Scholarly article on topic 'Role of continuous positive airway pressure in patients with combined sleep apnea syndrome without congestive heart failure'

Role of continuous positive airway pressure in patients with combined sleep apnea syndrome without congestive heart failure Academic research paper on "Medical engineering"

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Abstract of research paper on Medical engineering, author of scientific article — Shereen Farghaly, Alaa Thabet

Abstract Continuous positive airway pressure (CPAP) is a standard treatment of moderate and severe obstructive sleep apnea syndrome. However, its effect in patients with coexisting obstructive and central apneas is controversial. Objectives To determine the immediate response to CPAP in combined obstructive and central sleep apnea patients without heart failure. Methods Thirty seven consecutive patients with moderate and severe coexisting obstructive and central apneas (combined group) were prospectively enrolled in this cross sectional analytic study. All patients underwent a full night-attended and a full night CPAP titration polysomnography. Titration was considered successful if AHI<10 and the titration study included at least 15min in REM stage. Results On CPAP titration, the combined group showed significant improvement in sleep and respiratory polysomnographic parameters. Mean AHI was reduced from 71.9±30.3 to 8.39±5.15 (P =0.000). Whereas CPAP significantly reduced the central apnea index from 12.8±6.67 to 3.1±2.86 (P =0.000), the response to central events was variable (ranged from 20% to 100%). Overall results, 25 (67.6%) had successful titration with significant better response in females than males to CPAP than males (88.9% vs. 60.7%, P =0.019). Conclusion CPAP can be effective in combined obstructive and central apnea patients without heart failure with consideration of individual variability. A trial of CPAP titration should be done in those patients.

Academic research paper on topic "Role of continuous positive airway pressure in patients with combined sleep apnea syndrome without congestive heart failure"

Egyptian Journal of Chest Diseases and Tuberculosis (2016) xxx, xxx-xxx

The Egyptian Society of Chest Diseases and Tuberculosis Egyptian Journal of Chest Diseases and Tuberculosis

www.elsevier.com/locate/ejcdt www.sciencedirect.com

ORIGINAL ARTICLE

Role of continuous positive airway pressure in patients with combined sleep apnea syndrome without congestive heart failure

Shereen Farghaly1*, Alaa Thabet2

Chest Department, Assiut University Hospital, Egypt Received 31 December 2015; accepted 16 March 2016

HOSTED BY

KEYWORDS

Heart failure; Sleep apnea; CPAP;

Combined syndrome

Abstract Continuous positive airway pressure (CPAP) is a standard treatment of moderate and severe obstructive sleep apnea syndrome. However, its effect in patients with coexisting obstructive and central apneas is controversial.

Objectives: To determine the immediate response to CPAP in combined obstructive and central sleep apnea patients without heart failure.

Methods: Thirty seven consecutive patients with moderate and severe coexisting obstructive and central apneas (combined group) were prospectively enrolled in this cross sectional analytic study. All patients underwent a full night-attended and a full night CPAP titration polysomnography. Titration was considered successful if AHI <10 and the titration study included at least 15 min in REM stage.

Results: On CPAP titration, the combined group showed significant improvement in sleep and respiratory polysomnography parameters. Mean AHI was reduced from 71.9 ± 30.3 to 8.39 ± 5.15 (P = 0.000). Whereas CPAP significantly reduced the central apnea index from 12.8 ± 6.67 to 3.1 ± 2.86 (P = 0.000), the response to central events was variable (ranged from 20% to 100%). Overall results, 25 (67.6%) had successful titration with significant better response in females than males to CPAP than males (88.9% vs. 60.7%, P = 0.019).

Conclusion: CPAP can be effective in combined obstructive and central apnea patients without heart failure with consideration of individual variability. A trial of CPAP titration should be done in those patients.

© 2016 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-

nd/4.0/).

* Corresponding author at: Chest Department, Assiut University Hospital, Zip Code: 71111, Egypt. Tel.: +20 01003085436. E-mail addresses: shereen_hssn@yahoo.com (S. Farghaly), alaathabet35@yahoo.com (A. Thabet).

1 Has a role in design of study, analysis of results and discussion of results.

2 Has a role in design of study, revision of the results and decision of final publishing. Peer review under responsibility of The Egyptian Society of Chest Diseases and Tuberculosis.

http://dx.doi.org/10.1016/j.ejcdt.2016.03.006

0422-7638 © 2016 The Egyptian Society of Chest Diseases and Tuberculosis. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction

Sleep related breathing disorders (SRBD) have been recently classified into obstructive sleep apnea syndrome (OSAS), the central sleep apnea syndrome (CSAS) and Cheyne-Stokes respiration (CSR) [1]. Due to overlap of mechanisms of upper airway obstruction and ventilatory instability causing these disturbances, one patient could present with combination of obstructive and central events in one night. This condition is commonly present in patients with congestive heart failure but can interestingly occur without heart failure [2].

Continuous positive airway pressure (CPAP) acts as a pneumatic splint to the upper airway during sleep and corrects the obstruction. It therefore can improve oxygenation and sleep architecture [3]. While the treatment of obstructive sleep apnea syndrome is generally straight forward and successful with CPAP therapy, [4] treatment of sleep apnea with predominantly mixed apneas, CSA and CSR is not universally agreed upon. CSA occurring with episodes of obstructive or mixed apnea may respond to nasal CPAP therapy [5-7]. One possible explanation is that CPAP increases lung volume and oxygen stores and alleviates hypoxia. Also, it prevents the occurrence of upper airway narrowing or occlusion during central apnea resulting in decreasing ventilatory overshoot and stabilization of ventilation [8]. Other reports have demonstrated either no change or a worsening of apnea/hypopnea index (AHI) during acute administration of nasal CPAP [9,10]. Depending on these results, a trial of CPAP may be effective in treatment of patients with coexisting obstructive and central sleep apnea.

Aim of the study

To determine the immediate effect of CPAP on elimination of apneas, improvement of oxygenation and sleep architecture in combined obstructive and central sleep apnea patients without heart failure.

Patients and methods

Patient selection Inclusion criteria

We included adult patients with coexisting obstructive and central sleep disordered breathing (combined group) (diagnosed by polysomnography as total AHI p 15 and central AHI p 5 and the central AHI < 50% of total AHI).

To be eligible for enrollment in the study, patients should undergo full night diagnostic and full night CPAP titration polysomnographic study.

Exclusion criteria

• Patients with pure OSAS.

• Patients associated with other pulmonary diseases as COPD, asthma, interstitial lung disease, bronchiectasis etc.

• Patients with left-sided heart failure.

• Patients who developed claustrophobia or excessive mask leak (leak > 0.04 L/s > 20% of total sleep time) during CPAP titration.

• Patients with split night sleep study.

Study design

This cross-sectional analytic study was carried at the sleep laboratory of the Chest Department of Assiut University Hospital. An informed written consent was obtained from all the patients enrolled in the study. The study was approved by the Faculty of Medicine Ethics Committee, Assiut University. Over a period of one and half years, we assessed patients coming for full night polysomnography. Patients with moderate to severe combined sleep apnea were prospectively enrolled in the study and prepared for second full night attended CPAP titration sleep study.

Clinical assessment

Clinical history suggestive of sleep apnea syndrome was taken from the patients and their partner with a history of associated co-morbid disease as diabetes mellitus, hypertension or IHD. Physical assessment including anthropometric measurement of height, weight and body-mass index (BMI) and reviewing of patients pulmonary function tests, previous chest X-ray and echocardiography was carried out.

Polysomnography

All patients underwent full over-night attended diagnostic as well as therapeutic (on CPAP) polysomnography (Sleep Lab Pro, Jaeger, VIASYS Healthcare Hoechberg, Germany). On both the two nights, the polysomnogram systematically monitored electroencephalogram (EEG) (C3-A2, C4-A1), electro-oculogram (EOG), electromyogram of the chin (EMG), electrocardiogram (EKG), nasal and oral airflow (using oronasal flow thermistor in the diagnostic study and a piezoelectric pressure sensor to record mask pressure in the therapeutic study), thoracic and abdominal effort (using piezoelectric belts), limb movements (by means of EMG on anterior tibialis muscle), pulse oximetry, body position (recorded by a position sensor) and snoring sound level (by means of a microphone placed externally to the trachea).

CPAP titration

CPAP therapy was introduced with full night attended polysomnography within 3 weeks after the diagnostic study. All patients received CPAP via an oronasal mask which was selected individually. The auto mode of CPAP device (Resmed, Autoset spiritTM) with a pressure range of 4-20 cm H2O was used for automatic titration. It automatically increased or decreased mask pressure in response to snoring or the presence of apneas or hypopneas, thus acting to completely restore airway patency. It detected degree of obstruction by reviewing the shape of the inspiratory flow curve on a breath-by-breath basis. A normal unobstructed breath gives a smooth rounded curve shape, but, as the upper airway narrows, flattening of the curve occurs, altering the shape. The degree of flattening determines the response of the device [11]. Preparation of the patients was done by a technician who supervised the study, and adjusted the mask fit to compensate for leak and patient discomfort.

Polysomnography scoring

The polysomnograms were scored automatically and revised manually according to American academy of sleep medicine [12]. Apnea was defined as a complete cessation of airflow for more than 10 s. Obstructive apnea was an apnea with preserved respiratory effort. Central apnea is an apnea with absent respiratory effort. Hypopnea required an event of at least 10 s duration in association with a P30% drop in the baseline amplitude and a P4% desaturation from the baseline saturation. The AHI was calculated as the number of apnea and hypopnea events per hour of sleep. Desaturation was detected by drop of at least 4% below baseline. An arousal was defined as an abrupt change in the EEG frequency to alpha, theta, or faster frequency in non-rapid eye movement (NREM) sleep with an increase in submental EMG as well in rapid eye movement (REM) lasting at least 3 s [13].

After manual scoring of the different previous variables, a polysomnographic report was printed including data of sleep [total seep time (TST), sleep efficiency, sleep stages%], respiratory [total, NREM and REM AHI, obstructive and central events and oxygen indices (desaturation index (DI), average oxygen level, minimum oxygen level, time spent below 90% (T90)] and cardiovascular [slowest and fastest heart rate] parameters. In the report of the second night, data about different CPAP pressures applied during the study were detected. Titration was considered successful if overall results showed AHI < 5 and the study included at least 15 min in REM stage.

Statistical analysis

Statistical Package for the Social Sciences (SPSS-version 16) software was used for analysis of results. Results in this study were presented in mean ± standard deviation or number and percentage. The qualitative data were compared between the successful and non successful group using chi-square test. Paired sample student t-test was used to analyze quantitative polysomnographic data on CPAP compared to baseline. The difference was considered significant when P < 0.05.

Results

We included 37 with coexisting obstructive and central sleep apnea (combined group) for analysis. We excluded 62 patients with pure OSAS, 30 patients with associated pulmonary diseases and 9 patients with excessive leak during CPAP titration. The combined group was 67.6% male with a mean age of 51.22 ± 8.9. They were obese with mean BMI 40.21 ± 8.022. The demographic data are shown in Table 1.

On CPAP titration, the combined group showed a significant improvement in most polysomnographic variables. Sleep efficiency was significantly increased. Light sleep (stage 1 and stage 2) % of TST was significantly decreased with a significant increase in % of both of deep (i.e. stage 3) and REM sleep. Furthermore, CPAP significantly reduced all apneas events and improved oxygenation. Mean AHI was reduced from 71.9 ± 30.3 to 8.39 ± 5.15 (P = 0.000). Whereas CPAP significantly reduced the obstructive apnea index (OAI) from 29.50 ± 22.30 to 4.86 ± 3.6 (P = 0.000) (Fig. 1) and the central apnea index from 12.8 ± 6.67 to 3.1 ± 2.86 (P = 0.000), the response to central events was variable (ranged from

Table 1 Demographic data of the study group.

Variable (N = 37)

Age (mean ± SD) 51.22 ± 8.9

Gender (%) Male Female 28 (75.6%) 9 (24.3%)

Smoking habit (%) Smoker 16 (43.2%)

BMI (mean ± SD) 40.21 ± 8.022

Comorbidities (%) Hypertension Diabetes mellitus Ischemic heart disease 23 (62.2%) 14 (37.8%) 14 (37.8%)

Data expressed as number (%) or mean ± SD (standard deviation). BMI, body mass index.

so ■ 70 ■ 60 ■ _ 50 ■

I 4001

3020 ■ 10 -0 -

Baseline OAI CPAP OAI

Figure 1 The response of obstructive apnea index (OAI) to CPAP in patients with combined sleep apnea syndrome. CPAP significantly reduced the OAI from 29.50 ± 22.30 to 4.86 ± 3.6 (P = 0.000). The degree of response varies from 60% to 100%.

20% to 100%) (Fig. 2). Average (84.36 ± 6.76 vs. 90.37 ± 6.27, P = 0.000) and minimum (58.9 ± 17.5 vs. 79.45 ± 9.54, P = 0.000) oxygen saturation were significantly increased with a significant reduction in T90 (60.3 ± 47.9 vs. 7.75 ± 11.9, P = 0.000). Arousal index was significantly decreased from 33.98 ± 9.66 to 8.5 ± 6.16 (P = 0.000). Also CPAP significantly increased the slowest heart rate in the titration night compared to the diagnostic study (49.5 ± 9.01 vs. 37.08 ± 13.8, P = 0.000) (Table 2).

Overall results, 25 (67.6%) of the combined group had successful titration with AHI < 5. Among the combined group, Female patients showed better response to CPAP than males (88.9% vs. 60.7%, P = 0.019). Patients with successful initial CPAP titration had a significantly higher baseline total AHI, CAI, REM AHI than those who failed titration (Table 3).

Discussion

Obstructive sleep apnea syndrome is a common sleep related breathing disorder [14]. Many patients with OSAS show at

Baseline CAI CPAP CAJ

Figure 2 The response of central apnea index (CAI) to CPAP in patients with combined sleep apnea syndrome. CPAP significantly reduced the CAI from 12.8 ± 6.67 to 3.1 ± 2.86 (P = 0.000). Note (arrows) the wide variability of response of CAI (varies from 20% to 100%).

least a minor proportion of coexisting central disturbances

[15]. That may be likely due to the overlapping of mechanisms causing these disturbances. Obstructive apneas, probably through intermittent hypoxia, can increase the ventilatory response to subsequent apneas and produce central apneas

[16]. Stimulation of the mechanoreceptors of the upper airway when by obstructive efforts may favor the occurrence of central events through their action on the central drive to breathe

[17]. Ventilatory instability (an important pathophysiological disturbance found in obstructive apnea patients) which leads

to pharyngeal obstruction may also increase the ventilatory response to arousal and drives Pa CO2 below the apnea threshold during subsequent sleep causing central apnea [18]. In heart failure, there is evidence for an overnight shift in predominance of obstructive apneas to central apneas [19]. Although CPAP was considered the standard treatment of OSAS, there was little evidence in its role in patients with coexisting central and obstructive events.

Thus we carried out this study to evaluate the immediate effect of CPAP on patients with coexisting obstructive and central sleep apnea without congestive heart failure. On its effect on sleep variables, similar to previous studies [20-22] carried out on OSAS patients, it significantly improved all sleep variables. Light sleep (stage 1 and stage 2) (P < 0.001) percent was significantly decreased with a significant increase in both deep sleep (i.e. stage 3) and REM stage as a % of total sleep time (P < 0.001). On the other hand, Lofaso and coworkers [23] found an increase in slow-wave (71 ± 86 vs. 102 ± 149 min) but not REM sleep on APAP and Randerath et al. [24] found an increase in REM sleep but no change in slow-wave sleep compared to baseline. In heart failure patients with coexisting obstructive and Cheyne stoke breathing, Randerath et al. [25] reported no immediate improvement on sleep quality on CPAP but only after 3 months of treatment with a significant decrease in stage 1 and 2 (P < 0.01) and increase in stage 3 (P < 0.01).

The findings that CPAP significantly reduced all apnea events, arousal and improved oxygenation in our combined group were comparable with previous studies. In patients with congestive heart failure, Kasai et al. [26] and Randerath et al. [25] noted that a significant reduction of AHI is in the titration

Table 2 Polysomnographie parameters of the combined group (n = 37).

Variable Baseline (n = 37)s CPAP (n = 37) P-value

Mean ± SD Mean ± SD

Sleep parameters

TST (h) 4.56 ± 0.07 4.58 ± 0.94 0.345

Sleep efficiency (%) 88.39 ± 4.9 91.38 ± 4.9 0.016*

Stage 1 (%) 26.4 ± 12.9 18.5 ± 21.85 0.001*

Stage 2 (%) 50.6 ± 19.5 48.66 ± 18.76 0.024*

Stage 3 (%) 8.14 ± 13.2 13.12 ± 12.7 0.014*

REM (%) 9.11 ± 15.8 13.11 ± 12.85 0.015*

Respiratory parameters

AHI (event/h) 71.9 ± 30.3 8.39 ± 5.15 0.000*

NREM AHI 72.7 ± 30.7 7.45 ± 6.94 0.000*

REM AHI 50.36 ± 29.8 6.34 ± 7.34 0.000*

OAI 29.50 ± 22.30 4.86 ± 3.6 0.000*

Hypopnea index 12.5 ± 10.4 1.1 ± 0.93 0.000*

CAI 12.8 ± 6.67 3.1 ± 2.86 0.000*

DI (event/h) 54.48 ± 27.19 7.08 ± 4.8 0.000*

Average O2 (%) 84.36 ± 6.76 90.37 ± 6.27 0.000*

Minimum O2 (%) 58.9 ± 17.5 79.45 ± 9.54 0.000*

T90 (min) 60.3 ± 47.9 7.75 ± 11.9 0.000*

Arousal index (event/h) 33.98 ± 9.66 8.5 ± 6.16 0.000*

Cardiovascular parameters

Fastest heart rate 101.1 ± 19.6 103.1 ± 17.27 0.362

Slowest heart rate 37.08 ± 13.8 49.5 ± 9.01 0.000*

TST, total sleep time; AHI, apnea hypopnea index; OAI, obstructive apnea index; CAI, central apnea index; REM, rapid eye movement;

NREM, non-rapid eye movement; DI, desaturation index; T90, time spent below 90% in minutes.

* Significant.

Table 3 Potential predictors of successful initial CPAP titration in the combined group (n = 37).

Variable Successful titration Unsuccessful titration P-value

(N = 25) (N = 12)

Gender %

Male 17 (68.2%) 11 (39.3%) 0.019*

Female 8 (88.9%) 1 (8.3%)

BMI (mean ± SD) 41.34 ± 7.86 43.12 ± 8.32 0.509

ESS (mean ± SD) 10.21 ± 2.6 11.72 ± 2.9 0.105

Baseline AHI (mean ± SD) 62.01 ± 22.56 92.9 ± 22.2 0.000*

Baseline CAI (mean ± SD) 9.9 ± 2.45 15 ± 8.76 0.020*

Baseline NREM AHI (mean ± SD) 73.48 ± 23.1 82.9 ± 23.9 0.075

Baseline REM AHI (mean ± SD) 24.8 ± 14.74 81.48 ± 4.6 0.000*

Data expressed as number (%) or mean ± SD (standard deviation).

ESS, Epworth sleepiness scale; BMI, body mass index; AHI, apnea hypopnea index; CAI, central apnea index; NREM, non-rapid eye

movement; REM, rapid eye movement.

Significant.

study. In randomized short term trials [27-29] in which nocturnal CPAP was applied for one night, despite a significant improvement in total AHI and oxygen saturation, central AHI was reduced on CPAP by about 50%. The better results reported in this study (reduction of central AHI by 80%) might be due to that the previous studies evaluate patients with predominantly central apnea with exclusion of those with obstructive AHI > 10/h. Furthermore, all hypopneas were scored as obstructive events as we could not differentiate between central and obstructive hypopneas and thus the possibility of under estimation of central events in our cases. Interestingly, as in previous studies, [28,30] we observed that a reduction of central events was variable (varies from 20% to 100%). It was supposed that at the time CPAP caused immediate and complete suppression of obstructive sleep apnea in patients with [31] and without [32] CHF, its effects on CSA were gradual and time dependent. Studies applying gradual CPAP titration protocol and treatment for a period of 2-12 weeks showed a further improvement of central events by 50-65% than the first night [33,34,28]. As it was postulated that that breathing stability rather than upper airway collapsi-bility distinguishes patients with a combination of obstructive and central events from those with pure OSA, those patients were expected to take a period to adapt to CPAP [35]. It had been demonstrated that treatment of CSA with CPAP for a period of 2 weeks or longer stabilized the ventilatory control system by increasing nocturnal transcutaneous PCO2, [6] total body oxygen stores [36] and reducing ventilatory drive [34]. We hypothesized that central apneas induced by obstructive events following arousals or induced by negative mechanoreceptor stimulation could disappear after correction of obstruction by CPAP. The different mechanisms of the pathogenesis of patients with combined obstructive and central events led to heterogeneous response to CPAP. Those patients with patho-genesis other than ventilatory instability could show immediate improvement on CPAP.

Interestingly, female patients in our study showed a better response to CPAP than males. Generally, men had less stable sleep architecture with frequent arousals and shorter slow wave than women which might predispose them to respiratory control system instability [37] and thus the need for time to

show optimum response to CPAP. Furthermore the small number of females in our study could make this difference.

A problem in sleep apnea studies is the exact differentiation between obstructive and central hypopneas. Measurement of esophageal pressure is the gold standard approach to detect respiratory effort but is difficult to be applied in that study. Besides, limitations of this study included the small number of included patients but that was due to the limited inclusion criteria in that study to find this group of patients and also the absence of a definite cause of the presence of central events in those OSAS patients.

In conclusion, CPAP can be effective in combined obstructive and central apnea patients without heart failure with consideration of individual variability. So a trial of CPAP titration should be considered in every patient with combined sleep apnea syndrome without heart failure. Further studies are recommended to evaluate the long term effect of CPAP in those patients.

Conflict of interest

All authors declare there is absence of conflict of interest in this study. There is also no financial support by any organization.

Acknowledgments

The authors wish to express their thanks to sleep technicians in the Chest Department, Assiut University Hospital for their great help in arranging appointments and educating patients about the sleep study.

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