Background In 1981, Sullivan et al. in Australia firstly reported that the application of continuous positive airway pressure ventilation (CPAP) to treat sleep apnea and hypoventilation (SAHS) had achieved satisfactory efficacy, and in 1985, due to the improvement of the nasal mask technology, the transnasal CPAP treatment was widely used, and has now become the main means of treatment for adult patients with SAHS. In 1991, the bi-level positive airway pressure ventilator (BiPAP), which can adjust the inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure (EPAP), was applied to the clinic, and in 1993, the intelligent CPAP (Auto-CPAP), which is capable of increasing or decreasing the pressure in response to changes in the patient’s upper airway resistance, was introduced, with a good degree of comfort, and its technology has become more mature at present. Because CPAP is cheap, it is still the treatment of choice for most patients. China began to apply CPAP to treat SAHS in the early 1990s, and developed a domestic CPAP ventilator, which achieved good results. CPAP, also known as positive end-expiratory pressure under voluntary breathing (PEEP), refers to the application of a certain positive pressure to the airway throughout the respiratory cycle under the condition of sufficient voluntary breathing (Figure 1a). A small percentage of patients experience breath-holding discomfort during expiration, and for those with high CO2 levels, excessive CPAP pressure levels risk exacerbating CO2 retention.The BiPAP ventilator provides higher pressure support during inspiration and lower pressure levels in the expiratory phase (Fig. 1b), which provides increased comfort, effectively reduces CO2 levels, and is the primary mode of noninvasive ventilation for the treatment of respiratory failure. Auto-CPAP, on the other hand, provides feedback to increase or decrease the level of pressure provided based on the patient’s level of upper airway resistance and the presence or absence of respiratory events, including airflow limitation, snoring, hypoventilation, and apnea (Fig. 1c), which maintains the openness of the upper airway while effectively decreasing the mean therapeutic pressure. It can be used to assist with pressure titration in the sleep lab or in the home. Principle of transnasal mask continuous positive airway pressure (CPAP) in the treatment of SAHS The possible mechanisms of CPAP in the treatment of sleep apnea include, firstly, utilizing the “airflow support mechanism” of positive airflow to increase the positive pressure in the pharyngeal cavity to counteract the negative inspiratory pressure, to prevent the airway from collapsing, and to keep the upper airway open (Fig. 2); both computed tomography and nuclear magnetic resonance clearly show that the airway is open, and the airway can be kept open by decreasing the pressure level provided (Fig. 1c). Both computed tomography and nuclear magnetic resonance clearly show that the most significant effect of airway lateral dilatation (Figure 3). Positive-pressure ventilation increases lung volume and indirectly expands the upper airway. When lung volume increases, the stretching effect on the upper airway can increase the stiffness of the upper airway wall structure, thus producing an airway-opening effect. It has been shown that when negative pressure is applied to the chest and abdomen of patients with OSA, their AHI can be reduced accordingly. Third, airflow stimulates the pressure and mechanoreceptors in the upper airway, causing an increase in the tone of the upper airway dilator muscles. However, some studies have found that the “temporal” electromyographic activity of the upper airway muscles does not increase during CPAP treatment, and the increase in tension may be related to the increase in “tonic” activity of the muscles. Fourth, eliminate local tissue edema, reduce the thickness of the lateral wall of the pharynx; fifth, long-term application can improve the sensitivity of the respiratory center to low oxygen and high CO2, and improve the respiratory regulation function. Figure 2 Mechanisms of CPAP therapy to keep the upper airway open CPAP (a) Airflow pressure tidal volume CPAP (a) Airflow pressure tidal volume BiPAP (b) Ventilation volume pressure Auto-CPAP (c) Figure 1 Different kinds of noninvasive ventilation modes III.What kind of SAHS patients need long-term noninvasive ventilation therapy The severity of the condition of SAHS patients is the main basis for deciding whether the patients need to be treated with long-term home CPAP therapy. Although there is no recognized standard for evaluating the condition of SAHS, with the in-depth understanding of SAHS, especially the completion of multi-center clinical trials such as the Sleep heart health study (SHHS), evidence-based medical evidence has been provided for the development of the standard of treatment for SAHS. According to the U.S. Medicare policy, the reimbursement criteria for CPAP ventilators are: AHI > 15 breaths/h; 5< AHI > 14 breaths/h but with daytime symptoms, such as cognitive impairment, daytime somnolence, and comorbidities with hypertension and other cardiovascular disorders.CPAP includes various brands of CPAP and intelligent CPAP (auto-CPAP) ventilators. The main rationale is that the SHHS has demonstrated that an AHI of 15 beats/h or more can lead to an increase in cardiovascular and cerebrovascular complications. In our opinion, this criterion takes into account both laboratory indicators and clinical, and has a greater reference value. The appropriate CPAP pressure is the key to ensure the success of treatment, which should be able to remove apnea and snoring during all sleep periods and various positions, and eliminate upper airway airflow limitation (flow limitation) as much as possible. This optimal pressure can vary within a small range and is not an absolute value. CPAP pressure should be increased during supine sleep, REM sleep, weight gain, after heavy alcohol consumption, colds or rhinitis attacks. After a period of treatment, especially after significant weight loss, some patients require lower levels of pressure. , Figure 3 With increasing CPAP pressure, the inner diameter of the upper airway widens and respiratory airflow gradually returns to normal The goal of CPAP pressure titration is to discover the optimal therapeutic pressure for long-term CPAP application (Table 1). Traditionally, pressure titration can be done manually in the sleep room under the guidance of polysomnographic respiratory monitoring, and to ensure that the patient is able to sleep well and to build up the patient’s confidence in the treatment, the CPAP pressure can be set by switching to the more comfortable BiPAP ventilator. However, as this method is cumbersome, laborious and time-consuming, some simpler alternatives are available. One is to divide the patient’s sleep apnea monitoring time into two parts, the first half of the night to confirm the diagnosis and the second half to set the therapeutic CPAP pressure. In the United States, this may make some medical economic sense because of the expense of pressure titration. Our experience is that this method is feasible for critically ill patients and not very successful for mildly ill patients who are prone to underdiagnosis and treatment failure. The second is to set the pressure for CPAP treatment at the patient’s home after diagnosis, without the help of polysomnography. Our practice is to monitor the patient’s dynamic SaO2 at home with a portable oximeter on the first night, and use the result as the base value before treatment. Then in the daytime in the hospital by the technician to teach the patient to use the CPAP machine, combined with the patient’s body size, severity of the disease, choose an empirical therapeutic pressure, usually 8-12 cm water column, and in the patient’s lunch break to observe a few hours, and then ask the patient to take the CPAP machine home, and try it at night during sleep. Most patients can basically master the use of the machine and the adjustment of the nasal mask after 2-3 nights of study and trial. At the same time, the patient’s family members are instructed to pay attention to the occurrence of snoring or apnea during their sleep, and if so, the pressure is to be increased by 2 cm of water column, and to contact with the doctor by phone at any time to report on the situation of the use of the CPAP machine and solve the existing problems in a timely manner. After about 1 week of trial, the patient can master the use of the ventilator and snoring disappeared, the dynamic SaO2 during sleep was measured again, and compared with the results before treatment, such as the lowest SaO2 in 90% or more, no significant fluctuations in blood oxygen, proving that the pressure is appropriate, or continue to adjust the CPAP pressure upward. This model of combining daytime titration with home follow-up reduces both patient costs and the workload of sleep center staff, and is worth promoting in sleep laboratories with some experience. Third, machines that can automatically adjust the appropriate CPAP pressure are now available, which can apply the appropriate CPAP pressure according to the difference in upper airway resistance while the patient is sleeping. The optimal range of required CPAP pressure can be reported automatically the next day. However, the results must be read by an experienced physician to recognize possible air leaks and avoid overestimating the titrated pressure level. In addition, most auto-titrating Auto-CPAP machines give a pressure level that is at the 95% confidence limit level of the all-night maximum pressure, but sometimes this pressure is still low, and the patient may unconsciously remove the nasal mask or wake up suffocating during nighttime sleep during home therapy. For a small number of patients who failed to be debugged by the above methods were admitted to the wards and used CPAP machines under the close supervision of doctors and technicians. After 3-4 days of learning and debugging, most of them were able to achieve good results and could be discharged from the hospital after one week. Special attention should be paid to the fact that the optimal pressure level titrated in the sleep laboratory is often not the pressure level required by the patient in home therapy, and should be increased by 1-2 cm of water column as appropriate when prescribed. Table 1: Titration of CPAP therapeutic pressures Objectives Methods Evaluation Indications Reasons for Failure and Treatment Removal of apnea and severe hypoventilation Increase CPAP pressure by 1 cmH2O every 5-10 minutes, or within minutes or even several respiratory cycles if needed, usually up to 18 cmH2O Apply respiratory airflow pressure transducer to record apnea and severe hypoventilation 1. Nasal mask leak or open mouth Breathing 2. application of a mandibular support belt 3. application of warming humidification 4. switching to a BiPAP ventilator Removing inspiratory airflow limitation Increase CPAP pressure by 1 cmH2O every 10-15 minutes to a maximum of 18 cmH2O Apply a respiratory airflow pressure sensor to document airflow limitation leading to awakening 1. Nasal mask leakage or open-mouth breathing 2. application of a mandibular support belt 3. application of warming humidification 4. switching to a BiPAP ventilator Remove arousals and leg movements Increase CPAP pressure by 1 cmH2O every 5-10 minutes, but do not exceed the pressure required to remove airflow limitation by 4 cmH2O, or until CSA and hypoventilation occur EEG monitors arousals and limb movements If the frequency of CSA and hypoventilation events increases, decrease CPAP level to the pressure required to remove airflow limitation Remove oxygen desaturation Increase CPAP pressure by 1 cmH2O every 5-10 minutes, and then increase CPAP pressure by 4 cmH2O every 5-10 minutes. CPAP pressure 1 cmH2O every 5-10 minutes, but do not exceed the pressure required to remove airflow limitation 4 cmH2O, or until CSA and hypoventilation occur Monitor oxygen saturation 1, Oxygenation 2, Switch to BiPAP ventilator V. Side effects and management of CPAP therapy CPAP ventilator is non-invasive, simple and easy to use, and does not have serious side effects. According to the literature, caution should be exercised when using CPAP ventilator in SAHS patients with the following diseases. Chest CT or X-ray examination reveals the presence of pulmonary pustules with the possibility of spontaneous rupture; the presence of pneumothorax or mediastinal emphysema; markedly decreased blood pressure and uncorrected shock; intracranial pneumoperitoneum or cerebrospinal fluid leakage; and the application of CPAP should be avoided during the period of suffering from acute otitis media, and can be continued after the infection has improved. Other general side effects are shown in Table (2), which do not affect the long-term application of patients after timely treatment. Table 2: Side effects of CPAP treatment Classification of side effects Side effects Rhinitis Rhinorrhea Nasal congestion Mouth and nose dryness Rhinorrhea Nasal mask-related Skin breakouts and rashes Conjunctivitis caused by air leakage Airflow-related Chest discomfort Air swallowing Eardrum discomfort Effortful expiration Claustrophobia Pneumothorax (rare) Pneumoperitoneum in the cranium (rare) Other Noise Influence on family members Inconvenience 1.Help the patient to set up confidence CPAP treatment needs to be adhered to for a long time, and the doctor The doctor should patiently explain the knowledge of sleep apnea to the patient, obtain the cooperation of the patient and his/her family, and build up the confidence of successful treatment. 2. Unsatisfactory treatment effect on the first night does not mean treatment failure As many SAHS patients’ memory and comprehension are diminished, even under the strict guidance of experienced doctors, it usually takes three nights or even longer to try and feel the effect of the treatment before they can experience it more deeply. The key to shortening this time is for patients and their families to work closely with their doctors to solve any problems that arise during use in a timely manner. Strengthening the communication between patients can also help patients build up confidence in overcoming the disease and gain useful experience. In the early stage of CPAP treatment, there will be sleep rebound In the early stage of CPAP treatment, patients with severe SAHS will have abnormal increase in REM and NREM III, IV sleep, i.e. “sleep rebound”, which usually lasts for about 1 week. “Sleep rebound” is of great significance because in REM sleep, the patient’s ability to respond to multiple stimuli decreases, and it is difficult to wake up. If the pressure of CPAP is not enough, incomplete obstruction of the airway may occur, resulting in hypoventilation, which causes severe and long-lasting hypoxia. If the CPAP pressure is not enough, incomplete obstruction of the airway may occur, resulting in hypoventilation, causing severe and prolonged hypoxia. Therefore, close observation should be made at the beginning of the treatment, and it is important to set a CPAP pressure that is enough to overcome the obstruction of the airway during the REM sleep period in order to ensure the safety of the patient. 4. Handling of nasal mask leakage Nasal mask should be of appropriate size, comfortable and soft, and be replaced in time; the headband should be loosened and tightened appropriately, and the force should be balanced; for those with special facial shape, some soft materials can be padded between nasal mask and skin. 5. Skin allergy and nasal ulcers In the early stage of CPAP application, many SAHS patients have facial indentation or skin redness due to nasal mask compression and gas irritation, which can subside on their own a few hours after getting up. In addition to the correct and skillful use of the nasal mask, the nasal mask can be replaced with a bubble-type nasal mask, and soft pads can be placed between the skin and the nasal mask. If skin breakdown or severe allergy occurs, the CPAP ventilator should be discontinued. 6. Eye irritation or redness of the conjunctiva is related to eye irritation due to air leakage from the top of the nasal mask, and conjunctivitis may occur in severe cases, which requires adjustment of the size, position and tightness of the nasal mask. 7. Dry mouth Most SAHS patients have dry mouth before treatment, and it disappears naturally after treatment. If it does not disappear, it may be related to the setting of the CPAP pressure is not enough or too high, must be reset. If necessary, apply the mandibular support, strengthen the wetting. 8. Nasal congestion and nasal dryness 15~45% of patients will have nasal discomfort, in addition to the original nasal disease is not treated, and cold air stimulation caused by mucosal congestion and edema or allergic rhinitis acute attack are related. Strengthen wetting and warming, and ephedrine nasal drops before bedtime. If the patient develops allergic rhinitis, hormone drops can be applied. 9. Fear Some patients just put on the nasal mask, applying a small CPAP pressure on the self-consciousness of breathlessness and discomfort, very afraid, known as “claustrophobia”, not due to too high pressure, just a temporary psychological feeling. Patients should be asked to maintain a calm mood, according to their usual rhythm of breathing. Add the “pressure delay” function or switch to BiPAP ventilator will be reduced. 10. 10. Automatic interruption of treatment at night Some patients unknowingly remove the nasal mask in their sleep, and can not adhere to the application of the whole night, mostly in the early stage of treatment, which may be related to the pressure setting is not enough. It may be related to insufficient pressure setting. It may also be caused by setting the CPAP pressure too high or leakage of nasal mask. 11. The effect of noise CPAP ventilator has a certain noise, sometimes affecting the family and the patient’s sleep. CPAP ventilator can be replaced with a low noise CPAP ventilator, replace the exhalation valve, put the ventilator into a well-ventilated glass mask, and sleep with earplugs. 12. Long-term tolerance of CPAP ventilator in OSA patients The biggest problem in the use of CPAP is that some patients cannot insist on using it for a long time, and the literature reports that the long-term utilization rate is 60-80%. The performance of the machine, the severity of the patient’s condition, and the degree of awareness of the dangers of SAHS are all related to the ability to adhere to the application. Popularization of relevant scientific knowledge, experienced technical support, close follow-up during the treatment process, and timely treatment of various problems are the keys to ensure the long-term use of patients. 13. Treatment of CPAP treatment failure The majority of SHAS patients can tolerate CPAP treatment, and the success rate of trial in the sleep laboratory is more than 95%. It is very unlikely that treatment failure is due to the patient, but it is most likely due to the physician’s failure to follow up with the patient in a timely manner to deal with the problems encountered by the patient. Therefore, before determining whether a patient can tolerate CPAP therapy, it is important to actively look for reasons for treatment failure. One, unskilled or incorrect use of CPAP; two, improper pressure setting; three, correct diagnosis; four, poor performance of the machine, poorly sized or constructed nasal mask; five, comorbidities with other sleep-disordering disorders; and six, alcohol consumption or untreated nasal disorders. The following measures are considered for those with real treatment failure: i) switching to more comfortable BiPAP ventilator and intelligent CPAP ventilator; ii) jaw surgery, UPPP surgery or even tracheostomy; iii) wearing oral orthodontic devices. CPAP treatment for special patients 1. Central sleep apnea Central sleep apnea is less than 10%, mostly coexisting with OSA, and CPAP treatment is also effective. Daytime PaCO2 is not high, suitable for the application of CPAP; daytime CO2 retention of hypoventilation patients, the application of BiPAP ventilator is conducive to reducing respiratory function, eliminating CO2z retention. (2) People with complete loss of upper teeth The lower part of nasal mask depends on the support of upper dental arch to prevent air leakage. The CPAP ventilator can be used only after the upper teeth are completely lost and dentures are set or worn. 3. Hypothyroidism-induced apnea The use of thyroxine is the fundamental treatment. CPAP treatment before oral thyroid hormone can reduce hypoxia, improve cardiac function, and prevent organ damage caused by apnea when the body’s oxygen consumption increases due to hormone replacement therapy. After the thyroid hormone reaches the normal level, sleep apnea monitoring will be performed again, if the apnea disappears, CPAP treatment can be stopped, if it still occurs frequently, CPAP treatment needs to be applied for a long time. 4. COPD combined with OSA This kind of patient is called overlap syndrome, can be given in CPAP treatment at the same time of continuous oxygen inhalation.COPD acute exacerbation, such as CO2 obvious elevation, should be selected BiPAP ventilator, to prevent aggravation of CO2 retention. In addition, such patients often have poor tolerance for CPAP ventilator, and those with more severe cough should be treated with appropriate cough suppressant. Perioperative treatment of patients with SAHS Studies have shown that patients with OSA have an increased risk of asphyxia during preoperative anesthesia and postoperative recovery, and require appropriate monitoring and upper airway protection, especially for those who undergo surgery in and around the upper airway. For patients with severe SAHS undergoing elective surgery, 1-2 weeks of preoperative CPAP can be administered to correct the patient’s hypoxia and sleep disturbances, and to ameliorate the comorbid complications such as hypertension. After extubation from general anesthesia, sequential CPAP treatment can be carried out in time. A few patients with SAHS may be admitted to the hospital due to sudden aggravation of their conditions or serious complications such as acute respiratory failure, cardiovascular and cerebral vascular diseases. In most cases, noninvasive ventilation, especially BiPAP ventilator treatment, can achieve good results, and for a few patients who are unable to cooperate, who have vomiting, coughing, or whose blood pressure is unstable, they may need to be intubated or even tracheotomized, and then converted to CPAP or BiPAP after their conditions are stabilized. Special attention should be paid to the critically ill, the first active treatment, not the first sleep apnea monitoring. 7. Patients who are still drowsy during CPAP treatment The possible causes of drowsiness after CPAP treatment are shown in Table 3.These patients can be divided into two categories: one is that drowsiness improves obviously at the beginning of CPAP treatment, but drowsiness reappears after one stage of treatment; the other is that drowsiness has not improved during CPAP treatment. For this kind of patients, firstly, we should evaluate their CPAP compliance objectively, and secondly, we should know whether they are combined with other sleep disorders, such as episodic somnambulism and cyclic leg movement syndrome. The prevalence of comorbid SAHS in adults with episodic somnolence is as high as 50%-80%, and it is common to see patients with episodic somnolence presenting with SAHS. For the small number of patients who exclude the above causes but still have subjective or objective drowsiness, medications that can improve the symptoms of drowsiness, such as modafinil, can be taken concomitantly, and its use has been approved by the U.S. FDA. Table 3 Possible reasons for drowsiness after CPAP therapy Poor compliance Insufficient sleep duration Effects of medications Comorbidity with other sleep disorder disorders Depression Permanent brain damage due to sleep apnea 15. Follow-up during treatment of sleep apnea syndromes Studies have shown that if a patient with SAHS is allowed to purchase a CPAP ventilator alone with no follow-up, the success rate for long-term treatment is virtually nil, whereas 80% of patients who have a CPAP ventilator have a good follow-up. With good follow-up, 80% of patients can be effectively treated. CPAP therapy follow-up is not always necessary for repeat polysomnographic sleep apnea monitoring.