背景:经常规治疗措施延长且无法解决的便秘称为顽固性便秘。顽固性便秘的治疗具有挑战性,涉及药物或非药物治疗,以及手术方法。未解决的便秘会对生活质量产生负面影响,对卫生系统有额外的影响。因此,迫切需要确定有效和安全的治疗方法。
目的:评价治疗儿童顽固性便秘的疗效和安全性。
方法:我们搜索了CENTRAL,MEDLINE,Embase,两项审判登记至2023年6月23日。我们还检索了相关研究的纳入研究的参考列表。
方法:我们纳入了随机对照试验(RCT),比较任何药物,非药理学,或手术治疗安慰剂或其他活性比较剂,年龄在0至18岁之间的功能性便秘参与者对常规药物治疗无反应。
方法:我们使用标准Cochrane方法。我们的主要结果是症状缓解,排便频率,治疗成功,和不良事件;次要结局是大便稠度,痛苦的排便,生活质量,大便失禁的频率,腹痛,入院治疗,和学校缺席。我们使用GRADE来评估每个主要结果的证据的确定性。
结果:本综述包括10项RCTs,其中1278名儿童患有顽固性便秘。我们评估了一项研究在所有领域的偏倚风险较低。在六项研究中,对偏倚风险存在严重担忧。一项研究将注射160单位肉毒杆菌毒素A(n=44)与未指定的口腔粪便软化剂(n=44)进行了比较。我们非常不确定A型肉毒毒素注射是否能提高治疗成功率(风险比(RR)37.00,95%置信区间(CI)5.31至257.94;非常低的确定性证据,由于严重关注偏见和不精确的风险而降级)。仅报告了肉毒杆菌毒素A注射组的排便频率(平均间隔2.6天)。该研究没有报告其他主要结局的数据。一项研究比较了红霉素(n=6)和安慰剂(n=8)。报告的唯一主要结果是不良事件,两组均为0。由于担心偏见和严重不精确的风险,证据的确定性非常低。一项研究将12或24μg口服鲁比前列酮(n=404)每天两次与安慰剂(n=202)在12周内进行比较。治疗成功率可能几乎没有差异(RR1.29,95%CI0.87至1.92;低确定性证据)。我们还发现,鲁比前列酮可能导致不良事件几乎没有差异(RR1.05,95%CI0.91至1.21;中等确定性证据)。该研究没有报告其他主要结局的数据。一项研究在52周内比较了每周三周的直肠二辛基磺基琥珀酸钠和山梨糖醇灌肠剂(n=51)与0.5g/kg/天的聚乙二醇泻药(n=51)。我们非常不确定直肠二辛基磺基琥珀酸钠和山梨糖醇灌肠剂是否能提高治疗成功率(RR1.33,95%CI0.83至2.14;非常低的确定性证据,由于严重关注偏见和不精确的风险而降级)。每周排便频率的结果仅报告为使用线性混合模型的建模平均值。该研究没有报告其他主要结局的数据。一项研究将生物反馈治疗(n=12)与无干预(n=12)进行了比较。我们非常不确定生物反馈疗法是否能改善症状缓解(RR2.50,95%CI1.08至5.79;非常低的确定性证据,由于严重关注偏见和不精确的风险而降级)。该研究没有报告其他主要结局的数据。一项研究比较了使用2800Hz频率的20分钟直肠内电动肉毒杆菌毒素A和10国际单位/kg的肉毒杆菌毒素A剂量(n=30)与10国际单位/kg的肉毒杆菌毒素A注射(n=30)。我们非常不确定直肠内电动肉毒杆菌毒素A是否能改善症状缓解(RR0.96,95%CI0.76至1.22;非常低的确定性证据)或是否能增加排便频率(平均差异(MD)0.00,95%CI-1.87至1.87;非常低的确定性证据)。我们也非常不确定直肠内电动肉毒杆菌毒素A是否具有改善的安全性(RR0.20,95%CI0.01至4.00;非常低的确定性证据)。由于严重关注偏见和不精确的风险,这些结果的证据具有非常低的确定性。该研究没有报告治疗成功的数据。一项研究将注射60单位肉毒杆菌毒素A(n=21)与肛门内括约肌切除术(n=21)进行了比较。我们非常不确定注射肉毒杆菌毒素A是否能提高治疗成功率(RR1.00,95%CI0.75-1.34;非常低的确定性证据)。没有记录到不良事件。该研究没有报告其他主要结局的数据。一项研究将每天一次的0.04mg/kg口服普鲁卡洛必利(n=107)与安慰剂(n=108)在八周内进行了比较。口服普鲁卡必利可能导致排便频率的差异很小或没有差异(MD0.50,95%CI-0.06至1.06;中度确定性证据);治疗成功(RR0.96,95%CI0.53至1.72;中度确定性证据);和不良事件(RR1.15,95%CI0.94至1.39;中度确定性证据)。该研究没有报告症状缓解的数据。一项研究将经皮电刺激与假刺激进行了比较,另一项研究将营养师规定的地中海饮食与书面说明与书面说明进行了比较。这些研究没有报告我们预定的任何主要结果。
结论:我们发现,与安慰剂相比,口服鲁比前列酮可能在治疗成功率和不良事件方面几乎没有差异。基于适度的确定性证据,口服普鲁卡洛必利和安慰剂在排便频率上可能几乎没有差异,治疗成功,或不良事件。对于所有其他比较,由于对研究局限性和不准确性的严重关注,我们预定义的主要结局的证据的确定性非常低.因此,无法得出有力的结论。
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.
To evaluate the efficacy and safety of treatments used for intractable constipation in children.
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.
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.
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.
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.
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.