Nasal Continuous Positive Airway Pressure Treatment: Current Realities and Future

Transcription

1 Sleep, 19(9):S13I-S American Sleep Disorders Association and Sleep Research Society Nasal Continuous Positive Airway Pressure Treatment: Current Realities and Future *Michael Berthon-Jones, tsue Lawrence, :j:colin E. Sullivan and tron Grunstein *ResMed, North Ryde, Sydney, Australia; tcenter for Respiratory Failure and Sleep Disorders, Royal Prince Alfred Hospital, Sydney, Australia; and :t.department of Medicine, University of Sydney, Sydney, Australia Summary: Nasal continuous positive airway pressure (CPAP) is a highly effective treatment for obstructive sleep apnea syndrome. The apnea/hypopnea index (AHI) is reduced lo-fold, but the patient dropout rate is up to 30%, and usage is typically <5 hours per night. Titration, designed to make the best trade-off between effectiveness and side effects, is expensive. Autotitrating devices make this trade-off on a minute-by-minute basis, potentially reducing mean pressure delivery, reducing side effects, and increasing compliance. The aim of this study was to test the effectiveness of the AutoSet self-adjusting nasal CPAP system (ResMed, Sydney, Australia) in eliminating obstructive events and normalizing the arousal index. Forty-five subjects (41 males and 4 females with AHI) values of >0lhour were recruited, with written informed consent. Subjects slept for a diagnostic night, followed by a treatment night, in the laboratory, using the AutoSet system with full polysomnographic monitoring of respiratory and sleep variables. Arousals were scored using ASDA criteria. Hypopneas were scored when there was a 50% reduction in ventilation for > 10 seconds, associated with a 4% drop in oxygen saturation. For comparison, the ASDA arousal index in 16 normal subjects (without nasal CPAP) is provided. Results are given as mean::': standard error of the mean. AHI was reduced from 55 ::': 3 to 1.5 ::': 0.35 eventslhour (p < ). The arousal index was reduced from 65 ::': 3 to 18 ::': eventslhour (p < ), idcntical to the value in the 16 healthy normal subjects. There was a 158% ::': 1% increase in slow-wave sleep (p = 0.01) and a 186% ::': 7% increase in rapid eye movement sleep (p = 0.013). The AutoSet self-adjusting nasal CPAP system adequately treats obstructive sleep apnea syndrome on the first night under laboratory conditions. Key Words: Obstructive sleep apnea syndrome-nasal CPAP-Apnea/hypopnea index-autotitration. Nasal continuous positive airway pressure (CPAP) remains the treatment of choice for uncomplicated obstructive sleep apnea syndrome (OSAS). This paper reviews the effectiveness, compliance, and side effects of traditional fixed-pressure nasal CPAP treatment and discusses practical issues in the introduction of nasal CPAP therapy. Goals and possible uses of autotitrating devices are discussed. Principles of operation and clinical results using the ResMed AutoSet self-adjusting nasal CPAP system (Sydney, Australia) are presented as an example. Effectiveness of nasal CPAP therapy Nasal CPAP acutely reduces the apnea/hypopnea index (AHI) ten-fold (1-4). The obstructive AHI is typically reduced to zero, but central events often remain. Accepted for publication Iune Address correspondence and reprint requests to M. Berthon-Iones, ResMed, 8 Waterloo Road, North Ryde, Sydney 113, Australia. Over the next week, there is resolution of sleepiness, although this will return with even 1 night without CPAP therapy (5). Side effects in general are minor (6-8); they are related to the mask, the pressure itself, and to nasal drying. The most common side effect is discomfort from the mask. In 30% of patients, mouth leaks result in severe drying of the nasal mucosa, causing discomfort, congestion, rhinorrhea, and a large increase in nasal resistance (9,10). Treatment of these side effects is active humidification of the inspired air. Discomfort from the pressure itself can be in the form of difficulty exhaling, sore ribs, or air swallowing. Primary, as opposed to leak-induced, high nasal resistance should be treated medically or surgically as appropriate. CPAP therapy is extremely safe, and no serious events have occurred in patients with simple OSAS. Patients with coexisting brainstem cerebrovascular disease, cardiac failure, or acromegaly can have persistent central apneas on CPAp, and high-pressure CPAP itself induces iatrogenic central apneas, presumably via the S131

2 S13 M. BERTRON-JONES ET AL. Breuer-Hering mechanism (11). Patients with incipient or actual daytime respiratory failure from coexisting lung/chest wall disease show prolonged hypoventilation with hypoxemia and CO retention during sleep (1); this may be aggravated by high-pressure CPAP. Patients with coexisting severe cardiac failure and volume overload typically show increased ejection fraction on CPAp, but the reverse may occur in volumedepleted patients (13). Titration Titration is a trade-off between effectiveness and pressure-related side effects. The usual end-point is the abolition of obstructive apneas and hypopneas, and a normalization of the arousal index, while supine and in rapid eye movement (REM) sleep (14). Montserrat et a1. (15) demonstrated that it is possible to reach this end-point but that upper airway resistance can still be four times higher than normal. Residual high airway resistance can lead to repetitive arousals and insomnia (16). A further increase in pressure by cm H 0 normalizes resistance. Residual resistance can be avoided by increasing the pressure of CPAP until esophageal pressure swings are normalized or, alternatively, increasing pressure until the shape of the inspiratory flow-time curve is normalized (16-18). Compliance The dropout rate can be as high as 30% (6,19), with patients abandoning therapy during the first -4 weeks. Bilevel CPAP therapy appears to reduce the dropout rate (6). Concealed hour-meter recordings in those subjects continuing to use the device show a mean usage of 5 hours per day (6,19-1). There are few data on how to improve compliance, but we may speculate. Accurate mask fitting, with a daytime practice session on CPAP of 10 cm H 0, may be preferable to introducing CPAP to a hypoxic patient at 3:00 a.m. in a split-night study. Full-night titration to eliminate snoring and flattening of the inspiratory flow-time curve, proactive follow-up during the first weeks, early introduction of a humidifier, and correction of nasal pathology may all be of use. A ramp timer may enable the patient to drift off to sleep before the full pressure is reached. Obese patients and those requiring high pressure may find a bilevel nasal CPAP system more comfortable. Finally, in patients requiring higher pressures, an autosetting CPAP system may be of benefit. Autotitration The titration night is costly and labor intensive. Many strategies have been devised to avoid this expense, in- cluding prediction formulae (), split night studies (4), partner titration, and home stepwise titration. An alternative is to automate the titration process and determine a single pressure suitable for subsequent at-home fixedpressure treatment. This can potentially be done without polysomnography (e.g. in a general ward or clinic), in a semi-unattended or unattended manner (depending on the particular patient's general medical and psychological status), or even at home. This is essentially a laborsaving strategy, aimed at reducing the cost of the titration night. At home, autotitration can be performed over many nights (see below), so that questions such as "did the patient sleep in REM while supine" become irrelevant, and problems with mask leaks, compliance, etc., are automatically recorded. Patients requiring high or variable pressure can then go on to the long-term use of an autotitrating device. The device will automatically adjust to the patient's changing needs during the night, thereby reducing mean pressure delivery, but it is guaranteed to cover rare times of peak pressure requirement. Existing commercial devices use a variety of approaches, ranging from attempting to "break" an existing apnea by suddenly increasing the pressure, to responding to apneas and hypopneas after they have occurred, to preemptively preventing apneas and hypopneas by responding to indicators of upper airway instability. Some examples of results are shown in Table 1. The remainder of this paper will present the method of operation and clinical results achieved using the ResMed AutoSet system as a detailed example of what is possible. AutoSet clinical function The AutoSet system does not respond to apneas or hypopneas per se because it is counterproductive to increase pressure in response to central events with a wide-open airway. Instead, it is designed to respond to indicators of underlying obstruction (flow limitation and snoring). Figure 1 shows its response to some typical flow-time curves. Moderate to severe flattening will cause the CPAP to increase at 1.5 cm H 0 per minute. Therefore, if flattening were to continue unabated until the correct pressure was reached, the effective pressure would be achieved in less than 10 minutes. Because snoring indicates a more severe partial obstruction, it causes the pressure to rise by up to 1 cm H 0 per breath, depending on loudness. Therefore, if snoring were to continue unchanged until the correct pressure was reached, the effective CPAP would be achieved in less than one minute. The AutoSet system can distinguish apneas with an open versus a closed airway, and if desired, it can increase pressure in response to the latter. However, in most

3 NCPAP: REALITIES AND FUTURE S133 TABLE 1. Some autotitrating CPAP devices. Device Puritan Bennett MC+ Pierre Medical Morphee Plus DeVilbiss NCPAP 3 Respironics ResMed AutoSet ResMed AutoSet Reference (3) (4) (5) (6) (7) this study n Untreated AHI (eventslhour) ± ± ± Treated AHI (eventslhour) ± 0.3 not significantly different vs. manual titration 7.1 ± 0.9 Treated as % untreated ± 0.9 Puritan Bennett, Lenexa, KS; Pierre Medical, Verrieres Le Buisson, France; DeVilbiss, Somerset, PA; Respironics, Murrysville, PA; ResMed, Sydney, Australia. patients, the AutoSet system responds preemptively, so there are no closed airway apneas left to treat. Clinical trial of the AutoSet system Aim The aim of this trial was to determine whether the AutoSet system could adequately reduce the AHI and normalize the arousal index when used attended, on the first night of CPAP treatment. Subjects and methods Forty-five subjects (of whom four were female), with an untreated AHI of at least 0lhour, were recruited. Mean age was 54 years, and mean body mass index was 8 kg/m Informed consent was obtained, and the study was approved by the ethics committee of Royal Curvature 0.05 (raise pressure) ~ '\ / Curvature 0.15 (no action) '\ Fraction of Inspiratory Time Curvature 0.5 (drop pressure) FIG. 1. Software response to various flow-time curves (schematic). Inspiratory airflow is scaled so that mean inspiratory flow is one unit, and time is expressed as a fraction of inspiratory duration. The curvature index is a measure of the deviation from unit scaled flow over the middle 50% of inspiratory time (indicated schematically by shading). Left: a severely flattened curve typical of inadequate CPAP pressure (curvature index 0.05). The software responds by increasing the CPAP pressure at 0. cm H 0 per breath. Center: a breath showing slight flattening (curvature index 0.15). The CPAP pressure remains unchanged. Right: a typical awake breath (curvature index 0.5). The software assumes that this breath represents hyper-adequate CPAP pressure, and it reduces the flattening-induced component of the CPAP pressure exponentially to zero with a time constant of 0 minutes. Prince Alfred Hospital. Subjects slept for nights in the laboratory: a diagnostic night and an AutoSet treatment night, each with full polysomnographic monitoring of respiratory and sleep variables. Arousals were scored using the new ASDA criterion (9) [briefly, 3 seconds of alpha waves on the electroencephalogram (EEG)]. Hypopneas were scored when there was a 50% reduction in ventilation for more than 10 seconds, associated with a 4% drop in oxygen saturation. To determine a normal range for the arousal index, 16 unhabituated normal subjects were studied, sleeping under identical conditions but without CPAP. Results are reported as mean ± standard error of the mean (SEM) for diagnostic night, AutoSet night, and AutoSet night expressed as a percentage of diagnostic night. The statistical significance of the effect of treatment was calculated by repeated measures analysis of variance (ANOV A), following rank transform. The arousal index on the AutoSet system was compared with the arousal index in normal subjects using an unpaired t test. Results All 45 subjects showed a large improvement in AHI. Figure shows the number of respiratory disturbances per hour of sleep (AHI), both untreated (control night) and with nasal CPAP treatment (AutoSet). Figure 3 shows the arousal index on the diagnostic night and on the AutoSet night. The arousal index in 16 normal subjects is shown for comparison. The arousal index fell from a median value of 6 eventslhour untreated to 14 eventslhour on the treatment night (p < ). With two exceptions (due to intercurrent nocturnal myoclonus) the arousal index on the AutoSet system (18.1 ±.3 events/hour) was entirely comparable to that seen in normal subjects sleeping without nasal CPAp, but with otherwise identical conditions [18. ±.3, not significant (NS)]. There was an important and statistically significant increase in the percentage of slow-wave and REM sleep.

4 S Apnea-Hypopnealndex M. BERTRON-JONES ET AL. 10 o Arousal Index " c:: en --- c: > w 40 0 O~ ~r=~----~~-- Untreated AutoSet Normals FIG.. Apnea/hypopnea index on the diagnostic night and on the AutoSet night. Boxplots show median. interquartile range. and outliers. There was a large improvement in all subjects. Discussion These data demonstrate that the AHI using the AutoSet system is reduced to a satisfactory level, comparable with that reported in the literature using traditional fixed-pressure nasal CPAP therapy, and that the arousal index is normalized. Our finding of an arousal index of 18. eventslhour in normal subjects, using ASDA criteria, has been confirmed by Mathur and Douglas (8) in 55 normal subjects. They found a mean first night unhabituated ASDA arousal index of 1 eventslhour (8). Compliance after AutoSet titration Teschler et al. titrated an additional 0 subjects on the AutoSet system and confirmed the improvements in AHI, arousal indices, and sleep staging (7). They then restudied the subjects on fixed pressure CPAP therapy at the pressure that was exceeded only 5% of the night, after excluding any brief periods with high leak, and confirmed that the AHI, arousal index, and sleep staging improvements were maintained. Patients were sent home at the chosen fixed pressure. Compliance at 3 and 8 months following AutoSet system titration continued to be identical to that obtained in 100 control subjects 80 "-...c:: -- ~ 60 > 40 0 o O~ ~~ Untreated AutoSet Normals FIG. 3. American Sleep Disorders Association microarousal index on the diagnostic night and AutoSet night. Data from 16 normal subjects are shown for comparison. The microarousal index was normalized in all but two subjects. who had persistent arousals due to myoclonus. titrated manually, indicating that the AutoSet system can be used in place of manual titration. AutoSet system at home A small pilot study was performed using the AutoSet system at home. The aim of the study was to determine the within-night and day-to-day variability in titration pressure. Seven long-term CPAP users were switched to the AutoSet system for weeks. For any given night, the AutoSet titration pressure was calculated as the pressure that was exceeded only 5% of the night, as described above. The between-night, withinsubject standard deviation of the titration pressure was 0.75 cm H 0, indicating a modest night-to-night variability over weeks. Conversely, the median pressure was only 71 % ± 3% (mean ± SEM) of the AutoSet titration pressure and 57% ± 5% of the previously prescribed manual titration pressure. These results suggest that a home autotitrating device yields a worthwhile reduction in average pressure delivery. We speculate that this will lead to a worthwhile reduction in pressure-related side effects, particularly in subjects requiring high pressures for only part of the night.

5 NCPAP: REALITIES AND FUTURE Sl35 TABLE. Effect of AutoSet system on sleep and breathing ',. : ' AHI (events!hour) Median Obstructive AHI (events!hour) Median Microarousal index (events!hour) SWS (% time in bed) REM sleep (% time in bed) Untreated 55.5 ::': ::': ::': ::': ::': 1.0 AutoSet.3 ::': ::': ::': ::': ::': 1. n = 45. AHI, apnea/hypopnea index; SWS, slow-wave sleep; REM, rapid eye movement. Conclusions The aim of titration is to produce a good trade-off between side effects and elimination of respiratory events. Normalization of the shape of the inspiratory flow-time curve appears preferable to responding to apneas and hypopneas directly. The AutoSet self-adjusting nasal CP AP system uses this approach, and it produces excellent improvement in sleep and breathing, with a substantial reduction in mean pressure delivery. 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