Intravenous ondansetron reduced nausea but not pruritus following intrathecal morphine in children: Interim results of a randomized, double-blinded, placebo-control trial.

STUDY OBJECTIVE: This study's purpose was to determine if ondansetron can prevent pruritus after administration of intrathecal morphine in children, as has been demonstrated in adults. DESIGN: A double-blinded, randomized placebo-controlled trial. SETTING: Operating room and first 24 h postoperative inpatient stay at an academic children's hospital. PATIENTS: Forty-six children aged 3-17 years, who received 4-5 mcg/kg intrathecal morphine for urological or orthopedic procedures were included. INTERVENTIONS: Children were randomized to receive intravenous ondansetron (treatment) or saline placebo (placebo), prior to intrathecal morphine administration, and q6H for 24 h thereafter. Intraoperative anti-emetics and postoperative rescue treatments for pruritus and nausea were standardized. MEASUREMENTS: Patients were interviewed q6H for scored pruritus, nausea, and pain, using standardized scales. MAIN RESULTS: The trial was terminated for futility after interim analysis. Forty-six children were recruited and 45 completed data collection. No significant difference was found between both groups for incidence of pruritus (requiring treatment) [relative risk (RR) 0.9, 95% CI: 0.7, 1.2], during the first postoperative 24 h. Notably, the incidence of pruritus was 84% overall, much higher than rates in previously published studies. Intravenous ondansetron significantly reduced the incidence of nausea, compared with the placebo group [RR 0.5, 95% CI: 0.3, 0.9]. CONCLUSIONS: This study found no evidence for intravenous ondansetron as an effective preventative for pruritus following intrathecal morphine in children. However, this RCT did find that the rate of pruritus following intrathecal morphine administration may be significantly higher than previously thought. Nausea and vomiting (a secondary outcome) were reduced significantly in the treatment group. The negative findings of this study reinforce the potential dangers of extrapolating the drug effects seen in adults onto pediatric patients.

Investigation of Fiber-Driven Mechanical Behavior of Human and Porcine Bladder Tissue Tested Under Identical Conditions.

The urinary bladder is a highly dynamic organ that undergoes large deformations several times per day. Mechanical characteristics of the tissue are crucial in determining the function and dysfunction of the organ. Yet, literature reporting on the mechanical properties of human bladder tissue is scarce and, at times, contradictory. In this study, we focused on mechanically testing tissue from both human and pig bladders using identical protocols to validate the use of pigs as a model for the human bladder. Furthermore, we tested the effect of two treatments on tissue mechanical properties. Namely, elastase to digest elastin fibers, and oxybutynin to reduce smooth muscle cell spasticity. Additionally, mechanical properties based on the anatomical direction of testing were evaluated. We implemented two different material models to aid in the interpretation of the experimental results. We found that human tissue behaves similarly to pig tissue at high deformations (collagen-dominated behavior) while we detected differences between the species at low deformations (amorphous matrix-dominated behavior). Our results also suggest that elastin could play a role in determining the behavior of the fiber network. Finally, we confirmed the anisotropy of the tissue, which reached higher stresses in the transverse direction when compared to the longitudinal direction.

Intranodal lymphangiography and interstitial lymphatic embolization to treat chyluria caused by a lymphatic malformation in a pediatric patient.

Chyluria is characterized by chyle in the urinary tract and often presents as milky-white urine. We present a case of chyluria from a lymphatic malformation in a 13-year-old boy diagnosed using dynamic intranodal contrast-enhanced magnetic resonance (MR) lymphangiography. This report demonstrates the utility of intranodal lymphangiography and interstitial lymphatic embolization to treat a pediatric patient presenting with persistent chyluria. Glue migration into the urinary collecting system is a potential complication of this procedure that can be mitigated by adjusting the n-butyl cyanoacrylate dilution with Lipiodol.

Urodynamic and imaging findings in infants with myelomeningocele may predict need for future augmentation cystoplasty.

INTRODUCTION: Urologic issues are persistent and important causes of morbidity and mortality in patients with myelomeningocele. Classically, patients with elevated bladder pressures despite adherence to clean intermittent catheterization (CIC) and pharmacotherapy undergo augmentation cystoplasty (AC). Currently, there is little understanding of which infants are more likely to require AC later. OBJECTIVE: In this context, the authors studied whether unfavorable urodynamic or imaging findings in patients with myelomeningocele during infancy could predict future AC. The authors hypothesized that infants born with elevated bladder pressures, vesicoureteral reflux (VUR), and/or hydronephrosis would be more likely to undergo AC. STUDY DESIGN: The authors retrospectively identified patients with myelomeningocele at their institution who were followed-up since infancy (<1 year of age), with a minimum of eight continuous years of follow-up. Standard care protocol included cystometrogram, voiding cystourethrogram (VCUG), and renal ultrasound during infancy. The primary outcome was AC for elevated bladder pressures despite attempts at more conservative management with medical therapy and CIC. Specifically, the authors evaluated for differences in augmentation rates based on gender, level of lesion, presence of detrusor leak point pressure (DLPP) or end-fill pressure (EFP) greater than 40 cm H2O, presence of hydronephrosis, VUR, initiation of CIC, and initiation of antimuscarinics in infancy. The authors excluded patients who underwent surgical intervention for urinary incontinence. RESULTS: A total of 97 patients met the inclusion criteria. The median follow-up time was 13.8 years. Augmentation cystoplasty was performed for 17 patients (17.5%) at a median age of 114 months (9.5 years). Detrusor leak point pressure/EFP was greater than 40 cm H2O in 34.0% (33/97) of infant cystometrogram studies, while 30.9% (30/97) had VUR on infant VCUG and 20.6% (20/97) had hydronephrosis on infant renal ultrasound. Patients with DLPP/EFP greater than 40 cm H2O or VUR during infancy were more likely to undergo AC (P = 0.02 and P = 0.03, respectively). Binomial logistic regression revealed that DLPP/EFP greater than 40 cm H2O (odds ratio [OR]: 4.28, 95% confidence interval [CI]: 1.34-13.62) and VUR (OR: 3.73, 95% CI: 1.18-11.77) were independent risk factors for future AC. DISCUSSION: Infants with myelomeningocele and elevated bladder pressures and VUR should be closely monitored by urodynamic testing and imaging studies. Parents can be counseled regarding the potentially higher risk for future AC in these patients. Nonetheless, the majority of high-risk infants will safely avoid AC with conservative management.

Impact of Clinical Guidelines on Voiding Cystourethrogram Use and Vesicoureteral Reflux Incidence.

PURPOSE: To prevent over diagnosis and overtreatment of vesicoureteral reflux the 2007 NICE (National Institute for Health and Care Excellence) and 2011 AAP (American Academy of Pediatrics) guidelines recommended against routine voiding cystourethrograms in children presenting with first febrile urinary tract infections. The impact of these guidelines on clinical practice is unknown. MATERIALS AND METHODS: Using an administrative claims database (Clinformatics™ Data Mart) children who underwent voiding cystourethrogram studies or had a diagnosis of vesicoureteral reflux between 2001 and 2015 were identified. The cohort was divided into children age 0 to 2 and 3 to 10 years. Single and multiple group interrupted time series analyses (difference-in-difference) were performed with the guidelines as intervention points. The incidence of vesicoureteral reflux was compared across each period. RESULTS: Of the 51,649 children who underwent voiding cystourethrograms 19,422 (38%) were diagnosed with vesicoureteral reflux. In children 0 to 2 years old voiding cystourethrogram use did not decrease after the 2007 NICE guidelines were announced (-0.37, 95% CI -1.50 to 0.77, p = 0.52) but did decrease significantly after the 2011 AAP guidelines were announced (-2.00, 95% CI -3.35 to -0.65, p = 0.004). Among children 3 to 10 years old voiding cystourethrogram use decreased during the entire study period. There was a decrease in the incidence of vesicoureteral reflux in both groups that mirrored patterns of voiding cystourethrogram use. CONCLUSIONS: The 2011 AAP guidelines led to a concurrent decrease in voiding cystourethrogram use and incidence of vesicoureteral reflux among children 0 to 2 years old. Further studies are needed to assess the risks and benefits of reducing the diagnosis of vesicoureteral reflux in young children.

Vesicoureteral reflux and continuous prophylactic antibiotics.

Vesicoureteral reflux (VUR) management must be tailored based on the risk for further infections and renal scarring, gender, likelihood of spontaneous resolution, and parental preferences. Because we now understand that sterile VUR is benign and most reflux spontaneously resolves over time, the initial approach in majority of children is non-surgical with continuous antibiotic prophylaxis (CAP) and correction of bladder and bowel dysfunction. Despite increasing utilization of CAP over the past four decades, the efficacy of antibiotic prophylaxis has been questioned due to conflicting results of studies plagued with design flaws and inadequate subject sample size. The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial, which was designed to address many of the limitations from previous studies, provided much needed answers. In this review, we sought to describe the controversy surrounding VUR management, highlight the results of RIVUR trial, and discuss how the RIVUR findings impact our understanding of CAP in the management of VUR.

Unexpected ethical dilemmas in sex assignment in 46,XY DSD due to 5-alpha reductase type 2 deficiency.

Sex assignment at birth remains one of the most clinically challenging and controversial topics in 46,XY disorders of sexual development (DSD). This is particularly challenging in deficiency of 5-alpha reductase type 2 given that external genitalia are typically undervirilized at birth but typically virilize at puberty to a variable degree. Historically, most individuals with 5-alpha reductase deficiency were raised females. However, reports that over half of patients who underwent a virilizing puberty adopted an adult male gender identity have challenged this practice. Consensus guidelines on assignment of sex of rearing at birth are equivocal or favor male assignment in the most virilized cases. While a male sex of rearing assignment may avoid lifelong hormonal therapy and/or allow the potential for fertility, female sex assignment may be more consistent with external anatomy in the most severely undervirilized cases. Herein, we describe five patients with 46,XY DSD due 5-alpha-reductase type 2 deficiency, all with a severe phenotype. An inter-disciplinary DSD medical team at one of two academic centers evaluated each patient. This case series illustrates the complicated decision-making process of assignment of sex of rearing at birth in 5-alpha reductase type 2 deficiency and the challenges that arise when the interests of the child, parental wishes, recommendations of the medical team, and state law collide.

Bladder perforation after augmentation cystoplasty: Determining the best management option.

INTRODUCTION: Delayed bladder perforation is a well-described complication after augmentation cystoplasty. Although the frequency, risk factors, and diagnostic challenges are well documented, discussions regarding management strategies are sparse. OBJECTIVE: We evaluated our experience of managing augmented bladder perforation to interrogate the hypothesis that non-operative management can be used effectively. STUDY DESIGN: We retrospectively evaluated the management of 10 patients with augmented bladder perforations over a 16-year period (Jan 2000-Jan 2016). Patients who demonstrated clinical deterioration, severe peritonitis, or extensive extravasation on imaging underwent exploratory laparotomy and primary closure. Clinically stable patients with minimal extravasation were managed non-operatively with maximal bladder drainage, and those with loculated fluid collections in feasible locations for drainage underwent an image-guided percutaneous drain placement. RESULTS: Underlying diagnoses included four patients with myelomeningocele, three with sacral agenesis, two with spinal cord injuries, and one with bladder exstrophy. Three of the four patients with myelomeningocele had concomitant ventriculoperitoneal shunts. Six patients had continent catheterizable channel creation and two patients had bladder neck reconstructions during the original operation. Four patients were managed with exploratory laparotomy and primary closure. Among the six patients managed non-operatively, three underwent image-guided drain placement in addition to maximal bladder drainage. Four patients developed re-perforation. Two of the four surgically managed patients developed re-perforation. Two of the three patients managed only with maximal bladder drainage developed re-operation. None of the patients managed non-operatively with drain placement suffered from re-perforation. Four perforation episodes were alcohol-related, two occurred after high-impact sporting activity, and two patients reported non-compliant catheterization. DISCUSSION: Non-operative management with maximal bladder drainage and selective image-guided drain placement can be successfully deployed in clinically stable patients with limited extravasation. Ensuring low intraluminal detrusor pressures and empty bladder with maximal drainage is critical for spontaneous sealing of the perforation site. Exploratory laparotomy and primary closure remains our approach for those presenting with clinical deterioration or significant extravasation on imaging. The majority of our perforations and re-perforation episodes seemed to stem from preventable behavioral risk factors. CONCLUSIONS: Our findings support the hypothesis that non-operative management with maximal bladder drainage and image-guided drain placement can be effective in stable patients with limited extravasation.

Pediatric urethral catheter consultations: understanding driving factors.

PURPOSE: Pediatric urethral catheterization is often straightforward. However, it can be challenging and may require urological consultation. Possible critical factors are patient anatomy and comorbidities, and insertion technique. To better understand pediatric catheter consultations, we reviewed our experience. MATERIALS AND METHODS: All pediatric catheter consultations between July 2009 and June 2012 were identified. A retrospective review was then performed, focusing on demographics, reasons for consultation and difficulty of catheter placement. The 4 categories of difficulty noted were easy, challenging, extremely difficult and could not be placed. Patients were excluded from analysis if catheter placement was not needed, the consultation was for a catheterizable stoma or they were status post urological surgery. Statistical analyses were performed to evaluate associations between patient factors and difficulty of placement. RESULTS: A total of 93 consultations were identified, of which 57% were inpatient, 28% intraoperative and 15% other source. Of the inpatient consultations 75% were from an intensive care unit, the majority (80%) of which were for catheter placement, with the remainder for removal, nondraining catheter, trauma or other. After exclusions 65 patients remained, of whom 80% were male and 32% had a urological comorbidity. By difficulty level 69.2% of cases were easy, 15.4% were challenging, 9.2% were extremely difficult and 6.2% could not be placed. Location of consult, gender, urological comorbidity and history of prematurity were not significantly associated with difficult catheter placement. CONCLUSIONS: Pediatric catheter consultations are largely straightforward. Comorbidities do not significantly impact catheter placement. Correct catheter technique may be more important than patient comorbidities, giving us a basis to shape catheter insertion training within pediatric hospitals.

9p partial monosomy and disorders of sex development: review and postulation of a pathogenetic mechanism.

Deletion of the distal segment of 9p causes a syndrome comprising trigonocephaly, minor anomalies, and intellectual disability. Patients with this condition also frequently present with genitourinary abnormalities including cryptorchidism, hypospadias, ambiguous genitalia, or 46,XY testicular dysgenesis. The region responsible for the gonadal dysgenesis has been localized to 9p24.3 with the likely responsible gene identified as DMRT1. Similar to patients with other molecular causes of 46,XY gonadal dysgenesis, patients with partial del 9p have an increased risk of gonadoblastoma. We present two patients with 46,XY gonadal dysgenesis due to partial 9p monosomy. Both patients were also diagnosed with gonadoblastoma following gonadectomy at an early age. Chromosomal microarray analyses refined the cytogenetic abnormalities and allowed potential genotype-phenotype relationships to be determined. We also review the literature as it pertains to partial 9p monosomy, genital abnormalities and gonadoblastoma and note that a large percentage of affected patients present with two copy number variations. We propose that a two-hit mechanism may be involved in the incomplete penetrance and variable expressivity of partial 9p monosomy and an abnormal genital phenotype. The significant percentage of gonadoblastoma in patients with 46,XY complete gonadal dysgenesis due to partial 9p monosomy also continues to support the necessity of gonadectomy in this patient population.

The distal left Malone antegrade continence enema--is it better?

PURPOSE: The Malone antegrade continence enema is used for refractory fecal dysfunction in the pediatric neuropathic population. While various locations along the colon have been described, the optimal site for achieving efficient enemas remains unknown. We reviewed our experience with the Malone antegrade continence enema procedure and investigated functional outcomes and complications associated with proximal and distal locations. MATERIALS AND METHODS: We performed an institutional review board approved, retrospective chart review of 109 consecutive MACE procedures done by a single surgeon from 2000 to 2012. Preoperative patient characteristics, intraoperative techniques and postoperative outcomes were reviewed and statistical analysis was performed. RESULTS: Included in analysis were 90 patients treated with a total of 109 MACE procedures. Average age at operation was 13.8 years. Myelomeningocele was the most common diagnosis. Most patients underwent simultaneous urinary reconstruction. Stomal complications were most common (49% of patients). We compared the outcomes of proximal (cecal) MACE in 48 cases and distal (sigmoid colon) MACE in 55. Location did not affect the overall efficiency of fecal continence. Flush time was shorter for distal than for proximal MACE stomas (37.2 vs 61.2 minutes, p <0.001). Of the patients 15 underwent a total of 20 complete MACE revisions, including 12 proximal and 6 distal MACEs. As a channel, appendix was associated with a higher but not statistically significant stomal complication rate compared to colon (42% vs 25%). CONCLUSIONS: A cecal, transverse or colonic location for MACE results in acceptable outcomes. Distal MACE is associated with significantly shorter flush time and possibly fewer stomal complications. Stomal complications remain a frustrating reality of the MACE procedure.