sleep fragmentation. While CPAP remains the gold standard for moderate to severe OSA, its efficacy is contingent on consistent use, which is often suboptimal.¹ The ATS 2026 presentations underscored the necessity of understanding the underlying mechanisms of airway obstruction to implement more precise and effective non-CPAP therapies. These mechanisms include anatomical factors such as tonsillar hypertrophy, retrognathia, and a large tongue, as well as physiological factors like impaired upper airway dilator muscle activity, high ventilatory control loop gain, and low arousal threshold.²

Mechanistic and Multimodal Approaches

Hypoglossal nerve stimulation (HNS) has emerged as a viable option for select patients with moderate to severe OSA who have failed or are intolerant to CPAP. This therapy involves implanting a device that stimulates the hypoglossal nerve, thereby activating the genioglossus muscle and maintaining upper airway patency during sleep. Clinical trials have demonstrated significant reductions in the Apnea-Hypopnea Index (AHI) with HNS. For example, one study reported a mean AHI reduction of 68% (from 29.3 events/hour to 9.0 events/hour) and a mean oxygen desaturation index (ODI) reduction of 70% in patients with an AHI between 20 and 65 events/hour and a body mass index (BMI) less than 32 kg/m².³ Patient selection is critical, typically excluding those with complete concentric collapse at the soft palate, as identified via drug-induced sleep endoscopy (DISE).⁴

Surgical interventions for OSA encompass a range of procedures targeting specific anatomical obstructions. Uvulopalatopharyngoplasty (UPPP) aims to enlarge the oropharyngeal airway by removing excess tissue from the uvula, soft palate, and pharynx. While UPPP can be effective for some patients, its success rate varies, with AHI reduction rates ranging from 30% to 60% depending on patient selection and surgical technique.⁵ Maxillomandibular advancement (MMA) surgery, which repositions the maxilla and mandible forward, is considered one of the most effective surgical treatments for OSA, particularly in patients with retrognathia. MMA has been shown to achieve AHI reductions of 80% or more in highly selected patients.⁶ Other surgical options include genioglossus advancement, hyoid suspension, and tonsillectomy, often performed in combination to address multiple levels of obstruction.⁷

Oral appliance therapy (OAT), primarily using mandibular advancement devices (MADs), is a well-established treatment for mild to moderate OSA and for patients with severe OSA who cannot tolerate CPAP. MADs work by repositioning the mandible forward, thereby increasing the retrolingual and retro-palatal airway space. A meta-analysis of OAT found a mean AHI reduction of approximately 50%, with treatment success (AHI < 10 events/hour) observed in 50% to 70% of patients.⁸ The effectiveness of OAT is influenced by factors such as baseline AHI, BMI, and the degree of mandibular protrusion achieved.⁹

Emerging pharmacotherapy represents a promising, albeit nascent, area of OSA treatment. Current research focuses on drugs that target specific physiological deficits. For instance, medications that enhance upper airway dilator muscle activity, such as norepinephrine reuptake inhibitors, are under investigation.¹⁰ Additionally, drugs that stabilize ventilatory control (e.g., carbonic anhydrase inhibitors) or increase the arousal threshold (e.g., sedatives with specific receptor profiles) are being explored. While no pharmacological agent is currently approved specifically for OSA, early-phase trials are evaluating compounds that aim to improve pharyngeal muscle tone or reduce loop gain.¹¹ These agents, if successful, could offer a non-invasive, easily administered option, potentially as monotherapy or in combination with other treatments.