When the U.S. Food and Drug Administration (FDA) approved the Inspire hypoglossal nerve stimulator as a sleep apnea treatment in 2014, fewer than 130 people with obstructive sleep apnea (OSA) had undergone device implantation. Now, approximately 30,000 people use an implantable, pacemaker-like pulse generator to manage their OSA, and a slew of new devices and indications is set to further expand the use of hypoglossal nerve stimulation (HSN) treatment.
Explore This IssueFebruary 2023
“HNS is the most powerful CPAP [continuous positive airway pressure] alternative currently available,” said M. Boyd Gillespie, MD, MSc, a professor and chair of otolaryngology–head and neck surgery at the University of Tennessee Health Science Center in Memphis.
Patients and physicians alike are increasingly aware of the power and potential of HNS. “In the last year or two, we’ve had patients come in after seeing ads online or on TV about HNS; there seems to be more consumer-driven interest in the therapy now than before,” said Ryan J. Soose, MD, director of the sleep division and associate professor of otolaryngology at the University of Pittsburgh.
What we’ve found is that average usage of HNS is around six hours per night, compared to many studies that put CPAP usage at about three-and-a-half hours a night on average. —Ryan J. Soose, MD
Further exploration of and experience with HNS technology has also led to “a paradigm shift in how physicians manage refractory sleep apnea,” Dr. Soose said. “The field is moving away from excisional surgeries toward more physiologically sound, airway stabilizing techniques such as neurostimulation.”
HNS Fills a Need
CPAP remains the standard first-line treatment for OSA; it’s noninvasive, quite accessible, and highly effective when used appropriately. But consistent use is a challenge. Many patients (and would-be patients) find CPAP cumbersome and uncomfortable, and research has shown that up to 50% of patients who are prescribed CPAP will discontinue therapy within 12 months (Respiration. 2014;87:121–128).
“We’ve found that about a third of patients love CPAP, another third struggle with it, and then another third cannot tolerate it at all,” said Maria V. Suurna, MD, professor of clinical otolaryngology and director of sleep surgery at the University of Miami Miller School of Medicine.
[HNS] offers the best outcomes we’ve been able to offer with surgical treatment, with relatively low morbidity and side effects. —Maria V. Suurna, MD
Patients who can’t (or don’t) use CPAP as prescribed remain at risk for the neuropsychological and cardiovascular sequelae associated with OSA. HNS is generally a well-tolerated treatment option for many OSA patients who would otherwise go untreated. “Right now, hypoglossal nerve stimulation is probably the best alternative for people who cannot tolerate CPAP,” Dr. Suurna said. “It offers the best outcomes we’ve been able to offer with surgical treatment, with relatively low morbidity and side effects.”
In fact, real-world outcomes seem to be even better than those noted during initial clinical trials, which were performed on a very select group of patients: those with moderate to severe sleep apnea; a body mass index (BMI) of less than 32; an apnea-hypopnea index (AHI) between 15 and 65; and a previous unsuccessful trial of CPAP usage (N Engl J Med. 2014;370:139–149).
“The original trial showed that roughly two out of three patients had an excellent response, and one out of three patients had a suboptimal response,” said Dr. Gillespie, who participated in the trial. “That was good enough to meet the criteria for success for the trial, but still left some questions, especially among medical sleep physicians and payors, about whether that’s enough to justify undergoing a surgery to implant a fairly expensive device.”
After FDA approval, however, physicians continued to refine their surgical technique. “We learned that placing the stimulation electrode more distally on the nerve allowed us to better capture the muscles we want to stimulate while avoiding muscles we don’t want to stimulate,” Dr. Gillespie said. “We also started including the C1 branch of the nerve, which stimulates the geniohyoid muscle.”
Those tweaks led to improved outcomes, he said. According to post-market data that now include information on more than 4,000 patients, “the success rate for HNS at the community level is probably 75% to 80%,” Dr. Gillespie said.
Benefits of HNS treatment appear to be persistent. Three years after device implantation, the median AHI of patients included in the original trial was 6.2 events per hour, down from 28.2 events prior to implantation and 8.7 events one year post-implantation (Otolaryngol Head Neck Surg. 2016;154:181–188). Five years after implantation, the responder rate was 63%, with three-quarters of patients experiencing a greater than 50% decrease in AHI events and a total of fewer than 20 AHI events per hour. Patients also reported significant improvements in daytime sleepiness and quality of life. Residual disease burden at five years ranges from 10% to 22% (Otolaryngol Head Neck Surg. 2018;159:194–202). Results to date also suggest that the 20% or so of patients who experienced a less-than-optimal response still benefitted from HNS treatment.
“Even though some may still have moderate sleep apnea, you may have taken them down from severe sleep apnea,” Dr. Gillespie said. “And because most of these patients experience symptomatic improvement, if not physiologic, most of them continue to use the device.”
Physicians and researchers hypothesize that continued, consistent use of an HNS device, which must be turned on before sleep, is one reason patients typically experience good outcomes.
“What we’ve found is that average usage of HNS is around six hours per night, compared to many studies that put CPAP usage at about three-and-a-half hours a night on average,” Dr. Soose said.
Patients’ acceptance of the treatment and the preponderance of positive outcomes has led to a de facto expansion of the patient pool. “Based on the results so far, several payor organizations have liberalized the use of HNS to patients with greater than 65 apneic events per hour,” Dr. Gillespie said. And because clinical studies have found that results for patients with a BMI of 32 to 53 were noninferior to those with BMIs of 32 or below, some physicians offer HNS to patients with a BMI up to 35 (Laryngoscope. 2021;131:2616–2624).
Patients with lower body weights typically have higher success rates, however, Dr. Soose said. “We’ve also seen a two to three times better response rate in women compared to men, and a better response rate in older people rather than younger people.”
Not a Home Run
While generally well tolerated and effective in carefully selected patients, HNS should be one part of a comprehensive approach to manage obstructive sleep apnea. “Patients often come in quite unaware,” said Robson Capasso, MD, chief of sleep surgery, professor of otolaryngology–head and neck surgery, and associate dean of research at Stanford University School of Medicine in Calif. “Patients should be informed about all the details, and the need of a close relationship with the treatment team. Hypoglossal nerve stimulation is not a home run most of the time—it must be implemented in the context of a longitudinal care model for sleep apnea, and it requires some work with a clinician to figure out the right device settings that will keep the throat open without waking up the patient or causing discomfort.”
Surgical placement of the device is relatively straightforward. Using two incisions—one in the chest and one beneath the chin—the physician secures the generator in the chest, places a breathing sensor electrode near the ribs, and implants a stimulation electrode around the hypoglossal nerve. Patients typically go home within a few hours.
Postoperative recovery is relatively quick and usually uncomplicated, particularly compared to older surgical treatments for OSA, such as uvulopalatopharyngoplasty. Pain is minimal; most patients resume their usual activities within days. Surgical complications are rare and include bleeding, infection, pneumothorax, and nerve weakness or injury. “To date, I don’t think we’ve seen any permanent nerve injury,” Dr. Suurna said. “Sometimes patients might have a little bit of tongue weakness, but that’s resolved within a few days or weeks.”
After healing is complete—usually, about one month after surgery—patients return for a follow-up visit and initial device set-up. “We work together to find the functional threshold, increasing stimulation to the point where you can see nice movement of the tongue and airway opening,” Dr. Suurna said. “You don’t want to set the stimulation level too high initially. You want to identify the level that moves the tongue adequately but doesn’t cause discomfort.”
It’s best to err on the side of comfort during initial set up. “We’ve learned that one of the biggest predictors of non-use is stimulation-related discomfort,” Dr. Soose said. “So, even though we know we might get a little better apnea control by turning it up a little higher, we always start with optimal comfort settings.”
Patients must be taught to turn the device on at night and shown how to adjust the settings if needed. Most patients, Dr. Suurna said, find this pretty straightforward. After a month or two of home use, patients should undergo a sleep study (either at home or in a lab) and return to the clinic for assessment of their device usage and comfort, symptom response, and physiologic response. Additional programming adjustments can be made if needed. A patient who isn’t consistently using the device or is only using it a couple of hours nightly due to discomfort may benefit from a decreased amplitude level. Adjusting the pulse width and rate of electrical stimulation may also be helpful (Sleep. 2020;44(Supplement_1),S4-S10).
Once comfort and consistent usage have been achieved, annual check-ups are advised. “Over the long term, we sometimes have to make adjustments for either comfort or effectiveness,” Dr. Soose said. “That’s one of the benefits of this therapy compared to other surgeries: If a person’s weight or anatomy changes, we can tailor the treatment accordingly.”
Potential Pediatric Indications for HNS
Researchers are currently studying the utility of HNS in managing OSA in adolescents with Down syndrome. “Approximately 80% of children with Down syndrome have OSA, and that’s a difficult patient population to treat,” Dr. Gillespie said, “because they often have fairly severe sleep apnea and a high rate of CPAP noncompliance due to the discomfort of having something on their face.”
Physiologically, Down syndrome is often associated with hypotonia, which suggests that HNS may be uniquely positioned to treat sleep apnea in Down syndrome because of its effect on muscle tone, Dr. Soose said.
A multicenter Phase 1 clinical trial conducted between 2015 and 2021 that involved 42 adolescents with Down syndrome showed positive impact: a mean decrease in AHI of 12.9 events and a 12-month response rate (defined as a 50% increase in AHI) of 65.9%. Therapy adherence was excellent; the mean duration of nightly therapy was 9.0 hours, with 40 of 42 patients using the device at least four hours per night (JAMA Otolaryngol Head Neck Surg. 2022;148:522–528). Importantly, patients and families reported decreased daytime sleepiness and improved quality of life.
Quality-of-life improvements can be dramatic. Dr. Soose participated in the first surgical implantation of an HNS device in a pediatric patient with Down syndrome. The patient was an adolescent male who’d had a tracheostomy his whole life “because of bad sleep apnea,” Dr. Soose said. After implantation, device programming, and consistent usage, the patient was able to have his tracheostomy removed. “For the first time, he was able to go swimming with his friends because he didn’t have a trach,” Dr. Soose said.
Other families have reported cognitive and behavioral improvements with HNS treatment. In an interview with Stat News, Kate Dougherty said that her son Elliot, one of the 42 children with Down syndrome to participate in the phase 1 clinical trial, can focus better and no longer gets in trouble at school like he used to. His speech has also improved (Stat News. April 21,2021. https://www.statnews.com/2022/04/21/down-syndrome-sleep-apnea-inspire/).
A 2022 systemic review and meta analysis of nine articles investigating the use of HNS in 106 adolescents, collectively, with Down syndrome and OSA noted that “all studies showed that patients receiving hypoglossal nerve stimulation experience a significant decrease in apnea–hypopnea index (at least 50%)” (Front Neurol. 2022;13:1037926). A multicenter trial investigating the use of HNS in adolescents and young adults with Down syndrome is currently underway.
“The early results look very promising—at least as good as the general population with Inspire and maybe even better,” Dr. Soose said. Dr. Gillespie added that he expects FDA approval to cover preteens and teens with Down syndrome in the near future.
The device costs, all in, about $40,000. That’s certainly worthwhile if we’re reducing risk of stroke and heart disease. It may not be as worthwhile ifPages: 1 2 3 | Single Page