Can higher doses of oxybutynin improve efficacy in neurogenic bladder?
Can higher doses of oxybutynin improve efficacy in neurogenic bladder?
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DOI：
10.1097/01.ju.0000103274.38694.b1
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发表时间：
2004-02-01
影响因子：
6.6
通讯作者：
Chancellor, MB
中科院分区：
文献类型：
--
作者：
Bennett, N;O'Leary, M;Chancellor, MB
目的：我们评估的疗效和耐受性较高剂量的奥昔布宁氯化神经源性膀胱和多发性硬化症，脊髓损伤或Parkinson's disease.Materials和Methods患者：研究设计是一个前瞻性的，12周的剂量滴定试验控制释放奥昔布宁（OXY-XL）。在开始10 mg OXY-XL的起始剂量之前使用7天洗脱期。根据患者对疗效与副作用的感知，OXY-XL的剂量每周增加5 mg，最大剂量为30 mg/天。在基线、第6周和第12周完成排尿日记。记录排尿后残留量。研究入院标准包括排尿后残留小于200 ml。结果：在参加研究的39例患者中，22例有多发性硬化症，10例有脊髓损伤，7例有帕金森病。其中女性29人（74%），男性10人（26%）。在1周内，在超过50%的受试者中观察到每天排尿次数减少。在研究结束时，观察到24小时内排尿次数、排尿次数和尿失禁次数统计学显著减少。残余尿保持不变，从基线时的33.9 ± 7.6 ml降至12周后末次给药时的51.3 ± 10.4 ml（p = 0.17）。在为期12周的研究过程中，没有患者发生严重不良事件，也没有患者脱落。在研究结束时，20.5%的受试者保持在30 mg，15.4%在25 mg，23.1%在20 mg，15.4%在15 mg和25.6%在10 mg OXY-XL.Conclusions：积极剂量的OXY-XL是安全和有效的神经源性膀胱患者。与非神经源性膀胱过度活动症相比，在我们的研究中，74.4%的患者要求更高剂量的OXY-XL（每日15 mg或更高）。临床疗效可在1周内起效，剂量高达30 mg在该人群中耐受性良好且有效。由于神经系统疾病（包括脊髓损伤（SCI）、多发性硬化（MS）和帕金森病（PD））导致的排尿功能障碍的发展，对医疗保健专业人员提出了重大挑战。1泌尿系统症状和损伤类型通常不能很好地预测长期护理需求，因为症状与损伤程度并不准确相关。2脊髓损伤患者可能是脊髓的一个节段或脊柱的多个节段受伤。脑损伤也可能发生在隐匿或明显的情况下。神经损伤，这可能涉及副交感神经，交感神经和躯体神经纤维，导致一系列复杂的泌尿体征和症状。3，4尿急、尿频和尿失禁是MS患者的常见症状。失去正常膀胱控制会显著影响日常活动，可能会增加疲劳，并对生活质量产生负面影响。5据估计，80%或更多的MS患者在疾病过程中会表现出泌尿功能障碍的症状。6在MS的情况下，由脑或脊髓中的脱髓鞘引起的病变中断了下行和上行神经通路，特别是控制排尿的颈椎的后柱和侧柱。在对MS患者尿动力学模式结果的回顾中，逼尿肌反射亢进是最常见的诊断。7帕金森病是引起排尿功能障碍的最常见的神经系统疾病之一。膀胱过度活动和括约肌运动迟缓（横纹肌外排尿括约肌松弛受损）是PD患者常见的排尿功能障碍，抗胆碱能药物是目前控制膀胱过度活动症最有效的药物。通过阻断逼尿肌的受体，频率、尿急和失禁减少。最近，延长释放奥昔布宁已显示在治疗膀胱过度活动症的疗效。8我们使用日记、残余尿超声、尿分析、培养和敏感性测试作为有效性参数来评估控释奥昔布宁（OXY-XL）的有效性。我们还评估了12周治疗期间这种药物的主观疗效，安全性和耐受性。
Purpose: We evaluated the efficacy and tolerability of higher dose oxybutynin chloride in patients with neurogenic bladder and multiple sclerosis, spinal cord injury or Parkinson's disease.Materials and Methods: The study design was a prospective, 12-week dose titration trial of controlled release oxybutynin (OXY-XL). A 7-day washout period was used before initiation of the starting dose of 10 mg OXY-XL. Doses of OXY-XL were increased by 5 mg at weekly intervals to a maximum dose of 30 mg per day guided by patient perception of efficacy versus side effect. Voiding diaries were completed at baseline, and weeks 6 and 12. Post-void residuals were recorded. Criteria for study admission included post-void residual less than 200 ml.Results: Of the 39 patients enrolled in the study 22 had multiple sclerosis, 10 had spinal cord injury and 7 had Parkinson's disease. There were 29 women (74%) and 10 men (26%). Within 1 week a decrease in the number of voids per day was seen in greater than 50% of the subjects. At the end of the study statistically significant decreases in the number of voids in 24 hours, episodes of nocturia and incontinence episodes were observed. Residual urine remained unchanged from 33.9+-7.6 ml at baseline to 51.3+-10.4 ml after 12 weeks at the final dose (p = 0.17). No patient experienced serious adverse events and none dropped out during the course of the 12-week study. At the end of the study 20.5% of subjects remained on 30 mg, 15.4% on 25 mg, 23.1% on 20 mg, 15.4% on 15 mg and 25.6% on 10 mg OXY-XL.Conclusions: Aggressive dosing of OXY-XL is safe and effective in patients with neurogenic bladder. Compared with nonneurogenic overactive bladder, higher doses of OXY-XL (15 mg daily or greater) were requested by 74.4% of the patients in our study. The onset of clinical efficacy can occur within 1 week, and doses up to 30 mg are well tolerated and effective in this population.The development of voiding dysfunction as a result of neurological diseases, including spinal cord injury (SCI), multiple sclerosis (MS) and Parkinson's disease (PD), presents a significant challenge for the health care professional. 1 Urological symptoms and type of injury are often poor predictors of long-term care needs, as symptoms do not accurately correlate with level of injury. 2 People who suffer from SCI may have injured a single level of the cord or multiple levels of the spine. Brain insult may also occur either occult to obvious. Neural injury, which can involve parasympathetic, sympathetic and somatic nerve fibers, results in a complex array of urinary signs and symptoms. 3,4Urinary urgency, frequency and incontinence are common symptoms of those diagnosed with MS. Loss of normal bladder control significantly impacts daily activities, may enhance fatigue and negatively impacts quality of life. 5 It is estimated that 80% or more of people with MS will exhibit symptoms of urinary dysfunction during the course of the disease. 6 In cases of MS lesions resulting from demyelination in the brain or spinal cord interrupt the descending and ascending nerve pathways, especially the posterior and lateral columns of the cervical spine that control micturition. In a review of results of urodynamic patterns in MS detrusor hyperreflexia was the most common diagnosis. 7Parkinson's disease is one of the most common neurological entities causing voiding dysfunction. Bladder overactivity and sphincter bradykinesia (impairment of relaxation of the striated muscle external urinated sphincter) are common voiding dysfunctions seen in patients with PD.Anticholinergic medications are the most effective agents available today to control overactive bladder symptoms. By blocking receptors of the detrusor muscle, frequency, urgency and incontinence are decreased. Recently, extended release oxybutynin has shown efficacy in the treatment of overactive bladder symptoms. 8 We assess the effectiveness of controlled release oxybutynin (OXY-XL) using diaries, residual urine ultrasound, urinalysis, culture and sensitivity testing as parameters of effectiveness. We also evaluate subjective efficacy, safety and tolerability of this medication during the 12-week treatment period.