Efforts to minimize the side effects of CPAP therapy should be made in order to enhance the quality of patients’ lives and to increase the likelihood of good therapeutic compliance

f01a.jpg (15644 bytes)Nasal continuous positive airway pressure (nCPAP) therapy for obstructive sleep apnea (OSA) was first described in 1981 by Sullivan and colleagues.1 Since then, CPAP is the treatment of choice for the majority of patients with OSA. Several mechanisms have been proposed to account for the benefit of nCPAP therapy such as the positive airway pressure acting as an “airway splint” and keeping the collapsible area of upper airway patent; nCPAP may maintain upper airway patency by a reflex mediated via the increase in end-expiratory lung volume. However, there is evidence against a reflex-mediated reduction in upper airway resistance. NCPAP has been shown to depress electromyographic activity of the upper airway dilator muscles,2,3 and lung volume dependence of pharyngeal cross-sectional area in patients with OSA has been reported.4 A direct relationship between lung volume and upper airway patency may be due to traction created on mediastinal and upper airway structures5,6; however, this effect plays a minor role in variation of upper airway resistance or patency with lung volume.7 CPAP eliminates OSA whereas continuous negative extrathoracic pressure does not eliminate apnea with comparable augmentation of lung volume.8 Hence, benefit of nCPAP is due to positive pharyngeal pressure.

NCPAP Compliance
After a CPAP titration study,9 the initial acceptance rate by patients is 70% to 80%. Most patients report a subjective sensation of well-being, decrease in daytime sleepiness, increased alertness, relief of morning headaches, decreased nocturnal awakenings, and decreased irritability. Reduced daytime sleepiness has been reported just after 1 night of nCPAP therapy.10 Individuals who derive no subjective benefit from such a trial are poor candidates for home therapy with CPAP and are likely to exhibit lower compliance rates.9 About 90% of OSA patients will adhere to long-term CPAP.9 Patients abandoning CPAP do so during the first few months of therapy.9 Lower acceptance and compliance rates have been reported in North America as compared to Europe.9 The American Thoracic Society reported overall compliance rates of 50%.11

CPAP therapy is associated with some side effects related to the patient-device interface. These include skin abrasion or rash, conjunctivitis from air leak, and ulceration of the bridge of the nose12; sensation of high airflow or pressure, chest discomfort, aerophagia, sinus discomfort, smothering sensation, insomnia, rhinorrhea, nasal congestion or dryness, epistaxis, and, rarely, pneumothorax, pneumomediastinum, or pneumoencephalos13-15; the device is too cumbersome and inconvenient and interferes with the patient’s lifestyle; spousal intolerance (one patient’s wife said, “That machine has taken my husband away and I hate it”); and indefinite or lifetime use of CPAP.

Several studies have examined patient compliance with nCPAP therapy. Sullivan and coworkers16 reported the initiation of nCPAP therapy on 35 of 50 patients with sleep apnea who had good compliance over a period of 3 to 30 months. Frith and Cant17 found that 72% of patients used nCPAP from 3 to 22 months. Nino-Murcia et al18 defined compliance as continued use of the device by 83% of patients. When compliance was defined as nightly or nearly nightly use, only 67% of patients were found to be compliant.18 However, none of these studies evaluated the number of hours the device was used per night. Sanders et al 19 demonstrated that 85% of patients undergoing a trial of nCPAP in the sleep laboratory were satisfactory candidates for home therapy if there was amelioration of sleep-disordered breathing by the device and patient willingness to use the device on a long-term basis. They defined compliance as nightly use of CPAP and patients were deemed compliant if they did not sleep without CPAP therapy more than 1 hour per night; 75% of patients sent home on therapy were compliant over 10.3±8 months (mean ±SD) of follow-up.19 Waldhorn et al15 found that 85% of patients tolerated a laboratory trial of nCPAP and 76% of patients sent home to use the device were still using it after 14.5±10.7 months. These studies determined patient compliance through questionnaire or interview data. When we reviewed the studies that used objective data, such as timers on the device to measure compliance, the mean duration of using the device was 5.1±2.6 hours per night and 40% of patients used the CPAP mask more than 6 hours per night.20 Fletcher and Luckett21 reported an average of 6 hours of CPAP use per night by patients.

Studies have suggested that compliance improves with increased severity of daytime sleepiness.15 The frequency or side effects of CPAP including initial apnea-hypopnea index, gender, weight, or prescribed level of CPAP did not appear to discriminate compliant groups of patients from those who were noncompliant.21 In long-term studies, the most consistent correlation of the daily use of CPAP was with objective measures of OSA severity at the time of diagnosis including the apnea-hypopnea index, the movement arousal index reflecting sleep fragmentation, or oxygen-hemoglobin saturation during sleep.9 In most studies, the multiple sleep latency test (MSLT) or scoring sleepiness at the time of diagnosis was not significantly correlated with the subsequent use of CPAP.9 Patients with low compliance did not have higher pressure.22

Improving Therapeutic Compliance
• Minimizing Side Effects of NCPAP—Poor mask fit can be addressed by trying different sizes of commercially available masks or by having a mask custom made. Nasal dryness can be treated with saline nasal spray at bedtime, a room vaporizer, or warm humidification added to the CPAP system. Nasal steroid sprays or ipratropium bromide spray can help with rhinorrhea.13,15 If a patient has chest discomfort or difficulty tolerating CPAP, bilevel positive airway pressure can help to reduce the expiratory pressure.23

• Nasal Prong System—This system is helpful in individuals suffering from claustrophobia, anxiety, or panic disorder.9

• Full Face Mask—Some individuals cannot tolerate nasal masks or prongs or are unable to keep their mouth closed during CPAP even with the use of a chin strap to permit adequate positive intrapharyngeal pressure. In such situations, using a full face mask should be considered. There is a potential risk of aspiration of gastric contents if the patient wearing a full face mask vomits. Patients should be instructed not to eat anything for at least 3 hours before applying the CPAP mask. Safety valves should be incorporated in the circuit close to the patient to facilitate inhalation of fresh air and to minimize dead space in the event of machine malfunction. An alarm must be present to signal power failure.

• Pressure Ramping—The pressure ramping feature of CPAP allows the adjustment of the rate of rise in delivered pressure over time from a negligible level to that required to maintain upper airway patency during sleep. This allows a window of opportunity for the patient initiating sleep. There are no published data available on the effectiveness of pressure ramping in improving patient compliance.24

• Therapeutic Use of Auto-CPAP—In an excellent review by Krieger,24 the therapeutic use of auto-CPAP was addressed. The rationale of auto-CPAP is that requirements in mask pressure are not constant, but vary in a given patient depending on several factors including alcohol, use of drugs, body position during sleep, sleep state, and nasal permeability as influenced by weather or allergic conditions (short term).24 The long-term factors include body weight, hormonal status, and sleep deprivation. This device, by adjusting instantaneously to the patient’s needs, is expected to correct breathing abnormalities better than fixed pressure CPAP.24 However, no published studies comparing the respiratory disturbance index (RDI) with auto-CPAP to RDI with fixed CPAP have demonstrated that the new technology was better than fixed CPAP in reducing RDI in short-term or long-term comparisons.25 Auto-CPAP offers no benefit over fixed CPAP in terms of the apnea-hypopnea index or other outcomes, and there was no difference in compliance with treatment between auto-CPAP and fixed CPAP.24

Bilevel Positive Airway Pressure
When using CPAP, patients may experience a smothering sensation while exhaling against positive pressure, chest wall discomfort, or nasal or sinus pressure. There is a potential risk of barotraumas in individuals with bullous emphysema, and alveolar hypoventilation may occur with increased expiratory pressure. Hence, CPAP pressure may need to be reduced to a minimal effective pressure. Upper airway resistance has been shown to increase during expiration despite the absence of negative intrapharyngeal pressure.26 Sanders and Kern23 suggest that splinting positive pressure in the upper airway during inspiration and expiration is necessary to eliminate apneic events. They propose that less pressure would be required to maintain upper airway patency during expiration than during inspiration.23 During expiration, inherent upper airway instability is the primary factor that favors upper airway collapse. CPAP provides equal pressure during inspiration and expiration. With bilevel positive airway pressure, adjustment of inspiratory positive airway pressure (IPAP) and expiratory positive airway pressure is possible. Sanders and Kern23 believe that in patients with OSA, bilevel positive airway pressure can deliver a sufficient level to prevent upper airway collapse during expiration. IPAP would augment airway patency to eliminate partial obstructions (hypopneas) with hypoxemia or arousals from sleep. With bilevel positive airway pressure, patients can determine their own inspiratory flow and frequency, and maintain a more physiologic breathing pattern; inspiratory-expiratory pressure cycling can be achieved even in the presence of mild to moderate air leaks.23 Patients find bilevel positive airway pressure to be more comfortable than CPAP (greater comfort associated with exhalation against lower pressure).23

Bilevel positive airway pressure is a therapeutic alternative for individuals who find CPAP uncomfortable or in individuals with severe bullous emphysema. Because average mask pressures are lower on bilevel positive airway pressure, air leakage, nasal congestion and rhinorrhea, chest discomfort, and risk of hypoventilation are reduced. However, it is not clear whether compliance with bilevel positive airway pressure is better than nCPAP. Bilevel positive airway pressure provides inspiratory pressure support and can be used to provide nocturnal ventilatory assistance in patients with neuromuscular diseases or chest wall disorders and associated OSA.23

The built-in time counter of the CPAP machine measures the cumulative time that the apparatus is turned on (machine run time).9 The time counter permits recognition of low rates of use. Here, early intervention helps to improve adherence and use of CPAP. Close follow-up can improve compliance.

In a randomized crossover study, patients with mild to moderate OSA were subjectively more satisfied with an oral appliance than with CPAP. This was despite the fact that CPAP was objectively more effective at correcting snoring, OSA, and excessive daytime sleepiness.27 Oral appliances are indicated for patients with moderate to severe OSA who are intolerant of or refuse treatment with nCPAP.28 There is a move to combine oral appliances and CPAP in new products. One uses an appliance instead of a mask to hold the hose delivering the pressurized air through nasal pillows directly into the nares.28 The aim is to eliminate the claustrophobia and air leaks associated with nCPAP (two common problems contributing to poor compliance). This combined device also eliminates the need for head gear to keep the mask in place. Another device delivers the pressured air directly into the oral cavity.28

The lack of subjective benefit from CPAP appears to be a major factor having detrimental influences on adherence and compliance.9

Every effort should be made to minimize the side effects of CPAP in order to enhance the quality of patients’ lives and to increase the likelihood of compliance. In my practice, I find that the severity of sleep apnea is directly proportional to the symptomatic improvement and consequently to compliance. Patients with more severe OSA are expected to derive more benefit from CPAP, and this probably accounts for the association between indices of OSA severity and CPAP acceptance and use.9 Patients who have family members or friends using CPAP are more acceptable to this mode of therapy for sleep apnea. In my opinion, educating patients plays a large part in their compliance with CPAP. This entails having a display of various masks including nasal pillows for patients with claustrophobia, Epworth sleepiness scoring, videos on sleep apnea and CPAP therapy, and visiting Web sites about sleep disorders. I also discuss the long-term cardiovascular risk factors associated with sleep apnea if it is not treated; they include an increased risk of heart attacks, cardiac arrhythmias, congestive heart failure, and strokes. The risk of sleep-related accidents is also discussed including the risk of car accidents while falling asleep at the wheel, which is 15 times higher. This information is reviewed at each patient’s appointment in the clinic for sleep disordered breathing. It is important that sleep specialists and the staff of the sleep center provide continuing educational resources and support for patients.

Taj M. Jiva, MD, is clinical assistant professor of medicine, State University of New York at Buffalo, and a pulmonologist, intensivist, and sleep specialist at Buffalo Medical Group PC.

1. Sullivan CE, Issa FG, Berthon-Jones M, et al. Reversal of obstructive sleep apnoea by continuous positive airway pressure applied through the nares. Lancet. 1981;1:862-865.
2. Strohl KP, Redline S. Nasal CPAP therapy, upper airway activation, and obstructive sleep apnea. Am Rev Respir Dis. 1986;
3. Alex CG, Aronson RM, Onal E, et al. Effects of continuous positive airway pressure on upper airway and respiratory muscle activity. J Appl Physiol. 1987;62:2026-2030.
4. Hoffstein V, Zamel N, Phillipson EA. Lung volume dependence of pharyngeal cross-sectional area in patients with obstructive sleep apnea. Am Rev Respir Dis. 1984;
5. Van de Graff WB. Thoracic influence on upper airway patency. J Appl Physiol. 1988;65:2124-2131.
6. Begle RL, Sadr S, Skatrud JB, et al. Effect of lung inflation on pulmonary resistance during NREM sleep. Am Rev Respir Dis. 1990;141:854-860.
7. Series F, Cormier Y, Desmueles M. Influence of passive changes of lung volume on upper airways. J Appl Physiol. 1990;
8. Abbey NC, Cooper KR, Kwentus JA. Benefit of nasal CPAP in obstructive sleep apnea is due to positive pharyngeal pressure. Sleep. 1989;12:420-422.
9. Collard PH, Pieters TH, Aubert G, Delguste P, Rodenstein DO. Compliance with nasal CPAP in obstructive sleep apnea patients. Sleep Medicine Reviews. 1997;1:33-44.
10. Rajagopal KR, Bennett LL, Dillard TA, et al. Overnight nasal CPAP improves hypersomnolence in sleep apnea. Chest. 1986;90:172-176.
11. American Thoracic Society. Indications and standards for use of nasal continuous positive airway pressure (CPAP) in sleep apnea syndromes. Am J Respir Crit Care Med. 1994;150:1738-1745.
12. Stauffer JL, Fayter NA, McClure BJ. Conjunctivitis from nasal CPAP apparatus. Chest. 1984;86:802.
13. Strumpf DA, Harrop P, Dobbin J, et al. Massive epistaxis from nasal CPAP therapy. Chest. 1989;95:1141.
14. Jarjour NN, Wilson P. Pneumocephalus associated with nasal continuous positive airway pressure in a patient with sleep apnea syndrome. Chest. 1989;96:1425-1426.
15. Waldhorn RE, Herrick TW, Nguyen MC, O’Donnell AE, Sodero J, Potolicchio SJ. Long-term compliance with nasal continuous positive airway pressure therapy of obstructive sleep apnea. Chest. 1990;97:33-38.
16. Sullivan CE, Issa FG, Berthon-Jones M, et al. Home treatment of obstructive sleep apnoea with continuous positive airway pressure applied through a nose mask. Bull Eur Physiopathol Respir. 1984;20:49-54
17. Frith RW, Cant BR. Severe obstructive sleep apnea treated with long term nasal continuous positive airway pressure. Thorax. 1985;40:45-50.
18. Nino-Murcia G, McCann CC, Bliwise DL, et al. Compliance and side effects in sleep apnea patients treated with continuous positive airway pressure. West J Med. 1989;150:165-169.
19. Sanders MH, Gruendl CA, Rogers RM. Patient compliance with nasal CPAP therapy for sleep apnea. Chest. 1986;90:330-333.
20. ANTADIR. A multicenter survey of long term compliance with nasal CPAP treatment in patients with obstructive sleep apnea syndrome. Am Rev Respir Dis. 1990;
21. Fletcher EC, Luckett RA. The effect of positive reinforcement on hourly compliance in continuous positive airway pressure users with obstructive sleep apnea. Am Rev Resp Dis. 1991;143:936-941.
22. Kribbs NB, Pack AI, Kline LR, et al. Objective measurement of patterns of nasal CPAP use by patients with obstructive sleep apnea. Am Rev Respir Dis. 1993;147:887-895.
23. Sanders MH, Kern N. Obstructive sleep apnea treated by independently adjusted inspiratory and expiratory positive airway pressures via nasal mask. Physiologic and clinical implications. Chest. 1990;98:317-324.
24. Krieger J. Therapeutic use of auto-CPAP. Sleep Medicine Reviews. 1999;3:159-174.
25. Konermann M, Sanner BM, Vyleta M, et al. Use of conventional and self-adjusting nasal continuous positive airway pressure for treatment of severe obstructive sleep apnea syndrome: a comparative study. Chest. 1998;113:714-718.
26. Smith PL, Wise RA, Gold AR, et al. Upper airway pressure-flow relationships in obstructive sleep apnea. J Appl Physiol. 1988;64:789-795.
27. Ferguson KA, Onu T, Lowe AA, et al. A randomized crossover study of an oral appliance vs nasal-continuous positive pressure in the treatment of mild-moderate obstructive sleep apnea. Chest. 1996;
28. Cartwright R. What’s new in oral appliances for snoring and sleep apnea: an update. Sleep Medicine Reviews. 2001;5:25-32.