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Department of Respiratory and Sleep Medicine, Sleep Disorders Centre, Princess Alexandra Hospital, Woolloongabba, Australia
ABSTRACT
Current resources are inadequate to meet the demand for polysomnography, resulting in long waiting lists. This study aimed to evaluate the role of arbitrary-pressure continuous positive airway pressure (CPAP) as a method to reduce delays in commencing treatment. The study was of an open, randomized, parallel design. Ninety-one subjects with obstructive sleep apnea syndrome were randomized to either arbitrary-pressure CPAP based on body mass index before treatment polysomnography or to CPAP at settings determined by polysomnography. Both interventions resulted in similar improvements in clinical outcomes as determined by Epworth Sleepiness Score, Short Form-36 Quality of Life questionnaire, objective compliance, and subjective attitudes to treatment. There was higher sleep efficiency at treatment polysomnography in the group commenced at arbitrary pressure (81.8 ± 10.1% [mean ± SD] compared with 72.2 ± 18.0%, p = 0.01). Subjects unable to tolerate CPAP were identified by the use of arbitrary pressure, leading to a reduction in the proportion of "wasted" treatment polysomnograms (studies performed in subjects not persisting with treatment) relative to commencing therapy after treatment polysomnography (3 of 39 compared with 12 of 35, p = 0.01). This approach to initiating treatment with CPAP appears feasible when there are long waiting lists for polysomnography.
Key Words: arbitrary pressure continuous positive airway pressure obstructive sleep apnea
Obstructive sleep apnea syndrome (OSAS) is a common condition, with an estimated prevalence of 4% in men and 2% in women (1). Only a small proportion with this condition undergoes polysomnography and treatment (2). Despite this, resources for the diagnosis and management of OSAS are unable to cope with current demands (3). As community awareness improves and referrals to specialist sleep-disorder centers increase, resources will be even more limited.
OSAS is usually diagnosed by a laboratory-based overnight sleep study. Continuous positive airway pressure (CPAP) remains the recommended treatment in moderate to severe OSAS (4). CPAP is traditionally introduced at the time of an attended, overnight laboratory-based treatment sleep study. This overall approach is labor intensive and expensive and contributes to the long delays in the diagnosis and treatment of this condition. There are a number of strategies reported in the literature to address this shortfall in resources and long waiting lists, including the use of screening oximetry (5), split-night sleep studies (6, 7), partial sleep studies (8), and autotitrating CPAP (9, 10).
Fitzpatrick and coworkers (11) reported similar outcomes between standard laboratory-based CPAP titration and patient self-titration in CPAP-naive subjects. Similarly, some sleep centers routinely commence arbitrary-pressure CPAP before a formal pressure determination sleep study, predominantly in an attempt to reduce the delay to treatment, but this approach has never been formally evaluated. There are a number of potential advantages other than earlier treatment with CPAP. First, sleep architecture may be closer to normal if the subject is partially acclimatized to CPAP before the study. Second, the optimal pressure may differ if already established on therapy. The pressure requirement to control severe OSAS has been shown to be lower after 2 weeks of treatment with CPAP in one study (12), with changes in upper airway edema considered a possible mechanism. Finally, the use of arbitrary-pressure CPAP may identify subjects who will never accept this therapy, thereby avoiding an unnecessary sleep study.
The aim of this study was to evaluate the use of low arbitrary-pressure CPAP before the formal CPAP titration sleep study. This study was performed in response to the inability of our tertiary referral center to meet the demand for laboratory-based polysomnography, which resulted in long waiting lists, as experienced in many other centers. We hypothesized that arbitrary-pressure CPAP would be equivalent to CPAP introduced after a titration study in terms of compliance and improvements in subjective sleepiness and quality of life. Furthermore, we hypothesized that the practice would more normalize sleep architecture with the treatment sleep study, which in turn may reduce the risk of inaccurate CPAP titration in the event of reduced sleep efficiency or rapid eye movement (REM) sleep in the titration study.
METHODS
Subjects
Consecutive, eligible CPAP-naive subjects with OSAS were recruited from a tertiary referral sleep disorders center after diagnostic polysomnography. Subjects were excluded by severe hypoxemia during sleep (15% or more of sleep time at a saturation below 80%), nonobstructive sleep apnea (central apneas, more than 10 per hour), significant comorbidities (unstable ischemic heart disease with angina at rest or minimal exertion or neuromuscular disease affecting respiratory muscles), or a previous treatment sleep study. Informed consent was obtained from all subjects.
Protocol
The protocol is outlined in Figure 1 and was approved by the Research and Ethics Committee of Princess Alexandra Hospital (Woolloongabba, Australia). The study was of open, randomized, parallel design. Subjects were randomized to commence CPAP either after a CPAP titration sleep study (study-determined pressure) or at an arbitrary pressure before the treatment sleep study (arbitrary-pressure CPAP). Randomization was performed by the sealed envelope technique, by staff not involved with the study. The arbitrary pressure was selected according to body mass index (BMI): 8 cm H2O was used if BMI was less than 30, 10 cm H2O if BMI was 30eC35, and 12 cm H2O if BMI was 35 or more, but pressures were reduced if the subject was intolerant of the recommended setting (see the online supplement for details of the polysomnography analysis). The treatment sleep study was scheduled after the diagnostic study on a next-available basis. During the treatment sleep study, CPAP was increased to abolish snoring and features of flow limitation and to reduce the respiratory disturbance index to fewer than five events per hour. Responses to the Short Form-36 (SF-36) Quality of Life questionnaire and the Epworth Sleepiness Scale (ESS) (13), objective compliance (recorded from the inbuilt CPAP hour meter indicating hours of pump operation), and a linear visual analog score (VAS) of subjective feelings toward CPAP therapy were collected as indicated in Figure 1. A continuous measurement was obtained from the VAS in response to the following questions: "How easy do you currently find the use of CPAP" (ranging from "extremely difficult to use" = 0 to "extremely easy to use" = 10) and "What is your current attitude toward CPAP" (ranging from "intensely dislike" = 0 to "greatly like treatment" = 10). Unplanned clinical reviews (additional review outside scheduled appointments) and duration of this contact were logged. For the arbitrary-pressure group, CPAP settings were increased in the event of persistent snoring or somnolence or reduced if the subject was pressure intolerant. The CPAP setting was further adjusted at the CPAP titration study.
Statistical Analysis
All parameters are given as means ± SD. Objective CPAP compliance data were analyzed on an intention-to-treat basis. A computerized statistical software package was used for analysis (SigmaStat 3.0; SPSS, Chicago, IL). The primary outcome was ESS and secondary outcomes were objective compliance, quality of life, and the VAS of subjective feelings toward CPAP therapy. Calculations of sample size demonstrated that 88 subjects were required to demonstrate a difference of two in Epworth Sleepiness Scale with a power of 0.85 and = 0.05. Parametric values were compared by one-way analysis of variance and nonparametric values were compared by analysis of variance on ranks. Proportionate analysis (2) was used to compare rates of CPAP failure and rate of treatment sleep studies.
RESULTS
Subjects
Ninety-three subjects were approached for enrollment between January and December 2000. Two subjects refused participation. Ninety-one subjects were randomized (Figure 1). Six subjects did not commence arbitrary-pressure CPAP (five for financial reasons and one because of severe claustrophobia) and a further six subjects discontinued CPAP before the treatment sleep study (Figure 1). In the study-determined pressure cohort, seven subjects did not commence CPAP after the treatment sleep study (four for financial reasons and three because of dislike of treatment). Both groups were matched for age, sex, BMI, severity of OSA, and sleep architecture; however, there was a significant difference between the groups in arousal index (Table 1). Subjects in the arbitrary-pressure cohort commenced CPAP at pressures of 10.7 ± 1.0 cm H2O, increasing to 11.4 ± 2.0 cm H2O before the treatment study in response to persistent snoring or somnolence (p < 0.05 relative to starting pressure). Pressures were increased to 13.0 ± 2.0 cm H2O after the treatment sleep study (p < 0.001 compared with both starting and final arbitrary pressures).
Treatment Sleep Study
Treatment sleep study parameters are shown in Table 2. There was significantly higher sleep efficiency in the arbitrary-pressure cohort and a tendency toward a higher proportion of REM sleep. The study-determined optimal CPAP setting was significantly higher in the arbitrary-pressure CPAP cohort.
Time to Commencement of CPAP
The delay between the diagnostic sleep study and commencement of CPAP was significantly lower in the arbitrary-pressure cohort (Figure 2).
Epworth Sleepiness Scale
The changes in ESS with treatment are shown in Figure 3. There were significant improvements in ESS with both arbitrary-pressure CPAP and study-determined pressure CPAP relative to baseline. There was a tendency toward lower ESS in the study-determined pressure group both after 1 month of treatment (arbitrary pressure, 9.5 ± 6.0; study-determined pressure, 7.3 ± 4.5; p = 0.08) and after 3 months of treatment (arbitrary pressure, 9.2 ± 5.6; study-determined pressure, 6.9 ± 3.6; p = 0.07). Although the study was powered to detect a difference of two in ESS, statistical significance was not reached as the standard deviation of the measurement was greater than expected. There was also a tendency toward lower ESS in the arbitrary-pressure group 1 month after the CPAP titration study compared with the score after 3 months of arbitrary pressure (p = 0.09).
CPAP Compliance
There was no difference between groups in compliance 1 month after initiating therapy (arbitrary-pressure CPAP, 5.1 ± 2.5 hours; study-determined CPAP, 4.5 ± 2.2 hours; p = 0.44) or 3 months (arbitrary-pressure CPAP, 5.1 ± 2.4 hours; study-determined CPAP, 3.9 ± 2.5 hours; p = 0.12). The compliance in the arbitrary-pressure cohort represents compliance at arbitrary pressures before the CPAP titration study.
Side Effects and Unnecessary Treatment Studies
There was no difference in reported side effects between the groups (arbitrary-pressure CPAP, 35 reports; study-determined CPAP, 27 reports; p = 0.78). There was a tendency toward less unplanned clinical contact with subjects undergoing arbitrary-pressure CPAP (15.0 ± 7.9 minutes/subject compared with 22.3 ± 11.0 minutes/subject; p = 0.07). Whereas there was no difference in the total number of sleep studies performed between the groups, there were significantly fewer treatment sleep studies performed with members of the arbitrary-pressure group who did not continue with treatment (Table 3).
SF-36
Changes in SF-36 measures are shown in Figure 4. Significant improvements were seen in Vitality, Role-Emotional, and Mental Health domains in both groups; in General Health in the arbitrary-pressure group; and in Social Function in the study-determined pressure group. There were no significant differences between groups.
CPAP Ease of Use and Attitudes
There were no differences between groups in the VAS measures of Ease of Use and Attitudes to CPAP (Figure 5).
DISCUSSION
The conventional approach in the diagnosis and management of obstructive sleep apnea has been labor intensive and, as a consequence, there is often a significant shortfall between resources and demand. The usual result is a long waiting list for investigations. There have been a number of strategies proposed in the literature to address the discrepancy between resources and demand. Most of these have involved simpler diagnostic tools, particularly unattended-type studies including screening oximetry (5) or partial sleep studies (8). Another approach is to reduce the number of more expensive attended sleep studies by combining two diagnostic and treatment studies into a single-night split study (7). There have also been attempts to streamline the approach to treatment with CPAP. Autotitrating CPAP may reduce the need for a treatment sleep study based on the similarity between pressures recommended by conventional attended overnight sleep studies and unattended autotitrating CPAP studies (14). Furthermore, home autotitrating CPAP appears to result in similar outcomes compared with standard fixed-pressure CPAP after a laboratory-based treatment sleep study (10). Fitzpatrick and coworkers (11) have suggested that a treatment sleep study may not be required at all. These authors found similar outcomes between standard CPAP after a treatment sleep study and patient-directed CPAP titration dependent on response and tolerance.
This study was born out of a need to evaluate the clinical practice of initiating CPAP at an arbitrary pressure before a formal treatment sleep study. There were a number of potential benefits to this approach, including improved sleep architecture once the patient has acclimatized to CPAP, reduced delays to commencing CPAP, and avoidance of "wasted" sleep studies in patients who could not tolerate this treatment. The study demonstrated significantly higher sleep efficiency in subjects who were acclimatized to CPAP using arbitrary pressures before the treatment sleep study. There was also a tendency toward a higher proportion of REM sleep in this group. The possibility of bias needs to be considered as the cause of the improvements in sleep architecture, as subjects poorly tolerant of CPAP may have abandoned therapy before the CPAP titration study was performed. The optimal CPAP setting derived from the CPAP titration study was higher in the arbitrary-pressure group than in the study-determined pressure group. The improvement in sleep architecture in the arbitrary-pressure group is one possible explanation, assuming pressure requirements may have been higher with increased sleep efficiency and considering the tendency toward a higher proportion of REM sleep. The possibility of bias also needs to be considered for subjects requiring lower CPAP settings, who may have selectively not continued with arbitrary-pressure CPAP and proceeded to the CPAP titration study. This cannot be further evaluated with the present study design.
The most significant difference between groups was a reduction in the delay to commencing CPAP. This difference is a direct result of the study design. The reduction in the delay to treatment with the use of arbitrary-pressure CPAP is specific to centers where there are significant delays in performing polysomnography. There were similar improvements in ESS and Quality of Life responses with treatment and similar subjective ease of CPAP use, attitudes to CPAP, and compliance between arbitrary-pressure CPAP and study-determined pressure groups. There was, however, a tendency toward higher subjective sleepiness in subjects undergoing arbitrary-pressure CPAP before treatment polysomnography compared with both the study-determined pressure cohort and the arbitrary-pressure cohort after the titration study, possibly indicating that the arbitrary pressures were suboptimal. Variation in the measurement of ESS was greater than expected in the initial power calculation. Therefore the lack of statistical significance in ESS between the intervention groups may have reflected a Type II error. The adequacy of the arbitrary pressure was not directly assessed by polysomnography; however, there was a significant increase in treatment pressure after the CPAP titration sleep study in those subjects commenced beforehand on arbitrary-pressure CPAP, suggesting that the arbitrary pressures used were indeed suboptimal. Although there was the opportunity for adjusting pressure on the basis of clinical response, this was not the primary objective of the study, unlike in the study by Fitzpatrick and coworkers. Our data suggest that a CPAP titration sleep study is probably still required even if arbitrary-pressure CPAP has been employed, although this conclusion is influenced by the current study design. The findings of Fitzpatrick and coworkers suggest that empiric, patient-determined pressure adjustments alone may be sufficient.
A similar proportion of treatment sleep studies were performed in each cohort. However, fewer sleep studies were performed in subjects who did not persist with CPAP in the arbitrary-pressure CPAP cohort. Sleep studies were performed in only 3 of 39 subjects in the arbitrary-pressure CPAP group not continuing treatment and in 12 of 35 subjects in the study-determined pressure group not continuing treatment (p = 0.01). The reason for the difference is that, although similar proportions of subjects abandoned CPAP in both groups, subjects in the arbitrary-pressure group tended to do so before the treatment sleep study. Overall, there was no difference between the groups in reported side effects with treatment or in unplanned clinical contact (i.e., additional clinical contact beyond the study protocol). In fact, there was a tendency for reduced resource utilization per subject in the arbitrary-pressure cohort.
A potential risk of the use of arbitrary-pressure CPAP before a treatment sleep study is that patients may abandon treatment as a result of inadequate treatment pressures, particularly associated with suboptimal clinical response. The reasons subjects abandoned treatment fell into two broad categories. First, some subjects were unable to afford treatment. This problem will remain whether or not a treatment sleep study has been performed. Second, some subjects were unable to tolerate CPAP because of severe claustrophobia, pressure intolerance despite airway pressure reductions, or interface intolerance despite mask adjustment. Several subjects did report only partial clinical benefit with arbitrary-pressure CPAP, but no subject reported discontinuing arbitrary-pressure CPAP because of inadequate clinical response. Therefore, we do not believe that the limitations of arbitrary-pressure CPAP (possible suboptimal or excessive pressure delivery) are directly responsible for patients abandoning treatment. CPAP is an intrusive treatment and is poorly accepted by many patients. Long-term compliance with CPAP in one study was best predicted by compliance in the first 3 months of treatment (15), highlighting the difficulty in predicting tolerance to CPAP until the patient has actually experienced the treatment. The importance of experiencing CPAP to determine tolerance illustrates the potential benefit of performing trials with CPAP at arbitrary pressures before utilizing an expensive treatment sleep study.
In summary, the use of arbitrary-pressure CPAP before a treatment sleep study in centers with long delays in polysomnography results in similar clinical improvement relative to study-determined CPAP settings, improves treatment polysomnography sleep architecture, and reduces "wasted" treatment sleep studies (treatment studies performed on subjects who do not persevere with CPAP). A treatment sleep study is still indicated on the basis of these data, but further study is warranted to determine whether a treatment sleep study may not be required in some cases. This approach is beneficial in determining the use of polysomnography where facilities do not adequately meet demand and where there are delays in commencing CPAP after diagnosis with OSAS.
This article has an online supplement, which is accessible from this issue's table of contents at www.atsjournals.org
REFERENCES
Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle aged adults. N Engl J Med 1993;328:1230eC1235.
Young T, Evans L, Finn L, Palta M. Estimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and women. Sleep 1997;20:705eC706.
National Institutes of Health, National Commission on Sleep Disorders Research. Wake up America: a national sleep alert. Vol. 2: Working group reports. Washington, DC: U.S. Government Printing Office; 1994.
Loube D, Gay P, Strohl K, Pack A, White D, Collop N. Indications for positive airway pressure treatment for adult obstructive sleep apnea patients: a consensus statement. Chest 1999;115:863eC866.
Chiner E, Signes-Costa J, Arriero J, Marco J, Fuentes I, Sergado A. Nocturnal oximetry for the diagnosis of the sleep apnoea hypopnoea syndrome: a method to reduce the number of polysomnographies Thorax 1999;54:968eC971.
Yamashiro Y, Kryger M. CPAP titration for sleep apnea using a split-night protocol. Chest 1995;107:62eC66.
McArdle N, Grove A, Devereux G, Mackay-Brown L, Mackay T, Douglas N. Split-night versus full-night studies for sleep apnoea/hypopnoea syndrome. Eur Respir J 2000;15:670eC677.
Whittle A, Finch S, Mortimore I, MacKay T, Douglas N. Use of home sleep studies for diagnosis of the sleep apnoea/hypopnoea syndrome. Thorax 1997;52:1068eC1073.
Stradling J, Barbour C, Pitson D, Davies R. Automatic nasal continuous positive airway pressure titration in the laboratory: patient outcomes. Thorax 1997;52:72eC75.
Massie CA, McArdle N, Hart RW, Schmidt-Nowara WW, Lankford A, Hudgel DW, Gordon N, Douglas NJ. Comparison between automatic and fixed pressure positive airway pressure therapy in the home. Am J Respir Crit Care Med 2003;167:20eC23.
Fitzpatrick M, Alloway C, Wakeford T, MacLean A, Munt P, Day A. Can patients with obstructive sleep apnea titrate their own continuous positive airway pressure Am J Respir Crit Care Med 2003;167:716eC722.
Jokic R, Klimaszewski A, Sridhar G, Fitzpatrick M. Continuous positive airway pressure requirement during the first month of treatment in patients with severe obstructive sleep apnea. Chest 1998;114:1061eC1069.
Johns M. A new method for measuring daytime sleepiness: the Epworth Sleepiness Scale. Sleep 1991;14:540eC545.
Series F. Accuracy of unattended home CPAP titration in the treatment of obstructive sleep apnea. Am J Respir Crit Care Med 2000;162:94eC97.
McArdle N, Devereux G, Heidarnejad H, Engleman H, Mackay T, Douglas N. Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1999;159:1108eC1114.