The main objective of this international consensus document (ICD) on obstructive sleep apnea (OSA) is to provide guidelines based on a critical analysis of the latest literature to help healthcare professionals make the best decisions in the care of adult patients with this disease. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents).

The task force was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center, all of whom participated as consultants and conducted the systematic literature search.

The literature search strategy was primarily designed to identify systematic reviews published in the last 10 years in English or Spanish, followed by randomized clinical trials, observational studies, clinical practice guidelines, and economic studies according to the topic of each section. Validated methodological filters were used to identify the different types of study design.

The search was conducted on MEDLINE (via PubMed), EMBASE (via Ovid), The Cochrane Library, and CENTRAL (Appendix B available in online material).

An adaptation of the RAND-UCLA method1,2 was used for the preparation of this document. The responsible organizations and the general coordinator of the project established the topics for consensus and selected the experts and task force leaders.

Topics requiring a systematic search of the scientific literature were identified. Structured searches were conducted by expert documentalists. The document was subsequently developed from a draft drawn up by the leaders of each task force. The experts in each group expressed their agreement on the areas for consensus (Table 1 and Fig. 1).

Fig. 1.

Study methodology flow chart (adapted from RAND/UCLA).

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The upper airway of patients with obstructive apneas tends to collapse during sleep, resulting in total or partial airway occlusion. Breathing stops until a microarousal occurs, which reactivates the muscles and reopens the airway. Apnea occurs when the factors that tend to close the airway cannot be offset by the ability of the dilating muscles of the pharynx and/or respiratory centers to keep it open (Fig. 2).

Fig. 2.

Overview of the physiological and biological processes of obstructive sleep apnea. As shown in the top left section of the figure, upper airway obstruction is the result of an imbalance between forces that tend to keep it open (muscle activity) and forces that tend to close it (anatomical factors). This imbalance increases the collapsibility of the upper airway, resulting in the respiratory episode (apnea hypopnea). It is estimated that 19% of the general population has an apnea-hypopnea rate > 10/h3. These episodes involve a series of physiological changes (hypoxia, transient arousals, and intrathoracic pressure changes) and biological changes (inflammation, oxidative stress, etc.). Depending on individual adaptation phenomena, these episodes cause secondary disease in the form of symptoms and are risk factors for the development of various entities (HBP, among others). Several generic factors modulate predisposition to these consequences. AHI: apnea-hypopnea index; HBP: high blood pressure; OSA: obstructive sleep apnea.

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This ICD proposes updating the nomenclature of sleep apnea syndrome to reintroduce the term “obstructive” in the acronyms accepted in 2005, since it defines the nature of the disease and clearly differentiates it from central sleep apnea. We decided to simplify the nomenclature and to remove the word “hypopnea” and the word “syndrome”, which is an outdated term that fails to reflect the current reality of the disease. We therefore recommended the use of the term “obstructive sleep apnea” and the acronym “OSA”.

In this ICD, OSA is defined as the presence of one of the following criteria:

• 1

  Presence of an apnea-hypopnea index (AHI) ≥ 15/h that is predominantly obstructive.

• 2

  AHI ≥ 5/h accompanied by one or more of the following factors: excessive daytime sleepiness, non-restorative sleep, excessive tiredness, and/or impaired sleep-related quality of life, which cannot be explained by other causes.

For the assessment of OSA severity, the position of this ICD is that classifications based solely on AHI are limited and do not reflect the heterogeneity of the disease. In line with current thinking among the scientific community4,5, we have prioritized the search for new scores that reflect this heterogeneity and are predictors of the long-term effects of the disease. Since no validated score is currently available, and although the factors or cut-off points leading to a classification of severe are not clearly established, we recommend that the following be taken into account: AHI; time with oxygen saturation below 90%, reflecting hypoxemia; daytime sleepiness; degree of obesity measured by body mass index and comorbidities (risk factors and cardiovascular disease) associated with OSA (high blood pressure [HBP], especially if treatment-refractory or non-dipping; diabetes mellitus type 2 [DM2]; dyslipidemia; coronary disease; stroke; heart failure or atrial fibrillation) (Fig. 3).

Fig. 3.

Assessment of the severity of the patient with obstructive sleep apnea (OSA) based on various objective parameters recommended by this International Consensus Document. AHI: apnea-hypopnea index; HBP: high blood pressure; BMI: body mass index; CHF: congestive heart failure; CT 90%: accumulated time with oxygen saturation below 90%; CV: cardiovascular or cerebrovascular disease; CVD: cerebrovascular disease; CVRF: cardiovascular risk factors; DLP: dyslipidemia; DM2: diabetes mellitus type 2; EPWORTH: Epworth Sleepiness Scale; IHD: ischemic heart disease.

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OSA is one of the most prevalent sleep disorders, but epidemiological studies in the literature vary widely in terms of methodology, the inclusion of clinical series or population series, diagnostic criteria, and the assessment of severity. A recently published study that analyzed the global burden of this entity6 reported rates ranging between 4% and 30%. Results are summarized in Table 2.

The main pathophysiological mechanisms that underlie the association between OSA and its consequences are intermittent hypoxia, sleep fragmentation, intrathoracic pressure changes, and a number of intermediate elements (Fig. 4).

Fig. 4.

Consequences of obstructive sleep apnea (OSA) and associated pathophysiological mechanisms.

Adapted and reproduced with permission from the SEPAR Manual of Pulmonology and Thoracic Surgery.

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Table 3 summarizes the scientific evidence available on the association between OSA and its different consequences. OSA increases the risk of workplace and road traffic accidents. In the cardiovascular field, one of the manifestations for which the most evidence is available is arterial hypertension. The prevalence of OSA in DM2 is very high and OSA is an independent risk factor for developing DM2. OSA is also very common in coronary disease, but data on its clinical consequences and the effect of treatment are conflicting. OSA also increases the risk of stroke and may be associated with greater functional/cognitive impairment and higher mortality. Sleep-disordered breathing in heart failure is very prevalent, increases the risk of new episodes, and may increase mortality. Arrthythmias, pulmonary thromboembolism, and pulmonary arterial hypertension are also associated with a very high rate of OSA. Severe OSA is also associated with an increased risk of cancer, mortality, and tumor aggressiveness (melanoma), although current evidence is not yet strong. In neurocognitive terms, OSA causes major cognitive impairment (mainly in executive function, attention, and memory) and has a bidirectional association with depression.

Please refer to the online material for a detailed description of clinical presentation, physical examination, and complementary tests. In this section, we will only describe the diagnostic algorithm proposed in this ICD for indicating sleep studies.

As OSA is a highly prevalent disease, it should be managed at different healthcare levels in order to satisfy the demand for care7. Two diagnostic algorithms are proposed. In specialized centers (Fig. 5), patients with moderate-to-severe chronic respiratory disease, unstable cardiovascular disease, other suspected sleep disorders that can cause symptoms or coexist with OSA and some patients with anxiety-depression or insomnia may be candidates for polysomnography (PSG) studies. Patients with a low probability of disease, according to an expert evaluation, may be candidates for follow-up and correction of other influencing factors, or a decision may be taken to perform PSG or respiratory polygraphy. Patients with an intermediate to high probability of OSA can be evaluated by respiratory polygraphy.

Fig. 5.

Proposed algorithm for the diagnosis of patients with suspected obstructive sleep apnea (OSA) at a specialized level. AHI: apnea-hypopnea index; CPD: cardiopulmonary disease; EDS: excessive daytime sleepiness; PSG: polysomnography; RP: respiratory polygraphy; TD: therapeutic decision.

*Intermediate-high probability is defined as the presence of EDS (Epworth > 10) and 2 of the following 3 criteria: usual intense snoring, observed choking arousals or apneas, and/or arterial hypertension.

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A second algorithm is proposed for primary care (Fig. 6), in which patients with a high probability of disease due to excessive daytime symptoms (Epworth ≥ 12) could be evaluated by simplified studies with single- or double-channel devices based on oximetry and/or nasal pressure8. It should be emphasized that this management must always be conducted in coordination with a reference sleep laboratory that can offer the necessary support, using protocols adjusted to specific needs. A therapeutic decision could be made in primary care and coordinated by specialists, but these models may be less generalizable, and they would have to be used in specific, previously validated areas9.

Fig. 6.

Proposed diagnostic algorithm in patients with suspected obstructive sleep apnea (OSA) seen in primary care and coordinated with the reference sleep laboratory. AHI: apnea-hypopnea index; BMI: body mass index; CPD: cardiopulmonary disease; EDS: excessive daytime sleepiness; SS: simplified study (one or 2 channels corresponding to nasal pressure and oximetry); TD: therapeutic decision.

*High probability is defined as the presence of EDS (Epworth ≥ 12) and 2 of the following 3 criteria: habitual intense snoring, observed choking arousals or apneas, and/or arterial hypertension.

**In these cases, a manual analysis of the recording by the coordinating sleep laboratory may offer a more accurate diagnosis.

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The goals of OSA treatment are to resolve the signs and symptoms of the disease, restore sleep quality, normalize AHI, improve oxygen saturation as far as possible, reduce the risk of complications, and lower the costs of the disease. This ICD emphasizes that the various alternatives are combinable and recommends a multidisciplinary therapeutic approach.

All medical, surgical, and physical options for the treatment of OSA should be complementary, not exclusive. Each patient should be offered the widest range of possibilities, and all strategies should be applied rationally, either alone or in combination, and individually adapted after an in-depth study. The patient's role in therapeutic decision-making must be emphasized. This should be the standard approach in multidisciplinary teamwork1–3,6,8 (Fig. 7).

Fig. 7.

Multidisciplinary approach to obstructive sleep apnea (OSA): all interventions are combinable. CPAP: continuous positive airway pressure; DISE: drug-induced sleep endoscopy; UA: upper airway.

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It is important to note that before starting any of the therapeutic alternatives, the clinical diagnosis of OSA must be confirmed by a sleep study validated according to the previously recommended diagnostic algorithm. The therapeutic algorithm (Fig. 8) is as follows:

• 1

  Hygienic-dietary measures should be implemented (Fig. 9) in all patients with OSA, regardless of whether continuous positive airway pressure (CPAP) therapy is indicated.

  
  

  Fig. 9.

  Recommended hygienic-dietary measures for all patients with obstructive sleep apnea, irrespective of an indication of continuous positive airway pressure.

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• 2

  The patient must be evaluated to identify conditions associated with OSA and potentially reversible causes. Accordingly, this ICD recommends:

  • •

    Treatment of obesity: excess weight or obesity should be treated in all patients with OSA. Initial treatment should be part of a comprehensive, high-intensity program that includes behavioral strategies10. Severe obesity requires more durable strategies that should be evaluated in specialized units, where the use of anti-obesity drugs10 or surgery (for patients > 35 kg/m2) will be evaluated when conservative treatment fails11–14.

  • •

    Treatment of reversible causes: thyroid hormone replacement therapy is recommended in patients with OSA and hypothyroidism, so levels should be determined in case of clinical suspicion of hypothyroidism15. In case of gastroesophageal reflux, positional and dietary measures should be indicated, and treatment with proton pump inhibitors should be offered on an individual basis. If the patient presents tonsillar hypertrophy grade III/IV or severe dental or facial alterations, surgery to treat OSA should be considered.

Fig. 8.

Proposed therapeutic algorithm for obstructive sleep apnea (OSA). A more detailed description of the scientific evidence that supports this algorithm can be found in the online material. AHI: apnea-hypopnea index; BMI: body mass index; CPAP: continuous positive airway pressure; ENT: ear, nose, and throat; MAD: mandibular advancement devices.

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In any of these situations, the need for CPAP until treatment of the reversible cause becomes effective can be assessed.

• 3

  Indications for CPAP: CPAP is an effective treatment to reduce OSA severity, assessed according to AHI, and remains the treatment of choice in many of these patients16–29. Once the steps described above have been completed, the following recommendations for indicating CPAP, based on quality evidence evaluated according to currently available information in line with American Academy of Sleep Medicine guidelines30,31, should be followed.

A detailed explanation of the scientific evidence supporting selected cut-off points, symptoms and/or comorbidities used to determine the indication of CPAP can be found in the online material. This ICD recommends CPAP in:

• •

  Patients with a targeted diagnosis of moderate-severe OSA (AHI ≥ 15/h) with excessive daytime sleepiness (Epworth > 10), altered sleep-related quality of life (intense snoring, episodes of night choking, insomnia, morning headache, nocturia, impaired work or academic performance, social impact, and/or tiredness during the day) and/or HBP (especially if resistant or refractory).

• •

  In patients with no indication for CPAP due to AHI ≥ 15/h who do not present the above criteria, AHI between 5 and 15/h, or in whom CPAP is indicated but rejected (refusal to accept treatment or treatment unsuccessfully attempted for less than 4 weeks), alternative treatments should be assessed individually (mandibular advancement devices [MAD], positional treatment, surgery, etc.). These treatments and their indications are described in detail in the online material of this ICD.

• •

  Insufficient evidence is available to consistently recommend the use of CPAP to reduce the risk of death or cardiovascular or cerebrovascular events in adults who do not meet the 3 criteria listed above. These patients should be offered conservative treatment with monitoring of symptoms or an individualized assessment including a CPAP trial (with short-term reassessment of treatment continuity depending on efficacy and tolerance).

• •

  Similarly, in patients with OSA who have AHI < 15/h but are highly symptomatic or have a high burden of cardiovascular, cerebrovascular, or metabolic disease, a CPAP trial may be considered if the patient agrees. Current evidence suggests that CPAP may play a greater role in preventing cerebrovascular events than cardiovascular events32.

• •

  Alternative treatments should be considered individually if the therapeutic trial fails.

The scientific evidence supporting these recommendations and a more detailed description can be found in the online material.

Adequate pressure titration and monitoring of CPAP compliance are essential to achieve the treatment objectives described. Please refer to the online material for a detailed description of these factors. In short, this ICD recommends considering PSG pressure titration for patients with significant (severe COPD) or unstable cardiopulmonary disease (heart failure), complex sleep-disordered breathing (central sleep apnea, suspected incipient central sleep apnea, or obesity-hypoventilation syndrome), or when titration with simplified methods has not been possible. For all other patients, pressure titration with auto-CPAP provides a level of OSA control similar to PSG titration. It is essential that the patient be trained before titration is attempted. This document recommends visual analysis of the graph and selection of the minimum pressure that, regardless of leakage peaks, covers about 90% of the entire pressure graph. It is also recommended that at least 5 valid hours of recording be examined. Finally, empirical formula calculation should only be considered between the start of treatment and until the definitive titration study (auto-CPAP, CPAP with memory card, or manual titration) is performed.

Compliance during the first 3 months can predict long-term use of the device33, so careful attention in this period will be key to achieving adequate long-term compliance34. This ICD defines good adherence as the use of the device for at least 4 h/night on 70% of nights. The current evidence points to a dose-response relationship between hours of use and therapeutic response35,36, and the neurocognitive and cardiovascular effects of CPAP and the perceived benefits in quality of life depend on this compliance37. For this reason, we propose the concept of optimal compliance with a minimum of 6 h/night, an approach which has shown benefits in symptom control and morbidity. As for the type of device, the use of auto-CPAP has not been shown to increase the percentage of nights with more than 4 h use38,39. Therefore, its use is only recommended for patients with high or highly variable effective pressure throughout the night.

Interventions for improving adherence are described in detail in the online material. Since the evidence suggests that telemonitoring improves CPAP adherence40,41, this strategy should be considered during the initial period of CPAP treatment. If it is used, remote recording of CPAP parameters30,31 should include hours of use, residual AHI, unintentional leaks, and machine configuration30,31,42.

Multidisciplinary management with the participation of a sleep specialist, the nursing team, and the suppliers will be important in the follow-up of patients receiving CPAP. Primary care should be included in long-term monitoring.

All patients receiving CPAP should be monitored after the first month of treatment and a brief in-person review should be performed at 6 months. Adherence at 3 months can be determined from telemonitoring. If the treatment is well established, with good clinical response and no side effects, the patient may be referred to primary care for follow-up after the first year.

If the patient has frank and proven intolerance to CPAP (the patient has tried to use it for more than 4 weeks, but has not been able to adapt), withdrawal should be considered. If either rejection or intolerance cannot be rectified, other therapeutic alternatives should be considered. In the event of clear lack of adherence with an average use of less than 3 h/night, the patient should be included in a compliance program, preferably with a telemonitoring system, and re-evaluated after at least 3 months, before assessing the possible withdrawal of CPAP and an alternative therapeutic proposal. Occasionally, patients who use CPAP for less than 3 h/night report symptomatic improvements, so the decision to discontinue treatment should be individualized.

The surgical algorithm recommended in this ICD for use by ENT specialists and oral or maxillofacial surgeons is an update of the standard Stanford 2-tiered protocol (Fig. 10)43,44. In this era of personalized medicine, a precise indication for palatal and oropharyngeal surgeries may initially be made based on clinical findings and drug-induced sedation endoscopy (DISE)45–47, but skeletal surgery, especially bimaxillary advancement, may also be indicated as initial surgical treatment of OSA in patients with severe disease (AHI > 65 and/or concentric collapse on DISE and/or severe dental and facial alterations). An indication for surgery never definitively excludes other treatments, or vice versa. Refer to the online material for a more detailed description of the systematic review and indications for surgery in OSA patients.

Fig. 10.

Algorithm for indicating surgical treatment in obstructive sleep apnea (OSA) using personalized precision medicine. CAPSO: cautery-assisted palatal stiffening operation; CELL: coblator endoscopic lingual lightening; CPAP: continuous positive airway pressure; DISE: drug-induced sleep endoscopy; DOME: distraction osteogenesis maxillary expansion; ENT/MXF; ear, nose and throat/maxillofacial; MAD: mandibular advancement device; PSG: polysomnography; RP: respiratory polygraph; RX/CT: radiological studies; TORS: transoral robotic surgery; UA: upper airway; UPPP: uvulopalatopharyngoplasty. (1) In case of severe dental or facial alterations, bimaxillary advancement may be indicated directly, although CPAP will be prescribed until surgery is conducted. (2) In case of tonsillar hypertrophy grade ≥ 3, tonsillectomy may be indicated directly, although CPAP will be prescribed until surgery. (3) In case of CPAP intolerance after ORL evaluation, nasal surgery is recommended as soon as possible to improve intolerance and retitrate CPAP. (4) In case of CPAP intolerance after dental/maxillofacial evaluation, adaptation of MAD or assessment for orthognathic surgery is recommended. (5) In case of CPAP intolerance after ENT evaluation, DISE is recommended to determine the most appropriate upper airway treatment. (6) After intolerance to CPAP and failure of other surgeries, a repeat DISE is recommended. If collapse is non-concentric, hypoglossal neurostimulation may be indicated.

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The proposed algorithm moves on from the classic concept of soft tissue removal or skeletal modification44. It divides the surgical procedures to be performed according to the affected organ, and the choice of procedure is based primarily on the exploratory and diagnostic findings and on the final decision of the patient after all the options have been explained, none of which is either exclusive or prevailing. It is common for patients to have airway obstructions at different levels, so the current tendency is to perform multilevel surgery, in which, once the different sites of upper airway obstruction have been determined, a decision is made on the different procedures to be performed, alone or in combination, aiming to achieve optimal results48–51.

Recent randomized controlled trials have demonstrated the efficacy of MADs on various aspects of OSA as summarized in Table 4 (see also online material):

This ICD therefore recommends that52,53:

• •

  The diagnosis of OSA and the efficacy of MAD should always be determined by respiratory polygraphy or PSG.

• •

  The indications for MAD are:

  • 1

    Patients with OSA of any severity who are candidates for CPAP therapy but unable to adapt to it. MAD is principally indicated as an alternative to CPAP and should be available in sleep units in the public health system, or

  • 2

    Patients with mild to moderate OSA, minor symptoms, or troublesome snoring and no indication for CPAP or any other treatment.

• •

  Before prescribing an MAD, the dentist must perform an oral examination to rule out patients who do not meet dental inclusion criteria.

• •

  Current evidence supports the use of custom-made, adjustable devices.

• •

  Following assessment of the patient's suitability from the point of view of oral health, treatment should be implemented and followed up by a certified dentist or OSA sleep-disordered breathing expert working in coordination with a sleep unit. Respiratory polygraphy may be used by an experienced sleep dentist as a tool for MAD titration.

OSA is a heterogeneous disease in terms of both its pathophysiology and its polysomnographic expression and clinical presentation. In recent years, various OSA phenotypes have been described that are explained in depth in the online material of this document. This phenotype approach has helped improve our knowledge of the mechanisms involved in the disease and the development of different therapeutic strategies, and has contributed to the development of a more personalized medicine. Table 5 summarizes current evidence and indications for other alternative therapies (see also online material).

In light of the current evidence, the recommendations of this ICD on the role of primary care in the management of OSA patients are as follows:

• 1

  The involvement of primary care physicians is essential to improve the current situation of OSA underdiagnosis.

• 2

  The implementation of training plans in primary care improves the suspicion and diagnostic process of OSA.

• 3

  The criterion for clinical suspicion should be the presence of 2 of the 3 main symptoms: snoring, observed apneas, and/or excessive daytime sleepiness or unexplained intense tiredness.

• 4

  The situations that require urgent referral are summarized in Fig. 11:

  • a)

    Primary care diagnostic procedures should be performed in consensus with the reference sleep unit, working in a network.

  • b)

    At the moment, evidence on how to start CPAP treatment exclusively in a primary care setting is insufficient.

  • c)

    Most treatment follow-up requirements can be met in primary care.

  
  

  Fig. 11.

  Proposed algorithm for the referral of patients with suspected obstructive sleep apnea (OSA) from primary care. HBP: high blood pressure; BMI: body mass index; EDS: excessive daytime sleepiness.

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These activities should be conducted as indicated in Fig. 12. A more detailed explanation can be found in the online material.

Fig. 12.

Proposal for the main areas of primary care intervention in the care of patients with obstructive sleep apnea (OSA). HBP: high blood pressure; CPAP: continuous positive airway pressure; CVRF: cardiovascular risk factors; EDS: excessive daytime sleepiness.

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OSA is a highly prevalent disease with significant consequences. Its diagnostic and therapeutic management requires multidisciplinary treatment and involves all levels of care. Identification of possible reversible causes and assessment of all treatment options, all of which are combinable, will contribute to comprehensive patient management.

All the authors have participated in the study and read and approved the manuscript.

Pedro García Ramos states that he has collaborated with GSK, Laboratorios Ferrer, Angelini, Novartis, Almirall, Gebro Pharma, Rovi, Esteve, Recordati, MSD, and Teva. Carlos Teixeira states that he is an employee of Philips (Sleep and Respiratory Care Division). Francisco Javier Puertas Cuesta states that he has received fees for consultancy and speaking in courses and seminars from Jazz Pharmaceuticals, UCB Pharma, GSK, Esteve Teijin, and ResMed, and has received research grants from Philips. The other authors state that they have no conflict of interests with the manuscript.