Recent advances in treating constipation in children.

INTRODUCTION: Functional constipation (FC) is a common childhood condition, diagnosed via the Rome IV criteria. Standard therapy includes lifestyle and dietary modification followed by initiation of osmotic laxative therapy. About 30% of children continue to experience symptoms related to FC despite appropriate management. New pharmacologic, surgical, and neuromodulatory therapies for FC are now available for use in adult and pediatric populations. In 2023, the first pharmacologic agent, linaclotide, obtained FDA approval for treatment of FC in children 6-17 years old. AREAS COVERED: This article reviews current and emerging pharmacologic, surgical and neuromodulation therapies for the management of FC in pediatric patients. Efficacy and safety data regarding each of these modalities was reviewed and discussed. EXPERT OPINION: Advancements in therapeutics available for the management of FC necessitate further investigation on safety and efficacy in pediatric populations. Careful consideration should be taken in choosing an available treatment with limited pediatric evidence as adult and pediatric FC have different underlying pathophysiology and require different a therapeutic approach. Standardization of methodology and pediatric endpoints are needed to optimize ability to compare efficacy of different treatments. We predict the future of pediatric FC management will include a personalized approach to care, resulting in improved outcomes.

Using Polyethylene Glycol 3350 Plus Electrolytes in Constipated Hemodialysis Patients: A Case Series.

Appropriate management of constipation in hemodialysis patients has not been established, although constipation is the most frequent gastrointestinal complication in dialysis patients. We herein report the efficacy and safety of polyethylene glycol in constipated hemodialysis patients assessed prospectively. Seven patients using stimulant laxatives participated in this study. Polyethylene glycol was administered to reduce stimulant laxatives during the six-week intervention period. The amount of stimulant laxatives decreased and spontaneous bowel movements with ideal stool consistency increased significantly after the intervention. No serious adverse effects were observed throughout this study. In conclusion, polyethylene glycol can be a useful tool for managing constipated hemodialysis patients.

Ischemic colitis in an infant with constipation treated with stimulant laxative.

Ischemic colitis (IC), the most common form of intestinal ischemia, ranges from superficial mucosal and submucosal injury to full-thickness mural necrosis. As risk factors include cerebrovascular disease, hypertension, diabetes mellitus, prior abdominal surgery, irritable bowel syndrome, and constipation, IC typically occurs in elderly persons with multiple comorbidities rather than young children. A 1-year-old Japanese girl receiving a stimulant laxative for constipation since age 7 months was hospitalized for fever, vomiting, and hypovolemic shock. Her abdomen was swollen, and abdominal computed tomography showed colonic distension with abundant stool. Colonic decompression and intensive care brought about rapid improvement until persistent bloody diarrhea that commenced on day 17 of illness required transfer to another hospital, where colonoscopy on day 42 showed mucosal sloughing forming pseudomembranes, as well as focal stenosis. Contrast enema on day 45 confirmed stenosis with a "thumbprint" contour at the splenic flexure. Diagnosed with IC, she received parenteral nutrition and an elemental diet. Bloody diarrhea resolved by day 75. Colonoscopy and contrast enema on day 110 showed normal mucosa and resolution of stenosis. We believe that IC arose from constipation and stimulant laxative treatment and consider this to be the first report of infantile IC complicating constipation.

More opioids, more constipation? Evaluation of longitudinal total oral opioid consumption and self-reported constipation in patients with cancer.

PURPOSE: Opioid-induced constipation (OIC) is a distressing physical symptom for patients with cancer taking opioids. Total opioid consumption may contribute to developing worsening OIC-related symptoms. We completed a retrospective analysis examining the association of total daily opioid consumption on self-reported constipation in patients with cancer. METHODS: In over 5 clinic visits, we collected self-reported constipation scores and 24-h oral morphine equivalents (OME). We examined the association between OME and the presence of constipation (i.e., score > 3) and the relationship of OME between patients with or without constipation. RESULTS: Of 297 patients with cancer, we observed 57.8% with constipation and 42.4% without constipation at the first clinic visit. Age was similar in both groups (54.2 ± 14.5 vs. 56.4 ± 14.8 years [mean ± SD]) and the majority of patients were women (63.7% vs. 61.1%). The most common cancer type in patients with constipation was non-colorectal gastrointestinal (n = 25, 14.6%), while in patients without constipation was colorectal gastrointestinal (n = 25; 19.8%). Across visits, we observed weak or no association between OME and self-reported constipation (r = 0.01-0.27). At the first visit, higher mean OME was seen in patients who self-reported constipation (133.4 vs 76; p < 0.05). Age, sex, metastatic disease, and stimulant laxative use were not associated with constipation. CONCLUSIONS: We observed weak to no association between OME and constipation in patients with cancer. These results suggest a lack of a clear association between total opioid consumption and self-reported constipation.

Colon-targeted delivery of solubilized bisacodyl by doubly enteric-coated multiple-unit tablet.

A doubly enteric-coated multiple-unit tablet (DET) of bisacodyl (BD) was formulated to selectively deliver the stimulant laxative to the large intestine. Solubilized BD in surfactants was adsorbed into the porous carrier and primarily coated with different combinations of pH-sensitive polymers (Eudragit S and Eudragit L) and time-dependent release polymer (Eudragit RS). BD-loaded granules were compressed into tablets and coated again with pH-sensitive polymers (Eudragit S:Eudragit L=1:1). The multiple-unit tablet was optimized with respect to the granular coating compositions (Eudragit S:Eudragit L:Eudragit RS=5:1:4) and coating level (12.5%), and coating level on the tablet (25%), by evaluating in vitro release profile in continuous dissolution medium. Drug release from the optimized tablet was effectively retarded in the simulated gastric and small intestinal fluids (below 7%), but profound drug liberation was attained in the colonic fluid (over 50%). On the other hand, drug release from the marketed product (Dulcolax®, Boehringer Ingelheim Pharma), a reference drug, in the gastric and small intestinal fluids was reached to 30%, while that in the colonic fluid was only 7%. In an in vivo efficacy study in loperamide-induced constipated rabbits, a remarkable recovery in fecal secretion was observed in the DET-treated group 24h post-dosing, compared to vehicle-treated (p<0.05) and the marketed product-treated groups (p<0.05). Moreover, pharmacokinetic evaluation in the constipated rabbits revealed that the DET system significantly lowered the systemic exposure compared with the marketed product (p<0.05), by hindering drug release in the upper intestine, a preferential absorption site. Therefore, the novel colon-targeted delivery system may be an alternative for boosting pharmacological responses in the colon, while diminishing the intestinal irritation and/or systemic adverse effect of the stimulant laxative.

Effectiveness of senna vs polyethylene glycol as laxative therapy in children with constipation related to anorectal malformation.

PURPOSE: Constipation is present in 80% of children with corrected anorectal malformations, usually associated to rectal dilation and hypomotility. Osmotic laxatives are routinely used for idiopathic constipation. Senna is a stimulant laxative that produces contractions improving colonic motility without affecting the stool consistency. We designed this trial to study the effectiveness of Senna versus polyethylene glycol for the treatment of constipation in children with anorectal malformation. METHODS: A randomized controlled crossover design clinical trial, including a washout period, was conducted, including children with corrected anorectal malformations with fecal continence and constipation. The sample size was calculated for proportions (n=28) according to available data for Senna. Effectiveness of laxative therapy was measured with a three variable construct: 1) daily bowel movement, 2) fecal soiling, 3) a "clean" abdominal x-ray. Data analysis included descriptive statistics and a Fisher's exact test for the outcome variable (effectiveness). RESULTS: The study was terminated early because the interim analysis showed a clear benefit toward Senna (p = 0.026). The sample showed a normal statistical distribution for the variables age and presence of megarectum. The maximum daily dose of Senna (sennosides A and B) was 38.7mg and 17g for polyethylene glycol. No adverse effects were identified. CONCLUSION: Therapy with Senna should be the laxative treatment of choice as part of a bowel management program in children with repaired anorectal malformations and constipation, since the stimulation of colonic propulsion waves could lead to stool evacuation without modification of its consistency which can affect fecal continence. LEVEL OF EVIDENCE: I - randomized controlled trial with adequate statistical power.