Abstract
Obstructive sleep apnea (OSA) is the most common sleep respiratory disturbance. It is widely recognized as a risk factor for cardiovascular diseases. It usually presents with excessive daytime sleepiness, increasing the risk of accidents at work and transit. The prevalence of OSA continues to increase, imposing a global burden on public health and currently affects 10% of middle-aged men and 3% of women. 1
The main focus to treat OSA is to keep a continuous positive pressure in upper airways (CPAP—continuous positive airway pressure), besides weight loss; however, CPAP is not tolerable for long periods (a quarter of patients do not adjust within a few weeks and half of all patients quit after 1 year). 2 The causes of abandonment of OSA treatment with CPAP range from subjective complaints: discomfort (yarn, mask, noise), embarrassment, resistance to use, and prejudice to real complaints such as airway dryness, worsening of nasal conditions, feeling of suffocation, and stress, besides the high cost and successive maintenance of the device.
Other therapies are needed to reduce the symptoms that are not treated by CPAP. Among them, oral appliances for mandibular advancement are the most important ones, which have been the treatment of choice after CPAP. Oral appliances have been indicated in cases of failure to use CPAP in mild and/or moderate OSA and are equally effective in the treatment of OSA compared to CPAP. The mandibular advancement obtained with oral appliances increases the traction of the musculature, maintaining the airway opened. Unfortunately, there are few limitations for the use of oral appliances: dental and periodontal problems, temporomandibular joint disorder, and short- and long-term occlusal alterations of which we do not yet have clear answers to date due to a small number of long-term studies. 3
So, what would it be the next option to treat OSA when CPAP and oral appliances fail? What other methods can maintain muscle tonus during sleep?
As early as 1978, Remmers et al described the pathophysiology of upper airway obstruction in sleep apnea. 4 Since then, research groups have observed that electrical stimulation of the upper airways may result in an increased tonus of the upper airway dilator muscles, thus allowing patients to keep the upper airway unobstructed during sleep. 4
Hida et al, back in 1994, demonstrated that submental stimulation improved breathing disturbance, sleepiness in the daytime, and sleep quality. 5 In 2014, stimulation of the hypoglossal nerve using an implantable stimulator was approved by the US Food and Drug Administration for the treatment of OSA following the results of the STAR trial. 1 However, hypoglossal nerve stimulation is a surgically implantable electrode close to the hypoglossal nerve, therefore, a risky and costly procedure with many unwanted side effects, such as paresthesia, hypertonia of the tongue, successive arousals, hypersalivation, and fatigue muscle.
Previously, Miki et al demonstrated that transcutaneous electrical stimulation was effective in reducing the index and duration of sleep apnea and improved oxygen saturation. 6 Currently, there are many ways to stimulate upper airway dilator muscles: (a) invasively or not, (b) cyclical or continuous stimulation, (c) high- or low-intensity current, (d) neural or muscular stimulation, (e) variable frequencies of the current, (f) variable pulses, (g) uni- or bilateral stimulation, and (h) unipolar or bipolar current. 7 In 2011, a study showed that continuous transcutaneous electrical stimulation (CTES) was a viable and effective approach to stimulate the upper airway dilator muscles during sleep. 5
Hu et al used a biphasic electrical nerve stimulator consisting of an electric pulse generator, an apnea sensor, and percutaneous electrodes. 8 Twenty-two patients with severe OSA were included and tested the device during a split-night study. Each device was triggered if no nasal flow was detected for at least 5 seconds. The mean respiratory distress index decreased from 30.9/hour to 12.4/hour, while pacing was administered without significant changes in the micro-arousal index.
Pengo and Steier carried out the first randomized continuous electrical stimulation study in 366 patients (mean age: 50.8 years), both sexes, mean body mass index 29.6 kg/m2, Epworth Sleepiness Scale 10.5 points, median oxygen desaturation index 25.7/hour (range: 16.0-49.1), and median apnea–hypopnea index 28.1/hour (range: 19-57). The primary outcome improved when simulated stimulation (median: 26.9/hour; range: 17.5-39.5) was compared with active treatment (median: 19.5/hour; range: 11.6-40.0; P = .026), a modest mean reduction of 4.1/hour (95% CI: −0.6 to 8.9). Secondary outcomes on patient perception results indicated that electrical stimulation was well tolerated. Respondents (47.2%) were predominantly mild to moderate OSA. In this subgroup, the oxygen desaturation index was reduced by 10.0/hour (95% CI: 3.9-16.0; P < .001), and the apnea–hypopnea index was reduced by 9.1/hour (95% CI: 0-16.2; P = .004). They concluded that CTES of pharyngeal dilators muscles during a single night in patients with OSA improves upper airway obstruction and is well tolerated. 9
Currently, there are 7 studies that evaluated transcutaneous electrical stimulation for the treatment of OSA, and of these, only one randomized study evaluated continuous electric stimulation throughout the night. 6 -12 Therefore, although electrical stimulation has been shown to be effective among adults, the best moment to introduce this strategy is not known yet: whether continuous or intermittent; what levels of electrical stimulation for different degrees of apnea, associated comorbidities, age groups, and obesity; and its effects in the medium and long term.
Although the earliest study on electric stimulation dates back to the 1980s, few answers have been given since then about its mechanisms. More complex studies are needed to bring light to these unanswered questions. And perhaps transcutaneous electrical stimulation may emerge as a new alternative in OSA when CPAP and oral appliance fail. Is transcutaneous electrical stimulation a light at the end of the tunnel?
Footnotes
Authors’ Note
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