Prescrire Int. 2013 Jan;22(134):12-3.
Patients with spinal cord injury or multiple sclerosis are often troubled by urinary incontinence due to detrusor (bladder muscle) overactivity. For patients who use intermittent self-catheterisation, empirical treatments for urinary incontinence include: optimisation of catheterisation; anticholinergic drugs; and, in some cases, surgery. The indications of botulinum toxin type A (Botox, Allergan) in France have been extended to cover this situation when anticholinergic drugs are ineffective. Clinical evaluation is based on 2 double-blind randomised placebo-controlled trials in a total of 691 patients who had an average of about 32 episodes of urinary incontinence per week.These trials tested the efficacy of a total dose of 300 or 200 units of botulinum toxin type A. Six weeks after toxin injection into the bladder wall, about 40% of patients had no further episodes of incontinence, compared to 10% of patients who received placebo injections. The median duration of the effect was 42 to 48 weeks after a dose of 200 units (13 to 18 weeks with placebo). It remains to be shown whether botulinum toxin has any long-term benefits in terms of complications (hospitalisation, urinary tract infections, etc.). The main adverse effects of botulinum toxin injections in these patients were urinary tract infections (51% versus 36% with placebo) and urinary retention (18% versus 3%). Both differences were statistically significant, and these events were most frequent in patients who had not yet started to self-catheterise (mainly patients with multiple sclerosis). Cases of autonomic hyperreflexia with favourable outcome were also reported. Botulinum toxin type A has been marketed since the 1990s in other indications. It has been linked to life-threatening adverse effects on tissues at a distance from the injection site, following its diffusion throughout the body. Muscle weakness, asthenia and constipation have been reported. A negative effect on the course of multiple sclerosis cannot be ruled out. Botulinum toxin type A injection into the bladder wall necessitates cystoscopy, an invasive and very inconvenient procedure that requires antibiotic prophylaxis and sometimes anaesthesia. Cystoscopy also carries a risk of punctures and tears, etc. In practice, existing treatment options are unsatisfactory for patients in whom anticholinergic drugs fail to control urinary incontinence due to neurogenic detrusor overactivity. Botulinum toxin type A temporarily prevents incontinence for a few months in about one-third of patients, but it is difficult to administer. In experienced hands, it may be beneficial for patients with very troublesome incontinence who self-catheterise.
脊髓损伤或多发性硬化症患者常因逼尿肌(膀胱肌肉)过度活动而受尿失禁困扰。对于采用间歇性自我导尿的患者,尿失禁的经验性治疗方法包括:优化导尿;使用抗胆碱能药物;在某些情况下还包括手术。在法国,当抗胆碱能药物无效时,A型肉毒杆菌毒素(保妥适,艾尔建公司生产)的适应证已扩大到涵盖这种情况。临床评估基于两项双盲随机安慰剂对照试验,共有691例患者参与,这些患者平均每周约有32次尿失禁发作。这些试验测试了300单位或200单位总剂量的A型肉毒杆菌毒素的疗效。在将毒素注入膀胱壁六周后,约40%的患者不再出现尿失禁发作,而接受安慰剂注射的患者这一比例为10%。注射200单位剂量后,效果的中位持续时间为42至48周(安慰剂组为13至18周)。A型肉毒杆菌毒素在并发症(住院、尿路感染等)方面是否有任何长期益处仍有待证实。在这些患者中,注射A型肉毒杆菌毒素的主要不良反应是尿路感染(51%,而安慰剂组为36%)和尿潴留(18%,而安慰剂组为3%)。这两个差异均具有统计学意义,且这些事件在尚未开始自我导尿的患者(主要是多发性硬化症患者)中最为常见。也有自主神经反射亢进但预后良好的病例报告。A型肉毒杆菌毒素自20世纪90年代起就用于其他适应证。在其扩散至全身后,已发现它与远离注射部位的组织出现危及生命的不良反应有关。有报告称出现肌肉无力、乏力和便秘。不能排除其对多发性硬化症病程产生负面影响。向膀胱壁注射A型肉毒杆菌毒素需要进行膀胱镜检查,这是一种侵入性且非常不便的操作,需要预防性使用抗生素,有时还需要麻醉。膀胱镜检查也有穿刺和撕裂等风险。实际上,对于因神经源性逼尿肌过度活动导致抗胆碱能药物无法控制尿失禁的患者,现有的治疗选择并不令人满意。A型肉毒杆菌毒素可使约三分之一的患者在几个月内暂时避免尿失禁,但给药困难。在经验丰富的医生手中,它可能对自我导尿且尿失禁非常严重的患者有益。