Functional Urology
Transcutaneous interferential electrical stimulation for the management of non-neuropathic underactive bladder in children: a randomised clinical trial Abdol-Mohammad Kajbafzadeh, Lida Sharifi-Rad*, Seyedeh-Sanam Ladi-Seyedian and Sarah Mozafarpour Department of Pediatric Urology, Pediatric Urology Research Center, and *Department of Physical Therapy, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
Objectives To assess the efficacy of transcutaneous interferential electrical stimulation (IFES) and urotherapy in the management of non-neuropathic underactive bladder (UAB) in children with voiding dysfunction.
Patients and Methods In all, 36 children with UAB without neuropathic disease [15 boys, 21 girls; mean (SD) age 8.9 (2.6) years] were enrolled and then randomly allocated to two equal treatment groups comprising IFES and control groups. The control group underwent only standard urotherapy comprising diet, hydration, scheduled voiding, toilet training, and pelvic floor and abdominal muscles relaxation. Children in the IFES group likewise underwent standard urotherapy and also received IFES. Children in both groups underwent a 15session treatment programme twice a week. A complete voiding and bowel habit diary was completed by parents before, after treatment, and 1 year later. Bladder ultrasound and uroflowmetry/electromyography were performed before, at the end of treatment course, and at the 1-year follow-up.
therapy in IFES group, compared with only standard urotherapy in the control group [6.3 (1.4) vs 4.7 (1.3) times/ day, P < 0.002). The mean (SD) bladder capacity before treatment was 424 (123) and 463 (121) mL in the control and IFES groups, respectively, which decreased significantly at 1 year after treatment in the IFES group compared with the controls, at 227 (86) vs 344 (127) mL (P < 0.01). Maximum urine flow increased and voiding time decreased significantly in the IFES group compared with controls at the end of treatment sessions and 1 year later (P < 0.05). All the children had abnormal flow curves at the beginning of the study. The flow curve became normal in 14/18 (77%) of the children in the IFES group and six of 18 (33%) in the control group by the end of follow-up (P < 0.007). At the end of the treatment course, night-time wetting was improved in all children who had this symptom before the treatment in the IFES group (P < 0.01).
Conclusion Combining IFES and urotherapy is a safe and effective therapy in the management of children with UAB.
Results
Keywords
The mean (SD) number of voiding episodes before treatment was 2.6 (1) and 2.7 (0.76) times/day in the IFES and control groups, respectively, which significantly increased after IFES
voiding dysfunction, electrical stimulation, detrusor underactivity, underactive bladder, bladder
Introduction Underactive bladder (UAB), formerly referred to as a ‘lazy bladder’, is a form of voiding dysfunction that is not well appreciated in the literature. The International Children’s Continence Society (ICCS) defines UAB as impaired detrusor contractility and the need to increase intra-abdominal
© 2015 The Authors BJU International © 2015 BJU International | doi:10.1111/bju.13207 Published by John Wiley & Sons Ltd. www.bjui.org
pressure for complete voiding [1–3]. Children with UAB usually have a low voiding frequency, episodes of hesitancy, urge urinary incontinence (UI) or overflow UI. Also these children have a large-capacity bladder with incomplete emptying and high post-void residue urine volumes (PVRs), which often present with urinary tract infections ( UTIs) [1–3]. No effective pharmacotherapy exists to facilitate
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Kajbafzadeh et al.
bladder emptying. Muscarinic agonists have not shown efficiency in improving symptoms. Moreover, use of a blockers is also associated with adverse effects and is not approved for use in children [3]. This lack of effective pharmacotherapy has led to non-pharmacological alternatives. Urotherapy is a conservative method that involves child and family education, frequent voiding regimens, and toilet training, which is recommended to facilitate bladder emptying by increasing sensation of bladder fullness in these children [4]. The standard choice for bladder emptying in children resistant to urotherapy is clean intermittent catheterisation [3]. Electrical stimulation is used extensively today as an alternative option for a wide range of refractory clinical conditions including lower urinary tract syndromes in adults and children [5]. Interferential (IF) current is a type of electrical stimulation that uses two medium-frequency alternating currents to generate a low frequency beat effect in the tissue [6]. IF electrical stimulation (IFES) has been previously used to augment the strength of pelvic floor and deep skeletal muscles in adults [7,8], and has also shown benefits in decreasing constipation symptoms in children with slow transit constipation [9]. IFES has also been used for women with stress UI [10]. The widespread use of electrical stimulation for the treatment of lower urinary tract dysfunction in children along with the beneficial effects of IF current, led us to evaluate the safety and effectiveness of transcutaneous IFES in children with UAB during a 1-year follow-up.
Patients and Methods In all, 36 anatomically and neurologically normal children aged 5–13 years with urodynamically confirmed UAB were enrolled in this prospective study. The Institutional Ethics Committee of the Tehran University of Medical Sciences approved the study (project no. 26659) and informed written consent was obtained from all patients and their parents before the study. All procedures complied with the Declaration of Helsinki. Participants were recruited from patients who had been evaluated between June 2011 and October 2014 in the outpatient paediatric urology clinic at the Children’s Hospital Medical Center of the Tehran University of Medical Sciences. Based on ICCS recommendations, UAB was defined as voiding infrequency and straining with an interrupted pattern on uroflowmetry and detrusor underactivity on urodynamic evaluation. Urodynamic confirmation of UAB was made by reduced bladder sensation during filling phase, high cystometric bladder capacity, voiding contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete emptying within a normal time span, abdominal straining, and elevation of abdominal pressure
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during voiding [2]. According to the ICCS guidelines, flow patterns were defined as abnormal (interrupted, staccato and plateau) or normal (bell shape). As an interrupted pattern on uroflowmetry suggests UAB, we only enrolled children with this abnormal pattern in the present study [2]. Each peak in the flow pattern represents abdominal muscle straining producing the main force for urine emptying; in between each strain, the flow ceases. Also, abdominal pressure was monitored during uroflowmetry/electromyography (EMG). Study inclusion criteria were urodynamically confirmed UAB in children who had no response to medication, an interrupted flow pattern with a low maximum flow rate, prolonged voiding time, ≤3 voids/day and abdominal straining, a PVR of >20 mL, and aged ≥5 years. Exclusion criteria were children with mental retardation, neurological disorders, and anatomical defects. Of the 62 children with UAB assessed for eligibility, only 36 children were randomly assigned in a randomised clinical trial using random block sizes of four (ratio 1:1) into two equal treatment groups by a computer-generated list of random numbers. The IFES group (18 children) underwent standard urotherapy combined with IFES, while the control group (18) received only standard urotherapy without IFES. Evaluations Children had different lower urinary tract symptoms such as infrequency, voiding postponement, straining, UI and recurrent episodes of UTI with no response to conventional medical therapy. Before entering the study, a complete voiding diary was completed. Also, uroflowmetry/EMG and measurement of PVR were done by bladder ultrasound to evaluate UAB. All children underwent uroflowmetry/EMG in two separate sessions presenting an interrupted flow pattern with low peak flow rate, prolonged voiding time, and large voided volume. Participants in both groups underwent full urological evaluation, as well as physical and neurological investigations. The study evaluations comprised urine analysis and urine culture to assess UTI, kidney and bladder ultrasound to evaluate anomalies, bladder capacity and PVR, a bladder diary, X-ray imaging of the lumbo-sacral spine, uroflowmetry with EMG, and voiding cystourethrography (VCUG) for patients with a history of UTI. Expected bladder capacity was measured following the ICCS recommendation, using the formula: bladder capacity (mL) = ([age in years + 1] 9 30) [2]. Parents were asked to keep a 7-day voiding and bowel habit diary, including a 7-night recording of UI episodes to evaluate enuresis, and a 48-h daytime frequency and a volume chart comprised of episodes of wetting, voiding frequency, voided volume, fluid intake (time, volume and
Electrical stimulation for underactive bladder
type), defecation frequency, stool form, and episodes of faecal soiling. Constipation was defined with regard to the Rome III criteria as having two or more of following manifestations for at least 8 weeks: ≤2 defecations/week, ≥1 episode of UI/week after the acquisition of toileting skills, history of excessive stool retention, history of painful or hard bowel movements, presence of a large faecal mass in the rectum, and history of large diameter stools that may obstruct the toilet [11]. For all children in both groups, a 7-day voiding and bowel diary was recorded before, at the end of the treatment sessions and 1-year later. Results were then compared between the two groups. Patient Education and Treatment Programme Children in both groups (IFES and control groups) underwent a 15-session treatment programme twice a week in the urotherapy clinic at the Children Hospital Medical Center of the Tehran University of Medical Sciences. At every treatment session, all children (IFES and control groups) underwent standard urotherapy. In addition, in every treatment session children in IFES group received IFES. All parents and children (IFES and control groups) were trained about urinary and gastrointestinal tract function. Consecutively, normal drinking habit, scheduled voiding, the normal mechanism of toilet training, and the effects of high fibre diet on their treatment were described. Along with standard urotherapy, each child in the IFES group underwent IFES by a paediatric physiotherapist, twice a week with each session lasting for 20 min. During this period, optimal therapy (i.e., standard urotherapy alone or combined with IFES) performance was assured in all children (IFES and control group). After completion of the treatment courses, all children underwent monthly clinical visits during the 12month study in order to support the training programme and to enhance compliance. Standard Urotherapy Standard urotherapy was explained to both groups at the beginning of the study. Standard urotherapy included a simple explanation to the children and parents about urinary and gastrointestinal tract function, adapted fluid intake along with timed voiding (every 2 or 3 h), toilet training, and correction of voiding posture in addition to double voiding for patients with high PVRs. To obtain optimal toilet training, correct voiding posture and use of foot support in small children were practiced in every treatment session. Children were also taught to appropriately abduct the hip and relax abdominal and pelvic floor muscles during voiding while maintaining a strong voiding stream. All children received adequate training on appropriate contraction of pelvic floor muscles for 10 s, and then relaxing these muscles for 30 s in every treatment session. Stool regulation is a
necessary part of treatment for children with constipation; thus, a high fibre diet was recommended and children were asked to sit on the toilet three times a day after mealtime in a relaxed position for 5 min. Children in the IFES group likewise underwent standard urotherapy but in addition received IFES in every treatment session. IFES In all, 15 courses of IFES were applied for 20 min twice a week by a paediatric physiotherapist. The IFES generated a 4kHz carrier frequency and a beat frequency sweep at 5– 55 Hz, for a duration of 250 ls, and a repeated time of 6 s with adjustable amplitude (0–50 mA). The same IF current device (model 510 A, double-channels; NOVIN, Isfahan, Iran) was used for all the children. To deliver the current, two rectangular self-adhesive (2.5 9 3.5 cm) electrodes, one from each channel, were bilaterally placed on the skin of the symphysis pubis, and two other electrodes from each channel were placed crosswise on the skin under the ischial tuberosity; with this approach, the current from each channel crosses along the pelvic floor and bladder. The intensity was increased until the child reported a strong but comfortable level of sensory awareness. As maximum current intensity was below the pain threshold, children tolerated the current well. Outcome Measurement Primary outcome measures were evaluated, with respect to subjective parameters (presence or absence of daytime wetting, night-time wetting, number of voiding episodes, and constipation), as well as objective parameters (uroflowmetry/ EMG outcomes, flow pattern, UTI and PVR) at the end of the treatment. Secondary outcome measures (subjective and objective parameters) were evaluated at the 1-year follow-up. VCUG was performed in patients who had vesico-ureteral reflux (VUR) at the beginning of the study or had a new episode of UTI. Urine analysis and urine culture were assessed during the monthly clinical visits in all children who had symptomatic UTIs before their recruitment in the study. Sample Size and Statistical Analysis The sample size was 36 patients calculated to have 80% power (b = 0.2). The Statistical Package of Social Science software (version 18; SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. Categorical data were reported as frequencies and percentages. Continuous data were reported as the mean (SD). To analyse data, chi-square or Fisher’s exact tests were used. The Student’s t-test and Mann–Whitney U-test were used to compare variables between the control and IFES groups. In order to compare variables in each group
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before and after treatment, the Wilcoxon signed-rank test was used. A P < 0.05 was considered to indicate statistical significance.
symptom before treatment (P < 0.01). The changes in subjective parameters at the end of the treatment courses and at the 1-year follow-up in both groups are shown in Table 1.
Results
Objective Outcomes
In all, 21 girls and 15 boys with UAB were recruited in the present study. The control group comprised 11 girls and seven boys [mean (SD) age 9.2 (2.5) years] and the IFES group included nine boys and nine girls (mean [SD] age 8.4 [2.4] years). There was no significant difference in age, gender and subjective parameters between the two groups before treatment (P > 0.05). All randomised children completed the trial. A flow diagram of the study is shown in Fig. 1.
The mean (SD) bladder capacity before treatment was 424 (123) and 463 (121) mL in the control and IFES groups, respectively. The bladder capacity decreased significantly at 1 year after treatment in the IFES group compared with the Fig. 2 Change in the mean number of voiding episodes in the IFES and control groups at the end of treatment and at the 1-year follow-up.
Subjective Outcomes For the baseline voiding diary; the mean (SD) number of voiding episodes was 2.6 (1) times/day in the IFES group and 2.7 (0.76) times/day in the control group. Children in both groups had timed-voiding (every 2 or 3 h) during the study and the mean number of voiding episodes (without timedvoiding) after the end of the treatment courses and 1-year later on voiding diary, was significantly increased after IFES therapy in IFES group, compared with only standard urotherapy in control group, at 6.3 (1.4) vs 4.7 (1.3) times/ day (P < 0.002; Fig. 2).
Mean number of voiding episodes
9 Control IFES
8 7 6 5 4 3 2
Night-time wetting was improved at the end of treatment courses in all children in the IFES group who had this
Before treatment
At the end of treatment courses
Fig. 1 Flow diagram of the study. Assessed for eligibility (n=62)
Excluded (n=26) ¨ Not meeting inclusion criteria (n=17) ¨ Declined to participate (n=6) ¨ Other reasons (n=3) Randomized (n=36)
Allocation IFES + standard urotherapy Allocated to intervention (n=18) ¨ Received allocated intervention (n=18) ¨ Did not receive allocated intervention (n=0)
Standard urotherapy Allocated to intervention (n=18) Received allocated intervention (n=18) ¨ ¨ Did not receive allocated intervention (n=0)
Follow-Up Lost to follow-up (n=0) Discontinued intervention (n=0)
Lost to follow-up (n=0) Discontinued intervention (n=0)
Analysis Analysed (n=18) ¨ Excluded from analysis (n=0)
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Analysed (n=18) ¨ Excluded from analysis (n=0)
1-year follow-up
Electrical stimulation for underactive bladder
Table 1 Clinical features of children with UAB before and after treatment, and at the 1-year follow-up. Variable
Daytime wetting IFES group Control group Night wetting IFES group Control group Constipation IFES group Control group UTI IFES group Control group EMG activity during voiding IFES group Control group Abnormal voiding pattern IFES group Control group VUR IFES group Control group
Before treatment n/N (%)
P*
After treatment n/N (%)
P*
P*
1-year follow-up n/N (%)
5/18 (27) 3/18 (16)
0.631
1/18 (5.5) 1/18 (5.5)
0.104
2/18 (11) 1/18 (8)
0.074
8/18 (44) 7/18 (38)
0.581
0/18 5/18 (22)
0.016
1/18 (11) 5/18 (27)
0.086
5/18 (27) 3/18 (16)
0.423
1/18 (5.5) 2/18 (11)
0.546
0/18 2/18 (11)
0.145
7/18 (38) 11/18 (61)
0.182
2/18 (11) 5/18 (27)
0.206
2/18 (11) 6/18 (33)
0.145
12/18 (66) 9/18 (50)
0.310
2/18 (11) 6/18 (33)
0.109
3/18 (16) 6/18 (33)
0.324
18/18 (100) 18/18 (100)
1
3/18 (16) 11/18 (61)
0.006
4/18 (22) 12/18 (60)
0.007
2/18 (11) 4/18 (22)
0.369
6/18 (33) 8/18 (44)
0.494
– –
–
*Chi-square test; the bold number shows significant P values.
controls (P < 0.01; Fig. 3). The reduction in the PVR in the IFES group was significantly higher than in the control group at the two evaluations (P < 0.03; Table 2). Moreover, the reduction in PVR based on the percentage of the bladder volume in the IFES group was significantly higher than the controls at the two evaluations (P < 0.05, P < 0.04; Table 2). Of uroflowmetry parameters, maximum urine flow increased and voiding time decreased significantly in the IFES group compared with the controls at the end of treatment sessions and at 1 year later [mean (SD) 21 (8.3) vs 12.8 (4.8) mL/s; P < 0.002). All patients had abnormal flow curves at the beginning of the study. The flow curve became normal in 14/18 (77%) of the children in the IFES group and six of the 18 (33%) in the control group, respectively at the end of follow up (P < 0.007; Table 2). Parents and children reported no side-effects during and after IFES.
Discussion In the present study, we compared the effect of IFES plus urotherapy with urotherapy alone in the improvement of uroflowmetry characteristics and voiding symptoms in children with UAB. To the best of our knowledge, there is no similar study that evaluates and compares the effects of IFES with conventional urotherapy in management of UAB in children. The present study showed a significant decrease in PVR and mean bladder capacity, with an increase in the mean number of voiding episodes, as well as a normalisation of the uroflowmetry pattern in children who underwent a
combination of standard urotherapy and IFES compared with children who were treated with only standard urotherapy. A lack of effective pharmacotherapy has led to the development of non-pharmacological alternatives. Recently, delivery of intravesical electrical stimulation has emerged as an alternative [12,13]; however, it is an invasive and risky procedure in children and there is no controlled clinical trial for this technique. The goal in the management of UAB is to prevent upper tract damage, reduce PVR and prevent bladder over distention [14]. Although no definitive consensus exists on the appropriate definition of impaired bladder emptying, there is general agreement that afferent fibres, CNS, efferent fibres, and the detrusor muscles are contributing factors, with impaired detrusor contractility regarded as the most common cause [15,16]. IFES has several distinct features. Two medium frequency currents intersect in the target tissue producing a beating effect. The medium frequency currents decrease tissue impedance, penetrate more deeply and more easily, and cause less discomfort. Compared with other modes of electrical stimulation, patients may only feel a tingling sensation. Minimal discomfort ensures patients ‘compliance especially in the paediatric setting. Moreover, proper electrode placements deliver the electrical stimulation precisely at the desired point in the crossover area with the least unwanted effects on the surrounding organs. Another advantage of IFES is that it uses sweep frequencies, so that nerves do not accommodate to a constant signal. © 2015 The Authors BJU International © 2015 BJU International
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Pelvic IFES has been used to augment pelvic muscle strength as well as to restore the micturition neuronal reflex in adult and paediatric patients [17]. Hence, there is the potential for IFES to improve bladder emptying by affecting both neural and muscular properties. However, there is no report on the effectiveness of pelvic IFES in symptom improvements and uroflowmetric alterations. There is a considerable overlap between different lower urinary tract dysfunction conditions. For example, a child may start with holding manoeuvres that may be evident with toe-curling and leg movements to potentially inhibit detrusor Fig. 3 Change in mean blabber capacity in the IFES and control groups at the end of tratment and at the 1-year follow-up.
550
Control IFES
Mean Bladder capacity, mL
500 450 400 350 300 250 200 150
Before the treatment
At the end of treatment At 1-year follow-up courses
contraction and allow a greater than age-related capacity of urine to fill up the bladder. This process continues through dysfunctional voiding, and then voiding postponement, and finally with an UAB. Children with dysfunctional voiding show staccato flow curve on uroflowmetry studies. Although, this flow curve is irregular and fluctuating during voiding, the flow is continuous and never reaches zero during voiding. Children with UAB show an interrupted flow pattern on uroflowmetry. An interrupted flow curve shows discrete segments of urine flow, separated by segments with zero flow. This flow curve suggests an UAB in which each peak shows abdominal muscle straining producing the main force for urine emptying. In between each strain, the flow ceases. This flow pattern may be seen with incoordination between the bladder and external urethral sphincter [1,2]. In children with UAB, abdominal muscle contraction acts as the main force for bladder emptying due to decreased detrusor contractility. Each time a child contracts the abdominal muscles, i.e. straining, a peak appears in the flow curve causing an interrupted pattern [18]. In the present study, we showed that an interrupted flow pattern became normal in 77% of children undergoing IFES. Moreover, both groups improved sensation of bladder fullness marked by increased frequency of voiding. The PVR is an index of incomplete bladder emptying and is responsible for UTIs. A PVR of >20 mL implies abnormal bladder emptying. In our experience, IFES significantly reduced the PVR from a mean (SD) of 60 (32) to
Table 2 Uroflowmetry measurements and voiding episodes before and after treatment, and at the 1-year follow-up. Variable
Before treatment
Mean (SD) Bladder capacity, mL IFES group 424 (123) Control group 463 (121) Maximum urine flow, mL/s IFES group 10.2 (2.9) Control group 9.5 (2.4) Average urine flow, mL/s IFES group 5.8 (2.1) Control group 5.2 (2.2) Voided volume, mL IFES group 426 (133) Control group 407 (129) Voiding time, s IFES group 54.1 (20) Control group 65 (20) PVR, mL IFES group 60 (32) Control group 80 (48) PVR based on % of bladder volume IFES group 19.7 (10) Control group 15.7 (9.9) Voiding episodes, n/day IFES group 2.6 (1) Control group 2.7 (0.73) *
Student’s t-test; the bold number shows significant P values.
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P*
After treatment
P*
1-year follow-up
P*
0.374
238 (58) 366 (67)
Transcutaneous interferential electrical stimulation for the management of non-neuropathic underactive bladder in children: a randomised clinical trial Abdol-Mohammad Kajbafzadeh, Lida Sharifi-Rad*, Seyedeh-Sanam Ladi-Seyedian and Sarah Mozafarpour Department of Pediatric Urology, Pediatric Urology Research Center, and *Department of Physical Therapy, Children’s Hospital Medical Center, Pediatric Center of Excellence, Tehran University of Medical Sciences, Tehran, Iran
Objectives To assess the efficacy of transcutaneous interferential electrical stimulation (IFES) and urotherapy in the management of non-neuropathic underactive bladder (UAB) in children with voiding dysfunction.
Patients and Methods In all, 36 children with UAB without neuropathic disease [15 boys, 21 girls; mean (SD) age 8.9 (2.6) years] were enrolled and then randomly allocated to two equal treatment groups comprising IFES and control groups. The control group underwent only standard urotherapy comprising diet, hydration, scheduled voiding, toilet training, and pelvic floor and abdominal muscles relaxation. Children in the IFES group likewise underwent standard urotherapy and also received IFES. Children in both groups underwent a 15session treatment programme twice a week. A complete voiding and bowel habit diary was completed by parents before, after treatment, and 1 year later. Bladder ultrasound and uroflowmetry/electromyography were performed before, at the end of treatment course, and at the 1-year follow-up.
therapy in IFES group, compared with only standard urotherapy in the control group [6.3 (1.4) vs 4.7 (1.3) times/ day, P < 0.002). The mean (SD) bladder capacity before treatment was 424 (123) and 463 (121) mL in the control and IFES groups, respectively, which decreased significantly at 1 year after treatment in the IFES group compared with the controls, at 227 (86) vs 344 (127) mL (P < 0.01). Maximum urine flow increased and voiding time decreased significantly in the IFES group compared with controls at the end of treatment sessions and 1 year later (P < 0.05). All the children had abnormal flow curves at the beginning of the study. The flow curve became normal in 14/18 (77%) of the children in the IFES group and six of 18 (33%) in the control group by the end of follow-up (P < 0.007). At the end of the treatment course, night-time wetting was improved in all children who had this symptom before the treatment in the IFES group (P < 0.01).
Conclusion Combining IFES and urotherapy is a safe and effective therapy in the management of children with UAB.
Results
Keywords
The mean (SD) number of voiding episodes before treatment was 2.6 (1) and 2.7 (0.76) times/day in the IFES and control groups, respectively, which significantly increased after IFES
voiding dysfunction, electrical stimulation, detrusor underactivity, underactive bladder, bladder
Introduction Underactive bladder (UAB), formerly referred to as a ‘lazy bladder’, is a form of voiding dysfunction that is not well appreciated in the literature. The International Children’s Continence Society (ICCS) defines UAB as impaired detrusor contractility and the need to increase intra-abdominal
© 2015 The Authors BJU International © 2015 BJU International | doi:10.1111/bju.13207 Published by John Wiley & Sons Ltd. www.bjui.org
pressure for complete voiding [1–3]. Children with UAB usually have a low voiding frequency, episodes of hesitancy, urge urinary incontinence (UI) or overflow UI. Also these children have a large-capacity bladder with incomplete emptying and high post-void residue urine volumes (PVRs), which often present with urinary tract infections ( UTIs) [1–3]. No effective pharmacotherapy exists to facilitate
BJU Int 2016; 117: 793–800 wileyonlinelibrary.com
Kajbafzadeh et al.
bladder emptying. Muscarinic agonists have not shown efficiency in improving symptoms. Moreover, use of a blockers is also associated with adverse effects and is not approved for use in children [3]. This lack of effective pharmacotherapy has led to non-pharmacological alternatives. Urotherapy is a conservative method that involves child and family education, frequent voiding regimens, and toilet training, which is recommended to facilitate bladder emptying by increasing sensation of bladder fullness in these children [4]. The standard choice for bladder emptying in children resistant to urotherapy is clean intermittent catheterisation [3]. Electrical stimulation is used extensively today as an alternative option for a wide range of refractory clinical conditions including lower urinary tract syndromes in adults and children [5]. Interferential (IF) current is a type of electrical stimulation that uses two medium-frequency alternating currents to generate a low frequency beat effect in the tissue [6]. IF electrical stimulation (IFES) has been previously used to augment the strength of pelvic floor and deep skeletal muscles in adults [7,8], and has also shown benefits in decreasing constipation symptoms in children with slow transit constipation [9]. IFES has also been used for women with stress UI [10]. The widespread use of electrical stimulation for the treatment of lower urinary tract dysfunction in children along with the beneficial effects of IF current, led us to evaluate the safety and effectiveness of transcutaneous IFES in children with UAB during a 1-year follow-up.
Patients and Methods In all, 36 anatomically and neurologically normal children aged 5–13 years with urodynamically confirmed UAB were enrolled in this prospective study. The Institutional Ethics Committee of the Tehran University of Medical Sciences approved the study (project no. 26659) and informed written consent was obtained from all patients and their parents before the study. All procedures complied with the Declaration of Helsinki. Participants were recruited from patients who had been evaluated between June 2011 and October 2014 in the outpatient paediatric urology clinic at the Children’s Hospital Medical Center of the Tehran University of Medical Sciences. Based on ICCS recommendations, UAB was defined as voiding infrequency and straining with an interrupted pattern on uroflowmetry and detrusor underactivity on urodynamic evaluation. Urodynamic confirmation of UAB was made by reduced bladder sensation during filling phase, high cystometric bladder capacity, voiding contraction of reduced strength and/or duration, resulting in prolonged bladder emptying and/or a failure to achieve complete emptying within a normal time span, abdominal straining, and elevation of abdominal pressure
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© 2015 The Authors BJU International © 2015 BJU International
during voiding [2]. According to the ICCS guidelines, flow patterns were defined as abnormal (interrupted, staccato and plateau) or normal (bell shape). As an interrupted pattern on uroflowmetry suggests UAB, we only enrolled children with this abnormal pattern in the present study [2]. Each peak in the flow pattern represents abdominal muscle straining producing the main force for urine emptying; in between each strain, the flow ceases. Also, abdominal pressure was monitored during uroflowmetry/electromyography (EMG). Study inclusion criteria were urodynamically confirmed UAB in children who had no response to medication, an interrupted flow pattern with a low maximum flow rate, prolonged voiding time, ≤3 voids/day and abdominal straining, a PVR of >20 mL, and aged ≥5 years. Exclusion criteria were children with mental retardation, neurological disorders, and anatomical defects. Of the 62 children with UAB assessed for eligibility, only 36 children were randomly assigned in a randomised clinical trial using random block sizes of four (ratio 1:1) into two equal treatment groups by a computer-generated list of random numbers. The IFES group (18 children) underwent standard urotherapy combined with IFES, while the control group (18) received only standard urotherapy without IFES. Evaluations Children had different lower urinary tract symptoms such as infrequency, voiding postponement, straining, UI and recurrent episodes of UTI with no response to conventional medical therapy. Before entering the study, a complete voiding diary was completed. Also, uroflowmetry/EMG and measurement of PVR were done by bladder ultrasound to evaluate UAB. All children underwent uroflowmetry/EMG in two separate sessions presenting an interrupted flow pattern with low peak flow rate, prolonged voiding time, and large voided volume. Participants in both groups underwent full urological evaluation, as well as physical and neurological investigations. The study evaluations comprised urine analysis and urine culture to assess UTI, kidney and bladder ultrasound to evaluate anomalies, bladder capacity and PVR, a bladder diary, X-ray imaging of the lumbo-sacral spine, uroflowmetry with EMG, and voiding cystourethrography (VCUG) for patients with a history of UTI. Expected bladder capacity was measured following the ICCS recommendation, using the formula: bladder capacity (mL) = ([age in years + 1] 9 30) [2]. Parents were asked to keep a 7-day voiding and bowel habit diary, including a 7-night recording of UI episodes to evaluate enuresis, and a 48-h daytime frequency and a volume chart comprised of episodes of wetting, voiding frequency, voided volume, fluid intake (time, volume and
Electrical stimulation for underactive bladder
type), defecation frequency, stool form, and episodes of faecal soiling. Constipation was defined with regard to the Rome III criteria as having two or more of following manifestations for at least 8 weeks: ≤2 defecations/week, ≥1 episode of UI/week after the acquisition of toileting skills, history of excessive stool retention, history of painful or hard bowel movements, presence of a large faecal mass in the rectum, and history of large diameter stools that may obstruct the toilet [11]. For all children in both groups, a 7-day voiding and bowel diary was recorded before, at the end of the treatment sessions and 1-year later. Results were then compared between the two groups. Patient Education and Treatment Programme Children in both groups (IFES and control groups) underwent a 15-session treatment programme twice a week in the urotherapy clinic at the Children Hospital Medical Center of the Tehran University of Medical Sciences. At every treatment session, all children (IFES and control groups) underwent standard urotherapy. In addition, in every treatment session children in IFES group received IFES. All parents and children (IFES and control groups) were trained about urinary and gastrointestinal tract function. Consecutively, normal drinking habit, scheduled voiding, the normal mechanism of toilet training, and the effects of high fibre diet on their treatment were described. Along with standard urotherapy, each child in the IFES group underwent IFES by a paediatric physiotherapist, twice a week with each session lasting for 20 min. During this period, optimal therapy (i.e., standard urotherapy alone or combined with IFES) performance was assured in all children (IFES and control group). After completion of the treatment courses, all children underwent monthly clinical visits during the 12month study in order to support the training programme and to enhance compliance. Standard Urotherapy Standard urotherapy was explained to both groups at the beginning of the study. Standard urotherapy included a simple explanation to the children and parents about urinary and gastrointestinal tract function, adapted fluid intake along with timed voiding (every 2 or 3 h), toilet training, and correction of voiding posture in addition to double voiding for patients with high PVRs. To obtain optimal toilet training, correct voiding posture and use of foot support in small children were practiced in every treatment session. Children were also taught to appropriately abduct the hip and relax abdominal and pelvic floor muscles during voiding while maintaining a strong voiding stream. All children received adequate training on appropriate contraction of pelvic floor muscles for 10 s, and then relaxing these muscles for 30 s in every treatment session. Stool regulation is a
necessary part of treatment for children with constipation; thus, a high fibre diet was recommended and children were asked to sit on the toilet three times a day after mealtime in a relaxed position for 5 min. Children in the IFES group likewise underwent standard urotherapy but in addition received IFES in every treatment session. IFES In all, 15 courses of IFES were applied for 20 min twice a week by a paediatric physiotherapist. The IFES generated a 4kHz carrier frequency and a beat frequency sweep at 5– 55 Hz, for a duration of 250 ls, and a repeated time of 6 s with adjustable amplitude (0–50 mA). The same IF current device (model 510 A, double-channels; NOVIN, Isfahan, Iran) was used for all the children. To deliver the current, two rectangular self-adhesive (2.5 9 3.5 cm) electrodes, one from each channel, were bilaterally placed on the skin of the symphysis pubis, and two other electrodes from each channel were placed crosswise on the skin under the ischial tuberosity; with this approach, the current from each channel crosses along the pelvic floor and bladder. The intensity was increased until the child reported a strong but comfortable level of sensory awareness. As maximum current intensity was below the pain threshold, children tolerated the current well. Outcome Measurement Primary outcome measures were evaluated, with respect to subjective parameters (presence or absence of daytime wetting, night-time wetting, number of voiding episodes, and constipation), as well as objective parameters (uroflowmetry/ EMG outcomes, flow pattern, UTI and PVR) at the end of the treatment. Secondary outcome measures (subjective and objective parameters) were evaluated at the 1-year follow-up. VCUG was performed in patients who had vesico-ureteral reflux (VUR) at the beginning of the study or had a new episode of UTI. Urine analysis and urine culture were assessed during the monthly clinical visits in all children who had symptomatic UTIs before their recruitment in the study. Sample Size and Statistical Analysis The sample size was 36 patients calculated to have 80% power (b = 0.2). The Statistical Package of Social Science software (version 18; SPSS, Inc., Chicago, IL, USA) was used for statistical analysis. Categorical data were reported as frequencies and percentages. Continuous data were reported as the mean (SD). To analyse data, chi-square or Fisher’s exact tests were used. The Student’s t-test and Mann–Whitney U-test were used to compare variables between the control and IFES groups. In order to compare variables in each group
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before and after treatment, the Wilcoxon signed-rank test was used. A P < 0.05 was considered to indicate statistical significance.
symptom before treatment (P < 0.01). The changes in subjective parameters at the end of the treatment courses and at the 1-year follow-up in both groups are shown in Table 1.
Results
Objective Outcomes
In all, 21 girls and 15 boys with UAB were recruited in the present study. The control group comprised 11 girls and seven boys [mean (SD) age 9.2 (2.5) years] and the IFES group included nine boys and nine girls (mean [SD] age 8.4 [2.4] years). There was no significant difference in age, gender and subjective parameters between the two groups before treatment (P > 0.05). All randomised children completed the trial. A flow diagram of the study is shown in Fig. 1.
The mean (SD) bladder capacity before treatment was 424 (123) and 463 (121) mL in the control and IFES groups, respectively. The bladder capacity decreased significantly at 1 year after treatment in the IFES group compared with the Fig. 2 Change in the mean number of voiding episodes in the IFES and control groups at the end of treatment and at the 1-year follow-up.
Subjective Outcomes For the baseline voiding diary; the mean (SD) number of voiding episodes was 2.6 (1) times/day in the IFES group and 2.7 (0.76) times/day in the control group. Children in both groups had timed-voiding (every 2 or 3 h) during the study and the mean number of voiding episodes (without timedvoiding) after the end of the treatment courses and 1-year later on voiding diary, was significantly increased after IFES therapy in IFES group, compared with only standard urotherapy in control group, at 6.3 (1.4) vs 4.7 (1.3) times/ day (P < 0.002; Fig. 2).
Mean number of voiding episodes
9 Control IFES
8 7 6 5 4 3 2
Night-time wetting was improved at the end of treatment courses in all children in the IFES group who had this
Before treatment
At the end of treatment courses
Fig. 1 Flow diagram of the study. Assessed for eligibility (n=62)
Excluded (n=26) ¨ Not meeting inclusion criteria (n=17) ¨ Declined to participate (n=6) ¨ Other reasons (n=3) Randomized (n=36)
Allocation IFES + standard urotherapy Allocated to intervention (n=18) ¨ Received allocated intervention (n=18) ¨ Did not receive allocated intervention (n=0)
Standard urotherapy Allocated to intervention (n=18) Received allocated intervention (n=18) ¨ ¨ Did not receive allocated intervention (n=0)
Follow-Up Lost to follow-up (n=0) Discontinued intervention (n=0)
Lost to follow-up (n=0) Discontinued intervention (n=0)
Analysis Analysed (n=18) ¨ Excluded from analysis (n=0)
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Analysed (n=18) ¨ Excluded from analysis (n=0)
1-year follow-up
Electrical stimulation for underactive bladder
Table 1 Clinical features of children with UAB before and after treatment, and at the 1-year follow-up. Variable
Daytime wetting IFES group Control group Night wetting IFES group Control group Constipation IFES group Control group UTI IFES group Control group EMG activity during voiding IFES group Control group Abnormal voiding pattern IFES group Control group VUR IFES group Control group
Before treatment n/N (%)
P*
After treatment n/N (%)
P*
P*
1-year follow-up n/N (%)
5/18 (27) 3/18 (16)
0.631
1/18 (5.5) 1/18 (5.5)
0.104
2/18 (11) 1/18 (8)
0.074
8/18 (44) 7/18 (38)
0.581
0/18 5/18 (22)
0.016
1/18 (11) 5/18 (27)
0.086
5/18 (27) 3/18 (16)
0.423
1/18 (5.5) 2/18 (11)
0.546
0/18 2/18 (11)
0.145
7/18 (38) 11/18 (61)
0.182
2/18 (11) 5/18 (27)
0.206
2/18 (11) 6/18 (33)
0.145
12/18 (66) 9/18 (50)
0.310
2/18 (11) 6/18 (33)
0.109
3/18 (16) 6/18 (33)
0.324
18/18 (100) 18/18 (100)
1
3/18 (16) 11/18 (61)
0.006
4/18 (22) 12/18 (60)
0.007
2/18 (11) 4/18 (22)
0.369
6/18 (33) 8/18 (44)
0.494
– –
–
*Chi-square test; the bold number shows significant P values.
controls (P < 0.01; Fig. 3). The reduction in the PVR in the IFES group was significantly higher than in the control group at the two evaluations (P < 0.03; Table 2). Moreover, the reduction in PVR based on the percentage of the bladder volume in the IFES group was significantly higher than the controls at the two evaluations (P < 0.05, P < 0.04; Table 2). Of uroflowmetry parameters, maximum urine flow increased and voiding time decreased significantly in the IFES group compared with the controls at the end of treatment sessions and at 1 year later [mean (SD) 21 (8.3) vs 12.8 (4.8) mL/s; P < 0.002). All patients had abnormal flow curves at the beginning of the study. The flow curve became normal in 14/18 (77%) of the children in the IFES group and six of the 18 (33%) in the control group, respectively at the end of follow up (P < 0.007; Table 2). Parents and children reported no side-effects during and after IFES.
Discussion In the present study, we compared the effect of IFES plus urotherapy with urotherapy alone in the improvement of uroflowmetry characteristics and voiding symptoms in children with UAB. To the best of our knowledge, there is no similar study that evaluates and compares the effects of IFES with conventional urotherapy in management of UAB in children. The present study showed a significant decrease in PVR and mean bladder capacity, with an increase in the mean number of voiding episodes, as well as a normalisation of the uroflowmetry pattern in children who underwent a
combination of standard urotherapy and IFES compared with children who were treated with only standard urotherapy. A lack of effective pharmacotherapy has led to the development of non-pharmacological alternatives. Recently, delivery of intravesical electrical stimulation has emerged as an alternative [12,13]; however, it is an invasive and risky procedure in children and there is no controlled clinical trial for this technique. The goal in the management of UAB is to prevent upper tract damage, reduce PVR and prevent bladder over distention [14]. Although no definitive consensus exists on the appropriate definition of impaired bladder emptying, there is general agreement that afferent fibres, CNS, efferent fibres, and the detrusor muscles are contributing factors, with impaired detrusor contractility regarded as the most common cause [15,16]. IFES has several distinct features. Two medium frequency currents intersect in the target tissue producing a beating effect. The medium frequency currents decrease tissue impedance, penetrate more deeply and more easily, and cause less discomfort. Compared with other modes of electrical stimulation, patients may only feel a tingling sensation. Minimal discomfort ensures patients ‘compliance especially in the paediatric setting. Moreover, proper electrode placements deliver the electrical stimulation precisely at the desired point in the crossover area with the least unwanted effects on the surrounding organs. Another advantage of IFES is that it uses sweep frequencies, so that nerves do not accommodate to a constant signal. © 2015 The Authors BJU International © 2015 BJU International
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Pelvic IFES has been used to augment pelvic muscle strength as well as to restore the micturition neuronal reflex in adult and paediatric patients [17]. Hence, there is the potential for IFES to improve bladder emptying by affecting both neural and muscular properties. However, there is no report on the effectiveness of pelvic IFES in symptom improvements and uroflowmetric alterations. There is a considerable overlap between different lower urinary tract dysfunction conditions. For example, a child may start with holding manoeuvres that may be evident with toe-curling and leg movements to potentially inhibit detrusor Fig. 3 Change in mean blabber capacity in the IFES and control groups at the end of tratment and at the 1-year follow-up.
550
Control IFES
Mean Bladder capacity, mL
500 450 400 350 300 250 200 150
Before the treatment
At the end of treatment At 1-year follow-up courses
contraction and allow a greater than age-related capacity of urine to fill up the bladder. This process continues through dysfunctional voiding, and then voiding postponement, and finally with an UAB. Children with dysfunctional voiding show staccato flow curve on uroflowmetry studies. Although, this flow curve is irregular and fluctuating during voiding, the flow is continuous and never reaches zero during voiding. Children with UAB show an interrupted flow pattern on uroflowmetry. An interrupted flow curve shows discrete segments of urine flow, separated by segments with zero flow. This flow curve suggests an UAB in which each peak shows abdominal muscle straining producing the main force for urine emptying. In between each strain, the flow ceases. This flow pattern may be seen with incoordination between the bladder and external urethral sphincter [1,2]. In children with UAB, abdominal muscle contraction acts as the main force for bladder emptying due to decreased detrusor contractility. Each time a child contracts the abdominal muscles, i.e. straining, a peak appears in the flow curve causing an interrupted pattern [18]. In the present study, we showed that an interrupted flow pattern became normal in 77% of children undergoing IFES. Moreover, both groups improved sensation of bladder fullness marked by increased frequency of voiding. The PVR is an index of incomplete bladder emptying and is responsible for UTIs. A PVR of >20 mL implies abnormal bladder emptying. In our experience, IFES significantly reduced the PVR from a mean (SD) of 60 (32) to
Table 2 Uroflowmetry measurements and voiding episodes before and after treatment, and at the 1-year follow-up. Variable
Before treatment
Mean (SD) Bladder capacity, mL IFES group 424 (123) Control group 463 (121) Maximum urine flow, mL/s IFES group 10.2 (2.9) Control group 9.5 (2.4) Average urine flow, mL/s IFES group 5.8 (2.1) Control group 5.2 (2.2) Voided volume, mL IFES group 426 (133) Control group 407 (129) Voiding time, s IFES group 54.1 (20) Control group 65 (20) PVR, mL IFES group 60 (32) Control group 80 (48) PVR based on % of bladder volume IFES group 19.7 (10) Control group 15.7 (9.9) Voiding episodes, n/day IFES group 2.6 (1) Control group 2.7 (0.73) *
Student’s t-test; the bold number shows significant P values.
798
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P*
After treatment
P*
1-year follow-up
P*
0.374
238 (58) 366 (67)
