OUTCOMES OF CPAP TREATMENT IN A SLEEP LABORATORY SPECIALIZED IN NEUROPSYCHIATRY

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1 JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY 2004, 55, Suppl 3, J. ANTCZAK 1,2, P. GEISLER 2, R. POPP 2 OUTCOMES OF CPAP TREATMENT IN A SLEEP LABORATORY SPECIALIZED IN NEUROPSYCHIATRY 1 Department of Respiratory Research, Medical Research Center, Polish Academy of Sciences, Warsaw, Poland and 2 Department of Psychiatry, Sleep Disorders Center, University of Regensburg, Regensburg, Germany The rapidly increasing number of sleep laboratories implicates their specialization into various fields of sleep medicine. In our sleep laboratory that specializes in neuropsychiatry, patients with the symptoms typical for the obstructive sleep apnea/hypopnea syndrome (OSAHS) were routinely redirected to a local respiratory clinic. Some patients, however, admitted to our center for other reasons revealed OSAHS in nocturnal polysomnography. The purpose of this retrospective study was to assess the outcome of CPAP in treating the sleepiness in this group of patients. Our material consisted of 36 patients who started CPAP therapy due to OSAHS diagnosed in our laboratory in the year 2000 and who came for a routine checkup in The sleepiness was assessed by using the Epworth Sleepiness Scale (ESS). After CPAP, the mean group ESS score decreased from 10.9 ±4.4 to 8.5 ±4.3 points (P<0.01). Some patients showed, however, persisting excessive sleepiness (PTS) after CPAP, defined as ESS 12. We overviewed the documentation of those patients in search for the possible causes of PTS. We identified the following causes: narcolepsy - 1 patient, insufficient CPAP pressure - 1 patient, low CPAP compliance, fewer than 2 h/night, - 2 patients. In 5 other patients we found CPAP compliance to be between 2.0 and 4.5 h/night, which is less likely to be the cause of PTS. In 1 patient no cause was identified. Our patients showed relatively mild sleepiness before CPAP and only a slight improvement under CPAP. The CPAP noncompliance seems the most prevailing reason for CPAP failure, but in some patients the cause of PTS could not be unraveled by using standard diagnostic tools and some additional measures are to be employed to resolve the issue. Key words: apnea/hypopnea syndrome, CPAP therapy, persistent excessive sleepiness

2 16 INTRODUCTION The pathophysiology of the sleep apnea/hypopnea syndrome (OSAHS) encloses repetitive occlusions of upper airways leading to frequent hypoxemic episodes and arousals from sleep (1). As a consequence, a variety of symptoms occur, of which the excessive daytime sleepiness is the most predominant (2). Other symptoms include cognitive decrements, mood disorders, morning headaches and nycturia (2). Moreover, OSAHS is a risk factor for high blood pressure (3) and potentially for cerebrovascular diseases (4). The excessive daytime sleepiness due to OSAHS results in considerable social, professional and martial problems (2) and in an increase of the risk of vehicle accidents (5). For nearly twenty years, the continuous positive airway pressure (CPAP) is the treatment of choice in OSAHS, improving the breathing in sleep in 95% patients (6) and daytime symptoms in the majority of OSAHS patients (7). Most studies on CPAP effectiveness have focused on its ability of reverting excessive daytime sleepiness (8, 9, 10). The range of reported results stretches from a slight improvement (9) to full normalization of the daytime sleepiness after CPAP (10). A variety of correlates of good CPAP effectiveness have been elucidated, such as disease severity before CPAP (11), therapy compliance or the presence of additional conditions (obesity, periodic limb movement in sleep, or narcolepsylike symptoms) (12). However, no data seem to exist concerning the CPAP effectiveness among OSAHS patients treated in sleep laboratories of different specializations. Such specializations occur in recent years, as the number of sleep laboratories has steadily been increasing (meanwhile in Germany there are 282 sleep centers registered). OSAHS patients are admitted to sleep centers specialized in respiratory medicine to start CPAP treatment. Accordingly, in our neuropsychiatry sleep center, ambulatory patients presenting with marked OSAHS symptoms (snoring, apneas, excessive daytime sleepiness) or with positive apnea screening were most often redirected to the sleep laboratory at a local respiratory medicine clinic. A possible engagement of CPAP therapy in our center takes place in patients admitted for stationary care due to any unclear sleep symptoms (most often daytime sleepiness), in whom nocturnal polysomnography revealed an abnormal number of apneas and/or hypopneas with disordered sleep architecture. This procedure led to generation of a specific population of CPAP patients characterized by poor and atypical daytime OSAHS symptomatic. In the present study, we wished to characterize this population of our CPAP patients and to evaluate the effectiveness of CPAP in counteracting daytime sleepiness. Patients MATERIAL AND METHODS We retrospectively overviewed the documentations of all patients who had started their CPAP in our center in 2000 and who came for routine checkups one year later. Only were the patients

3 17 included who were treated with CPAP due to the obstructive sleep apnea/hypopnea syndrome, as classified on the basis of accepted international standards (ICD10 - G47.3; ICSD ), and not due to other-sleep related respiratory disorders. Evaluation of CPAP effects on sleepiness The daytime sleepiness was assessed by using the Epworth Sleepiness Scale (ESS) (13). The ESS score was obtained twice from the documentation of every patient; the first time directly before the start of CPAP and then at a follow-up visit after one year. For the evaluation of the CPAP failure rate we considered the excessive sleepiness as the ESS score 12. Characteristic of the CPAP patient population To characterize our group the following parameters were obtained from the documentation of each patient: Age, sex Body mass index (BMI) Apnea/Hypopnea index (AHI) before CPAP CPAP pressure Additionally, in subjects with documented persistent daytime sleepiness we overviewed the whole documentation looking for the probable cause of CPAP failure. Of interest, there were such conditions as: too low therapy usage (CPAP noncompliance), persistence of apneas and/or hypopneas at the follow-up due to insufficient CPAP pressure, and comorbidity with a potential impact on sleepiness. Statistical analysis For the whole group, the mean ESS scores and the number of subjects with ESS 12 before and after CPAP were compared. Additionally, we compared the group characteristics parameters between the patients with normalized sleepiness after CPAP and those with persistent daytime sleepiness. Due to a limited number of subjects, non-parametric tests (Wlicoxon Rank test, Mann Whitney U test, χ 2 test) were used for a statistical analysis. RESULTS Group characteristics Overall, we identified 36 patients (F/M - 5/31) diagnosed with OSAHS in our center in 2000, who started the CPAP therapy and came for a checkup one year later. The mean age was 53.0 ±10.6 yr and the mean BMI was 31.8 ±5.2 kg/m 2. The data concerning disease severity showed the mean AHI of 34.9 ±24.5 apneas/hypopneas per hour of sleep. In 5 of the subjects the AHI could not be obtained due to technical reasons. The mean CPAP pressure was 8.0 ±1.7 mbar. Three patients used a bi-level CPAP and their pressure was averaged for the analysis. CPAP effects on the daytime sleepiness The mean ESS score decreased significantly after one year of CPAP from 10.9 ±4.4 to 8.5 ±4.3 points (P<0.01). The patients with initially excessive sleepiness

4 18 20 ESS points Before CPAP After CPAP Fig. 1. Changes in ESS scores in OSAHS patients in the neuropsychiatric sleep center (BKR Regensburg, Germany) after one year of CPAP (n=36). (18 subjects) improved their ESS scores after CPAP from 14.4 ±2.4 to 9.3 ±4.3 points (P<0.001), whereas another18 patients with the initial ESS<12 remained nearly at the some level of sleepiness (7.4 ±2.7 vs. 7.7 ±4.3 points; ns). The rate of excessive daytime sleepiness decreased from 18 out of the 36 subjects (50%) before CPAP to 10 subjects (28%) after CPAP, but this decrease did not reach the statistical significance (P=0.06). Comparison of the parameters describing the characteristics of the CPAPnormalized patients and the patients with persistent excessive sleepiness revealed no significant differences between the two groups. The results of this analysis are shown in Table 1. Causes of CPAP failure (persistence of excessive sleepiness) The evaluation of the documentations revealed narcolepsy and an insufficient (too low) CPAP pressure in one patient each, and CPAP noncompliance (usage Table 1. Characteristics of CPAP-normalized patients and patients with persistent excessive sleepiness. PARAMETERS ESS<12 ESS 12 P n F/M 5/21 0/10 ns Age 55.4 ± ±12.5 ns BMI 32.3 ± ± 3.4 ns AHI before CPAP 37.8 ± ±18.6 ns CPAP pressure 7.9 ± ± 1.6 ns

5 19 Table 2. Examples of sleepiness level before and after CPAP in different studies with OSAHS patients. The present study is marked in bold. Before CPAP After CPAP Montserrat et al (16) 16 7 Henke et al (17) 16 8 Kingshott et al (18) 13 6 Engleman et al (19) 13 8 Engleman et al (20) 12 6 Monasterio et al (9) Antczak et al Redline et al (21) 10 9 rate under 2h/night) in two patients, as the probable causes of persistent excessive sleepiness. In further five patients we found CPAP usage rate at a level between 2 and 4.5 h/night, which corresponds to the minimum sufficient compliance given by a variety of literature reports (14, 15). In these patients we considered the noncompliance as the possible cause of persistent excessive sleepiness. In one another patient we could not find any cause of CPAP failure in improving the ESS score. DISCUSSION The results of our study indicate a relatively high level of sleepiness after CPAP therapy in OSAHS patients treated in a sleep laboratory of a neuropsychiatric profile. The majority of comparable studies revealed a lower average ESS after CPAP and there are only few reports of a higher ESS after CPAP than that found in our study (see Table 2). The rate of persistent daytime sleepiness seems to be relatively high as well, although we found only one study dealing with this topic (12). That study reported excessive sleepiness and tiredness after CPAP in only about 5% of treated patients, which is considerably less in comparison with the 28% in our study, even if the methodological differences in the assessing of daytime sleepiness are taken into account (12). Moreover, our patients showed a remarkable mild level of daytime sleepiness before CPAP. To the best of our knowledge, there is but one study showing a lower ESS score before CPAP among OSAHS patients than that found in the present study (see Table 2). This finding possibly supports the notion that the specialization of our sleep laboratory led to generation of a patient population with atypical sleep apnea, in which sleepiness, as the main symptom of OSAHS, was only mildly manifested. Table 2 also indicates that the initial mild sleepiness may be associated with a limited improvement after CPAP. The three out of eight

6 20 studies with the highest ESS score after CPAP also showed the lowest level of sleepiness before therapy. From the causes of persistent daytime sleepiness under CPAP, the therapy noncompliance seems the most prevailing and may have the potential impact on the general therapy outcome. The noncompliance can correspond to the limited decrease of sleepiness after therapy, as has been shown in a previous study (22). However, it should be considered that there is a variety of proposed minimal sufficient CPAP usage rates, ranging from 2.0 to 4.5 hours per night (22, 23). Thus, the impact of noncompliance on our CPAP outcome remains at this point disputable and requires an additional investigation. The most suitable one would be a next routine follow-up under improved compliance, which, however, according to the clinical experience might in some cases be hardly achievable. Other causes of CPAP failure consisted of narcolepsy and insufficient (too low) CPAP pressure. Both of these reasons have been mentioned previously (12). The number of our subjects was too limited to be able to state conclusively whether the influence of these two other reasons on therapy outcome in our study differed from that noted in previous studies. There was one patient in our group who did not present any condition attributable to his abnormal ESS score after CPAP. We searched the literature for the proposed causes of persistent daytime sleepiness, which could not be evaluated with our routine diagnostic tools that included nocturnal polysomnography with tibial muscle EMG, test of vigilance according to Quatember-Maly, physical interview with questioning about sleep hygiene, physical examination, wide-spectral blood laboratory examination, and the ESS. We found two other causes: persistently increased resistance of upper airways (22) and the irreversible brain damage due to nocturnal hypoxemia before the beginning of therapy (23). Thus, the necessity appears to extend our diagnostic procedures in certain cases of CPAP failure. Such additional procedures might consist of the measurement of esophageal pressure or oscillatory impedance and of positron emission tomography, but to set firm diagnostic standards in the case of unclear CPAP failures further research is required. Apart from some discrepancies in our results in comparison with other reports, as outlined above, our patients could be considered typical for OSAHS. The middle age of the patients lies within the known time span of the highest morbidity (24). The gender distribution is compatible with the data from other laboratories (11). The mean BMI and AHI are not unusual and are placed in the middle range of obesity and disease severity level seen in different sleep centers (11). We also compared these parameters (age, sex, BMI, CPAP pressure, and AHI) between the subgroup of patients with successfully normalized ESS and that in which sleepiness persisted. As none of the parameters showed a significant difference between the two subgroups, it is assumed that these parameters could not appreciably account for the persistence of daytime sleepiness. However, a greater number of study subjects would be required to settle this issue.

7 In conclusion, CPAP patients in our neuropsychiatric sleep center were characterized by a high level of subjective sleepiness and a high rate of persistent excessive sleepiness after long (one-year) treatment period. Moreover, in comparison with other studies the initial sleepiness was not severe. These results suggest that the sleep apnea patients treated in a sleep laboratory specialized in neuropsychiatry compose a specific OSAHS population, in which CPAP treatment has limited effectiveness. Using usual diagnostic tools, some of the reasons for CPAP failure can be elucidated, but a full understanding of the underlying mechanisms, which would improve therapy effectiveness, requires extended diagnostic procedures. Acknowledgments: This is a retrospective part of a bigger study that was subject to review and approval of the Ethics Committee of the Medical Faculty of Regensburg University (permit No. 02/147) in Regensburg, Germany. Preparation of this work for publication was supported by the statutory budget of the Polish Academy of Sciences Medical Research Center (Theme No. 1). 21 REFERENCES 1. Sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. The Report of an American Academy of Sleep Medicine Task Force. Sleep 1999; 22: Guilleminault C. Clinical features and evaluation of obstructive sleep apnea. In Principles and practice of sleep medicine, M H Kryger, T Roth, WC Dement (eds). Philadelphia, Saunders Company, 1994: Sharabi Y, Dagan Y, Grossman E. Sleep apnea as a risk factor for hypertension. Curr Opin Nephrol Hypertens 2004; 13: Diaz J, Sempere AP. Cerebral ischemia: new risk factors. Cerebrovasc Dis 2004; 17(Suppl 1): Findley LJ, Unverzagt ME, Suratt PM. Automobile accidents involving patients with obstructive sleep apnea. Am Rev Respir Dis 1988; 138: Becker M, Schneider H, Peter JH, von Wichert P. Die nasale Ventilation in der Therapie der SBAS. In Schlaf-Atmung-Kreislauf, JH Peter, T Penzel, W Cassel, P von Wichert (eds). Berlin, Springer Verlag, 2003: Lamphere J, Roehrs T, Wittig R, Zorick F, Conway WA, Roth T. Recovery of alertness after CPAP in apnea. Chest 1989; 96: Hardinge FM, Pitson DJ, Stradling JR. Use of the Epworth Sleepiness Scale to demonstrate response to treatment with nasal continuous positive airways pressure in patients with obstructive sleep apnoea. Respir Med 1995; 89: Monasterio C, Vidal S, Duran J et al. Effectiveness of continuous positive airway pressure in mild sleep apnea-hypopnea syndrome. Am J Respir Crit Care Med 2001; 164: Wittig R, Zorick F, Conway W, Ward J, Roth T. Normalization of the MSLT after six weeks of CPAP for sleep apnea syndrome. Sleep Res 1986; 15: Patel SR, White DP, Malhotra A, Stanchina ML, Ayas NT. Continuous positive airway pressure therapy for treating sleepiness in a diverse population with obstructive sleep apnea: results of a meta-analysis. Arch Intern Med 2003; 163:

8 Guilleminault C, Philip P. Tiredness and somnolence despite initial treatment of obstructive sleep apnea syndrome (what to do when an OSAS patient stays hypersomnolent despite treatment). Sleep 1996; 19(Suppl 9): S117-S Johns MW. A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 1991; 14: Sin DD, Mayers I, Man GC, Pawluk L. Long-term compliance rates to continuous positive airway pressure in obstructive sleep apnea: a population-based study. Chest 2002; 121: McArdle N, Devereux G, Heidarnejad H, Engleman HM, Mackay TW, Douglas NJ. Long-term use of CPAP therapy for sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1999; 159: Montserrat JM, Ferrer M, Hernandez L et al. Effectiveness of CPAP treatment in daytime function in sleep apnea syndrome: a randomized controlled study with an optimized placebo. Am J Respir Crit Care Med 2001; 164: Henke KG, Grady JJ, Kuna ST. Effect of nasal continuous positive airway pressure on neuropsychological function in sleep apnea-hypopnea syndrome. A randomized, placebocontrolled trial. Am J Respir Crit Care Med 2001; 163: Kingshott RN, Vennelle M, Hoy CJ, Engleman HM, Deary IJ, Douglas NJ. Predictors of improvements in daytime function outcomes with CPAP therapy. Am J Respir Crit Care Med 2000; 161: Engleman HM, Kingshott RN, Wraith PK, Mackay TW, Deary IJ, Douglas NJ. Randomized placebo-controlled crossover trial of continuous positive airway pressure for mild sleep apnea/hypopnea syndrome. Am J Respir Crit Care Med 1999; 159: Engleman HM, Martin SE, Kingshott RN, Mackay TW, Deary IJ Douglas NJ. Randomised placebo controlled trial of daytime function after continuous positive airway pressure (CPAP) therapy for the sleep apnoea/hypopnoea syndrome. Thorax 1998; 53: Redline S, Adams N, Strauss ME, Roebuck T, Winters M, Rosenberg C. Improvement of mild sleep-disordered breathing with CPAP compared with conservative therapy. Am J Respir Crit Care Med 1998; 157: Guilleminault C, Stoohs R, Clerk A, Simmons J, Labanowski M. From obstructive sleep apnea syndrome to upper airway resistance syndrome: consistency of daytime sleepiness. Sleep 1992; 15: S13-S Morisson F, Decary A, Petit D, Lavigne G, Malo J, Montplaisir J. Daytime sleepiness and EEG spectral analysis in apneic patients before and after treatment with continuous positive airway pressure. Chest 2001; 119: Malhotra A, White DP. Obstructive sleep apnoea. Lancet 2002; 360: Author s address: J. Antczak, Department of Respiratory Research, Medical Research Center, Polish Academy of Sciences, 5 Pawiñskiego St., PL Warsaw, Poland; phone/fax ; antczakj@cmdik.pan.pl