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Meta-Analysis
. 2024 Jun 19;6(6):CD014580.
doi: 10.1002/14651858.CD014580.pub2.

Treatments for intractable constipation in childhood

Morris Gordon  1 , Ciaran Grafton-Clarke  2   3 , Shaman Rajindrajith  4 , M A Benninga  5 , Vassiliki Sinopoulou  1 , Anthony K Akobeng  6
Affiliations
Meta-Analysis

Treatments for intractable constipation in childhood

Morris Gordon et al. Cochrane Database Syst Rev. .

Abstract

Background: Constipation that is prolonged and does not resolve with conventional therapeutic measures is called intractable constipation. The treatment of intractable constipation is challenging, involving pharmacological or non-pharmacological therapies, as well as surgical approaches. Unresolved constipation can negatively impact quality of life, with additional implications for health systems. Consequently, there is an urgent need to identify treatments that are efficacious and safe.

Objectives: To evaluate the efficacy and safety of treatments used for intractable constipation in children.

Search methods: We searched CENTRAL, MEDLINE, Embase, and two trials registers up to 23 June 2023. We also searched reference lists of included studies for relevant studies.

Selection criteria: We included randomised controlled trials (RCTs) comparing any pharmacological, non-pharmacological, or surgical treatment to placebo or another active comparator, in participants aged between 0 and 18 years with functional constipation who had not responded to conventional medical therapy.

Data collection and analysis: We used standard Cochrane methods. Our primary outcomes were symptom resolution, frequency of defecation, treatment success, and adverse events; secondary outcomes were stool consistency, painful defecation, quality of life, faecal incontinence frequency, abdominal pain, hospital admission for disimpaction, and school absence. We used GRADE to assess the certainty of evidence for each primary outcome.

Main results: This review included 10 RCTs with 1278 children who had intractable constipation. We assessed one study as at low risk of bias across all domains. There were serious concerns about risk of bias in six studies. One study compared the injection of 160 units botulinum toxin A (n = 44) to unspecified oral stool softeners (n = 44). We are very uncertain whether botulinum toxin A injection improves treatment success (risk ratio (RR) 37.00, 95% confidence interval (CI) 5.31 to 257.94; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Frequency of defecation was reported only for the botulinum toxin A injection group (mean interval of 2.6 days). The study reported no data for the other primary outcomes. One study compared erythromycin estolate (n = 6) to placebo (n = 8). The only primary outcome reported was adverse events, which were 0 in both groups. The evidence is of very low certainty due to concerns with risk of bias and serious imprecision. One study compared 12 or 24 μg oral lubiprostone (n = 404) twice a day to placebo (n = 202) over 12 weeks. There may be little to no difference in treatment success (RR 1.29, 95% CI 0.87 to 1.92; low certainty evidence). We also found that lubiprostone probably results in little to no difference in adverse events (RR 1.05, 95% CI 0.91 to 1.21; moderate certainty evidence). The study reported no data for the other primary outcomes. One study compared three-weekly rectal sodium dioctyl sulfosuccinate and sorbitol enemas (n = 51) to 0.5 g/kg/day polyethylene glycol laxatives (n = 51) over a 52-week period. We are very uncertain whether rectal sodium dioctyl sulfosuccinate and sorbitol enemas improve treatment success (RR 1.33, 95% CI 0.83 to 2.14; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). Results of defecation frequency per week was reported only as modelled means using a linear mixed model. The study reported no data for the other primary outcomes. One study compared biofeedback therapy (n = 12) to no intervention (n = 12). We are very uncertain whether biofeedback therapy improves symptom resolution (RR 2.50, 95% CI 1.08 to 5.79; very low certainty evidence, downgraded due to serious concerns with risk of bias and imprecision). The study reported no data for the other primary outcomes. One study compared 20 minutes of intrarectal electromotive botulinum toxin A using 2800 Hz frequency and botulinum toxin A dose 10 international units/kg (n = 30) to 10 international units/kg botulinum toxin A injection (n = 30). We are very uncertain whether intrarectal electromotive botulinum toxin A improves symptom resolution (RR 0.96, 95% CI 0.76 to 1.22; very low certainty evidence) or if it increases the frequency of defecation (mean difference (MD) 0.00, 95% CI -1.87 to 1.87; very low certainty evidence). We are also very uncertain whether intrarectal electromotive botulinum toxin A has an improved safety profile (RR 0.20, 95% CI 0.01 to 4.00; very low certainty evidence). The evidence for these results is of very low certainty due to serious concerns with risk of bias and imprecision. The study did not report data on treatment success. One study compared the injection of 60 units botulinum toxin A (n = 21) to myectomy of the internal anal sphincter (n = 21). We are very uncertain whether botulinum toxin A injection improves treatment success (RR 1.00, 95% CI 0.75 to 1.34; very low certainty evidence). No adverse events were recorded. The study reported no data for the other primary outcomes. One study compared 0.04 mg/kg oral prucalopride (n = 107) once daily to placebo (n = 108) over eight weeks. Oral prucalopride probably results in little or no difference in defecation frequency (MD 0.50, 95% CI -0.06 to 1.06; moderate certainty evidence); treatment success (RR 0.96, 95% CI 0.53 to 1.72; moderate certainty evidence); and adverse events (RR 1.15, 95% CI 0.94 to 1.39; moderate certainty evidence). The study did not report data on symptom resolution. One study compared transcutaneous electrical stimulation to sham stimulation, and another study compared dietitian-prescribed Mediterranean diet with written instructions versus written instructions. These studies did not report any of our predefined primary outcomes.

Authors' conclusions: We identified low to moderate certainty evidence that oral lubiprostone may result in little to no difference in treatment success and adverse events compared to placebo. Based on moderate certainty evidence, there is probably little or no difference between oral prucalopride and placebo in defecation frequency, treatment success, or adverse events. For all other comparisons, the certainty of the evidence for our predefined primary outcomes is very low due to serious concerns with study limitations and imprecision. Consequently, no robust conclusions could be drawn.

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Conflict of interest statement

MG: no relevant interests; published multiple Cochrane reviews relevant to the interventions in this review; NHS consultant; Co‐ordinating Editor for Cochrane Gut but was not involved in the editorial process or decision‐making for this review.

CGC: none known.

SR: no relevant interests; Professor of Paediatrics, Faculty of Medicine, University of Colombo, Sri Lanka.

MB: no relevant interests; Paediatric Gastroenterologist in an academic medical hospital.

VS: none known.

AA: no relevant interests; Physician, Sidra Medicine; Co‐ordinating Editor for Cochrane Gut but was not involved in the editorial process or decision‐making for this review.

Figures

1
1
Study flow diagram.
2
2
Risk of bias summary.
3
3
Risk of bias graph.
1.1
1.1. Analysis
Comparison 1: Botulinum toxin A injection versus stool softeners, Outcome 1: Treatment success
1.2
1.2. Analysis
Comparison 1: Botulinum toxin A injection versus stool softeners, Outcome 2: Stool consistency
1.3
1.3. Analysis
Comparison 1: Botulinum toxin A injection versus stool softeners, Outcome 3: Painful defecation
1.4
1.4. Analysis
Comparison 1: Botulinum toxin A injection versus stool softeners, Outcome 4: Faecal incontinence
2.1
2.1. Analysis
Comparison 2: Lubiprostone versus placebo, Outcome 1: Treatment success
2.2
2.2. Analysis
Comparison 2: Lubiprostone versus placebo, Outcome 2: Adverse events
2.3
2.3. Analysis
Comparison 2: Lubiprostone versus placebo, Outcome 3: Painful defecation
2.4
2.4. Analysis
Comparison 2: Lubiprostone versus placebo, Outcome 4: Faecal incontinence
2.5
2.5. Analysis
Comparison 2: Lubiprostone versus placebo, Outcome 5: Abdominal pain
3.1
3.1. Analysis
Comparison 3: Rectal sodium dioctyl sulfosuccinate and sorbitol versus oral polyethylene glycol laxatives, Outcome 1: Treatment success
3.2
3.2. Analysis
Comparison 3: Rectal sodium dioctyl sulfosuccinate and sorbitol versus oral polyethylene glycol laxatives, Outcome 2: Painful defecation
3.3
3.3. Analysis
Comparison 3: Rectal sodium dioctyl sulfosuccinate and sorbitol versus oral polyethylene glycol laxatives, Outcome 3: Faecal incontinence
3.4
3.4. Analysis
Comparison 3: Rectal sodium dioctyl sulfosuccinate and sorbitol versus oral polyethylene glycol laxatives, Outcome 4: Abdominal pain
4.1
4.1. Analysis
Comparison 4: Biofeedback therapy versus no intervention, Outcome 1: Non‐fulfilment of Rome criteria
5.1
5.1. Analysis
Comparison 5: Intrarectal electromotive botulinum toxin A versus botulinum toxin A injection, Outcome 1: Non‐fulfilment of Rome criteria
5.2
5.2. Analysis
Comparison 5: Intrarectal electromotive botulinum toxin A versus botulinum toxin A injection, Outcome 2: Frequency of defecation
5.3
5.3. Analysis
Comparison 5: Intrarectal electromotive botulinum toxin A versus botulinum toxin A injection, Outcome 3: Adverse events
5.4
5.4. Analysis
Comparison 5: Intrarectal electromotive botulinum toxin A versus botulinum toxin A injection, Outcome 4: Stool consistency
5.5
5.5. Analysis
Comparison 5: Intrarectal electromotive botulinum toxin A versus botulinum toxin A injection, Outcome 5: Painful defecation
5.6
5.6. Analysis
Comparison 5: Intrarectal electromotive botulinum toxin A versus botulinum toxin A injection, Outcome 6: Quality of life
5.7
5.7. Analysis
Comparison 5: Intrarectal electromotive botulinum toxin A versus botulinum toxin A injection, Outcome 7: Faecal incontinence
6.1
6.1. Analysis
Comparison 6: Botulinum toxin A injection versus myectomy of the internal anal sphincter, Outcome 1: Treatment success
6.2
6.2. Analysis
Comparison 6: Botulinum toxin A injection versus myectomy of the internal anal sphincter, Outcome 2: Adverse events
6.3
6.3. Analysis
Comparison 6: Botulinum toxin A injection versus myectomy of the internal anal sphincter, Outcome 3: Painful defecation
6.4
6.4. Analysis
Comparison 6: Botulinum toxin A injection versus myectomy of the internal anal sphincter, Outcome 4: Faecal incontinence
7.1
7.1. Analysis
Comparison 7: Prucalopride versus placebo, Outcome 1: Frequency of defecation
7.2
7.2. Analysis
Comparison 7: Prucalopride versus placebo, Outcome 2: Treatment success
7.3
7.3. Analysis
Comparison 7: Prucalopride versus placebo, Outcome 3: Adverse events
7.4
7.4. Analysis
Comparison 7: Prucalopride versus placebo, Outcome 4: Painful defecation
7.5
7.5. Analysis
Comparison 7: Prucalopride versus placebo, Outcome 5: Quality of life (child‐reported)
7.6
7.6. Analysis
Comparison 7: Prucalopride versus placebo, Outcome 6: Quality of life (parent‐reported)
7.7
7.7. Analysis
Comparison 7: Prucalopride versus placebo, Outcome 7: Faecal incontinence
7.8
7.8. Analysis
Comparison 7: Prucalopride versus placebo, Outcome 8: Abdominal pain
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References

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References to studies awaiting assessment

ACTRN12620000131954 {published data only}
    1. ACTRN12620000131954. Tranabdominal electric stimulation in the treatment of chronic constipation in children - TESCCO trial [Double blind randomised, placebo-controlled clinical trial of transcutaneous electric stimulation in the treatment of chronic constipation in children]. https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12620000... (first received 17 December 2019).
NCT05035784 {published data only}
    1. NCT05035784. RCE With FMT in the treatment of childhood constipation [Retrograde colonic enema with fecal microbiota transplantation vs retrograde colonic enema only in the treatment of childhood constipation]. clinicaltrials.gov/ct2/show/NCT05035784 (first received 5 September 2021).

References to ongoing studies

NCT05059756 {published data only}
    1. NCT05059756. PTNS and PFR in the treatment of childhood constipation [Percutaneous tibial nerve stimulation and pelvic floor rehabilitation in the treatment of childhood constipation]. clinicaltrials.gov/ct2/show/NCT05059756 (first received 28 September 2021).

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