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电刺激给药在儿童神经源性逼尿肌过度活动中递送肉毒毒素 A 的疗效-一项初步研究的结果。

Efficacy of electromotive drug administration in delivering botulinum toxin a in children with neuropathic detrusor overactivity-outcomes of a pilot study.

机构信息

Department of Paediatric Urology, Royal Manchester Children's Hospital, Manchester, M13 9WL, UK.

Department of Paediatric Urology, Royal Manchester Children's Hospital, Manchester, M13 9WL, UK.

出版信息

J Pediatr Urol. 2019 Oct;15(5):552.e1-552.e8. doi: 10.1016/j.jpurol.2019.05.028. Epub 2019 Jun 5.

Abstract

BACKGROUND

Intravesical botulinum toxin A (BtA) injection is well established in managing paediatric neuropathic detrusor overactivity (NDO). Electromotive drug administration (EMDA) is a less invasive method, which can be performed in the clinic, using pulsed electrical current for drug delivery via a urethral catheter. Few small studies report good outcomes following BtA via EMDA (BtA/EMDA) into bladders of children with NDO.

OBJECTIVE

The objective of this study is to assess the efficacy of BtA/EMDA in children with NDO, reduced bladder capacity and compliance.

METHODS

Twelve children with NDO on baseline urodynamic study were prospectively included. Pre-BtA/EMDA and post-BtA/EMDA results compared the following four parameters: maximal cystometric capacity, bladder compliance, maximal detrusor pressure (pDetmax) during detrusor overactivity and pDetmax at capacity. The Wilcoxon matched-pairs signed-rank test using Graphpad Prism 8 was used for analysis. Secondary outcomes include adverse effects and symptomatic improvement.

RESULTS

Fourteen episodes of BtA/EMDA were performed. Five patients received 3.3 IU/kg of Botox®, and five received 10 IU/kg (maximum 300 IU). Four patients received 10 IU/kg of Dysport®. Two patients in the Dysport®/EMDA group also received Botox®/EMDA more than six months previously. Thirteen of 14 post-EMDA results were completed and included in the paired analysis. No statistically significant improvements in any cystometric parameters were demonstrated. Eight patients subsequently had intravesical BtA injections with significant improvements in both cystometric parameters and symptoms. Two patients subsequently transitioned to adult services; one was commenced on mirabegron, and one has undergone ileocystoplasty with Mitrofanoff appendicovesicostomy.

DISCUSSION

Despite some evidence to support BtA/EMDA in children with NDO, the authors were unable to replicate previously published positive cystometric and symptomatic outcomes. In addition, BtA/EMDA performed poorly when compared with conventional intravesical BtA injections. This implies failure of EMDA to deliver BtA correctly to the target tissue. The large size of the BtA molecule or the abnormal bladder wall in NDO could account for the negative results. Thorough preparation and consultation was undertaken before this study with BtA/EMDA, and it is discouraging that the authors were unable to reproduce the positive results of other groups.

CONCLUSIONS

Although safe and acceptable to most patients, the authors cannot recommend the use of BtA/EMDA for NDO in children at present.

摘要

背景

经尿道注射肉毒毒素 A(Botulinum toxin A,BtA)已被广泛应用于治疗小儿神经性逼尿肌过度活动症(neuropathic detrusor overactivity,NDO)。电渗透给药(electromotive drug administration,EMDA)是一种微创方法,通过尿道导管使用脉冲电流将药物递送至膀胱。少数小型研究报告称,在小儿 NDO 患者中,通过 EMDA 给予 BtA(BtA/EMDA)治疗后,可获得良好的效果。

目的

本研究旨在评估 BtA/EMDA 对膀胱容量和顺应性降低的小儿 NDO 的疗效。

方法

前瞻性纳入 12 例在基线尿动力学检查中诊断为 NDO 的患儿。在接受 BtA/EMDA 治疗前后,比较以下 4 项参数:最大膀胱容量、膀胱顺应性、逼尿肌过度活动时的最大逼尿肌压力(maximal detrusor pressure,pDetmax)和膀胱容量时的 pDetmax。采用 Graphpad Prism 8 软件中的 Wilcoxon 配对符号秩检验进行分析。次要结局包括不良反应和症状改善。

结果

共进行了 14 次 BtA/EMDA 治疗。5 例患儿接受 3.3 IU/kg 的 Botox®,5 例接受 10 IU/kg(最大 300 IU),4 例接受 10 IU/kg 的 Dysport®。Dysport®/EMDA 组的 2 例患儿此前还接受了超过 6 个月的 Botox®/EMDA 治疗。14 次 EMDA 治疗中有 13 次完成了配对分析。未发现任何膀胱测压参数有统计学意义的改善。8 例患儿随后接受了膀胱内 BtA 注射治疗,膀胱测压参数和症状均有显著改善。2 例患儿随后转至成人泌尿科治疗,1 例开始服用米拉贝隆,1 例接受了回肠膀胱术和米托菲诺夫阑尾膀胱造口术。

讨论

尽管有一些证据支持 BtA/EMDA 治疗小儿 NDO,但本研究未能复制之前发表的阳性膀胱测压和症状改善结果。此外,与传统的膀胱内 BtA 注射相比,BtA/EMDA 的效果较差。这表明 EMDA 未能将 BtA 正确递送至目标组织。可能是由于 BtA 分子较大或 NDO 患儿的膀胱壁异常,导致了阴性结果。在进行本研究之前,对 BtA/EMDA 进行了充分的准备和咨询,但作者未能复制其他小组的阳性结果,这令人感到沮丧。

结论

尽管 BtA/EMDA 治疗对大多数患者是安全且可接受的,但目前作者不能推荐将其用于治疗小儿 NDO。

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