The main areas associated with improved CPAP compliance include humidification, mask interfaces, and better patient selection

f03a.jpg (6176 bytes)Continuous positive airway pressure (CPAP) is a very effective treatment for sleep disordered breathing (SDB). Its principal use is in obstructive sleep apnea syndrome (OSAS) where it is the treatment of choice.1 CPAP works by creating a “pneumatic splint” that prevents upper airway collapse.2 The hypothesis by the original authors was that closure of the upper airway was the result of an imbalance in the forces that normally keep the upper airway open. By increasing the pressure in the upper airway, CPAP reverses the transmural pressure gradient and prevents upper airway collapse. CPAP produces other beneficial effects, including improvement in function of pharyngeal dilator muscles,3 ventilatory drive,4 and upper airway morphology.5 Studies6 have shown that CPAP increases the size of the upper airway by approximately 20%, particularly in the lateral aspects. The other benefit is an increase in functional residual capacity (FRC), which improves oxygenation.7

About OSAS
SDB consists of a spectrum of several syndromes characterized by abnormal breathing during sleep. The mildest form is intermittent snoring and the most severe form is obesity hypoventilation syndrome (OHS). Between these extremes are disorders with gradually increasing severity and increasing morbidity and mortality. The prevalence of SDB is high. OSAS, defined by daytime sleepiness and an apnea/hypopnea index (AHI) of more than 15, is present in 4% of men and 2% of women.8

The consequences of untreated OSAS are numerous. OSAS is an independent risk factor for ischemic heart disease.9,10 Systemic hypertension occurs in 40% to 60% of patients with OSAS11 and its severity correlates with severity of OSAS. Pulmonary hypertension has been reported in 19%12 of patients. There is no confirmed association with cardiac arrhythmias13 or stroke.14 Patients with untreated OSAS have three to seven times more car accidents than other drivers.15 The psychological consequences are intellectual deterioration, as well as personality and behavioral changes. Finally, the 5-year survival was decreased in patients with untreated OSAS with an AHI over 20, particularly those under the age of 50.16

Given these consequences, CPAP plays a sentinel role in the treatment of OSAS.1 However, it is effective only when used. In most patients OSAS is a lifelong disease and therefore requires long-term CPAP treatment. Unfortunately, one of the main problems with CPAP therapy is poor compliance.

Improved CPAP Compliance
The main areas associated with improved CPAP compliance are humidification, automatic CPAP titration, intensive support for patients with early intervention, mask interfaces, and better patient selection.

Nasal side effects, like dryness, burning, and congestion in particular, were the reason to discontinue CPAP use in up to a third of patients.17 There are several mechanisms causing nasal side effects of which mouth leak seems particularly important.18,19

The nasal mucosa has a large capacity to heat and humidify inspired air. It recovers approximately one third of the water lost during inspiration from the expiratory flow. At high flow rates and during unidirectional flow (mouth leak), the nasal mucosa becomes unable to maintain adequate humidity in the inspired air. Subsequent nasal dryness releases vasoactive amines and leukotrienes that may cause increased nasal resistance.20,21

Heated humidity produces an improved CPAP compliance rate when compared with cold passover humidity and no humidity.22 Interestingly, there was no significant difference in compliance rates between cold passover humidity and no added humidity. It is believed that heated humidity increases compliance by reducing side effects, particularly nasal congestion. This observation was supported by other studies,23,24 and some recommend that heated humidity should be used as early as CPAP titration.22

Not all OSAS patients treated with CPAP require heated humidification. In one study,25 56% of patients treated with CPAP complained of nasal discomfort. In half of those patients symptoms improved with cold humidification, but the other half required a switch to heated humidification. Age over 60 years, drying medications, chronic mucosal disease, and previous uvulopalatopharyngoplasty (UPPP) were risk factors for the addition of heated humidification. Thus, the need for heated humidification may be predicted at the start of therapy. Since heated humidifiers are significantly more expensive than simple passover humidifiers,26 perhaps the above data will motivate medical care payors to start supporting the use of heated humidifiers.

Another approach to lessen nasal side effects, and particularly drying, is to prescribe face (oronasal) masks.25,27 However, compliance with face masks is lower than with nasal masks because of overall greater discomfort. Hopefully, design improvements will increase compliance with these mask interfaces.

PAP: Titration and Modalities
Titration studies can be performed as either split-night or full-night titrations. In the United States and Europe, because of economic considerations, the split-night approach is becoming more commonplace. The first half of the night consists of diagnostic polysomnography and the remainder is for CPAP titration.

For many patients, the negative aspect of the split-night titration is the experience of a “hastily fitted mask in the middle of the night followed by an unfamiliar blast of air.”28 Therefore, some believe that a shorter period for CPAP pressure titration and familiarization will lead to lower compliance rates after split-night studies.

Several small studies have compared results of CPAP compliance between split-night and full-night titrations29-31; overall CPAP acceptance and adherence were compatible with both approaches. The main criticism of these studies is that they were performed in tertiary care centers and in selected patients with good prestudy support. If future studies continue to support the split-night titration, then savings in time, money, and productivity may be realized.32,33

The extent of the relationship between high CPAP pressure and side effects with poor compliance is still controversial. Common sense suggests that a lower CPAP pressure level leads to less side effects and a better compliance rate. Some studies have confirmed that statement34 while others support the opposite.35 A few studies do not find any relationship between pressure level and compliance.36,37

With the presumption that lower mean airway pressure leads to better compliance, two alternative modes, or actually modifications, of CPAP were invented: bilevel positive airway pressure and auto-CPAP (APAP). The main potential advantage of both modes is elimination of apnea/hypopnea events with lower mean airway pressures. That is expected to result in lower pressure-related side effects and subsequently higher compliance rates.

In a study by Reeves-Hoché et al,38 there was no significant difference in compliance for randomized patients using either CPAP or bilevel positive airway pressure. However, there was a significantly higher dropout rate in the CPAP group, suggesting higher acceptance rates in the bilevel positive airway pressure group. There is no large-scale study directly comparing CPAP and bilevel positive airway pressure. A small but important study by Szumstein et al39 used bilevel positive airway pressure as a salvage therapy in patients who did not tolerate CPAP or where it was not effective. In that study, bilevel positive airway pressure was accepted in 75% of patients and the compliance rate at 6 months was 48% (nights treatment used). Without large-scale studies and definitive data, the current opinion is to commence patients on CPAP and reserve bilevel positive airway pressure for those who cannot tolerate CPAP or have limited benefit.

The mask pressure required to prevent upper airway collapse varies with sleep stage and body position. Conventional CPAP generates a preset pressure that frequently can be either high or low. The new “intelligent” APAP systems are able to detect respiratory events and adjust the mask pressure accordingly. They can be used as auto-titrating systems to determine the optimal fixed CPAP pressure or as auto-adjusting systems for long-term treatment. The presumed outcome is a decreased mean pressure with resulting decreased side effects and better compliance rates.

Several small studies40-43 have shown encouraging results with APAP systems. A study with 20 patients by Teschler and Barthon-Jones33 revealed a reduction of the main airway pressure of up to 37% with no decreased effectiveness when compared with conventional CPAP. Two larger studies, one with 50 patients44 and the other with 60 patients,45 confirmed findings from previous studies. The mean mask pressure was significantly lower (8.1±2.5 cm H2O vs 6.7±1.7 cm H2O55 and 10.6±0.4 cm H2O vs 6.4±0.4 cm H2O56) and the compliance rate was higher in both APAP groups. On the basis of these studies, it seems that APAP would be beneficial in many OSAS patients except those who require low pressure to treat their obstructive events.

These APAP systems are significantly more expensive than conventional CPAP systems and thus the cost-benefit of APAP systems needs to be determined.46 More research is necessary to determine what subgroups of patients may benefit the most from APAP systems. These units could be beneficial for elderly patients (less sleep disturbance with lower pressure) or for patients who require very different CPAP pressure levels depending on body position or sleep stage.44

It is known that the CPAP compliance rate is significantly higher in Europe than in North America (80% vs 46% at 3 months).47 Also, fewer patients abandon CPAP in Europe than in the United States (5%-19% vs 19%-37%).48 In addition to cultural differences, perhaps Europe provides overall better patient support. Several studies have confirmed that more intensive support, and also simple follow-up measures, increases CPAP compliance rates.49,50

Hoy et al49 compared CPAP compliance using standard support and an intensive educational program including nursing support. As expected, the average CPAP use was significantly higher (5.4 hours vs 3.8 hours per night) in the intensive support group. The authors estimated the additional cost for the intensive support at $1,500 per patient. Obviously, the full cost-benefit of such intensive support needs to be further evaluated.

Out of the three main types of interfaces, the first choice is either a nasal mask or a nasal pillow. As noted, nasal masks are more comfortable and have higher compliance rates than oronasal masks,24,51 but oronasal masks are an alternative for patients who have nasal obstruction or significant mouth leak. Two studies52,53 have failed to confirm a higher incidence of potentially fatal complications with oronasal masks like aspiration of vomitus or asphyxiation during flow generator failure. Finally, a new generation of oral interfaces under development may lessen nasal symptoms and abolish the need for headgear; their impact on compliance remains unknown.

There is no definite agreement on what factors predict CPAP compliance when therapy is initiated. Reeves-Hoché et al54 did not find associations among AHI, age, sex, weight loss, or years of formal education with CPAP compliance. Collard et al55 believes all OSAS patients should have an objective CPAP compliance assessment. However, according to McArdle et al,56 the more severe the OSAS (higher AHI, higher movement arousal index, and higher oxygen desaturation during sleep), the more likely the patient is going to use CPAP. It seems that the main motivation to use CPAP is the impact daytime sleepiness has on life quality. Notably, in one study,57 only 50% of patients with an AHI over 15 accepted CPAP even when offered therapy free of charge.

In a study by Hoy et al,49 compliance was better when the patient initiated a self-referral for treatment rather than their partner. After 6 months of treatment, CPAP usage remained relatively intact in the self-referred group and declined in the partner-referred group. Another large study, aiming to identify patients who are likely to continue with CPAP treatment, found that a trial of just 1 week might be appropriate. On the basis of these studies, there is evidence that compliance may improve simply by selecting patients who are more likely to use CPAP.

Is CPAP compliance really low?
There is no standard definition of CPAP compliance because there is no definite agreement on frequency and duration of optimal CPAP treatment. In some studies,54,59 new patients were expected to use CPAP effectively for at least 4 hours on 70% of the days to qualify as regular users. Moreover, when discussing CPAP compliance, we need to differentiate between three types of CPAP compliance: subjective—based on patient reports; objective—based on the time treated with CPAP; and effective—based on the actual time a patient is treated at an appropriate pressure. While patients tend to subjectively overestimate their CPAP use by up to an hour, objective compliance recorded with hour counter meters is surprisingly close to effective compliance obtained with true pressure-time recordings.

Second, is subjective and objective improvement in symptoms equivalent to good compliance? We believe it is. It is known that CPAP use correlates with symptomatic improvement. No definite agreement on the minimum CPAP requirement exists. Early studies have chosen 4 hours as a cutoff point and today, after 8 years, that seems to be a fairly close estimate.54,59

CPAP has a residual or carry-over effect, which can decrease the severity of OSAS for the rest of the night after only 4 hours of use.60 Two studies47,61 have confirmed a benefit in cognitive function, daytime sleepiness, snoring, mood, and quality of life when CPAP is used 3 and 3.4 hours per night, respectively. However, these residual effects of CPAP last only for 3 to 4 hours and are lost if it is not used every night.62

The first studies63-65 investigating CPAP compliance were based on patient self-reports. The reported compliance ranged from 63% to 90% (nights device used). However, the first study to measure objective CPAP compliance54 noted a compliance of 68% with an average effective CPAP use of 4.28 ± 1.03 hours per night. In the often-quoted study by Kribbs et al,62 76% of patients reported a use in excess of actual use and only 46% met the criteria for regular users. However, in a European study,47 75% of patients met those criteria.

After a CPAP trial,48 70% to 80% of patients accept CPAP and 5% to 37% of those will eventually abandon CPAP. Lack of benefit was the main reason for abandoning CPAP in 25% of patients.66 Other reasons included anxiety, inconvenience, noise, difficulty falling asleep, mask discomfort, frequent nocturnal awakenings, and partner complaints.40 Price was a problem in 28% of patients and 10% stopped using CPAP mostly because of financial problems.63,67 Side effects were reported equally in both compliant and noncompliant patients. It seems that tolerance of these side effects is lower in patients with mild OSA (AHI <15).17

Compliance with CPAP usage with regard to patients with OSA may not be lower than in other diseases. It is known that compliance with inhalers in bronchial asthma and medication in hypertension is less than 50%.68,69 In a study70 of patients prescribed long-term supplemental oxygen of more than 15 hours per day, the compliance rate was only 45%. Epileptic patients were compliant with their medication only 39% of the time71 and similar results were noted with other chronic diseases.

A presumed CPAP compliance of well over 50%, at least in Europe, seems better than compliance for most chronic diseases.47 An important point is that it is much more convenient to take a tablet or use an inhaler than to use CPAP all night every night. To have to use CPAP “appears to be a life sentence to a bulky, unsightly, external appendage, rather like a colostomy bag—it may be necessary but it certainly isn’t romantic.”72 Nevertheless, while CPAP compliance can be improved, it may not be “low” after all.

Tony Sicenica, MD, is a fellow of pulmonary medicine, and Lewis R. Kline, MD, is director of the Center for Sleep Disorders, both at Western Pennsylvania Hospital, Pittsburgh. Kline is also an associate professor of medicine, Temple University School of Medicine, Philadelphia.

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