第二军医大学  2015, Vol. 36 Issue (4): 447-449   PDF    
琥珀酸索利那新在控制经尿道膀胱肿瘤电切术后膀胱刺激症状中的价值
李磊1,2, 曹智1, 许传亮1, 韦荣超1, 张振声1, 孙颖浩1    
1. 第二军医大学长海医院泌尿外科, 上海 200433;
2. 安徽省六安市中医院泌尿外科, 安徽 237006
摘要目的 探讨索利那新在控制经尿道膀胱肿瘤电切术后膀胱刺激症状中的价值。方法 116例诊断为非肌层浸润性膀胱癌的患者纳入本研究,患者被随机分为试验组和对照组。所有患者均接受经尿道膀胱肿瘤电切术和术后即刻表柔比星灌注治疗;试验组患者于术前6 h和术后连续3 d每天口服索利那新5 mg,对照组患者口服安慰剂;于术后6、12、24、48和72 h分别记录膀胱刺激症状评分。结果 膀胱刺激症状的发生率从93.1%(对照组)下降到67.2%(试验组)(P=0.001);在各个观测时间点对照组膀胱刺激症状的严重性均高于试验组(P<0.05或P<0.01)。结论 索利那新可有效改善经尿道膀胱肿瘤电切术后膀胱刺激症状。
关键词索利那新;膀胱肿瘤;手术后并发症;膀胱刺激症状;留置导尿    
Solifenacin succinate in improving bladder irritative symptoms after transurethral resection of bladder tumors
LI Lei1,2, CAO Zhi1, XU Chuan-liang1, WEI Rong-chao1, ZHANG Zhen-sheng1, SUN Ying-hao1    
1. Department of Urology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
2. Department of Urology, Lu'an Hospital of Traditional Chinese Medicine, Lu'an 237006, Anhui, China
Abstract: Objective To explore the value of solifenacin in managing bladder irritative symptoms after transurethral resection of bladder tumor. Methods A total of 116 patients with the diagnosis of non-muscle invasive bladder carcinoma were enrolled in the present study, and they were randomly allocated into experiment group and control group. All patients received transurethral resection of bladder cancer and immediate postoperative instillation of epirubicin. Patients in the experiment group also received solifenacin 5 mg at 6 h before surgery and once a day after surgery for 3 d, while the patients in the control group received placebo. The incidences and severity of catheter related bladder discomfort were recorded at 6, 12, 24, 48 and 72 h after surgery. Results The incidence rate of bladder irritative symptoms significantly decreased from 93.1% in the control group to 67.2% in the experiment group(P=0.001). Compared with the control group, the severity of bladder irritative symptoms in the experiment group was significantly improved at all time points (P<0.05 or P<0.01). Conclusion Solifenacin is effective for managing bladder irritative symptoms after transurethral resection of bladder tumors.
Key words: solifenacin;urinary bladder neoplasms, postoperative complications;bladder irritative symptoms;catheterization    

经尿道膀胱肿瘤电切术是治疗非肌层浸润性膀胱癌的主要手段[1],患者术后常发生明显的膀胱刺激症状;在术后导尿管留置期间,其发生率高达90%[2];电切术后膀胱刺激症状给患者带来巨大痛苦,并可导致继发性膀胱痉挛和膀胱出血等并发症。索利那新作为一种新型乙酰胆碱M受体阻断剂,已被证明在膀胱过度活动症的治疗中有明显疗效[3, 4];而膀胱过度活动症和电切术后膀胱刺激症状有类似的发病机制。本研究旨在通过设计一项随机对照单盲试验来探讨索利那新在控制经尿道膀胱肿瘤电切术后膀胱刺激症状中的价值。 1 资料和方法 1.1 一般情况

收集2011年6月至2012年12月第二军医大学长海医院泌尿外科收治的116例患者纳入本研究。患者年龄49~78岁,平均(59.49±9.32)岁,男女比例为83∶33。病例纳入标准:无远处转移的非肌层浸润性膀胱癌;排除标准:尿路梗阻、神经源性膀胱、膀胱结石、既往盆腔放射治疗、青光眼、盆腔炎、尿路感染、慢性疼痛、终末期肾病和服用抗胆碱能药物等。术前血常规、肝肾功能、心电图、X线胸片、腹部B超均未见明显异常。本研究获第二军医大学长海医院伦理委员会批准,所有患者均签署知情同意书。 1.2 研究方案与疗效对比

将患者随机分为试验组(n=58)和对照组(n=58),两组之间年龄、一般情况、既往病史、肿瘤分期和风险评估等情况均无统计学意义。因为琥珀酸索利那新(安斯泰来,批准文号:国药准字J20090109)于给药后3~8 h血药浓度达到峰值,半衰期为45~68 h[5],所以试验组患者在术前6 h口服索利那新5 mg,对照组口服安慰剂。术中麻醉采用蛛网膜下隙阻滞麻醉,以1 mL/10 s的速度注入0.5%布比卡因2.5 mL;待麻醉平面确实后行经尿道膀胱肿瘤电切术,术中切除所有可见肿瘤组织及肿瘤周边1 cm正常黏膜,深及肌层;操作完成后由另一名医师核查确认完整清除所有肿瘤;留置18 F导尿管,注水20 mL;所有患者接受术后即刻表柔比星30 mg灌注治疗1次。术后所有患者口服环丙沙星预防感染至拔除导尿管后3 d;治疗组患者每天口服索利那新5 mg,对照组患者口服安慰剂,拔除导尿管后停药。术后3 d拔除导尿管,个别患者可根据实际情况延长1~2 d。安慰剂同治疗药物在大小、颜色、气味和外观上无明显差别。 1.3 疗效评价

于术后6、12、24、48和72 h分别记录膀胱刺激评分,评分标准:0分,无明显尿频、尿急等不适;1分,仅询问时诉说轻度尿频、尿急等不适,但可以忍受;2分,主动向医生诉尿频、尿急、膀胱区轻度疼痛等不适,要求药物治疗,但不伴有肢体反应;3分,主动频繁诉说尿频、尿急、膀胱区疼痛等不适,可伴有烦躁不安、呻吟、四肢紧张及拔尿管等情况[2, 6]1.4 统计学处理

用SPSS 18.0软件进行统计学分析。计量资料以x±s 表示,采用t检验;计数资料进行χ2检验。检验水准(α)为0.05。 2 结 果

对照组患者膀胱刺激症状发生率达93.1%;而试验组发生率为67.2%(P=0.001)。同对照组相比,试验组在所有时间点膀胱刺激症状的严重程度均降低(P<0.05或P<0.01)。见表 1

表 1 试验组和对照组膀胱刺激症状发生情况比较
3 讨 论

经尿道膀胱肿瘤电切使膀胱平滑肌暴露于尿液,留置导尿管,持续膀胱冲洗和表柔比星灌注化疗等因素可以刺激位于膀胱壁内的传入神经,引起传出神经末梢乙酰胆碱的释放,导致膀胱平滑肌不自主收缩,导致相关刺激症状的发生。膀胱刺激症状给患者带来巨大痛苦,影响患者术后平稳恢复,并可导致膀胱痉挛、术后出血加重等并发症。此外,膀胱刺激症状还可严重影响患者睡眠质量,精神健康和身体健康[7]

索利那新可特异性阻断M3受体,对M2受体的阻断效能很小;它对膀胱平滑肌的亲和力比对唾液腺的亲和力高3.6倍[8];在抑制唾液腺分泌方面,比奥西布宁小40倍,比托特罗定小79倍[9]。研究表明,索利那新可以减轻60%患者的尿频症状,约有40%完全消失,并可改善除尿急外其他膀胱刺激症状[10, 11, 12]。此外,在一组经坦索罗辛治疗无效的顽固性膀胱过度活动患者中,经过12周的治疗,索利那新可显著改善尿频等症状[13]

我们的研究表明,在经膀胱尿道肿瘤电切术后6 h,膀胱刺激症状的发生率从93.1%(对照组)下降到67.2%(试验组)。Agarwal等[6, 14]在两项研究中分别报道术前1 h口服托特罗定可将膀胱刺激症状发生率降低19%和25%;而奥西布宁可将膀胱刺激症状发生率降低23%。在这两项研究中,患者接受的手术方式分别为肾脏或输尿管的腹腔镜手术或开放手术和经皮肾镜碎石术;手术本身对膀胱无明显损伤,术后导致膀胱不适的主要因素是留置尿管。而在本研究中,经尿道膀胱肿瘤电切术本身对膀胱有明确损伤作用,理论上引起膀胱不适的严重程度高于Agarwal等[6, 14]研究中单纯留置导尿管引起膀胱不适的严重程度。在这种情况下,索利那辛治疗组膀胱刺激症状发生率的下降程度类似于Agarwal等[6, 14]研究中托特罗定和奥西布宁治疗组膀胱刺激症状发生率的下降程度,从另一个侧面突出了索利那辛在治疗膀胱刺激症状中的重要价值。

在Agarwal等[6, 14]的两项研究中,术前应用托特罗定和奥西布宁可明显降低术后膀胱刺激症状的严重性。本研究中,在术后6、12、24、48、72 h,伴有中度以上(膀胱刺激症状评分≥2分)膀胱刺激症状的患者在试验组中各有19例(32.8%)、12例(20.1%)、15例(25.9%)、12例(20.1%)、7例(12.1%),而在对照组中则各有27例(46.6%)、29例(50%)、25例(43.1%)、21例(36.2%)、17例(29.3%);对照组中伴有中度以上膀胱刺激症状的患者比例高于试验组。而统计分析也提示,在各个时间点索利那辛治疗组膀胱刺激症状的严重性均明显低于对照组,说明索利那辛可明显提高患者术后生活质量,使术后恢复更加平稳。

综上所述,经尿道膀胱肿瘤电切术后膀胱刺激症状的发生率较高,索利那新可显著降低经尿道膀胱肿瘤电切术后膀胱刺激症状的发生率和严重性。

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