Publications From the International Children's Continence Society

Pediatric Urology

RIU0497_12-07.qxd 12/8/10 12:39 AM Page e202 REVIEWING THE LITERATURE News and Views From the Literature Pediatric Urology Publications From the International Children’s Continence Society Reviewed by Ellen Shapiro, MD New York University School of Medicine, New York, NY [Rev Urol. 2010;12(4):e202-e204 doi: 10.3909/riu0497] © 2010 MedReviews ®, LLC Incontinence Two of the 10 articles published from the International Children’s Continence Society (ICCS) present the latest knowledge about the evaluation of daytime urinary incontinence (in the absence of nocturnal enuresis) and monosymptomatic nocturnal enuresis (MNE).1 The ICCS previously published an article standardizing terminology for lower urinary tract function.2 The article by Hoebeke and colleagues reviews methods for assessment of children with daytime urinary incontinence using evidence from the literature and assembling it in this standardized document.1 The article emphasizes the importance of taking an accurate medical history and questioning the child when possible. They suggest that, although experienced practitioners treating children with lower urinary tract dysfunction can usually diagnose their problems, others may prefer to use scoring systems such as that by Akbal and colleagues.3 A voiding diary of fluid intake and output during a 24-hour period as well as keeping track of urinary frequency and voided volumes can be useful. A similar chart should be kept for bowel habits. The physical examination should determine if bladder distension or fecal impaction is present. Also, neurologic testing e202 VOL. 12 NO. 4 2010 REVIEWS IN UROLOGY will assess the integrity of sacral segments. Noninvasive testing includes a renal/bladder ultrasound and uroflow studies. The authors indicate that residual urine  10% of the expected bladder capacity for age (in cc) is significant. The ultrasound also provides information on the presence of constipation. A bladder base impression and rectal width  3 cm in the absence of an urge to have a bowel movement is a significant indicator of constipation. When there is significant urinary frequency and irritative symptoms, a urinalysis is recommended not only to assess for urinary tract infection (UTI) but also for pH and calcium content because the group from Vanderbilt has reported hypercalciuria in a subgroup of dysfunctional voiding syndromes in childhood.4 The uroflowmetry measures the urinary stream during voiding and quantifies the volume voided over a unit of time.1 The Qmax refers to the peak or maximal flow rate in milliliters per second and the Qave reflects average flow per unit of time. Generally, Qave is usually  50% but  85% of the Qmax value. The uroflow curve is normally bell shaped in all healthy children, but will change when the voided volume is  50% of the expected bladder capacity for age. The authors note that the uroflow studies may help identify those who need video-urodynamic studies. The authors propose that patients with thick-walled bladders on ultrasound and obstructed flow patterns and dilated lower ureters may have reflux or poor compliance. These patients, in addition to those who have failed all conventional therapy, should undergo video-urodynamic studies. They stress in their article that the voiding cystourethrogram should not be part of the routine assessment of most children with urinary incontinence. Forthcoming reports from the ICCS will discuss effective treatments for daytime incontinence. The second article by Nevéus and colleagues discusses recommendations for treating children with monosymptomatic RIU0497_12-07.qxd 12/7/10 9:54 PM Page e203 Pediatric Urology nocturnal enuresis (MNE).5 Evidence was gathered from the literature and expert opinion and was reviewed by the members of the ICCS. MNE infers that the nighttime incontinence occurs in the absence of any other lower urinary tract symptoms. Although the article is focused on children, it is also useful in dealing with adults with MNE. The authors review the primary evaluation including a careful history to assess for daytime voiding or bowel dysfunction. If either of these is present, it needs to be treated before embarking on therapies for MNE. It is also important to determine whether the child is bothered by nighttime wetting because this will influence motivation to become dry. If the physical examination is unremarkable and the urinalysis shows no glucosuria, proteinuria, or infection, therapeutic alternatives should be discussed with parents of children age 6 years and older. Although the authors do not recommend routine ultrasound of the kidneys, studies have suggested screening for boys older than age 6 because, on occasion, boys with posterior urethral valves have a late presentation manifested by only MNE.6 The authors stress the importance of keeping a calendar of wet and dry nights. They also note the importance of voiding first thing in the morning, before retiring, and regularly during the day. Evening fluid and solute intake should be minimized but liberalized during the day, especially in the morning and early afternoon. The authors discuss the conditioning alarm therapy. If the alarm has been successful, they recommend that the child drink a modest amount of extra water 1 hour before bed. If, after 1 month, they remain continent at night, the alarm is discontinued. Desmopressin has a low curative potential with only about 30% of children responding completely. Not only does it have an antidiuretic effect but, in addition, there may be a central nervous system antienuretic effect. Desmopressin is most efficient in children with nocturnal polyuria, which is nocturnal urine production  130% of expected bladder capacity for age and normal bladder reservoir function (maximum voided volume  70% of expected bladder capacity for age). Other children placed on desmopressin may have failed alarm therapy or are not candidates for the conditioning alarm. Desmopressin is very safe except when children drink liquids excessively prior to bedtime. This can lead to water intoxication, hyponatremia, and seizures. In December 2007, the US Food and Drug Administration (FDA) issued a formal warning on the potential for intoxication which I review carefully with parents each time I prescribe desmopressin. I advise that the child drink only with dinner. The authors recommend that the desmopressin be taken at least 1 hour before going to sleep with a small amount of water—and restricting fluids for an additional 8 hours. This will assure that the maximal renal concentrating effect and minimal diuresis is attained 1 to 2 hours after taking the medication whether they start with the higher dosing schedule and taper it or use the titrated dosing schedule. The authors recommend a short “drug holiday” to assess medication efficacy. Another therapeutic alternative is the anticholinergic compounds. There have been several open, nonrandomized studies indicating beneficial effects in therapy-resistant children with enuresis. This has been corroborated by a recent randomized, placebo-controlled study by Austin and colleagues examining combination desmopressin and anticholinergic medication for nonresponders to desmopressin.7 The authors note that, once beginning anticholinergic therapy, the antienuretic effects should appear within 2 months or sooner. Parents should be warned to watch for constipation and should return within 4 to 6 weeks for a postvoid residual and urinalysis when using these medications. They also discuss the use of tricyclic antidepressants. These drugs are thought to be third-line therapy at tertiary care centers because there have been safety concerns in the past. A 50% response rate has been shown in some children. Usually imipramine 25 to 50 mg is administered at bedtime and larger doses are given to children older than age 9 years. After 1 month, the child is reevaluated. If there is partial response, desmopressin may be added. Tolerance of this drug can occur so a drug holiday of at least 2 weeks interspersed every third month is recommended to lessen this risk. The authors suggest an electrocardiogram (EKG) prior to imipramine treatment, especially in those children with a history of palpitations or syncope or any sudden cardiac death or unstable arrhythmia in the family. I always obtain a pretreatment EKG and this is reassuring to parents once they learn of the potential cardiac side effects. The authors note mood change, nausea, and insomnia as side effects that may occur before nocturnal continence is attained. Other therapies have included acupuncture, treatment of hypercalciuria, and noncardiotoxic alternatives to imipramine. At a recent pediatric urology meeting, hypnosis for MNE was discussed as a successful therapeutic alternative, and provides a concise guideline for practitioners for the treatment of MNE. Vesicoureteral Reflux Cannon and the investigators from Children’s Hospital in Boston determined whether improvement in reflux on serial imaging predicts resolution of vesicoureteral reflux.8 They evaluated 965 children who had a minimum of 2 years of follow-up. They noted the initial reflux grade VOL. 12 NO. 4 2010 REVIEWS IN UROLOGY e203 RIU0497_12-07.qxd 12/7/10 9:54 PM Page e204 Pediatric Urology continued and the grade on serial imaging up to 5 years following diagnosis. The authors found several factors that were predictive of reflux resolution. Multivariant analysis showed that male sex, age younger than 1 year at diagnosis, lower grade at presentation, and unilateral reflux were independent predictors of reflux resolution. Additional independent predictors of reflux resolution were reflux improvement on imaging 1 year after diagnosis or improvement from the previous year at any point during follow-up. These data may be useful in counseling families and in therapeutic decision making. Another article evaluated predictive factors for the resolution of congenital high-grade vesicoureteral reflux in infants. Sjöström and investigators9 from Gothenburg, Sweden, evaluated 80 males and 35 females, most of whom were diagnosed with UTI (71%) or after prenatal ultrasound (26%). Reflux was bilateral in 70%. Maximum grade of reflux was Grade III in 16%, Grade IV in 45%, and Grade V in 39%. Overall spontaneous resolution was 38% with complete resolution occurring in 26% and downgrading to Grade I-II in 12%. The mean age for spontaneous resolution was 27 months. Urodynamic studies demonstrating bladder dysfunction, with bladder capacity 200% or greater than expected capacity, and residual volume of 25% of bladder capacity or greater were negative predictors of reflux resolution. A breakthrough infection occurred in 47% and was associated with increasing grade of reflux. Renal scan abnormalities were noted in 85% at the start of the study. The scan abnormalities were generalized in 63%, focal in 23%, and bilateral in 20%. There was no difference in the distribution of renal damage by grade of reflux. The highest grades of reflux were negative prognostic factors for resolution of reflux. Lower rates of resolution were observed in patients with renal abnormalities and subnormal renal function. Lower resolution was also noted in patients with breakthrough infections and passive reflux on cystograms. There were no differences in resolution depending on gender, the finding of overactive bladder contractions, or pre- or postnatal diagnoses or unilateral versus bilateral reflux. This study used complete resolution as well as Grade I-II as endpoints with no further follow-up studies. Because the authors were able to specifically identify renal scan abnormalities, poor bladder emptying, and breakthrough infections as predicting less than 10% chance of having reflux resolve before age 3, this may help to identify patients who might benefit from e204 VOL. 12 NO. 4 2010 REVIEWS IN UROLOGY early surgical intervention. It also may help to identify those patients with high-grade reflux who may benefit from continued conservative management despite initially high-grade vesicoureteral reflux. Testicular Microlithiasis Goede and the investigators from Alkmaar, the Netherlands, evaluated 199 congenitally undescended testes and 350 acquired undescended testes and determined by ultrasound the incidence of microlithiases.10 The congenitally undescended testes underwent only one sonogram whereas the acquired undescended testes were followed prospectively. Thirteen boys, 5 with congenitally undescended testis and 9 with acquired undescended testis had microlithiases. The finding was not dependent on age, side of the undescended testis, or whether the undescended testis was congenital or acquired. The rate of testicular microlithiases in this study was 2.8%, which is slightly lower than that reported in the asymptomatic general population. The exact meaning of this finding is unclear and long-term follow-up into adulthood may be indicated to determine the impact of this finding. References 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. Hoebeke P, Bower W, Combs A, et al. Diagnostic evaluation of children with daytime incontinence. J Urol. 2010;183:699-703. Nevéus T, von Gontard A, Hoebeke P, et al. The standardization of terminology of lower urinary tract function in children and adolescents: report from the Standardisation Committee of the International Children’s Continence Society. J Urol. 2006;176:314-324. Akbal C, Genc Y, Burgu B, et al. Dysfunctional voiding and incontinence scoring system: quantitative evaluation of incontinence symptoms in pediatric population. J Urol. 2005;173:969-973. Parekh DJ, Pope JC IV, Adams MC, Brock JW 3rd. The role of hypercalciuria in a subgroup of dysfunctional voiding syndromes of childhood. J Urol. 2000;164(3 Pt 2):1008-1010. Nevéus T, Eggert P, Evans J, et al. Evaluation of and treatment for monosymptomatic enuresis: a standardization document from the International Children’s Continence Society. J Urol. 2010;183:441-447. Schober JM, Dulabon LM, Woodhouse CR. Outcome of valve ablation in latepresenting posterior urethral valves. BJU Int. 2004; 94:616-619. Austin PF, Ferguson G, Yan Y, et al. Combination therapy with desmopressin and an anticholinergic medication for nonresponders to desmopressin for monosymptomatic nocturnal enuresis: a randomized, double-blind, placebocontrolled trial. Pediatrics. 2008;122:1027-1032. Cannon GM Jr, Arahna AA, Graham DA, et al. Improvement in vesicoureteral reflux grade on serial imaging predicts resolution. J Urol. 2010;183:709-713. Sjöström S, Sillén U, Jodal U, et al. Predictive factors for resolution of congenital high grade vesicoureteral reflux in infants: results of univariate and multivariate analyses. J Urol. 2010;183:1177-1184. Goede J, Hack WWM, van der Voort-Dedens LM, et al. Testicular microthiasis in boys and young men with congenital or acquired undescended (ascending) testes. J Urol. 2010;183:1539-1544.