Obstructive sleep apnea in adults

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

The goals of treatment are to improve quality of life, to reduce mortality and morbidity, and to resolve the symptoms and signs of the condition. Reduction of the Apnea-Hypopnea Index (AHI) and hypoxemia, control of hypertension, and control of hyperglycemia are intermediate outcome measures.

The treatment approach may be selected based on the severity of disease. Possible concurrent treatments include weight loss, positional therapy, pharmacotherapeutic agents (modafinil, armodafinil, solriamfetol, or pitolisant for residual sleepiness), and sleep hygiene education.

Continuous positive airway pressure (CPAP)

CPAP is recommended as first-line therapy for the treatment of OSA, and is the treatment of choice for severe OSA (AHI ≥30 episodes/hour).[70]

The proposed mechanism is pneumatic splinting of the airway, thereby decreasing the closing pressure of the pharynx. The treatment pressure level may be determined in the sleep laboratory, or at home using an auto-titrating device.[69][70][103] An auto-titrating device may expedite treatment initiation, be better tolerated by some, may reduce aerophagia, and can adapt pressure to variable conditions such as weight changes and alcohol intake.[70] However, the absence of a sleep technician precludes exchange of interfaces and troubleshooting problems during sleep.

CPAP improves survival and sleepiness, and may possibly improve mood and cognitive function.[24][63][104][105][106][107][108][109][110] CPAP therapy appears to reduce motor vehicle accident risk.[26][111]

CPAP therapy may also:[112][113][114][115][116][117][118][119]

modestly reduce blood pressure (approximately 2-4 mmHg SBP) and
reduce incidence and risk of recurrence of atrial fibrillation, particularly in younger patients.

Cardiovascular disease may not be reduced with CPAP use in nonsleepy patients.[120][121][122] CPAP use does not appear to result in weight loss or improved glycemic control.[123][124][125]

For patients with mild (AHI of 5-15 episodes/hour) to moderate (AHI 15-30 episodes/hour) OSA, evidence for beneficial outcome is inconsistent.[70][126] CPAP is, however, recommended as a first-line therapy (along with oral appliances) for symptomatic patients.

CPAP adherence can be low

Adherence to CPAP may be compromised by claustrophobia, rhinitis, technical problems, pressure intolerance, and social rejection of the apparatus. Using objective monitoring, it has been shown that only 46% of patients were using CPAP for ≥4 hours for 71% of all nights studied.[127]

In the US, Medicare requires an assessment of adherence within 12 weeks to demonstrate minimal use of 4 hours a night in at least 5 of 7 nights a week, and clinical benefit.[67] A key priority is better assessment of the full benefits of CPAP (limited by the lack of long-term randomized trials).[128][129]

Measures to improve CPAP adherence

Patient preparation, education, comfort, and fit of the interface may affect adherence and acceptance of CPAP. Therefore, proper fit of the interface is critical. Interface selection should be guided by patient preference. Nasal interfaces are preferable to oronasal interfaces as they are more comfortable and result in lower effective pressures. Oronasal interfaces may be used in patients with persistent mouth opening in sleep.[130] A chin strap may also be considered to reduce oral air leak.[131] Interface desensitization and trial of various interfaces based on patient preference may be used for claustrophobic patients.

Patient support, education, and behavioral interventions, such as cognitive behavioral therapy, can improve adherence.[132] [ ] [ ] [ ] Telemedicine-based intervention appears to be effective.[133]

Nasal resistance is associated with CPAP nonacceptance, and nasal surgery may be used to lower nasal resistance and possibly promote improved CPAP adherence.[134][135][136][137][138] Intranasal corticosteroid application may improve adherence in patients with rhinitis or turbinate hypertrophy.[139]

Nonbenzodiazepine soporifics, such as eszopiclone, have been used to improve CPAP titration and may potentially improve adherence in selected patients.[140]

Review of data obtainable from current CPAP devices may be used to troubleshoot patterns of use and assess for excessive system air leak rates and persistent obstructions. This, in turn, may lead to intervention for improved usage.

Patients prefer autoadjusting and bilevel PAP to CPAP, but evidence for improved outcome is lacking or not clinically significant.[141][142] [ ] Heated humidified air may be considered, but data regarding CPAP adherence in adults are not compelling.[143][144] Expiratory pressure relief (e.g., C-flex) use does not seem to increase adherence time.[145] Currently, there is no robust evidence from systematic reviews and meta-analyses to indicate that modifications to CPAP have a clinically significant impact upon patient adherence.[146]

If regular CPAP use is not accomplished or symptoms do not sufficiently improve, then oral appliances, surgery, or hypoglossal neurostimulation should be considered.

Complications of CPAP therapy

Include sleep disturbance, rhinitis, dermatitis, conjunctivitis, aerophagia, dyspnea, and dentofacial changes.[70][147] Skin reactions and mask discomfort, in addition to the symptoms described, may lead to noncomplicance.[148]

Oral appliances

Oral appliances are recommended for the treatment of mild to moderate OSA (AHI of 5-15 episodes/hour and 15-30 episodes/hour, respectively) in patients who prefer them to CPAP therapy, or who do not tolerate CPAP therapy.[149][Evidence B]What are the effects of oral appliance therapy compared with no therapy or continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea?[149] Oral appliance therapy may be used as second-line therapy for patients with severe OSA (AHI ≥30 episodes/hour) who are CPAP-intolerant. Oral appliance effectiveness should be assessed using a sleep test when the AHI is >15.

In patients with severe OSA, successful AHI reduction is usually better with CPAP.[149][150][151][152] Symptoms and quality-of-life outcomes are similar for CPAP and oral appliances.[150][151][153]

Absence of trismus, presence of sufficient stable dentition or implants for appliance retention, and presence of manual dexterity are prerequisites for oral appliance use.

Mandibular repositioning appliances (MRAs)

Less effective than CPAP at lowering the AHI but may be better tolerated.[149][154] Favorable patient characteristics for successful treatment using MRAs are younger age, lower body mass index, higher degree of mandibular protrusion (75%), smaller neck, mildly elevated AHI, and positionally dependent AHI.[150] Lower pressure levels in a PAP trial (<12 cm or <10.5 cm), or the depth and morphology of flow pattern in polysomnography, may also predict better AHI response to oral appliance therapy.[155] The mechanism of action of MRAs includes tongue advancement, lateral pharyngeal dilation, and increased airway wall tension. Awake fiberoptic endoscopy may be useful to predict response to oral appliance therapy.[86] Drug-induced sleep endoscopy (DISE) may also be performed to assess potential responsiveness.[156]

Tongue-retaining devices

Second-line appliance therapy in patients in whom MRAs cannot be used, such as patients with macroglossia or who are edentulous.[150] Their effectiveness and tolerance is lower than for MRAs.[157][158]

Oral appliance therapy adherence

Monitoring is possible using temperature-based sensor systems that are attached to the oral appliance.[159]

If adherence to an oral appliance treatment regimen is low, consider:

Reducing jaw protrusion for discomfort problems
Troubleshooting appliance fit, ensuring symmetry (even intercuspation [proper fitting cusp-fossa of opposing teeth]), addressing temporomandibular joint problems, and/or applying posterior stops
Using or reattempting CPAP treatment: CPAP is more effective for AHI reduction, and reuse for those with moderate to severe condition is recommended
Using a different type of appliance: decision made based on dental anchoring mechanism/location and discomfort
Treating nasal obstruction
Undergoing upper airway surgery: for patients who cannot tolerate oral appliances or CPAP

Complications of oral appliance therapy include oral dryness, tooth discomfort, hypersalivation, occlusal changes, tooth movement, jaw pain, and treatment failure.

Upper airway surgery

Upper airway surgery is indicated in adults when CPAP or oral appliances are not accepted, have failed, or have not been tolerated. Surgery is also indicated for patients with discrete anatomic lesions, such as palatine or lingual tonsils, whose treatment is straightforward and is likely to effectively treat the OSA. Upper airway (pharyngeal) procedures expand or stabilize the pharynx.

Oropharyngeal procedures include uvulopalatopharyngoplasty, tonsillectomy, lateral pharyngoplasty, transpalatal advancement pharyngoplasty, expansion sphincter pharyngoplasty, barbed reposition pharyngoplasty, and maxillomandibular advancement (MMA).[160][161][162][163] Hypopharyngeal approaches include genioglossus advancement, hyoid suspension, midline glossectomy, tongue suture suspension, epiglottoplasty, and MMA. Multiple procedures may be performed simultaneously or in a staged fashion to reach the treatment end point.[164]

Surgical outcomes

Surgery for OSA may improve quality of life, reduce the signs and symptoms of OSA, and lower cardiovascular risk and premature mortality.[165][166][167][168][169][170][171][172][173] Surgery usually reduces, but does not completely normalize, the AHI in most patients.[174][175][176]

One meta-analysis of 274 studies (conducted by the AASM) reported that surgery as a rescue therapy demonstrated a clinically significant reduction in AHI, BP, excessive sleepiness, RDI, snoring, and oxygen desaturation index; an increase in lowest oxygen saturation and sleep quality; and an improvement in quality of life in adults with OSA who are intolerant or unaccepting of PAP therapy. The analyses demonstrated that surgery as an adjunctive therapy results in a clinically significant reduction in optimal PAP pressure and improvement in PAP adherence in adults with OSA who are intolerant or unaccepting of PAP due to side effects associated with high pressure requirements.[177]

Surgery carries risks and is most appropriate for CPAP- and oral appliance-nonadherent patients. Patients with discrete anatomic loci (e.g., hypertrophic tonsils in a young adult) can be effectively treated with surgery and thus avoid the need for ongoing life-long therapy. MMA is highly effective at treating the AHI and can improve quality of life, but it is not readily accepted by most patients (because it may result in considerable morbidity, e.g., neurosensory dysfunction).[178] Nasal surgery improves quality of life and sleepiness in OSA patients but reduces the AHI infrequently (about 17% of patients).[179][180]

Complications of surgery

Include airway obstruction, bleeding, hematoma, infection, pain, dysphagia, velopharyngeal insufficiency, dysarthria, throat dryness, pharyngeal stenosis, worsening of AHI, death (very rarely), and, in the case of skeletal surgery, may also include loss of dentition, fracture, paresthesias, malocclusion, and fistula.

Preoperative evaluation

The preoperative evaluation includes the modified Malampati position where the tongue to palate relation is assessed with the tongue at rest in the oral cavity. Awake fiberoptic endoscopy is performed to exclude nasal polyps or tumors and to assess structures and sites mediating obstruction. DISE may also be performed preoperatively to identify loci for treatment, and pattern and degree of upper airway collapse.

Patients who appear to have obstruction by multiple anatomic elements may undergo a combination of palatal and hypopharyngeal procedures, and/or MMA. The selection of particular procedures for a patient is directed by the apparent sites and structures mediating obstruction, and by patient preference. Usually the AHI severity does not determine the method used.[181][182][183] Alternatively, the upper airway obstruction may be bypassed by performing a tracheotomy.

Persistent postoperative OSA

Patient preference informs the approach. Consideration may be given to retrying CPAP or oral appliances. Implantable hypoglossal neurostimulation may be appropriate in selected patients.

If CPAP or oral appliances are not accepted or tolerated, additional surgical treatment to address residual sites or structures mediating anatomic obstruction may be an option. In cases of severe OSA, in addition to pharyngeal procedures, surgical options include more aggressive procedures such as tracheotomy or MMA, which are very effective at normalizing the AHI but are less often accepted by patients.

Hypoglossal nerve stimulation

An implantable hypoglossal neurostimulation system (Inspire) improved objective and subjective measurements of OSA severity in an uncontrolled cohort study.[184] The system consists of an implantable pulse generator that stimulates the medial branch of the hypoglossal nerve via an electrode cuff, implanted unilaterally. Stimulation is phasic and is timed based on respiratory signals obtained from a sensor implanted on the chest wall. The therapy thus does not require the patient to wear any device on the face or intraorally, and is activated using a remote control. The treatment is indicated for CPAP intolerance or nonacceptance in patients with AHI ≥15, BMI <32, and who do not have complete concentric upper airway collapse during drug-induced sleep endoscopy (DISE). Hypoglossal nerve stimulation may be more effective in patients who require lower PAP treatment levels.[185]

In postmarketing studies, effectiveness (at least a 50% reduction in AHI and a final AHI <20) is approximately 65%.[186][187] Patient-reported outcomes for quality of life and sleepiness are also improved.[186][188] AHI outcome reporting for this system, however, has largely been derived from a company database that includes AHI values based on the treatment AHI (the best AHI during a titration study), and may not reflect the AHI during the full night.[189]

Concurrent persistent hypersomnolence

Armodafinil is partially effective at treating residual sleepiness in patients treated for OSA, as is modafinil.[139][190] Treatment complications include headaches, insomnia, nervousness, and rhinitis. Armodafinil or modafinil may be added to CPAP to reduce somnolence.

Pitolisant, a selective histamine H3-receptor antagonist/inverse agonist, is approved by the European Medicines Agency (EMA) to improve wakefulness and reduce excessive daytime sleepiness in adults with OSA. In the US, it is currently approved by the Food and Drug Administration (FDA) only for excessive daytime sleepiness or cataplexy in patients with narcolepsy. Pitolisant is used when other treatments, such as CPAP, have not satisfactorily improved excessive daytime sleepiness or cannot be tolerated by the patient.[191][192][193] One meta-analysis of individual patient data concluded that pitolisant significantly improved excessive daytime sleepiness and fatigue compared with placebo.[191]

Solriamfetol, a dopamine-norepinephrine reuptake inhibitor approved for the treatment of OSA by the FDA and EMA, reduces excess sleepiness in patients with OSA and narcolepsy.[194][195] Longer-term solriamfetol efficacy (up to 50 weeks) has been demonstrated.[196]

The UK National Institute for Health and Care Excellence (an independent public body that provides national guidance and advice to improve health) does not recommend pitolisant or solriamfetol for adults with obstructive sleep apnea because of uncertainty of evidence relating to the former, and lack of evidence of improved patient quality of life with solriamfetol use.[197][198]

Concurrent obesity

Weight loss is recommended for overweight or obese patients with OSA.[12][139] Systematic reviews and meta-analyses conclude that intensive lifestyle interventions that lead to weight loss are effective in the treatment of OSA, and improve daytime sleepiness.[199][200][201] Improvement in AHI may be lost with subsequent weight gain, and it is recommended that the importance of maintaining lower weight is emphasized to patients.[12][202][203]

Bariatric surgery is considered for patients with a BMI of >40 kg/m², or for patients with lower BMI with comorbidities, as it may lower the AHI and reduce cardiopulmonary disease severity.[139][204]

Bariatric surgery may offer markedly greater improvement in BMI and AHI than nonsurgical alternatives.[205] It should be noted that, despite considerable weight loss, OSA may not be eliminated, or may recur (without weight gain).[206] Therefore, all obese patients should be monitored for signs and symptoms of OSA, and polysomnography performed if OSA is suspected.

Patients with low AHI in nonsupine position

Positional therapy is used to maintain a nonsupine sleep position in individuals in whom AHI is low in a nonsupine position; polysomnographic documentation of effectiveness is advised. Positional therapy is more effective in young patients and those with a low body mass index. It is a heterogeneous treatment method including lateral or upright sleep and the use of special pillows, shirts, electronic vibrational devices, or other means to prevent sleep in the supine position. Evidence for positional therapy is promising; however, reliable long-term data is lacking.[207]

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