Published ahead of print on October 2, 2003, doi:10.1164/rccm.200304-542OC
© 2003 American Thoracic Society Randomized Short-term Trial of Two AutoCPAP Devices versus Fixed Continuous Positive Airway Pressure for the Treatment of Sleep ApneaPulmonary Division, University Hospital of Zürich, Zürich, Switzerland Correspondence and requests for reprints should be addressed to Konrad E. Bloch, M.D., Pulmonary Division, Universitätsspital Zürich, Rämistrasse 100, CH-8091 Zürich, Switzerland. E-mail: pneubloc{at}usz.unizh.ch
We evaluated the efficacy of two different continuous positive airway pressure devices with automatic mask pressure adjustment (autoCPAP) in comparison with fixed CPAP in treating obstructive sleep apnea syndrome in 29 patients. The mean (± SE) apneahypopnea index was 46 ± 4 per hour and the Epworth score was 14.2 ± 0.7. Patients were treated over three consecutive 1-month periods with three regimens in random order: an autoCPAP device responding to apneahypopnea and snoring, another autoCPAP device responding to snoring and changes in flow contour, and fixed CPAP at the 90th pressure percentile titrated by autoCPAP over 2 weeks. Allowed pressure in the autoCPAP mode was 4 to 15 cm H2O. At the end of each treatment period, symptoms, quality of life, vigilance, and nocturnal breathing disturbances were evaluated. All three treatment modalities improved symptoms, quality-of-life domains, and apneahypopnea index significantly and to a similar degree. Mean (± SE) maintenance-of-wakefulness time increased by 4.5 ± 1.8, 6.0 ± 1.5, and 6.1 ± 1.4 minutes with DeVilbiss AutoAdjust LT, AutoSet T, and fixed-pressure CPAP, respectively (p < 0.001 vs. baseline, p = not significant for comparisons among the three modalities). We conclude that both autoCPAP devices were equally effective as fixed-pressure CPAP in improving major outcomes during short-term therapy of sleep apnea.
Key Words: obstructive sleep apnea autoCPAP continuous positive airway pressure therapy compliance Nocturnal application of continuous positive airway pressure (CPAP) via nasal mask is the standard therapy for the obstructive sleep apnea syndrome. Its regular use improves excessive sleepiness, cognitive performance, and quality of life (1, 2). Conventionally, the therapeutic mask pressure, i.e., the minimal pressure that eliminates abnormal respiratory events, is determined by manual titration over the course of a night in the sleep laboratory. Alternatively, automatic computer-controlled CPAP titration (autoCPAP) may be performed over one or several nights (3). AutoCPAP devices adjust pressure by feedback control according to patterns of pressure, flow, or other signals recorded during treatment. Analysis of the pressure applied during unattended autoCPAP titration may serve to determine therapeutic pressure for subsequent treatment with conventional CPAP at a fixed pressure (4, 5). The concept of long-term CPAP treatment with a fixed mask pressure has been challenged because the pressure required to maintain upper airway patency in patients with sleep apnea varies over a night depending on body position (6), sleep state, and other factors. CPAP requirements may also change over the course of several weeks to months due to changes in upper airway properties as well as variation in body weight. This has led to the assumption that continuous adaptation of mask pressure to the actual needs of the patient by autoCPAP might improve effectiveness of CPAP therapy by preventing sleep disturbances from unnecessarily high mask pressures during major parts of the night, by enhancing comfort, and by improving treatment adherence (7). In fact, mean mask pressure applied during autoCPAP home therapy is generally lower than the pressure level prescribed in the same patients on the basis of manual titration (7, 8). Furthermore, some (7, 9) but not all studies (8) revealed a higher treatment adherence with autoCPAP as compared with conventional fixed CPAP. However, in several studies major outcomes of sleep apnea therapy, i.e., subjective sleepiness, objective vigilance, or cognitive performance, were not improved by autoCPAP compared with fixed-pressure CPAP (10, 11), or these outcomes had not been evaluated (7, 12). One report even suggests that variation in mask pressure during autoCPAP therapy might induce sleep disturbances (13). Assessment of the potential role of autoCPAP therapy in the home is further complicated by differences in technical characteristics of devices from various manufacturers as recently suggested by bench tests (14). The clinical relevance of these laboratory findings remains still uncertain. Therefore, the purpose of the current study was to compare the efficacy of autoCPAP applied by devices from two different manufacturers with that of conventional fixed-pressure CPAP in the domiciliary therapy of patients with the obstructive sleep apnea syndrome. Subjective symptoms, quality of life, and objective vigilance were major outcomes. We employed a randomized, controlled, crossover protocol to test the hypothesis that two autoCPAP devices that incorporate different event definitions and algorithms for pressure control differ in treatment effects among each other and in comparison with conventional fixed CPAP. Some of these results have been previously reported in the form of an abstract (15).
Patients Consecutive patients with obstructive sleep apnea syndrome based on complaints of excessive sleepiness, snoring, and apneahypopnea index higher than 10/hour were asked to participate in the study if they were naive to CPAP therapy. Informed consent was obtained, and the protocol was approved by the hospital ethics committee.
AutoCPAP Devices
Protocol
Measurements and Outcomes
Vigilance and sleep studies.
Treatment data.
Statistical Analysis Clinically relevant treatment effects were defined as changes in the Epworth score by 2 points (1), in the SF-36 vitality score by 10 points (2), and in sleep resistance time by 4 to 5 minutes (1). Power calculations indicated that with a sample size of 29, a nonsignificant result for these major outcomes (p > 0.05) was correct with a probability of 95%, 95%, and 64% (sleep resistance time of 4 minutes) or 82% (sleep resistance time of 5 minutes), respectively. Equivalence of treatment effects by the different modalities was evaluated by computing confidence intervals of differences in treatment effects according to Jones and coworkers (26) (see also methods description in the online supplement).
Patients Of 31 recruited patients, 29 completed the trial. Two patients were not able to undergo follow-up examinations, one due to lack of time and the other because he moved away. The analysis was performed on the remaining 29 patients (6 females). Their mean age (± SE) was 53 ± 2 years and their body mass index was 33.3 ± 1.3 kg/m2. The symptom scores and results of vigilance and sleep studies at baseline are listed in Table 1 for comparison with effects of the three treatment modalities. Confidence intervals of the differences in treatment effects of the three modalities are graphically presented in Figure E1 in the online supplement.
Outcomes In a first analysis, we compared the effects of treatment with fixed-pressure mode between the AutoSet T and the DeVilbiss AutoAdjust LT. There was no statistically significant difference in any assessed outcome. Furthermore, neither was there any difference in baseline characteristics nor in any outcome of fixed CPAP therapy among patients in whom the pressure level for this modality was derived from the 90th pressure percentile of the AutoSet T and the DeVilbiss AutoAdjust LT, respectively, during the 2-week adaptation period. Therefore, the results obtained with fixed-pressure mode by the two devices were treated as one treatment modality that served as the control for comparison with results achieved by the two devices in automatic mode. These data are presented in Table 1. There was no effect of the order of applied treatment modalities for any of the assessed outcomes.
Symptoms and Subjective Assessment The effect size, an indicator of the magnitude of treatment benefit, was large for Epworth scores with all three treatment modalities (24): effect sizes were 1.32 for AutoSet T in the automatic mode, 1.57 for DeVilbiss AutoAdjust LT in the automatic mode, and 1.50 for the fixed-pressure mode. Effect sizes on SF-36 vitality scores were 0.63 for AutoSet T in the automatic mode, 0.65 for DeVilbiss AutoAdjust LT in the automatic mode, and 0.78 for the fixed-pressure mode. The overall benefit during treatment with all three modalities was equally high (Table 1). At the end of the study, all the patients were highly motivated to continue CPAP therapy. When asked whether they preferred any one of the pressure settings they had received over the course of the 3 months, 21 of the 29 patients had no preference. Four patients favored a variable pressure setting (automatic mode), whereas four other patients favored the fixed-pressure mode. As explanation for the preference, a shorter latency to fall asleep and less sleep disruption were mentioned. Seventeen patients preferred one autoCPAP device brand, 11 patients the other brand (p = not significant), and 1 patient had no preference. Details in handling, size, weight, and noise level during use were the most frequently cited reasons for the preference. Skin irritation, air leaks, dry mouth or nose were the most frequent side effects experienced by 3 to 10 patients (1034%) during the 3 treatment periods. The severity of side effects was mild and their prevalence differed neither among automatic or fixed-pressure CPAP modes nor among the two different devices. The details on side effects are listed in Table E2 of the online supplement.
Vigilance and Sleep Studies
Treatment Data Mean mask pressures during months with therapy in fixed-pressure mode were 8.4 ± 0.3 cm H2O (range, 511 cm H2O). These pressures were higher by a mean of 1.3 and 1.9 cm H2O than the mean median values during automatic mode with the AutoSet T and DeVilbiss AutoAdjust LT, respectively (p < 0.01 for comparisons of both autoCPAP devices vs. fixed CPAP) (Table 1). On the other hand, the 95th percentile of applied pressures during automatic mode therapy with either device exceeded pressures during fixed mode therapy (Table 1). Medians and 90th percentiles of pressure applied by the two devices over the course of the months with automatic mode treatment did not statistically differ among each other. The mean difference in median pressure applied by AutoSet T minus the corresponding value for the DeVilbiss AutoAdjust LT was +0.6 (95% confidence interval, -0.2 to +1.3) cm H2O (p = not significant). The mean difference in the 90th percentile of pressure applied by the two devices was -0.1 (95% confidence interval, 0.9 to +0.8) cm H2O (p = not significant). The variability of mask pressure during months with treatment in autoCPAP mode was quantified by the ratio of the 90th to the 50th percentile of applied pressure. This ratio differed among the two devices with greater values for the DeVilbiss AutoAdjust LT than for the AutoSet T (Table 1). We further investigated a potential effect of individual pressure requirements during autoCPAP therapy on pressure variability. We found a negative correlation among the ratio of the 90th to the 50th percentile and median pressure for AutoSet T (y = 1.55 0.04x, R2 = 0.41, p < 0.0005, see Figure E3 in the online supplement), indicating that in patients with higher median pressures, the variability of pressure was relatively less pronounced with this device. The corresponding correlation was not statistically significant for pressures applied by the DeVilbiss AutoAdjust LT (see Figure E3 in the online supplement). To investigate whether pressure variability decreased over the time course of autoCPAP treatment, as suggested in a study in patients with position-dependent sleep apnea (27), the ratio of the 90th to the 50th percentile of applied pressure was compared among the 2-week adaptation period and each of the three subsequent 1-month autoCPAP treatment periods. None of these comparisons revealed any differences, suggesting that pressure variability did not change over time (see Figure E4 in the online supplement). Furthermore, neither the 90th nor the 50th pressure percentiles differed between the 2-week adaptation period and the subsequent 1-month period with the corresponding device in automatic mode (see Figure E5 in the online supplement). A comparison among the four patients who preferred treatment in the automatic mode with the four patients who preferred treatment with the fixed-pressure mode, and with patients who did not have any preference did not reveal any statistically significant difference in body mass index, Epworth scores, sleep resistance times, and apneahypopnea indices at baseline (data not shown). In addition, among these patient groups, there was no difference in median applied mask pressures during automatic mode and fixed-pressure mode treatment (data not shown)or in the pressure variability during automatic mode treatment as estimated by the 90th to the 50th percentile ratio of applied pressure. This ratio was 1.38 ± 0.03 for the four patients preferring the automatic mode and 1.36 ± 0.06 for those four patients preferring fixed-pressure mode (p = not significant).
Our single-blinded, randomized crossover study revealed that autoCPAP home therapy over 1 month was equal to CPAP therapy at a fixed pressure in improving major outcomes of obstructive sleep apnea treatment such as subjective and objective sleepiness, quality of life, and nocturnal respiration. The direct comparison of two different autoCPAP devices employed in our study suggests that differences in event detection and algorithms of pressure adjustment implemented in these specific devices did not have a detectable impact on outcomes as both devices improved obstructive sleep apnea symptoms equally well. The benefits of CPAP therapy observed in the current study with automatic and fixed-pressure mode in patients with moderate to severe obstructive sleep apnea are similar to those reported in previous studies with conventional fixed CPAP treatment (1, 2). To allow comparisons of the magnitude of treatment effects achieved in different domains we computed effect sizes. Effect sizes achieved in our patients on Epworth scores (i.e., effect sizes, 1.321.57), SF-36 vitality scores (effect sizes, 0.630.78), and performance in vigilance testing (effect sizes, 0.570.71 on sleep resistance time in the OSLER tests) by all three treatment modalities are moderate to large (24, 28). With a mean nightly use of 5.5 to 5.6 hours during automatic and fixed-pressure mode therapy, respectively, treatment adherence in the current study was similar to the 5.4 hours observed with fixed CPAP treatment in patients with comparable severity of the disease (1) but higher than the 2.8 hours/night found in some patients with milder sleep apnea (29). We have performed treatment in the control period with both types of autoCPAP devices operating in fixed-pressure mode at the 90th pressure percentile titrated during 2 weeks. The 90th rather than the 95th pressure percentile was used because previous studies with the AutoSet T have revealed that the 95th pressure percentile during automatic titration was slightly higher than corresponding manually titrated pressures (by 911% corresponding to 0.71.3 cm H2O) (4, 8), whereas the 90th percentile closely approximated optimal CPAP determined during polysomnography (5). The effects we observed with fixed CPAP are similar to those achieved in previous trials using manual titration (1, 2). Others have shown that there is no systematic difference between automatic titration by AutoSet T and manual titration (5), and we found no difference between the 90th pressure percentiles applied by AutoSet T and DeVilbiss AutoAdjust (Table 1). Thus, it is unlikely that the automatic titration by a computer algorithm we used has biased our results compared with previous trials where CPAP was manually titrated by a technician during one single night in the laboratory. Data on efficacy of home therapy over several weeks by autoCPAP devices are still scant. In one crossover trial in 10 patients, apneahypopnea indices recorded by AutoSet T over 2 months automatic therapy were similar to those during fixed-pressure CPAP at a manually titrated level (8). In another investigation (9), 44 patients selected according to their requirements for a high therapeutic CPAP of more than or equal to 10 cm H2O received treatment by AutoSet T in automatic mode and at the manually titrated fixed pressure, each over 6 weeks in a randomized crossover design. In that study, autoCPAP treatment was associated with improved sleep symptom scores and better SF-36 vitality and mental health scores as compared with fixed-pressure CPAP. In addition, average nightly CPAP use was reported to be greater in automatic than in fixed-pressure mode (mean average hours/night, 6.1 vs. 4.5, respectively), and median pressures were lower in automatic mode (mean median pressure, 6.9 vs. 10.7 cm H2O, respectively). There was no difference in subjective sleepiness as assessed by Epworth scores among the two treatment modes, and vigilance was not objectively assessed (9). Our data extend these findings by showing no additional benefit of autoCPAP over fixed CPAP therapy by AutoSet T regarding subjective and objective sleepiness, perceived energy, interference with daily tasks and quality of life, and treatment compliance in unselected patients requiring therapeutic pressures in the range of 5 to 11 cm H2O (Table 1). A randomized parallel study evaluated home therapy by the DeVilbiss AutoAdjust LT in automatic and fixed-pressure mode over 3 to 6 months, respectively, in two groups of 23 and 25 patients with obstructive sleep apnea (7). Although the mean number of nights with more than 4 hours of CPAP use per night was greater in the automatic mode group than in the fixed-pressure group (6.5 vs. 5.7 nights/week), the average hours per night on CPAP did not differ among the groups. Mean mask pressure was lower in the automatic group (6.5 vs. 8.1 cm H2O). The reduction in the respiratory disturbance index during polysomnographies with the two treatment modes was similar (7). No data on sleepiness and other symptoms were provided. Our investigation closes this gap by demonstrating similar improvements of symptoms and measured sleep resistance times by the DeVilbiss AutoAdjust LT in the automatic and fixed-pressure mode (Table 1). Our investigation is the first clinical comparison among two different brands of autoCPAP devices. We did not find any significant differences in symptoms, objectively measured vigilance, and nocturnal breathing disturbances during treatment indicating that superiority of any of the treatment modalities was unlikely (Table 1). To further analyze the question of equal efficacy we examined whether the confidence intervals of differences in various treatment effects fell within a range judged as clinically relevant (26) (see Figure E1 in the online supplement). This comparison suggested equivalent effects of the two devices operating in either automatic or fixed-pressure mode on quality of life and nocturnal breathing disturbances. Medians and 90th percentiles of applied pressures did not statistically differ among the AutoSet T and the DeVilbiss AutoAdjust LT (Table 1). However, the variability of pressure expressed as the ratio of the 90th to the 50th percentile of applied pressure was greater for the DeVilbiss AutoAdjust LT (Table 1, Figure E3 in the online supplement). In addition, there was a negative correlation among the median applied pressure and the variability of pressure for the AutoSet T but not for the DeVilbiss AutoAdjust LT (see Figure E3 in the online supplement). Although this illustrates differences in event detection and/or algorithms of pressure adjustment between the two devices, the clinical relevance of the finding is questionable. The lack of any measurable difference in outcomes achieved by the two autoCPAP devices in automatic and fixed-pressure CPAP therapy suggests that the hypothetical advantages or disadvantages of one or the other modality are minor at best. In contrast to one report on patients with position-dependent sleep apnea (27), we did not observe a reduction in mask pressure variability with autoCPAP over the course of several weeks treatment (see Figure E4 in the online supplement). Other autoCPAP devices than the two examined in the current study have been evaluated in few investigations (1012, 30, 31). However, the results available to date do not allow firm conclusions on their potential role in sleep apnea therapy. In none of the studies has a clear advantage over fixed-pressure CPAP regarding major outcomes such as objective sleepiness, symptoms or quality of life been demonstrated during long-term therapy.
Conclusions
SLEEP SYMPTOMS QUESTIONNAIRE (MODIFIED FROM REFERENCE 17) Energy level: "During the last week, how would you rate your level of energy?" Likert scale (1) fresh as a daisy; (6) tired to death. Interference with daily tasks: "During the last week, to what extent has sleepiness interfered with your life?" Likert scale (1) no interference; (6) totally. Performance ability: "During the last week, how would you rate your ability to perform tasks at home and at work?" Likert scale (1) best: alert, concentrate, well; (6) worst: feel foggy, tired.
Supported by grants from the Lung League of Zürich, the Lung League of Schaffhausen, Lamprecht AG, Zürich, and Labhardt AG, Basel, Switzerland. This article has an online supplement, which is accessible from this issue's table of contents online at www.atsjournals.org Conflict of Interest Statement: O.S. has no declared conflict of interest; T.B. has no declared conflict of interest; F.M. has no declared conflict of interest; E.W.R. has no declared conflict of interest; K.E.B. has no declared conflict of interest. Received in original form April 17, 2003; accepted in final form September 27, 2003
This article has been cited by other articles:
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||