1. CPAP and BPAP Titration BY AHMAD YOUNES PROFESSOR OF THORACIC MEDICINE Mansoura faculty of medicine

2. Titration of Positive airway pressure Positive airway pressure (PAP) devices such as CPAP and BPAP are used to treat SDB. At an optimal pressure, PAP devices eliminate SDB events without creating pressure-related side effects. The gold standard method for identifying the optimal pressure is attended overnight laboratory based polysomnography during which a sleep technologist manually titrates the PAP devices to eliminate SDB events, such as apneas, RERAs, and snoring

3. Using a nasal pressure transducer or a thermistor during the titration portion of the polysomnography may not be feasible because of problems obtaining a good seal with the mask interfaces. During a titration study, recordings from the airflow signal generated by the PAP device, or estimating the airflow through measuring the pressure difference between the mask and the outlet machine using a transducer, are acceptable methods to detect apneas, hypopneas, and RERAs. Titration protocols to identify the optimal pressure for PAP devices to treat SDB vary widely among sleep centers. Therefore, it is very likely that the same patient undergoing a titration study at different accredited centers may end up with different optimal pressures.

4. SPLIT-NIGHT TITRATION The criteria that is typically used is an AHI of 40 or more per hour with a minimum of 120 minutes of sleep, or an AHI of 20 to 40 per hour accompanied by significant oxygen de-saturation. The Center for Medicare & Medicaid services (CMS) requires either :- (1)the documentation of an AHI of 15 or more per hour with a minimum of 30 events, or (2)an AHI of 5 to 14 per hour with a minimum of 10 events, along with documentation of one of the following: excessive sleepiness, impaired cognition, mood disorder, insomnia, hypertension, ischemic heart disease, or history of stroke.

5. The optimal pressure for PAP devices to treat SDB is the effective pressure that eliminates SDB events without creating any untoward pressure-related side effects for the patient. Pressures lower than the optimal pressure, apart from inadequately treating the SDB, may also result in mouth breathing and claustrophobic symptoms. Pressures exceeding the optimal pressure may lead to air leaks, mouth breathing, worsening of nasal congestion, and rhinorrhea ; exacerbate central apneas; and of course lead to difficulty tolerating the PAP, resulting in decreased overall adherence. The optimal pressure should be effective in all sleep positions and sleep stages.

6. GOALS OF PAP TITRATION The goal of PAP titration is to identify the optimal pressure that 1- eliminates SDB events (apneas, hypopneas, RERAs, oxygen desaturation, and snoring), 2- restores normal respiratory patterns, and 3- improves the patient’s quality of sleep. The optimal pressure from PAP that accomplishes all this should be adequate during all stages of sleep and in all sleep positions (particularly supine position), because the severity of OSA is commonly worse during sleep in the supine position, and during REM sleep, whereas the severity of CSA might be worse during supine and non- REM sleep.

7. Optimal titration is obtained when the AHI is < 5 per hour for at least 15 minutes and includes supine REM sleep at the optimal pressure. Good titration reduces the AHI to < 10 per hour and includes supine REM sleep at the selected pressure on the PAP device. Adequate titration is obtained when the AHI cannot be reduced to < 10 per hour, but is reduced by 75% from baseline, or when the titration grading of optimal and good are obtained even though supine REM sleep did not occur. An unacceptable titration occurs if any one of the above grades are not met, at which time a repeat titration is necessary. Repeat full titration is also needed if only adequate titration was obtained, especially if it was part of a split- night protocol.

8. PREPARATION FOR PAP TITRATION The AASM practice parameters recommend that all eligible patients receive adequate PAP education, hands- on demonstration, careful mask fitting, and acclimatization to the PAP device before titration. PAP education before titration could be in the form of a video describing sleep apnea, consequences of untreated sleep apnea, rationale for the use of PAP, the process involved during the diagnostic and PAP titration polysomnogram,and side effects related to the PAP and mask interfaces. Showing and explaining the device along with its parts and equipment,and having the patient try on the mask interface to experience the pressure generated by the device, are all important steps before implementing PAP titration.

9. Indications for CPAP Most patients with OSA can be effectively treated with CPAP, which serves as a passive pneumatic splint to keep the upper airway from collapsing during sleep. It also tends to increase lung volumes and exerts tracheal traction (tracheal tug mechanism) to prevent collapsibility of the upper airway. The use of CPAP in reducing CSA (particularly in CSA/CSR and primary CSA) was found in some studies showing improvement in the left ventricular ejection fraction and Epworth sleepiness scale Therefore, performing a CPAP titration for CSA is reasonable to assess for effectiveness before switching to a different PAP device, such as BPAP in the spontaneous timed mode (BPAP-ST) or adaptive servo-ventilators. CPAP may not be effective in treating CSA caused by opioid use.

10. CPAP TITRATION At the start of CPAP titration, pressure is usually initiated at 4 to 5 cm H2O. Some patients may experience insufficient pressure at the start of titration, even with pressure at 5 cm H2O. In these cases, the pressure can be increased until the patient is comfortable and then, once the patient falls asleep, the pressure is reduced in decrements of 1 cm H2O at 5-minute intervals until SDB returns or the patient awakens. CPAP is then increased incrementally by 1 cm H2O at intervals of no less than 5 minutes until all SDB events are eliminated. CPAP increments are performed in the presence of at least two obstructive apneas, or at least three hypopneas, or at least five RERAs, or at least 3 minutes of loud snoring.

11. CPAP TITRATION The recommended maximum pressure to titrate CPAP is 20 cm H2O, at which time BPAP titration will need to be considered if SDB events are still occurring. Adding supplemental oxygen for sleep-related hypoxemia or hypoventilation may also need to be considered. If the SDB events are not controlled with CPAP because of patient complaints of increased pressure side effects (even at CPAP <20 cm H2O),then adding a humidifier for nasal congestion or instituting a pressure-relief mechanism at end expiration, such as with C-flex or expiration pressure relief, should be considered. If SDB events are persistent, one may then need to proceed with BPAP.

13. CPAP TITRATION The optimal pressure is attained in the supine position and REM sleep for at least 15 minutes if possible. If this is not attainable, a repeat titration study should be considered. If the patient is unwilling to undergo or insurance does not cover another night titration, clinicians could consider prescribing the best pressure attained on the titration with a follow-up overnight oximetry on the optimal CPAP settings. Some prescribers might advocate an auto-CPAP in these situations. A follow-up study is usually required on auto-CPAP to ascertain whether the SDB is well controlled.

14. CPAP TITRATION The titration protocol using CPAP for CSA/CSR is a bit different from that for OSA. Titration with CPAP can be started at 4 to 5 cH2O, and then titrated upwards by 1 cm H2O every 5 minutes until CSA/CSR is eliminated. CPAP beyond 10 cm H2O is unlikely to be helpful in controlling CSA/CSR, although exploring higher pressures may sometimes help identify the optimal pressure for treating CSA/CSR. Persistent or worsening CSA on CPAP titration will necessitate BPAP titration. Also, although CPAP can decrease the AHI to less than 5 per hour in OSA, this may not occur in CSA/CSR.

15. Treatment-Emergent CSA Some patients may have central apneas that become apparent after CPAP alleviates OSA during CPAP titration. This event is commonly referred to as treatment-emergent CSA, or complex sleep apnea. One option is to proceed directly to adaptive servo- ventilation to address treatment-emergent CSA on CPAP to treat OSA. This approach may lead to the use of an expensive device without proven long-term benefits. Second approach is to decrease CPAP by 1 to 2 cm H2O and monitor for 5 to 10 minutes. If central apneas persist, pressure can be decreased further by 1 to 2 cm H2O as long as no recurrence of OSA is seen.

16. Treatment-Emergent CSA This downward titration can be attempted until the centrals disappear as long as OSA does not recur. If centrals persist or OSA recurs at a lower pressure, then proceeding with one of the other approaches discussed is advisable. A third approach is to perform an upward titration with CPAP, not beyond 5 cm H2O above the pressure that eliminated the OSA. This upward titration may help in certain cases, especially when the central apneas may have been misclassified as OSA. If central apneas worsen with this upward titration, the pressure should be lowered to the previous level that alleviated OSA.

17. Treatment-Emergent CSA BPAP may also be tried. Data suggest that these central apneas dissipate over time with CPAP use. Therefore, some providers may choose to treat these patients with CPAP for 2-to 3-months before repeating another titration study. If central apneas persist on CPAP with the repeat titration study, then treatment should proceed using other modalities, such as adaptive servoventilation

19. BPAP TITRATION Upper airway instability in OSA tends to occur during not only the inspiratory phase but also the expiratory phase; hence the rationale in using BPAP. The EPAP tends to stabilize the upper airway at end expiration so that the airway is sufficiently patent to permit the patient to trigger delivery of IPAP by generating low-level inspiratory volume or flow during the subsequent effort. The IPAP level is set to prevent upper-airway closure and partial obstruction (hypopnea) during the inspiratory phase of breathing. Different types of BPAP devices are available, with the most commons being the conventional spontaneous mode (patients may breathe with their own frequency, with the BPAP supporting both phases of respiration based on the pressure settings of IPAP and EPAP) and the backup rate mode (BPAP-ST mode) guarantees a certain number of pressure cycles (or breaths) per minute, which changes to the higher pressure (IPAP) if the patient does not initiate a breath within a specified period. Inspiratory time must be set on the BPAP-ST machines, which tells the machine the maximum time allowed for inspiration.

20. Indications for BPAP Use Several studies comparing the effectiveness of BPAP and CPAP, with and without coexisting respiratory disorders, showed no differences in the improvement of AHI, ESS, sleep quality, no differences have been seen in adherence or comfort level in the treatment of OSA without coexisting respiratory disorders. OSA who have comorbid obesity and daytime hypercapnia prefer BPAP over CPAP in the treatment of OSA. BPAP still tends to be considered for OSA treatment, even in patients without comorbid respiratory disorders, particularly when they are unable to tolerate CPAP because of a high pressure requirement or have persistent OSA on CPAP even at a pressure of 20 cm H2O.

21. Indications for BPAP Use The use of BPAP is well defined in patients presenting with acute respiratory failure related to COPD exacerbation. The role of BPAP during sleep in patients with stable chronic COPD and chronic hypercapnic respiratory failure is less well defined Guidelines, BPAP can be considered in the presence of symptoms such as fatigue, morning headache, or daytime hypersomnolence, and one of the following: (1)PaCO2 > 55 mm Hg, (2) PaCO2 of 50 to 54 mm Hg and nocturnal oxygen saturation of 88% or less for 5 minutes while receiving oxygen therapy of >2 L/min), or (3) PaCO2 of 50 to 54 mm Hg and hospitalization related to recurrent episodes (>2 in a 12-month period) of hypercapnic respiratory failure.

22. Indications for BPAP Use BPAP coverage in patients with restrictive thoracic disorders are: 1- documentation exists of a progressive neuromuscular disorders or severe thoracic cage abnormality. 2- either (a) PaCO2 of > 45 mm Hg while the patient is awake and breathing the usual FIO2 or (b) sleep oximetry shows an oxygen saturation of 88% of less for at least 5 continuous minutes, performed while the patient is breathing the usual FIO2, or (c) for a progressive neuromuscular disorders (only),maximal inspiratory pressure is < 60 cm H2O or forced vital capacity is < 50% predicted ;and -COPD does not contribute to the patient’s pulmonary limitation BPAP in the ST mode is useful to treat patients with CSA syndromes, specifically primary CSA and CSA/CSR. BPAP-ST can also be used in CSA caused by opioids.

23. BPAP titration for OSA

24. Patients requiring BPAP to treat OSA normally do not require an ST mode; the S mode is usually sufficient. If a patient is switched from CPAP to BPAP, the EPAP is started at the CPAP level at which the obstructive apneas were eliminated. Otherwise, the EPAP is started at 4 cm H2O and increased in increments of 1 cm H2O at intervals no shorter than 5 minutes until the obstructive apneic events are eliminated. The IPAP in all these situations is usually started 4 cm H2O higher than the EPAP, and titrated upward along with the EPAP in increments of 1 cm H2O, maintaining the IPAP–EPAP difference at 4 cm H2O until the obstructive apneic events are treated. Increases in IPAP and EPAP are performed if at least two obstructive apneas are observed. Once the optimal EPAP is obtained to eliminate the obstructive apneic events, the IPAP is then increased in increments of 1 cm H2O every 5 minutes in the presence of at least three hypopneas or five RERAs, or at least 3 minutes of loud snoring.

25. BPAP titration for OSA The maximum recommended IPAP is 30 cm H2O in adults because of reports of increased risk for barotrauma when IPAP exceeds 30 cm H2O. The minimum IPAP–EPAP differential is 4 cm H2O and the maximum IPAP–EPAP differential is 10 cm H2O. The AASM task force recommends not adjusting the BPAP settings in the event of oxygen desaturation-resaturation as long as they are not associated with any obstructive events. The members do not recommend exploration by increasing the IPAP above the optimal pressure that achieved control of SDB events. If a patient develops treatment-emergent central apneas, 1- decreasing the IPAP could be attempted. If this does not help, 2- changing to the ST mode with backup rate might be helpful.

26. BPAP titration for CSA Most if not all patients require a BPAP-ST mode rather than an S mode to treat CSA. If CSA worsens with BPAP, changing to adaptive servo-ventilation should be considered. If OSA is mixed with CSA during the diagnostic polysomnogram, the EPAP is usually started at the CPAP level that eliminated the OSA events. Otherwise, the EPAP is usually started at 4 cm H2O, with the IPAP at 4 cm H2O higher than EPAP along with ST backup rate. The backup rate is usually started below the patient’s spontaneous awake breathing rate and then increased slowly after the patient falls asleep. If central apneic episodes persist, the backup rate is increased by 1 to 2 breaths every 5 minutes to a maximum of 16 breaths per minute or until the trigger artifact from the BPAP-ST results in a flow signal. If there is a trigger artifact from the ST backup rate with very minimal flow, the IPAP is increased at increments of 1 cm H2O every 5 minutes until the hypopneic events are corrected. Once the airflow improves or apneic events are controlled, the ST backup rate and IPAP are not titrated further. If the patient is uncomfortable with the increase in respiratory rate, the rate is decreased slowly to 12 breaths per minute or to a rate that the patient is comfortable, without necessarily compromising the titration.

27. BPAP titration for CSA In the presence of obstructive apneic events in patients with CSA, the EPAP is increased by 1 cm H2O every 5 minutes, maintaining an IPAP–EPAP difference, until the obstructive apneic events are corrected. Subsequent titration of IPAP is based on the presence of hypopneas and central apneas. The authors do not recommend the maximum IPAP to exceed 20 cm H2O and recommend maintaining the minimum IPAP–EPAP at 4 cm H2O. Also, increasing the IPAP-EPAP differential has the potential to worsen CSA by decreasing PaCO2. Every effort should be made to identify the optimal BPAP settings during supine and non-REM sleep, because CSA tends to worsen during these situations. If CSA events are persistent after the maximum IPAP of 20 cm H2O is reached, other modalities should be considered, such as adaptive servoventilation to treat CSA.

28. BPAP titration for COPD BPAP is started in the S mode. BPAP use for COPD in the setting of acute respiratory failure used high inspiratory pressure in the range of 15 to 20 cm H2O, to help with gas exchange. Increasing the pressure support increases tidal breathing, resulting in increased minute ventilation and improvement in hypercapnia. Presence of OSA with apneic episodes should be treated by adjusting the EPAP to eliminate apneas while maintaining an IPAP-EPAP difference of 4 cm H2O. EPAP and IPAP are increased in increments of 1 cm H2O every 5 minutes. If OSA is not a concern and no apneic episodes occur, the EPAP is usually left alone and the IPAP is slowly increased by increments of 1 cm H2O every 5 minutes to correct hypopneas and hypoventilation in patients with COPD. Maximum IPAP–EPAP difference exceeding 15 cm H2O may become uncomfortable for patients.

29. BPAP titration for COPD Every effort should be made to assess and titrate BPAP during REM sleep because patients with COPD are most vulnerable to hypoventilation during this stage. Some may require a backup rate with the ST mode during REM sleep. With the machine triggered breaths, a pressure support of 4 cm H2O (IPAP-EPAP difference) may not be sufficient to deliver adequate tidal volume. In these situations,the IPAP will need to be increased to deliver adequate tidal volume. Despite obtaining adequate BPAP settings to treat hypoventilation, occasionally supplemental oxygen is required (for sleep-related hypoxemia) if oxyhemoglobin desaturations persist. An arterial blood gas is obtained within a few minutes of waking to assess PaCO2 levels.

30. BPAP titration for neuromuscular disorders BPAP is usually started in the ST mode with a rate at or near the patient’s spontaneous breathing rate (generally at least 10–12 breaths per minute) for patients with neuromuscular disorders. If OSA is not a concern, the EPAP is initially set low (4–6 cm H2O) with the IPAP generally 4 cm H2O higher. Patients with neuromuscular disorders patients may find higher EPAP settings to be uncomfortable due to difficulty exhaling. Therefore the titration of EPAP and IPAP may need to proceed slowly. The EPAP is increased in increments of 1 cm H2O in intervals no shorter than 15 minutes to eliminate apneic events. Once the optimal EPAP is obtained based on elimination of apneic episodes at a pressure that is comfortable for the patient, the IPAP is then adjusted by increments of 1 cm H2O in intervals no shorter than 15 minutes to eliminate hypopneas and hypoventilation.

31. BPAP titration for neuromuscular disorders In patients with only neuromuscular disorders, it is unlikely that they will need supplemental oxygen. The predominant underlying pathophysiology is hypoventilation during sleep, which normally should be corrected by BPAP alone. Use of supplemental oxygen alone (without BPAP) in patients with neuromuscular disorders may depress the drive to breathe. Every effort should be made to titrate BPAP during REM sleep since patients with neuromuscular disorders are most vulnerable to hypoventilation during this stage. The initial requirement for the back up rate occurs during REM sleep when hypoventilation is the worst resulting in the patient not triggering the BPAP. Obtaining an arterial blood gas within a few minutes of waking up the following morning of the titration is also recommended to assess PaCO2 levels.

32. SUPPLEMENTAL OXYGEN TITRATION If the patient’s awake supine baseline oxyhemoglobin saturation is less than 88%, supplemental oxygen is usually initiated at 1 L/min at the start of the PAP titration and titrated upward by 1 L/min at intervals no shorter than 15 minutes. Supplemental oxygen should be started during the titration study if the patient’s oxyhemoglobin saturation is less 88% for 5 or more minutes in the absence of OSA events. Supplemental oxygen is titrated up at a rate of 1 L/min at intervals no shorter than 15 minutes to maintain oxyhemoglobin saturation of more than 88%.

33. SUPPLEMENTAL OXYGEN TITRATION Patients who have persistent sleep-related hypoxemia or hypoventilation that is not effectively treated with a PAP device will need supplemental oxygen to maintain oxyhemoglobin saturation of more than 88%. In these situations, supplemental oxygen is connected to the PAP device outlet and not the mask. Patients who were on supplemental oxygen before PAP titration are likely to need a higher amount of oxygen with the PAP device because of higher flow rates reducing the effective oxygen concentration for a given supplemental oxygen flow. Ideally in those patients who required supplemental oxygen or upward titration of the previously used oxygen, an arterial blood gas is performed the following day, usually within a few minutes of waking, to assess for hypercapnia.