Date Published: May 24, 2019
Publisher: Public Library of Science
Author(s): Stéphanie van der Lely, Martina D. Liechti, Werner L. Popp, Melanie R. Schmidhalter, Thomas M. Kessler, Ulrich Mehnert, Peter F.W.M. Rosier.
During electrical stimulation in the lower urinary tract for the purpose of current perception threshold and sensory evoked potential recording, we observed that bladder volume increased rapidly. The aim of this prospective randomised comparative proof-of-concept study was to quantify urine production per time during stimulation of the lower urinary tract using different stimulation frequencies.
Ninety healthy subjects (18 to 36 years old) were included. Forty females and 50 males were randomly assigned to one of the following study groups: dome, trigone or proximal, membranous (males only) or distal urethra. Starting from 60mL prefilling, stimulation was performed at two separate visits with a 14 French custom-made catheter using randomly applied frequencies of 0.5Hz, 1.1Hz, 1.6Hz (each with 500 stimuli). After each stimulation cycle per frequency, urine production was assessed. Main outcome measures represented urine production during stimulation, daily life and their ratio.
Lower urinary tract electrical stimulation increased urine production per time compared to bladder diary baseline values. Linear mixed model showed that frequency (p<0.001), stimulation order (p = 0.003), intensity (p = 0.042), and gender (p = 0.047) had a significant influence on urine production. Location, visit and age had no significant influence. Urine production is increased during electrical stimulation with a bigger impact of higher frequencies. This might be relevant for methodological aspects in the assessment of lower urinary tract afferent function and for patients with impaired renal urine output. Inhibition of renal sympathetic nerve activity by vagal afferents may be the underlying mechanism.
Current perception threshold (CPT) and sensory evoked potential (SEP) recording are established techniques in neurophysiology to test human afferent nerve function and integrity, respectively. This also seems to be a promising approach for advanced sensory assessment of the lower urinary tract (LUT), which our group has investigated in healthy women and men with normal bladder function [1, 2]. Interestingly, during such neurophysiological studies using electrical LUT stimulation, we frequently observed that bladder volume seemed to increase rapidly over a short period of time. Apart from an online presentation that mentioned a similar observation during the assessment of bladder electrical stimulation on urine production in patients with acute decompensated heart failure , the literature on this topic is scarce and there is a lack of knowledge regarding functional interrelation of LUT stimulation and renal urine production. Thus, in this proof-of-concept study we aimed to quantify and validate our observations in terms of different stimulation frequencies, intensities and LUT locations. This is relevant from a physiological point of view since there is not yet a clear concept on the relationship between LUT electrical stimulation and urine production per time (UPT), which may be of clinical interest for diuretic treatment in cardio-vascular pathologies. Furthermore, it is important for measurements such as LUT CPT [4, 5] and SEP recording [1, 2] because rapidly changing bladder volumes may affect desire to void sensation altering susceptibility for electrical current as well as measurement accuracy due to electrode dislocation from the expanding bladder wall .
This prospective parallel-group study was approved by the local ethics committee (Kantonale Ethikkommission Zürich), registered at clinicaltrials.gov (Identifier: NCT02272309), and performed in accordance with the Declaration of Helsinki. Data were collected and managed using REDCap electronic data capture tools . All subjects provided written informed consent prior to inclusion.
Ninety subjects (40 females, 50 males) with a median age of 23.6 years (range: 18.3–35.8 years) were included for the analysis. Baseline characteristics are shown in Table 1 and S1A–S1E Table. One subject was excluded from a few statistical analyses due to a missing urine volume value after one stimulation cycle. Subjects reported mild, temporary, and self-limited (1–5 days) dysuria after 109 out of 180 measurements (62 out of 90 subjects) and mild, temporary, and self-limited (1–3 days) haematuria after 9 out of 180 measurements (9 subjects out of 90). Otherwise, all subjects tolerated the procedures well and no symptomatic UTI was reported.
This is the first study investigating the relationship between LUT electrical stimulation and urine production. Electrical stimulation significantly increased UPT compared to baseline BLD values. The urine production during electrical stimulation increased to such an extent that even considering baseline BLD values from daytime only (DT1) still resulted in a 3.3 fold increase in UPT.
There was a clear effect of LUT electrical stimulation on UPT shown in healthy subjects with a greater impact of higher frequencies. This might not only be relevant for methodological aspects in the assessment of LUT afferent function but also for patients with impaired urine production. The mechanisms behind our findings are still unclear warranting further investigations to confirm validity and to find physiological explanations for the mechanism of action.