INJ Search

CLOSE


Int Neurourol J > Volume 19(3); 2015 > Article
Wang, Huang, Zong, and Zhang: The Efficacy of Continuous Positive Airway Pressure Therapy on Nocturia in Patients With Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis

ABSTRACT

Purpose:

To assess the efficacy of the continuous positive airway pressure (CPAP) on nocturia in patients with obstructive sleep apnea (OSA).

Methods:

A literature review was performed to identify all published clinical trials of CPAP for the treatment of nocturia. The search included the following databases: MEDLINE, Embase, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated.

Results:

Five publications involving a total of 307 patients were used in the analysis, which compared the number of incidents of nocturia before and after CPAP treatment. We found that patients with OSA and nocturia who were treated with CPAP had a significant decrease in the frequency of nocturia and the volume of urine associated with it. The mean number of nocturia incidents (standardized mean difference [SMD], –2.28; 95% confidence interval [CI], –2.42 to –2.15; P<0.00001) and the associated urine volume (SMD, –183.12; 95% CI, –248.27 to –117.98; P<0.00001) indicated that CPAP was effective. Besides, the Epworth Sleepiness Scale (SMD, –5.88; 95% CI, –6.56 to –5.21; P<0.00001) and the CPAP apnea-hypopnea index (SMD, –31.57; 95% CI, –33.87 to –29.28; P<0.00001) indicated that CPAP significantly improved the quality of sleep.

Conclusions:

This meta-analysis indicates that CPAP maybe an effective treatment for reducing nocturia associated with OSA and improving the quality of life of such patients.

left
    right

    INTRODUCTION

    Nocturia has been defined by the International Continence Society as “the complaint that the individual has to wake up at night one or more times to void” [1]. Nocturia is a common problem for patients who suffer from obstructive sleep apnea (OSA) syndrome [2-4]. Schatzl et al. [5] found that the prevalence of nocturia increases with age, from 3.4% in men younger than 30 years to 32.4% in those aged 60 years or older. Generally, older men with nocturia were often assumed to have benign prostatic hyperplasia and women were assumed to have an overactive bladder or reduced bladder capacity. However, Lundgren [6] believe that nocturia may be associated with nocturnal polyuria.
    OSA is characterized by repetitive occlusion of breathing in the upper airway. It is one of the most common respiratory disorders, affecting up to 20% of the general population [7]. Krieger et al. [8] found that the rate of nocturia was significantly greater in patients with OSA than in healthy controls. Umlauf et al. [9] reported that nocturnal urine volume and atrial natriuretic peptide (ANP) excretion are elevated in patients with OSA.
    Continuous positive airway pressure (CPAP) is an effective treatment for middle-aged patients with moderate-to-severe OSA syndrome [10]. Some articles reported that CPAP treatment not only improves breathing in OSA patients but also decreases the frequency of nocturia and the associated urine volume [11,12]. Although these studies indicate that CPAP is an effective treatment for nocturia, thus far, no meta-analysis has been performed to confirm this claim.
    Therefore, we conducted a meta-analysis to evaluate the efficacy of CPAP in treating nocturia among patients with OSA.

    MATERIALS AND METHODS

    Search Strategy

    Clinical studies describing the effectiveness of CPAP in treating nocturia in patients with OSA were included in this review. They were identified by searching the MEDLINE (1966 to July 2015), Embase (1974 to July 2015), and Cochrane Controlled Trials Register databases. We also searched the reference lists of the retrieved studies. The following keywords were used in the search as text word or subject headings: CPAP, nocturia, OSA, meta-analysis, clinical trial. No ethical approval was sought for this study, as it was a systematic review and meta-analysis of published manuscripts.

    Inclusion Criteria and Trial Selection

    Clinical trials reporting the incidence of nocturia in patients with OSA who underwent CPAP were included. Two reviewers independently selected the articles for inclusion by assessing the eligibility of full papers against the review inclusion criteria. Disagreements were resolved by discussion, if necessary, with a third reviewer. A flowchart of the study selection process is shown in Fig. 1.

    Quality Assessment

    The quality of the retrieved clinical trials was assessed using the Jadad scale [13]. All the identified clinical trials were included in the meta-analysis regardless of the quality score. The methodological quality of each study was assessed according to how patients were allocated to the arms of the study, the concealment of allocation procedures, blinding, and data loss due to attrition. The studies were then classified qualitatively according to the guidelines published in the Cochrane Handbook for Systematic Reviews of Interventions v.5.1.0 [14]. On the basis of these quality assessment criteria, each study was rated and assigned to one of the following three quality categories: A, if all quality criteria were adequately met, the study was deemed to have a low risk of bias; B, if one or more of the quality criteria was only partially met or was unclear, the study was deemed to have a moderate risk of bias; or C, if one or more of the criteria was not met or not included, the study was deemed to have a high risk of bias.

    Data Extraction

    The following data were extracted from each eligible study: (1) the name of the clinical trial; (2) the number of patients in each group; (3) the therapy that the patients received; (4) the country in which the study was conducted; and (5) the data collected including the frequency of nocturia and the associated urine volume, the Epworth Sleepiness Scale (ESS), and the apnea-hypopnea index (AHI).

    Statistical Analysis and Meta-Analysis

    A meta-analysis was performed to assess the outcome of CPAP for patients with OSA. It was carried out using RevMan v.5.1.0 (Cochrane Collaboration, Oxford, UK) [14]. When binary variables were reported, odds ratio (OR) or risk ratio was used for analysis. Continuous parameters were analyzed by computing the mean difference or standardized mean difference (SMD) by using the DerSimonian and Laird random-effects model [15]. The pooled effects were determined using the z test; P<0.05 was considered statistically significant for all analyses. The Cochrane chi-square test and inconsistency (I²) measure were used to evaluate the heterogeneity among studies, thus describing the extent of true inconsistency in results across trials [16]. I²<25% reflects a small level of inconsistency, and I²>50% reflects significant inconsistency.

    RESULTS

    Characteristics of the Individual Studies

    The database search revealed 49 articles largely suitable for inclusion in our meta-analysis. However, based on the selection criteria, 39 articles were excluded after reading the titles and abstracts of the articles. Of the remaining 10 articles, 3 were not trials and 2 lacked useful data. Finally, 5 articles [11,12,17-19] were included in the analysis (Fig. 1). The baseline characteristics of the studies included in our meta-analysis are listed in Table 1.

    Quality of the Individual Studies

    In all 5 clinical trials, the processes used for randomization were well described. All included a power calculation to determine the optimal sample size (Table 2). The quality score assigned to each included study was ‘B and A’ (Table 2). A funnel plot was used to make a qualitative estimate of the publication bias of the studies, and no evidence of bias was found (Fig. 2).

    Efficacy

    The mean number of nocturia incidents

    Five clinical trials, representing 307 participants, included data on nocturia (Fig. 3). The pooled estimate of SMD between the pre- and posttreatment groups was –2.28, and the 95% confidence interval (CI) was –2.42 to –2.15 (P<0.00001). This result shows that CPAP treatment produced a statistically significant reduction in the mean number of nocturia incidents.

    Night-time urine volume (mL)

    Two clinical trials, representing 40 participants, included night-time urine volume data (Fig. 4). The pooled estimate of SMD between the pre- and posttreatment groups was –183.12, and the 95% CI was –248.27 to –117.98 (P<0.00001). This result shows that CPAP produces statistically significant reductions in night-time urine volume.

    Change of ESS ratings

    Four of the clinical trials, representing 131 participants, assessed participants using the ESS (Fig. 5). Based on our analysis, the pooled estimate of SMD between the pre- and posttreatment groups was –5.88, and the 95% CI was –6.56 to –5.21 (P<0.00001). This result shows that CPAP produced statistically significant reductions in study participants’ ESS ratings.

    Change of AHI

    Three of the clinical trials, representing 85 participants, included the AHI (Fig. 5). The pooled estimate of SMD between the pre- and posttreatment groups was –31.57, and the 95% CI was –33.87 to –29.28 (P<0.00001). This result shows that CPAP produced statistically significant reductions in the AHI of study participants.
    Miyauchi et al. [12] reported that urinary concentrations of Na, Cl, and K were significantly decreased after CPAP treatment (P=0.004, P=0.007, and P=0.025). Moreover, they also found that total International Prostate Symptom Score (IPSS) was significantly decreased after CPAP treatment (P =0.03). Besides, Liu and Liu [19] reported that the osmotic concentration of nocturia urine was significantly increased after CPAP treatment (P<0.05) and the concentration of ANP was significantly decreased after CPAP treatment (P<0.01).

    DISCUSSION

    Nocturia is a common problem among older adults and appears to negatively impact sleep quality [20,21]. Even though nocturia is often attributed to problems of the bladder, it is common and often serious in patients with OSA [22,23]. OSA is a potential reason of nocturia. In patients with OSA, the frequency with which nocturia occurs more than once in one night is reported to increase by 52%–77%, depending on the severity of the breathing problems associated with the sleep disorder [24,25]. CPAP treatment maintains the airway patency by supplying air with positive pressure, and is hence an effective treatment for OSA. Some studies reported that CPAP treatment improves not only the breathing difficulties associated with the sleep disorder but also the urinary symptoms, including nocturia [26-28].
    Our study reveals that nocturia (P<0.00001) and night-time urine volume (P<0.00001) were significantly decreased after CPAP treatment. The mean number of nocturia incidents was decreased by 2.28. Mean night-time urine volume (mL) was decreased by 183.12 mL. The results show that treatment with CPAP provides both statistically significant and, more importantly, clinically relevant improvements in nocturia and reduction in night-time urine volume. Miyauchi et al. [12] reported that reduction in nocturia may be primarily due to reduction in night-time urine volume. Moreover, they also found that total IPSS and quality of life scores were significantly improved after CPAP treatment [12]. An earlier study reported that patients with OSA exhibit greater urinary flows and a reduction in the percentage of filtered sodium that is reabsorbed [29]. In addition, Umlauf et al. [9] found that both night-time urine volume and ANP excretion are elevated in patients with a high RDI (respiratory disturbance index, which was calculated by dividing the total number of events of apnea plus hypopnea by the total sleep time). Therefore, we thought one possible reason for the beneficial effect of CPAP treatment on nocturia may have to do with the reduced release of ANP. CPAP therapy can effectively relieve obstruction of the airway, avoiding excessive expansion of the cardiac atrium, which is induced by intrathoracic negative pressure. At the same time, CPAP can effectively reduce night-time hypoxemia, thereby avoiding pulmonary hypoxic contraction. All of these factors can significantly reduce the secretion of ANP at night. Hence, patients with OSA after CPAP treatment had a significant reduction in nocturia. In other words, CPAP treatment eliminates negative intrathoracic pressure and thereby reduces secretion of ANP. This leads to the reduction of nocturnal urine volume and urinary electrolyte excretion at night and, consequently, relieves the nocturia.
    Additionally, our study reveals that significant improvements in the ESS ratings (P<0.00001) and AHI (P<0.00001) were observed after CPAP treatment. As a consequence, sleep quality was improved by a smoother respiratory pattern and a lower probability of arousal from a full bladder.
    The positive pressures applied in CPAP were 4–20 cm H2O, which is presumably a measure of pressure using a column of water, which reduces sleepiness and is marginally cost effective. Hence, we believe that CPAP 4–20 cm H2O is an effective treatment for nocturia in patients with OSA.
    There are some important limitations to our analysis. Data on the treatment of CPAP were derived from a relatively small-sized sample because cohort sizes of a few of the studies were not large. The long-term safety, efficacy, and persistence of CPAP cannot be extrapolated from this article. In addition, data from unpublished studies were not included in the analysis. Such factors may have resulted in a bias. Besides, CPAP is usually not a sufficient treatment for complex sleep-related breathing disorders, including mixed sleep apnea syndrome with central and obstructive apneas, chronic obstructive pulmonary disease etc. However, the included studies did not distinguish between the mixed sleep apnea syndromes. We think that a carefully layered analysis should be applied, but owing to the limited data available, further studies are required. We suggest that more high-quality trials with larger samples are needed to learn more about the efficacy of CPAP for the treatment of nocturia.
    In conclusion, this meta-analysis indicates that CPAP appears to be an effective treatment for reducing nocturia and improving the quality of life of patients with OSA.

    NOTES

    Conflict of Interest
    No potential conflict of interest relevant to this article was reported.

    REFERENCES

    1. Van Kerrebroeck P, Abrams P, Chaikin D, Donovan J, Fonda D, Jackson S, et al. The standardization of terminology in nocturia: report from the standardization subcommittee of the International Continence Society. BJU Int 2002;90 Suppl 3:11-5. PMID: 12445092
    crossref pmid
    2. Moriyama Y, Miwa K, Tanaka H, Fujihiro S, Nishino Y, Deguchi T. Nocturia in men less than 50 years of age may be associated with obstructive sleep apnea syndrome. Urology 2008;71:1096-8. PMID: 18400277
    crossref pmid
    3. Pressman MR, Figueroa WG, Kendrick-Mohamed J, Greenspon LW, Peterson DD. Nocturia. A rarely recognized symptom of sleep apnea and other occult sleep disorders. Arch Intern Med 1996;156:545-50. PMID: 8604961
    crossref pmid
    4. Flemons WW, Tsai W. Quality of life consequences of sleep-disordered breathing. J Allergy Clin Immunol 1997;99:S750-6. PMID: 9042067
    crossref pmid
    5. Schatzl G, Temml C, Schmidbauer J, Dolezal B, Haidinger G, Madersbacher S. Cross-sectional study of nocturia in both sexes: analysis of a voluntary health screening project. Urology 2000;56:71-5. PMID: 10869627
    crossref pmid
    6. Lundgren R. Nocturia: a new perspective on an old symptom. Scand J Urol Nephrol 2004;38:112-6. PMID: 15204390
    crossref pmid
    7. Young T, Palta M, Dempsey J, Skatrud J, Weber S, Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med 1993;328:1230-5. PMID: 8464434
    crossref pmid
    8. Krieger J, Petiau C, Sforza E, Delanoe C, Hecht MT, Chamouard V. Nocturnal pollakiuria is a symptom of obstructive sleep apnea. Urol Int 1993;50:93-7. PMID: 8460456
    crossref pmid
    9. Umlauf MG, Chasens ER, Greevy RA, Arnold J, Burgio KL, Pillion DJ. Obstructive sleep apnea, nocturia and polyuria in older adults. Sleep 2004;27:139-44. PMID: 14998251
    crossref pmid
    10. McDaid C, Griffin S, Weatherly H, Duree K, van der Burgt M, van Hout S, et al. Continuous positive airway pressure devices for the treatment of obstructive sleep apnoea-hypopnoea syndrome: a systematic review and economic analysis. Health Technol Assess 2009;13:iii-iv, xi-xiv, 1-119, 143-274. crossref
    11. Guilleminault C, Lin CM, Goncalves MA, Ramos E. A prospective study of nocturia and the quality of life of elderly patients with obstructive sleep apnea or sleep onset insomnia. J Psychosom Res 2004;56:511-5. PMID: 15172207
    crossref pmid
    12. Miyauchi Y, Okazoe H, Okujyo M, Inada F, Kakehi T, Kikuchi H, et al. Effect of the continuous positive airway pressure on the nocturnal urine volume or night-time frequency in patients with obstructive sleep apnea syndrome. Urology 2015;85:333-6. PMID: 25623679
    crossref pmid
    13. Jadad AR, Rennie D. The randomized controlled trial gets a middle-aged checkup. JAMA 1998;279:319-20. PMID: 9450719
    crossref pmid
    14. Higgins JP, Green S. Cochrane handbook for systematic reviews of interventions. version 5.1.0 [Internet]. London: Cochrane Collaboration; c2015 [updated 2011 Mar] [cited 2015 Apr]. Available from: http://www.cochrane-handbook.org/.
    15. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-88. PMID: 3802833
    crossref pmid
    16. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60. PMID: 12958120
    crossref pmid pmc
    17. Margel D, Shochat T, Getzler O, Livne PM, Pillar G. Continuous positive airway pressure reduces nocturia in patients with obstructive sleep apnea. Urology 2006;67:974-7. PMID: 16635510
    crossref pmid
    18. McMillan A, Bratton DJ, Faria R, Laskawiec-Szkonter M, Griffin S, Davies RJ, et al. Continuous positive airway pressure in older people with obstructive sleep apnoea syndrome (PREDICT): a 12-month, multicentre, randomised trial. Lancet Respir Med 2014;2:804-12. PMID: 25172769
    crossref pmid
    19. Liu S, Liu L. Effect of treatment with continuous positive airway pressure on nocturnal polyuria in patients with obstructive sleep apnea syndrome. Zhonghua Jie He He Hu Xi Za Zhi 2001;24:158-60. PMID: 11802958
    pmid
    20. Kim SO, Choi HS, Kim YJ, Kim HS, Hwang IS, Hwang EC, et al. Impact of nocturia on health-related quality of life and medical outcomes study sleep score in men. Int Neurourol J 2011;15:82-6. PMID: 21811697
    crossref pmid pmc
    21. Miranda ED, Gomes CM, Torricelli FC, de Bessa J Junior, de Castro JE, Ferreira BR, et al. Nocturia is the lower urinary tract symptom with greatest impact on quality of life of men from a community setting. Int Neurourol J 2014;18:86-90. PMID: 24987561
    crossref pmid pmc
    22. Warley AR, Stradling JR. Abnormal diurnal variation in salt and water excretion in patients with obstructive sleep apnoea. Clin Sci (Lond) 1988;74:183-5. PMID: 3276443
    crossref pmid
    23. Ulfberg J, Thuman R. A non-urologic cause of nocturia and enuresis: obstructive sleep apnea syndrome (OSAS). Scand J Urol Nephrol 1996;30:135-7. PMID: 8738060
    crossref pmid
    24. Kaynak H, Kaynak D, Oztura I. Does frequency of nocturnal urination reflect the severity of sleep-disordered breathing? J Sleep Res 2004;13:173-6. PMID: 15175098
    crossref pmid
    25. Oztura I, Kaynak D, Kaynak HC. Nocturia in sleep-disordered breathing. Sleep Med 2006;7:362-7. PMID: 16564213
    crossref pmid
    26. Kiely JL, Murphy M, McNicholas WT. Subjective efficacy of nasal CPAP therapy in obstructive sleep apnoea syndrome: a prospective controlled study. Eur Respir J 1999;13:1086-90. PMID: 10414408
    crossref pmid
    27. Fitzgerald MP, Mulligan M, Parthasarathy S. Nocturic frequency is related to severity of obstructive sleep apnea, improves with continuous positive airways treatment. Am J Obstet Gynecol 2006;194:1399-403. crossref
    28. Cruz IA, Drummond M, Winck JC. Obstructive sleep apnea symptoms beyond sleepiness and snoring: effects of nasal APAP therapy. Sleep Breath 2012;16:361-6. PMID: 21365185
    crossref pmid
    29. Krieger J, Imbs JL, Schmidt M, Kurtz D. Renal function in patients with obstructive sleep apnea. Effects of nasal continuous positive airway pressure. Arch Intern Med 1988;148:1337-40. PMID: 3288160
    crossref pmid

    Fig. 1.
    Flowchart of the study selection.
    inj-19-3-178f1.tif
    Fig. 2.
    Funnel plot of the studies represented in our meta-analysis.
    inj-19-3-178f2.tif
    Fig. 3.
    Change in nocturia conditions after continuous positive airway pressure treatment versus before treatment. SD, standard deviation; CI, confidence interval; df, degrees of freedom; IV, inverse variance; Fixed, fixed effect model.
    inj-19-3-178f3.tif
    Fig. 4.
    Change in night-time urine volume after continuous positive airway pressure treatment versus before treatment. SD, standard deviation; CI, confidence interval; df, degrees of freedom; IV, inverse variance; Fixed, fixed effect model.
    inj-19-3-178f4.tif
    Fig. 5.
    Changes to the Epworth Sleepiness Scale and apnea-hypopnea index after continuous positive airway pressure treatment versus before treatment. SD, standard deviation; CI, confidence interval; df, degrees of freedom; IV, inverse variance; Fixed, fixed effect model.
    inj-19-3-178f5.tif
    Table 1.
    Study and patient characteristics
    Study Therapy in experimental group Country Sample size (n)
    Duration of treatment (mo) Inclusion population
    Experimental Control
    Guilleminault et al. (2004) [11] CPAP USA 31 31 1 Males, 65 years and older, with either (1) snoring and daytime fatigue or sleepiness, with sleep disordered breathing or (2) difficulty initiating sleep or waking up too early, were considered for the study.
    Margel et al. (2006) [17] CPAP Israel 97 97 3 After polysomnography, those found to have OSA and were not to make changes in any existing medical treatment
    Miyauchi et al. (2015) [12] CPAP Japan 51 51 1 Older than 20-year-old subjects undergoing polysomnography owing to suspicious diagnosis of OSAS because of loud snoring, nocturnal choking, or daytime sleepiness.
    McMillan et al. (2014) [18] CPAP UK 113 113 12 Consecutive patients aged 65 years or older with newly diagnosed OSAS.
    Liu and Liu (2001) [19] CPAP China 15 15 1 Patients undergoing polysomnography owing to suspicious diagnosis of OSAS because of loud snoring, nocturnal choking, or daytime sleepiness.

    CPAP, continuous positive airway pressure; OSA, obstructive sleep apnea; OSAS, obstructive sleep apnea syndrom.

    Table 2.
    Quality assessment of individual study
    Study Allocation sequence generation Allocation concealment Blinding Loss to follow-up Calculation of sample size Statistical analysis Intention-to-treat analysis Level of quality
    Guilleminault et al. (2004) [11] A A B 0 YES t-test and Kruskal-Wallis test YES B
    Margel et al. (2006) [17] A A B 0 YES Student paired t-test YES B
    Miyauchi et al. (2015) [12] A A B 0 YES Wilcoxon signed rank test YES B
    McMillan et al. (2014) [18] A A A 0 YES t-test and Kruskal-Wallis test YES A
    Liu and Liu (2001) [19] A B B 0 YES Student paired t-test YES B

    A, all quality criteria met (adequate): low risk of bias; B, one or more of the quality criteria only partly met (unclear): moderate risk of bias.

    TOOLS
    Share :
    Facebook Twitter Linked In Google+
    METRICS Graph View
    • 5 Crossref
    • 7 Scopus
    • 3,389 View
    • 22 Download


    ARTICLE & ORGAN
    Article Category

    Browse all articles >

    Organ

    Browse all articles >

    ISSUES
    DISEASES & TOPICS
    Diseases

    Browse all articles >

    Topics

    Browse all articles >

    AUTHOR
    INFORMATION

    Editorial Office
    Department of Urology, Kangbuk Samsung Medical Center, Sungkyunkwan University School of Medicine,
    29 Saemunan-ro, Jongno-gu, Seoul 03181, Korea
    Tel: +82-2-2001-2237     Fax: +82-2-2001-2247    E-mail: choys1011@naver.com

    Copyright © 2017 by Korean Continence Society. All rights reserved.

    Powerd by M2community

    Close layer
    prev next