Hypothesis / aims of study
Nocturia causes poor sleep quality by prompting nocturnal voids during the first uninterrupted sleep period
(FUSP). Nocturia decreases FUSP, and FUSP is a potentially valuable metric that correlates with changes in perceived sleep duration, depth, quality of sleep for the entire night, efficiency, and latency, as evaluated by Pittsburgh Sleep Quality Index (PSQI)(1). FUSP is closely associated with slow-wave or non-REM sleep. Sleep stages has four categories, and slow-wave sleep occurs during Stages N3 and N4. Stages N3 and N4 commonly occur during the first two sleep cycles (approximately 180 min after falling asleep) and are considered important for high-quality sleep(2). We hypothesize that desmopressin treatment for nocturia will improve subjective and objective sleep quality. Subjective sleep quality, estimated by a quality-of-life questionnaire, was improved by desmopressin treatment(3). Desmopressin prolonged FUSP, suggesting that the slow-wave sleep time might have been prolonged, although this is not factual. We investigate the change in subjective and objective sleep quality using electroencephalography (EEG) and PSQI post-desmopressin administration in patients with nocturia due to nocturnal polyuria.
Study design, materials and methods
Twenty male patients (≥65 years old) with nocturnal polyuria participated. The inclusion criteria were nocturnal frequency ≥2, nocturnal polyuria index (NPi) ≥0.33, the first uninterrupted sleep period (FUSP) ≤2.5 h, concentration of serum sodium ≥135 mEq/L, and estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73m2. The participants were provided with desmopressin 50 μg (as MINIRINMELT® OD Tablets 25 μg / 50μg; Ferring Pharmaceuticals Co., Ltd., Tokyo, Japan) to be orally administered once daily before going to bed. The study design is shown in the Figure. Visual analogue scale (VAS) was used as an additional indicator of subjective sleep quality. The VAS is a measurement instrument that asks patients to rate their sleep from “I could sleep well” (left end of the scale) to “I could not sleep at all” (right end of the scale). Subjective sleep quality was assessed using the length between the left end and the point at which a patient records their sleep rating. The primary endpoint was change in duration of slow-wave sleep (non-rapid eye movement sleep Stages 3 and 4) as evaluated by EEG at 28 days from baseline. The Wilcoxon test was used to compare the datasets between before treatment and around 28 days after treatment. Differences were considered significant at P<0.05, and all data were expressed as median (interquartile range).
Results
Five participants dropped out: EEG recordings of four could not be performed owing to sweating, and one experienced hyponatremia owing to desmopressin. The characteristics of 15 participants, whose data were analyzed, were as follows: age 74.0 (70.5, 76.0), post-void residual 14.5 (0.0, 24.8), body mass index 22.3 (20.9, 24.3), eGFR 70.7 (61.1, 88.2). Night-time urinary frequency and NPi significantly decreased and FUSP was significantly prolonged after treatment. Although VAS increased, time of slow-wave sleep and PSQI Global score were not significantly different between pre- and post-treatment (Table).
Interpretation of results
Our hypothesis was rejected possibly because of the difference in the age groups of participants. In a previous study which demonstrated the association between changes in PSQI Global score and FUSP, the participants were younger (mean age 62.0; standard deviation 13.1)(1) than in this study. The tendency for the duration of slow-wave sleep to decrease with age likely influenced the results.