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CPAP TREATMENT MAY REDUCE EPISODES OF NOCTURIA By Regina Patrick, RPSGT, RST

person with nocturia awakens one or more times to urinate Aduring a period. Nocturia is difficult to treat because it Continuous positive airway pressure (CPAP) is used to counteract typically occurs in conjunction with other disorders. Undiagnosed upper airway collapse in OSA. In this treatment, pressurized air obstructive (OSA) can contribute to nocturia. However, flows through a mask that fits over the nose or nose and mouth physicians often do not ask patients complaining of nocturia about into the upper airway, and pushes against upper airway structures symptoms of OSA. This oversight may contribute to difficulties in to prevent their collapse during sleep. As a result, intermittent treating nocturia. collapse and arousals are prevented and a person has more consolidated sleep. Nocturia may be caused by lower urinary tract disorders (e.g., enlarged prostate, , cystitis [bladder inflamma- One theory on how OSA may contribute to nocturia focuses tion]); systemic disorders (e.g., congestive , , on the excretion of atrial natriuretic peptide (ANP), a powerful metabolic disorders); disorders (e.g., chronic renal failure); vasodilator that heart cells release into the bloodstream to reduce 7 and drugs (e.g., furosemide) or foods (e.g., , alcohol) that high fluid volume in the body. When ANP reaches the kidneys, cause (i.e., induce ). Alpha-adrenergic blockers it inhibits the secretion of renin and aldosterone secretion. This and anticholinergic drugs (both of which reduce urine production) inhibition increases urine production. may be used to treat nocturia. During the upper airway blockage in an OSA episode, a person The prevalence of nocturia is unclear because few studies have makes increasingly strong efforts to breathe. As the lungs press specifically focused on this symptom. One study1 in 1996 reported against the heart with each effort to breathe, the heart erroneously a prevalence of 58 percent and 66 percent in women and in men, senses that there is an excessive fluid volume. In response to this respectively, who are 50–59 years, and a prevalence of 72 percent false signal, the heart cells increase their production of ANP, and 31.91 percent in women and men, respectively, who are older which may then induce the production of urine and result in than 80 years. More recent studies report a prevalence of 11 nocturia. percent–31 percent.2-5 Some research indicates that the prevalence of nocturia among patients with OSA ranges 40 percent‒50 Another possibility for the interconnection between OSA and percent (using the criterion of ≥ 2 voids per night).6 nocturia is the impact of oxidative stress resulting from intermit- tent episodes of apnea-induced hypoxia. In a study8 that used a rat In OSA, the upper airway muscles relax excessively during sleep, model of OSA, the investigators noted increased levels of bladder which allows tissues such as the tonsils and adenoids to be drawn oxidative stress markers (e.g., malondialdehyde and oxidation into the airway and block airflow. A person makes increasingly protein products), instability of the (when relaxed strong efforts to breathe as the blood oxygen level falls. The this muscle allows the bladder to store urine; it contracts during decrease in the oxygen level ultimately triggers a brief arousal. urination), bladder noncompliance, increased spontaneous bladder On arousing, the upper airway muscle tone is restored and the contractions, and increased urinary frequency and total urine airway opens, thereby allowing the person to take a few deep output in rats exposed to OSA conditions. Oxidative stress may quick breaths to restore the oxygen level. Once the oxygen level similarly contribute to nocturia in humans, although this factor is restored, the person resumes sleep, which may set the stage for has not been investigated in depth. another apnea event. How CPAP treatment improves nocturia in people with OSA REGINA PATRICK, RST, RPSGT is unclear. It may be that CPAP treatment reduces nocturia by impacting the renin-angiotensin-aldosterone system. Renin Regina Patrick, RST, RPSGT, has been (pronounced “REE-nin”), angiotensin, and aldosterone are three in the sleep field for more than 20 years hormones that work in conjunction (i.e., the renin-angiotensin-al- and works as a sleep technologist at dosterone system) to maintain fluid homeostasis in the body. A the Wolverine Sleep Disorders Center in disruption in this system can lead to increased urination. Tecumseh, Mich.

Various researchers have investigated the impact of CPAP

A2 Zzz 26.2 | June 2017 9 treatment on the renin-angiotensin-aldosterone system. For moderate to severe OSA. They divided the men into two groups example, in 1991, Follenius9 and colleagues investigated the effect by age: < 50 years and ≥ 50 years. Nocturia was defined as ≥ 2 of CPAP treatment on plasma levels of renin and aldosterone episodes of nighttime urination. (There is some controversy in in men with OSA. The men were divided into the untreated the literature whether one void is “abnormal”; therefore, some group or CPAP-treated group. For two nights, the plasma levels researchers consider two or more voids as “abnormal.”) They of renin and aldosterone were measured every 10 minutes. In found that the severity of nocturia was correlated with the severity the CPAP-treated men, Follenius noted diminished excretion of OSA in the younger group (i.e., < 50 years old), compared to of urine, increased plasma volume, a significant increase in the the older group (i.e., ≥ 50 years). Treatment by CPAP reduced mean levels of plasma renin and aldosterone, and similar plasma the number of nocturia episodes in 75 percent of the younger renin activity as that of people without sleep apnea. Continuous patients and in 90 percent of the older patients. Maeda suggests positive airway pressure treatment also restored the circadian that, because the number of nighttime urinations can be easily rhythmicity of renin and aldosterone production. Based on these monitored by urologists and general physicians, this symptom may findings, Follenius concluded that apnea-induced sleep disruption be a useful for screening tool for patients with moderate to severe was associated with the loss of the circadian rhythmicity of renin OSA, especially in patients younger than 50 years old. production, and that the restoration of the rhythmicity of renin and aldosterone production may contribute to the normalization To what extent CPAP treatment decreases nocturia episodes is of urine production after CPAP treatment. unclear because many studies investigating this have involved a small number of patients.11 With this in mind, Rahnama’i12 For patients who may be unwilling or unable to tolerate CPAP and colleagues used a large number of participants to assess the treatment, some research indicates that nocturia can be improved incidence of nocturia in CPAP-treated OSA patients. The study when apnea is treated by other means. In a recent Korean study, involved 256 patients. The patients answered a questionnaire Hyoung Keun Park10 and colleagues found that patients whose about their nocturia episodes before and after CPAP treatment. OSA was treated by uvulopalatopharyngoplasty (UPPP, a surgery The patients were subdivided into seven groups, based on the that opens the upper airway by removing the uvula, tonsils, and number of nightly nocturia episodes: (1) no nocturia episodes other upper airway tissues) had fewer nocturia episodes after this before or after treatment; (2) one nocturia episode; (3) two surgical treatment. In their study, 66 men with OSA underwent nocturia episodes; (4) three nocturia episodes; (5) four nocturia UPPP. The overall success rate of UPPP in their study was 73 episodes; (6) five nocturia episodes; and (7) seven nocturia percent. Patients were evaluated preoperatively and postoperative- episodes. Rahnama’i found that the prevalence of nocturia among ly for lower urinary tract symptoms, based on the International the patients was 69 percent and that CPAP treatment reduced Prostate Symptom Score and Overactive Bladder Symptom nocturia episodes in 65 percent of the patients. No patient had an Score questionnaires. Approximately 53 percent of the patients increase in nocturia with CPAP treatment. Rahnama’i concluded experienced a significant decrease in the number of nocturia that a clear relationship exists between OSAS treatment and the episodes and other urinary symptoms (e.g., overactive bladder). reduction of nocturia episodes. On dividing patients by treatment success or treatment failure 10,12,13 (i.e., apnea episodes did not decrease by 50 percent or more), Some studies have included men and women with nocturia Park noted that the success group had a significant posttreat- and OSA, and report a reduction in nocturia episodes in both sexes ment decrease in the number of nocturia episodes, whereas the when treated for OSA. However, physicians, even those in the field failure group did not. Based on these results, Park concluded of , often do not ask male or female patients complaining of that nocturia and other urinary symptoms can be improved by nocturia about symptoms of OSA. This oversight may contribute surgically correcting OSA. to the difficulty in relieving nocturia episodes and may lead to a 

patient being treated for a different problem. For example, some Continued on Page 10 Many studies that have investigated the beneficial effects of CPAP older men may erroneously be treated for prostate enlargement treatment on nocturia have focused on older men because the risk when the nocturia is related to OSA. Physicians need to consider of nocturia increases as men age because of prostate enlargement. asking patients complaining of nocturia, especially patients who do However, some research indicates that CPAP treatment helps not have kidney or (in men) prostate problems, about symptoms of nocturia in younger men, as demonstrated in a study by Takahiro sleep apnea (e.g., loud , awakening gasping for air, daytime Maeda6 and colleagues. In their study, the researchers investigated sleepiness). If a proves the patient has OSA, then the prevalence of nocturia among men with newly diagnosed treating it may improve nocturia.

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REFERENCES

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3. Zumrutbas AE, Bozkurt AI, Alkis O, et al. The prevalence 10. Park HK, Paick SH, Kim HG, et al. Nocturia improvement of nocturia and nocturnal : can new cutoff values with surgical correction of sleep apnea. International Neuro- be suggested according to age and sex? International Neuro- urology Journal. 2016;20:329-334. urology Journal. 2016;20:304-310. 11. Wang T, Huang W, Zong H, et al. The efficacy of con- 4. Schatzl G, Temml C, Schmidbauer J, et al. Cross-sectional tinuous positive airway pressure therapy on nocturia in study of nocturia in both sexes: Analysis of a voluntary patients with : A systematic review health screening project. Urology. 2000;56:71-75. and meta-analysis. International Neurourology Journal. 2015;19:178-184. 5. Yoshimura K, Terada N, Matsui Y, et al. Prevalence of and risk factors for nocturia: Analysis of a health screening 12. Rahnama’i M, Degaillier S, Ewoldt T, et al. Reduction of program. International Journal of Urology. 2004;11:282-287. nocturia in patients treated with C-PAP for obstructive sleep apnea syndrome. Bristol, United Kingdom: International 6. Maeda T, Fukunaga K, Nagata H, et al. Obstructive Continence Society; 2016. Abstract #9. sleep apnea syndrome should be considered as a cause of nocturia in younger patients without other void- 13. Miyazato M, Tohyama K, Touyama M, et al. Effect of ing symptoms. Canadian Urological Association Journal. continuous positive airway pressure on nocturnal urine pro- 2016;10(7-8):E241-E245. duction in patients with obstructive sleep apnea syndrome. Neurourology Urodynamics. 2017;36:376-379. 

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A2 Zzz 26.2 | June 2017