- Email: [email protected]
A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment
Sleep Medicine xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
Sleep Medicine journal homepage: www.elsevier.com/locate/sleep
Original Article
A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment q Matthew R. Ebben a,⇑, Mariya Narizhnaya a, Alan Z. Segal a, Daniel Barone a, Ana C. Krieger a,b a b
Department of Neurology, Center for Sleep Medicine, Weill Cornell Medical College, 425 East 61st Street, 5th Floor, New York, NY 10065, USA Department of Medicine, Center for Sleep Medicine, Weill Cornell Medical College, 425 East 61st Street, 5th Floor, New York, NY 10065, USA
a r t i c l e
i n f o
Article history: Received 1 November 2013 Received in revised form 17 January 2014 Accepted 20 January 2014 Available online xxxx Keywords: CPAP Full face mask Oronasal mask Nasal mask Obstructive sleep apnoea Hypopnoea Treatment
a b s t r a c t Introduction: It has been found that mask style can affect the amount of continuous positive airway pressure (CPAP) required to reduce an apnoea/hyponoea index (AHI) to <5/h on a titration study. However, it was not previously known whether switching from one CPAP mask style to another post titration could affect the residual AHI with CPAP. The purpose of this study was to investigate the differences in residual AHI with CPAP treatment between oronasal and nasal masks. Methods: Twenty-one subjects (age mean (M) = 62.9, body mass index (BMI) M = 29.6 kg/m2) were randomised (14 subjects completed the protocol) to undergo an in-laboratory CPAP titration with either a nasal mask or an oronasal mask. Subjects were then assigned this mask for 3 weeks of at-home CPAP use with the optimal treatment pressure determined on the laboratory study (CPAP M = 8.4 cm of H2O). At the end of this 3-week period, data were collected from the CPAP machine and the subject was given the other mask to use with the same CPAP settings for the next 3 weeks at home (if the nasal mask was given initially, the oronasal one was given later and vice versa). On completion of the second 3-week period, data on residual AHI were again collected and compared with the first 3-week period on CPAP. Results: A Wilcoxon Signed-Rank Test (two-tailed) revealed that residual AHI with CPAP treatment was significantly higher with the oronasal compared with the nasal mask (z = 3.296, p < 0.001). All 14 subjects had a higher residual AHI with the oronasal versus nasal mask, and 50% of the subjects had a residual AHI >10/h in the oronasal mask condition, even though all of these subjects were titrated to an AHI of <5/h in the laboratory. Conclusion: A higher residual AHI was seen in all patients with the use of an oronasal mask compared with a nasal mask. Switching to an oronasal mask post titration results in an increase in residual AHI with CPAP treatment, and pressure adjustment may be warranted. Ó 2014 Elsevier B.V. All rights reserved.
1. Introduction Positive airway pressure (PAP) continues to be the most effective treatment for obstructive sleep apnoea (OSA) [1]. A number of studies have shown the benefits of PAP treatment on measures of daytime function for patients treated for OSA [2–5]. Untreated OSA has been associated with adverse medical conditions including congestive heart failure [6–8], stroke [9,10], pulmonary [11–13] and systemic hypertension [14–16], cancer [17] and increased mortality [18]. PAP therapy consists of a blower unit
q
Registered on Clinicaltrials.gov: protocol #1108011845.
⇑ Corresponding author. Tel.: +1 (646) 962 9313; fax: +1 (646) 962 0455. E-mail addresses: [email protected] (M.R. Ebben), man2019@med. cornell.edu (M. Narizhnaya), [email protected] (A.Z. Segal), dab9129@ med.cornell.edu (D. Barone), [email protected] (A.C. Krieger).
(a medical quality air compressor) connected by a hose to a mask sealed to the patient’s face in order to pressurise the upper airway. The four primary categories of masks are: oral (covers only the mouth), nasal (covers only the nose), nasal pillows (seals at the nares), and oronasal (covers both the nose and mouth). The fact that continuous positive airway pressure (CPAP), when used, is highly effective in the majority of patients with OSA may be the reason why few studies have investigated the differences in efficacy between different types of equipment. However, since the initial conception of CPAP, some researchers have questioned whether oronasal masks could be used to successfully pressurise the upper airway [19]. The first small-scale studies investigating this issue showed conflicting results, likely due to the differences in study design [20–22]. The previous studies that found oronasal interfaces to be effective in treating sleep-disordered breathing utilised subjects with nasal obstruction [20,22]. Moreover, one
http://dx.doi.org/10.1016/j.sleep.2014.01.011 1389-9457/Ó 2014 Elsevier B.V. All rights reserved.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
2
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx
study investigating an oral-only mask also found that this mask style effectively treated sleep apnoea [23]. In contrast, a study that did not focus on an oral-only method of pressure delivery found the oronasal mask to be ineffective in eliminating airway obstruction [21]. More recently, Teo et al. [24] conducted a study showing that when oronasal versus nasal masks are compared with the use of auto-titrating CPAP, the use of the oronasal mask resulted in a significantly higher apnoea/hyponoea index (AHI) compared with that of the nasal mask, which suggests that mask style may result in an inadequate auto-titration. A similar result was also found by Bakker et al. [25]; however, in this study, although a significant difference was found in residual AHI between mask styles, residual events continued to be within the proper treatment range with all tested masks. Alternatively, our group [26] found that when patients are manually titrated on CPAP, the oronasal mask resulted in significantly higher pressures for patients with moderate to severe OSA compared with standard nasal and nasal pillow masks. This finding was confirmed by a large-scale correlational study that was recently published [27]. Regardless of these findings, it is common clinical practice to switch between mask styles without making adjustments to the level of PAP. We hypothesised that switching between mask styles, post CPAP titration, would result in a change in residual respiratory events, and we designed a randomised prospective crossover study to test this hypothesis. The goal of the current study was to investigate if switching from an oronasal to a nasal mask or vice versa post titration will result in a change in residual respiratory events with CPAP treatment. 2. Methods The Institutional Review Board at Weill Cornell Medical College granted approval for this study (approval #1108011845). Informed consent was obtained for each participant in this study. 2.1. Subjects A total of 21 subjects that included men (n = 14) and women (n = 7) with moderate and severe OSA, who presented for office follow-up prior to CPAP titration, consented to mask randomisation (see Table 1 and Fig. 1) from 26 September 2011 to 16 July 2013. Out of the 21 subjects randomised, 14 completed the study. Each subject demonstrated OSA based on the American Academy of Sleep Medicine (AASM) definition of an AHI of P16/h on an allnight sleep recording. All subjects were evaluated and sleep recordings were performed at the Weill Cornell Center for Sleep Medicine. All subjects were CPAP naïve and had no previous history of airway surgeries. 2.2. Polysomnogram Previously described standard techniques were employed to diagnose OSA on all-night sleep recordings using Grass Technologies TwinÒ digital polysomnographs (Natus Neurology Incorporated-Warwick, RI) with an integrated Nonin clip oximetry (see Tables 2 and 3 for polysomnogram (PSG) measures from baseline and CPAP titration studies). Standard polysomnograph montage and digital filter settings recommended by the AASM were employed [28]. Respiratory effort was measured by SleepsenseÒ inductive plethysmography belts (S.L.P. Inc.- Elgin, IL) placed around the rib cage and abdomen. Airflow was determined by the Pro-Tech PTAF liteÒ pressure transducer (Phillips-RespironicsAndover, MA) on the baseline study. The nasal cannula for the pressure transducer was placed at the level of the upper lip in
midline position. A continuous electrocardiogram recorded heart rate and rhythm. During the titration study, participants were randomly assigned to either ResMed VPAP™ Tx (n = 7) or RespironicsÒ OmniLab Advanced (n = 7) PAP machines (Andover, MA) using a CPAP setting. Airflow and mask leak were recorded from these PAP machines. Respiratory events were classified according to AASM criteria: an apnoea was defined as a decrease in peak nasal pressure of >90% of baseline, lasting at least 10 s. Hypopnea was defined by a decrease of >30% of the baseline nasal pressure, lasting at least 10 s and associated with a P4% drop in the oxyhaemoglobin saturation. 2.3. Masks Two models of ResMed masks, Mirage™ FX and Quattro™ FX (San Diego, CA), were randomly assigned to the subjects on the night of titration. Mirage™ FX is a nasal mask and Quattro™ FX is an oronasal mask that covers both the nose and mouth. We chose these two masks because at the time of the study they were the most commonly used standard nasal and oronasal masks used in our laboratory. 2.4. Protocol Subjects were randomised to either the nasal or oronasal mask on the night of the CPAP titration study. A randomised envelope, which contained the name of the mask to be used on the study night, was placed by the recruiting physician in the subjects’ chart for the night-time titration study. Before starting the study, the night-time technician would open the sealed envelope that specified the mask style to use on the titration night. The entire set of randomised envelopes was created by author MRE at the beginning of the study (once the envelopes were created, they were shuffled to mix up the mask styles), and a set of envelopes was given to each subject recruiter before starting the study. During the titration study, the sleep technicians were instructed to increase the PAP in 1 cm of H2O increments until the AHI was 65/h, and they were required to wait for at least 10 min between pressure changes. Once completed, the study was scored by a registered sleep technician and was reviewed by a board-certified sleep specialist. The subjects were scored in the same manner as the rest of our clinical patients, and the scoring technicians were not made aware of the fact that these data were being used for a research study. Based on a review of the study, subjects were prescribed CPAP at the lowest pressure that reduced their AHI to 65/h with the mask used on the study night. Only one subject had a residual AHI of >5/h with treatment. This subject was in the nasal mask titration group and had a residual AHI with treatment of 5.5/ h. All subjects in the oronasal titration group had a residual AHI with treatment of 65/h on the CPAP titration night. After 3 weeks of CPAP with the first randomised mask, data were collected from the CPAP machine and the subject was given the other mask to use with CPAP for the next 3 weeks (if the nasal mask was given initially, the oronasal one was given later and vice versa). At the conclusion of the second 3-week study period, the subject was informed as to which mask reduced AHI the most based on the data collected from the CPAP machine. All machines used at-home collected AHI and leakage values daily. The machines used at home were the ResMed S9 Elite™ (n = 6) (San Diego, CA) and PhillipsRespironics REMstarÒ Pro (n = 8) (Andover, MA). Variability in insurance coverage and durable medical equipment contracts accounted for these differences in machine allocation. Furthermore, the machines used for in-laboratory titration differed from the at-home units, as the laboratory models were specifically designed for manual titration by a night-time sleep technician.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
3
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx Table 1 Demographic data. Subject inclusion status Completed study (N = 14)
Age Neck size (inches) BMI (kg/m2) Gender Women Men
Withdrew from study (N = 7)
Mean
SD
Min
Max
62 16 30
15 2 6
31 12 18
83 18 40
Count
3 11
Mean
SD
Min
Max
73 17 34
9 3 10
58 14 23
84 22 50
Count
4 3
Fig. 1. One subject was excluded due to treatment-induced central apnoeas with CPAP, and three subjects refused to complete the titration study. One subject was excluded because he/she was given the wrong mask (non-randomised) on the titration study. In the oronasal group, five subjects refused to use the mask during this study arm. Two subjects refused to use the nasal mask during the nasal arm of the study. All seven subjects withdrew voluntarily from the study because of mask discomfort. The demographic characteristics and baseline PSG data from these seven subjects did not differ from the 14 subjects who proceeded to study completion and data analysis (p < 0.05; a Bonferroni correction was used). Originally, an allocation ratio of 1:1 was planned, but due to the early stoppage of the study a ratio of 1.3:1 (oronasal to nasal) was achieved.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
4
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx
Table 2 Polysomnogram measures from the baseline study (n = 14).
Total sleep time (min) Sleep efficiency (%) Percentage of N1 Percentage of N2 Percentage of N3 Percentage of REM Mean SaO2 in non-REM Mean SaO2 in REM Lowest SaO2 Baseline AHI Baseline RDI
Mean
SD
339.14 70.19 23.84 63.16 1.68 11.39 93.67 92.86 81.86 36.45 38.89
64.43 12.66 12.81 11.74 3.58 5.45 2.00 3.74 5.84 14.51 14.25
Table 3 Polysomnogram measures from the CPAP titration study (with baseline AHI and RDI). Mask used for CPAP titration study (n = 14)
Total sleep time (min) Sleep efficiency Percentage of N1 sleep Percentage of N2 sleep Percentage of N3 sleep Percentage of REM sleep Mean SaO2 in REM sleep Mean SaO2 in non-REM sleep Lowest SaO2 Mask leak (lpm) Final AHI with optimal treatment Final RDI with optimal treatment Final CPAP
Nasal (n = 7)
Oronasal (n = 7)
Mean
SD
Mean
SD
332.64 76.84 9.43 69.66 3.39 17.57 92.23 92.46 88.57 8.57 1.61 3.80 7.42
92.09 12.40 6.26 8.09 3.46 5.90 4.17 3.47 4.04 6.21 1.86 2.37 2.44
346.79 76.89 16.09 58.53 8.74 16.66 96.10 95.57 93.43⁄ 17.21⁄ 0.77 2.83 9.29
86.74 21.58 12.22 13.52 10.33 10.48 1.47 1.29 2.07 12.46 1.20 1.71 4.15
Note: Values with a ‘⁄’ superscript are significantly different at p < 0.05 in the twosided test of equality for column means. Equal variance was not assumed. No significant differences were seen after Bonferroni correction.
3. Sample size We initially performed a power analysis based on an expected d = 0.75 (based on previous work) with a two-tailed a of 0.05 and a b of 0.20 with a power of 0.80, and determined that 30 subjects would be sufficient to show a significant difference in residual AHI with a paired t-test. However, an interim analysis of the data was performed because it was noted that all subjects using the oronasal mask had more respiratory events with this therapy. Due to the noted difference in mask efficacy, further patient recruitment was stopped. 4. Data analyses Data analyses were performed using SPSS 21 (IBM, Corp., Armonk, New York, USA). Data for residual AHI on CPAP were positively skewed. Therefore, a related-sample’s Wilcoxon Signed– Rank Test (two-tailed) was used. Due to the interim analysis, a correction was made to reduce the chance of type I error. Using tables provided by Fairbanks and Madsen [29], which were based on the Pocock method of correcting for type I error in sequential testing, we set a significance threshold of p < 0.0056 for the primary analysis (residual AHI). This adjusted p-value is based on two stages of testing with an initial a of 0.01. We chose to drop the a from 0.05 to 0.01 based on Pocock’s recommendation [30] that reducing the chance of type I error to 1% (and establishing a Pocock boundary) sufficiently reduces the risk of incorrectly rejecting the null hypothesis when unplanned testing is performed. Owing to the inability of some subjects to use the mask interfaces required by
the study, a per-protocol analysis was performed (see Fig. 1 for more information on subjects who discontinued the study). Comparisons of differences on polysomnographic measures are described in Table 3. In order to control the type I error for these additional tests, a Bonferroni correction was applied. 5. Results The results indicated that residual AHI with the oronasal mask was significantly higher (based on a p < 0.0056) than with the nasal mask (z = 3.296, p < 0.001). The residual AHI by quartile in the nasal group was: 25th = 1.025, 50th (median) = 2.25 and 75th = 4.875. The quartiles for residual AHI in the oronasal group were: 25th = 3.175, 50th (median) = 7.90 and 75th = 12.650. Graph 2 shows the residual AHI for each subject, with each mask style, by the mask used for the initial titration with CPAP. During oronasal mask treatment seven subjects had a residual AHI of >10/h, compared with only one subject during the nasal mask treatment. There was no significant difference between subjects who had a residual AHI of >10/h and those that did not have an increase of >10/h with the oronasal mask in terms of gender, BMI, neck size, baseline AHI or lowest SaO2 on baseline PSG. However, there was a trend towards significance in age. The subjects with a residual AHI >10/ h appeared to be older (M = 68, standard deviation (SD) = 12.12) versus (M = 55.71, SD = 16.64), t(6) = 1.577, p = 0.14. The standardised effect size index was d = 0.85. All 14 subjects had a higher residual AHI during treatment with the oronasal mask versus the nasal mask, when titrated initially with either the oronasal or nasal mask. No significant difference was found in average minutes of nightly CPAP usage (out of all days) between nasal and oronasal masks (M = 310.13, SD = 103.78) versus (M = 276.53, SD = 134.65), t(13) = 1.385, p = 0.188. There was no significant difference in the final AHI of the titration study between the two different models of PAP machines (ResMed VPAP™ vs. RespironicsÒ OmniLab Advanced) t(12) = 0.651, p = 0.53. Moreover, there was no significant difference in residual AHI between the two CPAP machine models (ResMed S9 Elite™ and Phillips-Respironics REMstarÒ Pro) used at home with either mask style (nasal: t(12) = 0.527, p = 0.61, oronasal: t(12) = 1.457, p = 0.19) (Fig. 2). 6. Discussion This study confirmed our hypothesis that switching between mask styles post titration can result in an increase in residual AHI with CPAP treatment. Importantly, when using an oronasal mask, 50% of the subjects had a residual AHI >10/h, even though all of these subjects were titrated to an AHI of <5/h in the laboratory. This difference may, in part, be due to differences in flow limitation measures used to calculate AHI with the CPAP machine, as compared with laboratory-determined AHI, which includes measures of oxygen desaturation and flow reduction. However, this alone does not completely explain the increase in residual AHI with the oronasal mask because only one subject had a residual AHI >10/h with nasal mask treatment. Additionally, our findings suggest that many patients who are initially titrated on a nasal mask will need a pressure increase to maintain effective treatment when switched to oronasal therapy. Our previous study, performed in the laboratory setting, showed that the average CPAP difference between oronasal and nasal masks (in patients with a very severe baseline AHI) was 6 cm of H2O [26]. In the post-titration, outpatient setting, CPAP may need to be empirically increased to account for a change due to an oronasal mask; however, a significant subset of patients may require a laboratory retitration to accurately determine their pressure requirement on oronasal therapy.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx
We considered titrating all the subjects initially with the nasal mask, and then switching them to the oronasal mask after a period of time on the nasal mask at home. However, we chose the current design because it more closely reflects what often happens in clinical practice. Our current design found that even when a patient is titrated initially with an oronasal mask, switching to a nasal mask reduces the residual AHI with treatment. This finding may be useful to some clinicians looking to reduce AHI without increasing CPAP in patients currently using a full face mask. Furthermore, our study design had the potential to demonstrate superiority for either mask type, not biasing a priori in favour of one mask type or the other. One theory for the difference in efficacy between oronasal and nasal masks is that the application of PAP simultaneously through the nasal and oral pharynx has different mechanical effects on the collapsible portion of the upper airway compared with exclusively oral or nasal pressure delivery. Kuna and Remmers [19] originally speculated that oronasal masks would not effectively treat OSA because the airway dynamics of pressure applied orally and nasally simultaneously causes a posterior force against the soft tissues in the upper airway that would prevent the opening of the airway. Alternatively, the difference in efficacy between these two mask styles may be due to the posterior force exerted by the lower portion of the oronasal mask, which rests against the mandible and may force the jaw into the upper airway. This additional source of airway restriction may need to be overcome during treatment by increased PAP. Of note, mask leakage was greater in the oronasal mask compared with the nasal mask (see Table 3). However, in our previous investigation [26], mask leakage was not significantly different between the nasal and oronasal mask used, yet
5
significantly higher pressures were required to treat sleep-disordered breathing. Therefore, we do not believe that differences in mask leakage account for the results in this study. Another difference we found between mask styles in this study was the overall usage of CPAP at home. Subjects used CPAP with the nasal mask an average of 34 min more than with the oronasal mask. Although not significantly different (p = 0.188), this suggests that subjects were able to tolerate the nasal mask better than the oronasal mask. This view is bolstered by the fact that more subjects refused to complete the study protocol due to the oronasal mask compared with the nasal mask (see Fig. 1). Although the current study is appropriately powered to answer our main hypothesis, one limitation of this study is that a greater number of subjects would be required to identify the characteristics of subjects that respond poorly to the oronasal mask. Moreover, we only investigated standard nasal masks, and not nasal pillows in this study. Therefore, we cannot say with certainty that our current findings will apply to nasal pillows as well; however, our previous work found standard nasal and nasal pillow masks to have similar efficacy in treating sleep-disordered breathing [26]. As the laboratory AHI was calculated by visual analysis of respiratory data and the at-home AHI was calculated by machine, there may be differences in absolute AHI values. This does not negate, however, the significant increases in machine-generated AHI values when patients were switched to oronasal masks and treated with pressures determined previously to be effective for nasal mask therapy. Another limitation in our study was the use of two different manufacturer’s machines in assessing residual AHI at home. However, given the highly significant difference found between the residual AHI of the two mask styles, and the overall
Fig. 2. Each number along the X-axis indicates an individual subject. Seven subjects were titrated with the nasal mask (the first rectangle in the graph), used it for 3 weeks and then received the oronasal mask for 3 weeks. Seven subjects received the oronasal mask on the CPAP titration study (the second rectangle in the graph), used it for 3 weeks and then received the nasal mask for 3 weeks. The symbols on the graph represent the residual AHI with treatment for each mask style, as well as the baseline AHI from the initial polysomnogram. The diamond indicates the residual AHI with the nasal mask, the circle represents the residual events with the oronasal mask and the square represents the baseline AHI. The length of the line between the symbols illustrates the difference in AHI between conditions. The grey horizontal line indicates an AHI of 10/h. Of the subjects initially titrated with the nasal mask, 71% had a residual AHI >10/h with the oronasal mask. Only 29% of subjects titrated with an oronasal mask had a residual AHI >10/h while using this mask style at home.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
6
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx
similarity between CPAP machines, our results are unlikely to be due to differences in the home machines used. Moreover, because we used a within-subject design, each subject used only one make of machine at home, and all subjects had more residual respiratory events with the oronasal mask compared with the nasal mask style. In summary, care should be taken when switching patients’ post-CPAP titration from nasal to oronasal masks, as the residual AHI with treatment with the oronasal mask will be higher than that with the nasal mask. However, additional data are needed to determine why oronasal masks are not as effective as nasal-only masks in eliminating upper airway obstruction. Our group is currently working on new studies to answer this question. Conflict of Interest The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2014.01.011.
Acknowledgements We would like to recognise Dr. Charles P. Pollak who was an original collaborator on this work, an early innovator in the field of sleep medicine and a mentor to author MRE. R.I.P 1941-2012. No funding was provided for this study. References [1] Kushida CA, Littner MR, Hirshkowitz M, Morgenthaler TI, Alessi CA, Bailey D, et al. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep 2006;29(3):375–80. [2] Jenkinson C, Davies RJ, Mullins R, Stradling JR. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 1999;353(9170): 2100–5. [3] Sin DD, Mayers I, Man GC, Ghahary A, Pawluk L. Can continuous positive airway pressure therapy improve the general health status of patients with obstructive sleep apnea?: a clinical effectiveness study. Chest 2002;122(5): 1679–85. [4] Hui DS, Ko FW, Chan JK, To KW, Fok JP, Ngai JC, et al. Sleep-disordered breathing and continuous positive airway pressure compliance in a group of commercial bus drivers in Hong Kong. Respirology 2006;11(6):723–30. [5] Kushida CA, Nichols DA, Holmes TH, Quan SF, Walsh JK, Gottlieb DJ, et al. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep 2012;35(12):1593–602. [6] Javaheri S, Parker TJ, Liming JD, Corbett WS, Nishiyama H, Wexler L, et al. Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations. Circulation 1998;97(21): 2154–9. [7] Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med 1999;160(4):1101–6.
[8] Sanner BM, Konermann M, Sturm A, Muller HJ, Zidek W. Right ventricular dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J 1997;10(9):2079–83. [9] Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005;353(19):2034–41. [10] Thorpy M. Obstructive sleep apnea syndrome is a risk factor for stroke. Curr Neurol Neurosci Rep 2006;6(2):147–8. [11] Kessler R, Chaouat A, Weitzenblum E, Oswald M, Ehrhart M, Apprill M, et al. Pulmonary hypertension in the obstructive sleep apnoea syndrome: prevalence, causes and therapeutic consequences. Eur Respir J 1996;9(4): 787–94. [12] Chaouat A, Weitzenblum E, Krieger J, Oswald M, Kessler R. Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients. Chest 1996;109(2):380–6. [13] Sanner BM, Doberauer C, Konermann M, Sturm A, Zidek W. Pulmonary hypertension in patients with obstructive sleep apnea syndrome. Arch Intern Med 1997;157(21):2483–7. [14] Pepperell JC, Davies RJ, Stradling JR. Systemic hypertension and obstructive sleep apnoea. Sleep Med Rev 2002;6(3):157–73. [15] Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342(19):1378–84. [16] Young T, Peppard P, Palta M, Hla KM, Finn L, Morgan B, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997;157(15):1746–52. [17] Nieto FJ, Peppard PE, Young T, Finn L, Hla KM, Farre R. Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study. Am J Respir Crit Care Med 2012;186(2):190–4. [18] Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O’Connor GT, et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med 2009;6(8):e1000132. [19] Kuna ST, Remmers JE. Neural and anatomic factors related to upper airway occlusion during sleep. Med Clin North Am 1985;69(6):1221–42. [20] Sanders MH, Kern NB, Stiller RA, Strollo Jr PJ, Martin TJ, Atwood Jr CW. CPAP therapy via oronasal mask for obstructive sleep apnea. Chest 1994;106(3):774–9. [21] Smith PL, Wise RA, Gold AR, Schwartz AR, Permutt S. Upper airway pressure– flow relationships in obstructive sleep apnea. J Appl Physiol 1988;64(2): 789–95. [22] Prosise GL, Berry RB. Oral-nasal continuous positive airway pressure as a treatment for obstructive sleep apnea. Chest 1994;106(1):180–6. [23] Beecroft J, Zanon S, Lukic D, Hanly P. Oral continuous positive airway pressure for sleep apnea: effectiveness, patient preference, and adherence. Chest 2003;124(6):2200–8. [24] Teo M, Amis T, Lee S, Falland K, Lambert S, Wheatley J. Equivalence of nasal and oronasal masks during initial CPAP titration for obstructive sleep apnea syndrome. Sleep 2011;34(7):951–5. [25] Bakker JP, Neill AM, Campbell AJ. Nasal versus oronasal continuous positive airway pressure masks for obstructive sleep apnea: a pilot investigation of pressure requirement, residual disease, and leak. Sleep & breathing = Schlaf & Atmung [Internet]; 2011 Jul 29. Available from:. [26] Ebben MR, Oyegbile T, Pollak CP. The efficacy of three different mask styles on a PAP titration night. Sleep Med 2012;13(6):645–9. [27] Borel JC, Tamisier R, Dias-Domingos S, Sapene M, Martin F, Stach B, et al. Type of mask may impact on continuous positive airway pressure adherence in Apneic patients. PLoS ONE 2013;8(5):e64382. [28] Iber C, American Academy of Sleep Medicine. The AASM manual for the scoring of sleep and associated events: rules, terminology, and technical specifications. Westchester, IL: American Academy of Sleep Medicine; 2007. [29] Fairbanks K, Madsen R. P values for tests using a repeated singificance test design. Biometrika 1982;69(1):69–74. [30] Pocock SJ. When (not) to stop a clinical trial for benefit. JAMA 2005;294(17): 2228–30.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
Contents lists available at ScienceDirect
Sleep Medicine journal homepage: www.elsevier.com/locate/sleep
Original Article
A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment q Matthew R. Ebben a,⇑, Mariya Narizhnaya a, Alan Z. Segal a, Daniel Barone a, Ana C. Krieger a,b a b
Department of Neurology, Center for Sleep Medicine, Weill Cornell Medical College, 425 East 61st Street, 5th Floor, New York, NY 10065, USA Department of Medicine, Center for Sleep Medicine, Weill Cornell Medical College, 425 East 61st Street, 5th Floor, New York, NY 10065, USA
a r t i c l e
i n f o
Article history: Received 1 November 2013 Received in revised form 17 January 2014 Accepted 20 January 2014 Available online xxxx Keywords: CPAP Full face mask Oronasal mask Nasal mask Obstructive sleep apnoea Hypopnoea Treatment
a b s t r a c t Introduction: It has been found that mask style can affect the amount of continuous positive airway pressure (CPAP) required to reduce an apnoea/hyponoea index (AHI) to <5/h on a titration study. However, it was not previously known whether switching from one CPAP mask style to another post titration could affect the residual AHI with CPAP. The purpose of this study was to investigate the differences in residual AHI with CPAP treatment between oronasal and nasal masks. Methods: Twenty-one subjects (age mean (M) = 62.9, body mass index (BMI) M = 29.6 kg/m2) were randomised (14 subjects completed the protocol) to undergo an in-laboratory CPAP titration with either a nasal mask or an oronasal mask. Subjects were then assigned this mask for 3 weeks of at-home CPAP use with the optimal treatment pressure determined on the laboratory study (CPAP M = 8.4 cm of H2O). At the end of this 3-week period, data were collected from the CPAP machine and the subject was given the other mask to use with the same CPAP settings for the next 3 weeks at home (if the nasal mask was given initially, the oronasal one was given later and vice versa). On completion of the second 3-week period, data on residual AHI were again collected and compared with the first 3-week period on CPAP. Results: A Wilcoxon Signed-Rank Test (two-tailed) revealed that residual AHI with CPAP treatment was significantly higher with the oronasal compared with the nasal mask (z = 3.296, p < 0.001). All 14 subjects had a higher residual AHI with the oronasal versus nasal mask, and 50% of the subjects had a residual AHI >10/h in the oronasal mask condition, even though all of these subjects were titrated to an AHI of <5/h in the laboratory. Conclusion: A higher residual AHI was seen in all patients with the use of an oronasal mask compared with a nasal mask. Switching to an oronasal mask post titration results in an increase in residual AHI with CPAP treatment, and pressure adjustment may be warranted. Ó 2014 Elsevier B.V. All rights reserved.
1. Introduction Positive airway pressure (PAP) continues to be the most effective treatment for obstructive sleep apnoea (OSA) [1]. A number of studies have shown the benefits of PAP treatment on measures of daytime function for patients treated for OSA [2–5]. Untreated OSA has been associated with adverse medical conditions including congestive heart failure [6–8], stroke [9,10], pulmonary [11–13] and systemic hypertension [14–16], cancer [17] and increased mortality [18]. PAP therapy consists of a blower unit
q
Registered on Clinicaltrials.gov: protocol #1108011845.
⇑ Corresponding author. Tel.: +1 (646) 962 9313; fax: +1 (646) 962 0455. E-mail addresses: [email protected] (M.R. Ebben), man2019@med. cornell.edu (M. Narizhnaya), [email protected] (A.Z. Segal), dab9129@ med.cornell.edu (D. Barone), [email protected] (A.C. Krieger).
(a medical quality air compressor) connected by a hose to a mask sealed to the patient’s face in order to pressurise the upper airway. The four primary categories of masks are: oral (covers only the mouth), nasal (covers only the nose), nasal pillows (seals at the nares), and oronasal (covers both the nose and mouth). The fact that continuous positive airway pressure (CPAP), when used, is highly effective in the majority of patients with OSA may be the reason why few studies have investigated the differences in efficacy between different types of equipment. However, since the initial conception of CPAP, some researchers have questioned whether oronasal masks could be used to successfully pressurise the upper airway [19]. The first small-scale studies investigating this issue showed conflicting results, likely due to the differences in study design [20–22]. The previous studies that found oronasal interfaces to be effective in treating sleep-disordered breathing utilised subjects with nasal obstruction [20,22]. Moreover, one
http://dx.doi.org/10.1016/j.sleep.2014.01.011 1389-9457/Ó 2014 Elsevier B.V. All rights reserved.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
2
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx
study investigating an oral-only mask also found that this mask style effectively treated sleep apnoea [23]. In contrast, a study that did not focus on an oral-only method of pressure delivery found the oronasal mask to be ineffective in eliminating airway obstruction [21]. More recently, Teo et al. [24] conducted a study showing that when oronasal versus nasal masks are compared with the use of auto-titrating CPAP, the use of the oronasal mask resulted in a significantly higher apnoea/hyponoea index (AHI) compared with that of the nasal mask, which suggests that mask style may result in an inadequate auto-titration. A similar result was also found by Bakker et al. [25]; however, in this study, although a significant difference was found in residual AHI between mask styles, residual events continued to be within the proper treatment range with all tested masks. Alternatively, our group [26] found that when patients are manually titrated on CPAP, the oronasal mask resulted in significantly higher pressures for patients with moderate to severe OSA compared with standard nasal and nasal pillow masks. This finding was confirmed by a large-scale correlational study that was recently published [27]. Regardless of these findings, it is common clinical practice to switch between mask styles without making adjustments to the level of PAP. We hypothesised that switching between mask styles, post CPAP titration, would result in a change in residual respiratory events, and we designed a randomised prospective crossover study to test this hypothesis. The goal of the current study was to investigate if switching from an oronasal to a nasal mask or vice versa post titration will result in a change in residual respiratory events with CPAP treatment. 2. Methods The Institutional Review Board at Weill Cornell Medical College granted approval for this study (approval #1108011845). Informed consent was obtained for each participant in this study. 2.1. Subjects A total of 21 subjects that included men (n = 14) and women (n = 7) with moderate and severe OSA, who presented for office follow-up prior to CPAP titration, consented to mask randomisation (see Table 1 and Fig. 1) from 26 September 2011 to 16 July 2013. Out of the 21 subjects randomised, 14 completed the study. Each subject demonstrated OSA based on the American Academy of Sleep Medicine (AASM) definition of an AHI of P16/h on an allnight sleep recording. All subjects were evaluated and sleep recordings were performed at the Weill Cornell Center for Sleep Medicine. All subjects were CPAP naïve and had no previous history of airway surgeries. 2.2. Polysomnogram Previously described standard techniques were employed to diagnose OSA on all-night sleep recordings using Grass Technologies TwinÒ digital polysomnographs (Natus Neurology Incorporated-Warwick, RI) with an integrated Nonin clip oximetry (see Tables 2 and 3 for polysomnogram (PSG) measures from baseline and CPAP titration studies). Standard polysomnograph montage and digital filter settings recommended by the AASM were employed [28]. Respiratory effort was measured by SleepsenseÒ inductive plethysmography belts (S.L.P. Inc.- Elgin, IL) placed around the rib cage and abdomen. Airflow was determined by the Pro-Tech PTAF liteÒ pressure transducer (Phillips-RespironicsAndover, MA) on the baseline study. The nasal cannula for the pressure transducer was placed at the level of the upper lip in
midline position. A continuous electrocardiogram recorded heart rate and rhythm. During the titration study, participants were randomly assigned to either ResMed VPAP™ Tx (n = 7) or RespironicsÒ OmniLab Advanced (n = 7) PAP machines (Andover, MA) using a CPAP setting. Airflow and mask leak were recorded from these PAP machines. Respiratory events were classified according to AASM criteria: an apnoea was defined as a decrease in peak nasal pressure of >90% of baseline, lasting at least 10 s. Hypopnea was defined by a decrease of >30% of the baseline nasal pressure, lasting at least 10 s and associated with a P4% drop in the oxyhaemoglobin saturation. 2.3. Masks Two models of ResMed masks, Mirage™ FX and Quattro™ FX (San Diego, CA), were randomly assigned to the subjects on the night of titration. Mirage™ FX is a nasal mask and Quattro™ FX is an oronasal mask that covers both the nose and mouth. We chose these two masks because at the time of the study they were the most commonly used standard nasal and oronasal masks used in our laboratory. 2.4. Protocol Subjects were randomised to either the nasal or oronasal mask on the night of the CPAP titration study. A randomised envelope, which contained the name of the mask to be used on the study night, was placed by the recruiting physician in the subjects’ chart for the night-time titration study. Before starting the study, the night-time technician would open the sealed envelope that specified the mask style to use on the titration night. The entire set of randomised envelopes was created by author MRE at the beginning of the study (once the envelopes were created, they were shuffled to mix up the mask styles), and a set of envelopes was given to each subject recruiter before starting the study. During the titration study, the sleep technicians were instructed to increase the PAP in 1 cm of H2O increments until the AHI was 65/h, and they were required to wait for at least 10 min between pressure changes. Once completed, the study was scored by a registered sleep technician and was reviewed by a board-certified sleep specialist. The subjects were scored in the same manner as the rest of our clinical patients, and the scoring technicians were not made aware of the fact that these data were being used for a research study. Based on a review of the study, subjects were prescribed CPAP at the lowest pressure that reduced their AHI to 65/h with the mask used on the study night. Only one subject had a residual AHI of >5/h with treatment. This subject was in the nasal mask titration group and had a residual AHI with treatment of 5.5/ h. All subjects in the oronasal titration group had a residual AHI with treatment of 65/h on the CPAP titration night. After 3 weeks of CPAP with the first randomised mask, data were collected from the CPAP machine and the subject was given the other mask to use with CPAP for the next 3 weeks (if the nasal mask was given initially, the oronasal one was given later and vice versa). At the conclusion of the second 3-week study period, the subject was informed as to which mask reduced AHI the most based on the data collected from the CPAP machine. All machines used at-home collected AHI and leakage values daily. The machines used at home were the ResMed S9 Elite™ (n = 6) (San Diego, CA) and PhillipsRespironics REMstarÒ Pro (n = 8) (Andover, MA). Variability in insurance coverage and durable medical equipment contracts accounted for these differences in machine allocation. Furthermore, the machines used for in-laboratory titration differed from the at-home units, as the laboratory models were specifically designed for manual titration by a night-time sleep technician.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
3
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx Table 1 Demographic data. Subject inclusion status Completed study (N = 14)
Age Neck size (inches) BMI (kg/m2) Gender Women Men
Withdrew from study (N = 7)
Mean
SD
Min
Max
62 16 30
15 2 6
31 12 18
83 18 40
Count
3 11
Mean
SD
Min
Max
73 17 34
9 3 10
58 14 23
84 22 50
Count
4 3
Fig. 1. One subject was excluded due to treatment-induced central apnoeas with CPAP, and three subjects refused to complete the titration study. One subject was excluded because he/she was given the wrong mask (non-randomised) on the titration study. In the oronasal group, five subjects refused to use the mask during this study arm. Two subjects refused to use the nasal mask during the nasal arm of the study. All seven subjects withdrew voluntarily from the study because of mask discomfort. The demographic characteristics and baseline PSG data from these seven subjects did not differ from the 14 subjects who proceeded to study completion and data analysis (p < 0.05; a Bonferroni correction was used). Originally, an allocation ratio of 1:1 was planned, but due to the early stoppage of the study a ratio of 1.3:1 (oronasal to nasal) was achieved.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
4
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx
Table 2 Polysomnogram measures from the baseline study (n = 14).
Total sleep time (min) Sleep efficiency (%) Percentage of N1 Percentage of N2 Percentage of N3 Percentage of REM Mean SaO2 in non-REM Mean SaO2 in REM Lowest SaO2 Baseline AHI Baseline RDI
Mean
SD
339.14 70.19 23.84 63.16 1.68 11.39 93.67 92.86 81.86 36.45 38.89
64.43 12.66 12.81 11.74 3.58 5.45 2.00 3.74 5.84 14.51 14.25
Table 3 Polysomnogram measures from the CPAP titration study (with baseline AHI and RDI). Mask used for CPAP titration study (n = 14)
Total sleep time (min) Sleep efficiency Percentage of N1 sleep Percentage of N2 sleep Percentage of N3 sleep Percentage of REM sleep Mean SaO2 in REM sleep Mean SaO2 in non-REM sleep Lowest SaO2 Mask leak (lpm) Final AHI with optimal treatment Final RDI with optimal treatment Final CPAP
Nasal (n = 7)
Oronasal (n = 7)
Mean
SD
Mean
SD
332.64 76.84 9.43 69.66 3.39 17.57 92.23 92.46 88.57 8.57 1.61 3.80 7.42
92.09 12.40 6.26 8.09 3.46 5.90 4.17 3.47 4.04 6.21 1.86 2.37 2.44
346.79 76.89 16.09 58.53 8.74 16.66 96.10 95.57 93.43⁄ 17.21⁄ 0.77 2.83 9.29
86.74 21.58 12.22 13.52 10.33 10.48 1.47 1.29 2.07 12.46 1.20 1.71 4.15
Note: Values with a ‘⁄’ superscript are significantly different at p < 0.05 in the twosided test of equality for column means. Equal variance was not assumed. No significant differences were seen after Bonferroni correction.
3. Sample size We initially performed a power analysis based on an expected d = 0.75 (based on previous work) with a two-tailed a of 0.05 and a b of 0.20 with a power of 0.80, and determined that 30 subjects would be sufficient to show a significant difference in residual AHI with a paired t-test. However, an interim analysis of the data was performed because it was noted that all subjects using the oronasal mask had more respiratory events with this therapy. Due to the noted difference in mask efficacy, further patient recruitment was stopped. 4. Data analyses Data analyses were performed using SPSS 21 (IBM, Corp., Armonk, New York, USA). Data for residual AHI on CPAP were positively skewed. Therefore, a related-sample’s Wilcoxon Signed– Rank Test (two-tailed) was used. Due to the interim analysis, a correction was made to reduce the chance of type I error. Using tables provided by Fairbanks and Madsen [29], which were based on the Pocock method of correcting for type I error in sequential testing, we set a significance threshold of p < 0.0056 for the primary analysis (residual AHI). This adjusted p-value is based on two stages of testing with an initial a of 0.01. We chose to drop the a from 0.05 to 0.01 based on Pocock’s recommendation [30] that reducing the chance of type I error to 1% (and establishing a Pocock boundary) sufficiently reduces the risk of incorrectly rejecting the null hypothesis when unplanned testing is performed. Owing to the inability of some subjects to use the mask interfaces required by
the study, a per-protocol analysis was performed (see Fig. 1 for more information on subjects who discontinued the study). Comparisons of differences on polysomnographic measures are described in Table 3. In order to control the type I error for these additional tests, a Bonferroni correction was applied. 5. Results The results indicated that residual AHI with the oronasal mask was significantly higher (based on a p < 0.0056) than with the nasal mask (z = 3.296, p < 0.001). The residual AHI by quartile in the nasal group was: 25th = 1.025, 50th (median) = 2.25 and 75th = 4.875. The quartiles for residual AHI in the oronasal group were: 25th = 3.175, 50th (median) = 7.90 and 75th = 12.650. Graph 2 shows the residual AHI for each subject, with each mask style, by the mask used for the initial titration with CPAP. During oronasal mask treatment seven subjects had a residual AHI of >10/h, compared with only one subject during the nasal mask treatment. There was no significant difference between subjects who had a residual AHI of >10/h and those that did not have an increase of >10/h with the oronasal mask in terms of gender, BMI, neck size, baseline AHI or lowest SaO2 on baseline PSG. However, there was a trend towards significance in age. The subjects with a residual AHI >10/ h appeared to be older (M = 68, standard deviation (SD) = 12.12) versus (M = 55.71, SD = 16.64), t(6) = 1.577, p = 0.14. The standardised effect size index was d = 0.85. All 14 subjects had a higher residual AHI during treatment with the oronasal mask versus the nasal mask, when titrated initially with either the oronasal or nasal mask. No significant difference was found in average minutes of nightly CPAP usage (out of all days) between nasal and oronasal masks (M = 310.13, SD = 103.78) versus (M = 276.53, SD = 134.65), t(13) = 1.385, p = 0.188. There was no significant difference in the final AHI of the titration study between the two different models of PAP machines (ResMed VPAP™ vs. RespironicsÒ OmniLab Advanced) t(12) = 0.651, p = 0.53. Moreover, there was no significant difference in residual AHI between the two CPAP machine models (ResMed S9 Elite™ and Phillips-Respironics REMstarÒ Pro) used at home with either mask style (nasal: t(12) = 0.527, p = 0.61, oronasal: t(12) = 1.457, p = 0.19) (Fig. 2). 6. Discussion This study confirmed our hypothesis that switching between mask styles post titration can result in an increase in residual AHI with CPAP treatment. Importantly, when using an oronasal mask, 50% of the subjects had a residual AHI >10/h, even though all of these subjects were titrated to an AHI of <5/h in the laboratory. This difference may, in part, be due to differences in flow limitation measures used to calculate AHI with the CPAP machine, as compared with laboratory-determined AHI, which includes measures of oxygen desaturation and flow reduction. However, this alone does not completely explain the increase in residual AHI with the oronasal mask because only one subject had a residual AHI >10/h with nasal mask treatment. Additionally, our findings suggest that many patients who are initially titrated on a nasal mask will need a pressure increase to maintain effective treatment when switched to oronasal therapy. Our previous study, performed in the laboratory setting, showed that the average CPAP difference between oronasal and nasal masks (in patients with a very severe baseline AHI) was 6 cm of H2O [26]. In the post-titration, outpatient setting, CPAP may need to be empirically increased to account for a change due to an oronasal mask; however, a significant subset of patients may require a laboratory retitration to accurately determine their pressure requirement on oronasal therapy.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx
We considered titrating all the subjects initially with the nasal mask, and then switching them to the oronasal mask after a period of time on the nasal mask at home. However, we chose the current design because it more closely reflects what often happens in clinical practice. Our current design found that even when a patient is titrated initially with an oronasal mask, switching to a nasal mask reduces the residual AHI with treatment. This finding may be useful to some clinicians looking to reduce AHI without increasing CPAP in patients currently using a full face mask. Furthermore, our study design had the potential to demonstrate superiority for either mask type, not biasing a priori in favour of one mask type or the other. One theory for the difference in efficacy between oronasal and nasal masks is that the application of PAP simultaneously through the nasal and oral pharynx has different mechanical effects on the collapsible portion of the upper airway compared with exclusively oral or nasal pressure delivery. Kuna and Remmers [19] originally speculated that oronasal masks would not effectively treat OSA because the airway dynamics of pressure applied orally and nasally simultaneously causes a posterior force against the soft tissues in the upper airway that would prevent the opening of the airway. Alternatively, the difference in efficacy between these two mask styles may be due to the posterior force exerted by the lower portion of the oronasal mask, which rests against the mandible and may force the jaw into the upper airway. This additional source of airway restriction may need to be overcome during treatment by increased PAP. Of note, mask leakage was greater in the oronasal mask compared with the nasal mask (see Table 3). However, in our previous investigation [26], mask leakage was not significantly different between the nasal and oronasal mask used, yet
5
significantly higher pressures were required to treat sleep-disordered breathing. Therefore, we do not believe that differences in mask leakage account for the results in this study. Another difference we found between mask styles in this study was the overall usage of CPAP at home. Subjects used CPAP with the nasal mask an average of 34 min more than with the oronasal mask. Although not significantly different (p = 0.188), this suggests that subjects were able to tolerate the nasal mask better than the oronasal mask. This view is bolstered by the fact that more subjects refused to complete the study protocol due to the oronasal mask compared with the nasal mask (see Fig. 1). Although the current study is appropriately powered to answer our main hypothesis, one limitation of this study is that a greater number of subjects would be required to identify the characteristics of subjects that respond poorly to the oronasal mask. Moreover, we only investigated standard nasal masks, and not nasal pillows in this study. Therefore, we cannot say with certainty that our current findings will apply to nasal pillows as well; however, our previous work found standard nasal and nasal pillow masks to have similar efficacy in treating sleep-disordered breathing [26]. As the laboratory AHI was calculated by visual analysis of respiratory data and the at-home AHI was calculated by machine, there may be differences in absolute AHI values. This does not negate, however, the significant increases in machine-generated AHI values when patients were switched to oronasal masks and treated with pressures determined previously to be effective for nasal mask therapy. Another limitation in our study was the use of two different manufacturer’s machines in assessing residual AHI at home. However, given the highly significant difference found between the residual AHI of the two mask styles, and the overall
Fig. 2. Each number along the X-axis indicates an individual subject. Seven subjects were titrated with the nasal mask (the first rectangle in the graph), used it for 3 weeks and then received the oronasal mask for 3 weeks. Seven subjects received the oronasal mask on the CPAP titration study (the second rectangle in the graph), used it for 3 weeks and then received the nasal mask for 3 weeks. The symbols on the graph represent the residual AHI with treatment for each mask style, as well as the baseline AHI from the initial polysomnogram. The diamond indicates the residual AHI with the nasal mask, the circle represents the residual events with the oronasal mask and the square represents the baseline AHI. The length of the line between the symbols illustrates the difference in AHI between conditions. The grey horizontal line indicates an AHI of 10/h. Of the subjects initially titrated with the nasal mask, 71% had a residual AHI >10/h with the oronasal mask. Only 29% of subjects titrated with an oronasal mask had a residual AHI >10/h while using this mask style at home.
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011
6
M.R. Ebben et al. / Sleep Medicine xxx (2014) xxx–xxx
similarity between CPAP machines, our results are unlikely to be due to differences in the home machines used. Moreover, because we used a within-subject design, each subject used only one make of machine at home, and all subjects had more residual respiratory events with the oronasal mask compared with the nasal mask style. In summary, care should be taken when switching patients’ post-CPAP titration from nasal to oronasal masks, as the residual AHI with treatment with the oronasal mask will be higher than that with the nasal mask. However, additional data are needed to determine why oronasal masks are not as effective as nasal-only masks in eliminating upper airway obstruction. Our group is currently working on new studies to answer this question. Conflict of Interest The ICMJE Uniform Disclosure Form for Potential Conflicts of Interest associated with this article can be viewed by clicking on the following link: http://dx.doi.org/10.1016/j.sleep.2014.01.011.
Acknowledgements We would like to recognise Dr. Charles P. Pollak who was an original collaborator on this work, an early innovator in the field of sleep medicine and a mentor to author MRE. R.I.P 1941-2012. No funding was provided for this study. References [1] Kushida CA, Littner MR, Hirshkowitz M, Morgenthaler TI, Alessi CA, Bailey D, et al. Practice parameters for the use of continuous and bilevel positive airway pressure devices to treat adult patients with sleep-related breathing disorders. Sleep 2006;29(3):375–80. [2] Jenkinson C, Davies RJ, Mullins R, Stradling JR. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomised prospective parallel trial. Lancet 1999;353(9170): 2100–5. [3] Sin DD, Mayers I, Man GC, Ghahary A, Pawluk L. Can continuous positive airway pressure therapy improve the general health status of patients with obstructive sleep apnea?: a clinical effectiveness study. Chest 2002;122(5): 1679–85. [4] Hui DS, Ko FW, Chan JK, To KW, Fok JP, Ngai JC, et al. Sleep-disordered breathing and continuous positive airway pressure compliance in a group of commercial bus drivers in Hong Kong. Respirology 2006;11(6):723–30. [5] Kushida CA, Nichols DA, Holmes TH, Quan SF, Walsh JK, Gottlieb DJ, et al. Effects of continuous positive airway pressure on neurocognitive function in obstructive sleep apnea patients: the Apnea Positive Pressure Long-term Efficacy Study (APPLES). Sleep 2012;35(12):1593–602. [6] Javaheri S, Parker TJ, Liming JD, Corbett WS, Nishiyama H, Wexler L, et al. Sleep apnea in 81 ambulatory male patients with stable heart failure. Types and their prevalences, consequences, and presentations. Circulation 1998;97(21): 2154–9. [7] Sin DD, Fitzgerald F, Parker JD, Newton G, Floras JS, Bradley TD. Risk factors for central and obstructive sleep apnea in 450 men and women with congestive heart failure. Am J Respir Crit Care Med 1999;160(4):1101–6.
[8] Sanner BM, Konermann M, Sturm A, Muller HJ, Zidek W. Right ventricular dysfunction in patients with obstructive sleep apnoea syndrome. Eur Respir J 1997;10(9):2079–83. [9] Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V. Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 2005;353(19):2034–41. [10] Thorpy M. Obstructive sleep apnea syndrome is a risk factor for stroke. Curr Neurol Neurosci Rep 2006;6(2):147–8. [11] Kessler R, Chaouat A, Weitzenblum E, Oswald M, Ehrhart M, Apprill M, et al. Pulmonary hypertension in the obstructive sleep apnoea syndrome: prevalence, causes and therapeutic consequences. Eur Respir J 1996;9(4): 787–94. [12] Chaouat A, Weitzenblum E, Krieger J, Oswald M, Kessler R. Pulmonary hemodynamics in the obstructive sleep apnea syndrome. Results in 220 consecutive patients. Chest 1996;109(2):380–6. [13] Sanner BM, Doberauer C, Konermann M, Sturm A, Zidek W. Pulmonary hypertension in patients with obstructive sleep apnea syndrome. Arch Intern Med 1997;157(21):2483–7. [14] Pepperell JC, Davies RJ, Stradling JR. Systemic hypertension and obstructive sleep apnoea. Sleep Med Rev 2002;6(3):157–73. [15] Peppard PE, Young T, Palta M, Skatrud J. Prospective study of the association between sleep-disordered breathing and hypertension. N Engl J Med 2000;342(19):1378–84. [16] Young T, Peppard P, Palta M, Hla KM, Finn L, Morgan B, et al. Population-based study of sleep-disordered breathing as a risk factor for hypertension. Arch Intern Med 1997;157(15):1746–52. [17] Nieto FJ, Peppard PE, Young T, Finn L, Hla KM, Farre R. Sleep-disordered breathing and cancer mortality: results from the Wisconsin Sleep Cohort Study. Am J Respir Crit Care Med 2012;186(2):190–4. [18] Punjabi NM, Caffo BS, Goodwin JL, Gottlieb DJ, Newman AB, O’Connor GT, et al. Sleep-disordered breathing and mortality: a prospective cohort study. PLoS Med 2009;6(8):e1000132. [19] Kuna ST, Remmers JE. Neural and anatomic factors related to upper airway occlusion during sleep. Med Clin North Am 1985;69(6):1221–42. [20] Sanders MH, Kern NB, Stiller RA, Strollo Jr PJ, Martin TJ, Atwood Jr CW. CPAP therapy via oronasal mask for obstructive sleep apnea. Chest 1994;106(3):774–9. [21] Smith PL, Wise RA, Gold AR, Schwartz AR, Permutt S. Upper airway pressure– flow relationships in obstructive sleep apnea. J Appl Physiol 1988;64(2): 789–95. [22] Prosise GL, Berry RB. Oral-nasal continuous positive airway pressure as a treatment for obstructive sleep apnea. Chest 1994;106(1):180–6. [23] Beecroft J, Zanon S, Lukic D, Hanly P. Oral continuous positive airway pressure for sleep apnea: effectiveness, patient preference, and adherence. Chest 2003;124(6):2200–8. [24] Teo M, Amis T, Lee S, Falland K, Lambert S, Wheatley J. Equivalence of nasal and oronasal masks during initial CPAP titration for obstructive sleep apnea syndrome. Sleep 2011;34(7):951–5. [25] Bakker JP, Neill AM, Campbell AJ. Nasal versus oronasal continuous positive airway pressure masks for obstructive sleep apnea: a pilot investigation of pressure requirement, residual disease, and leak. Sleep & breathing = Schlaf & Atmung [Internet]; 2011 Jul 29. Available from:
Please cite this article in press as: Ebben MR et al. A randomised controlled trial on the effect of mask choice on residual respiratory events with continuous positive airway pressure treatment. Sleep Med (2014), http://dx.doi.org/10.1016/j.sleep.2014.01.011