前瞻性随机对照研究生物反馈和口服醋酸去氨加压素治疗儿童原发性遗尿症的疗效

A randomized control trial study of biofeedback and DDAVP in children with primary nocturnal enuresis

目的通过前瞻性RCT比较生物反馈和口服醋酸去氨加压素(DDAVP)两种治疗方法对儿童原发性遗尿症(PNE)的效果。方法2005年7月至2006年1月在复旦大学附属儿科医院确诊为PNE的患儿,随机分为DDAVP和生物反馈治疗组,疗程1个月,于治疗结束时(第1次)和治疗后3个月(第2次)进行随访,随访指标包括排尿日记,尿流率,尿液水通道蛋白-2(AQP2)水平。选择同期的健康儿童及因骨折、多指畸形和斜颈等无水代谢紊乱并无遗尿的患儿共16例作为正常对照组,检测尿液AQP2水平。结果PNE患儿50例,平均年龄(8.4±0.9)岁。①第1次随访时,DDAVP组治愈率40%,总有效率64%;生物反馈组两者分别为48%和92%。第2次随访时,DDAVP组的治愈率20%,总有效率52%,复发率20%,生物反馈组三者分别为40%、84%和8%。两次随访总有效率生物反馈组皆显著高于DDAVP组。②生物反馈组治疗前和第1、2次随访时最大尿流率分别为(15.8±1.7)mL·s-1和(22.5±2.2)mL·s-1、(18.1±2.0)mL·s-1;尿量分别为(141.7±20.6)mL和(201.1±15.1)mL、(156.4±31.5)mL;正常尿流曲线构成比分别为28%和60%、58%;逼尿肌-括约肌协调构成比分别为40%和72%、66%。其中第1次随访时最大尿流率、尿量和逼尿肌-括约肌收缩协调者比例较治疗前皆明显增加(P<0.05),正常尿流曲线构成比治疗后2次随访较治疗前均明显增高(P<0.05)。DDAVP组治疗前和第1、2随访时尿量分别为(192.8±51.5)mL和(127.1±47.6)mL、(182.5±47.3)mL;排尿时间分别为(17.0±3.3)s和(10.2±5.2)s、(14.5±5.1)s;正常尿流曲线构成比分别为52%和50%、54·5%;逼尿肌-括约肌收缩协调构成比分别为36%和37·5%、40·9%。其中第1次随访时尿量和排尿时间较治疗前明显减少(P<0.05)。③PNE患儿晨尿尿液AQP2两条带(相对分子质量29000和43000)的灰度[(0.3±0.1)和(4.4±1.2)]显著低于正常对照组[(16.4±6.1)和(31.5±6.9)](P<0.05)。DDAVP组治疗前和第1、2次随访时灰度在29000处分别为(0.2±0.1)和(15.8±2.3)、(4.4±1.2);在43000处灰度分别为(4.9±1.4)和(17.0±2.8)、(6.4±2.4)。第1次随访时两条带灰度和第2次随访时29000处灰度明显高于治疗前(P<0.05)。生物反馈组治疗前和第1、2次随访时灰度在29000处分别为(0.4±0.2)和(1.2±0.8)、(2.9±1.3);在43000处为(3.9±1.90)和(4.9±2.4)、(5·1±1·6),前后灰度差异皆无统计学意义。结论生物反馈和DDAVP均是治疗PNE的有效方法。生物反馈治疗在4个月内的总有效率高于DDAVP,值得在PNE患儿中开展使用。生物反馈治疗对改善膀胱-尿道功能紊乱有帮助,而DDAVP治疗则可以提高尿液中AQP2水平。

Objective Primary nocturnal enuresis （PNE） is the most common voiding problem in children. There is a great demand for the treatment of PNE despite absence of underlying diseases because it is socially unacceptable by and can be very distressing to the patients and their parents. We evaluated the efficacy of biofeedback （BFB） therapy in childrens with PNE to DDAVP treatment in a randomized control trial （RCT）. Methods PNE children who were diagnosed by nephrologists or urologists of childreng hospital of Fudan University were divided randomly into two groups from July 2005 to January 2006. The biofeedback group received computer-assisted biofeedback program, sphincter contraction and relaxation can be transformed into visual signals. Both therapies were carried out for one month and then three monthg follow-up were taken. Parameters of follow-up included enuresis diary,urine flow rate and AQP2 in urine. Results 50 PNE patients were recruited （26 boys and 24 girls） , whose mean age was （8.4 ± 0.9） years. There was equilibrious in age and gender in two groups divided randomly. At the end of treatment, the cure rate was 40% and total effective rate was 64% in DDAVP group while there were 48% and 92% respectively in biofeedback group. Total effective rate in the biofeedback group was significantly higher than that in the DDAVP group. Three months later, the cure rate was 20% , total effective rate was 52% and relapse rate was 20% in the DDAVP group while they were 40% , 84% and 8% respectively in the biofeedback group. The total effective rate in the biofeedback group was still significantly higher than that in the DDAVP group. The relapse rate and the cure rate in the biofeedback group were not different from those in the DDAVP. Uroflowmetry findings showed that in the biofeedback group the maximum flow rate before the treatment ,at the end of the treatment and three months later was （15.8 ± 1.7） mL±·^ -1, （22.5±2.2） mL ·^-1 and （18. 1 ±·2.0） mL·^ -1 respectively;and voided volume was （ 141.7 ±20. 6） mL, （201. 1 ±15. 1 ） mL and （ 156. 4 ±31.5） mL respectively. Both results increased after the biofeedback treatment （ P 〈 0. 05 ） , but there was no difference between pre-treatment and the second follow-up. Ratio of normal flow curve was 28% , 60% and 58.3% respectively, which increased at the second follow-up （P 〈 0. 05）. Ratio of patients who had coordinative detrusor-sphineter contraction was 40% , 72% and 66.3% respectively, which increased after the treatment but decreased three months later. In DDAVP group the voided volume before the treatment,at the end of the treatment and three months later was （192.8.＋51.5） mL, （127. 1 ±47.6） mL and （182.5 ±47.3） mL respectively; and voiding time was （ 17.0 ± 3.3） s, （ 10.2 ± 5.2） s and （ 14. 5 ± 5.1 ） s respectively. Both results decreased after the treatment （ P 〈0. 05） , but there was no difference between pre-treatment and at the second follow-up. Ratio of normal flow curve was 52% , 50% and 54. 5% and ratio of patients who had coordinative detrusor-sphincter contraction were 36% , 37.5% and 40. 9% respectively. Both results were not different from that before the treatment. Two bands of AQP2 （29 000 and 43 000） were detected in the morning urine. Density of the two bands of patients were （0.3 ±0.1） and （4.4 ±1.2） while they were （16.4 ±6. 1） and （31.5±6.9） respectively in the controls. Results in patients were significantly lower than that of the controls. Density of 29 000 bands of patients in the DDAVP group before the treatment, at the end of the treatment and three months later were （0. 2 ± 0. 1 ） , （ 15.8 ± 2.3 ） and （4. 4 ± 1.2） while they were （4. 9 ± 1.4） , （ 17.0 ± 2.8） and （6. 4 ±2.4） of 43 000 respectively. Data at the end of the treatment were significantly higher than those before but three months later the results of 43 000 decreased. The data of patients in the biofeedback group was （0.4±0. 2） , （1.2 ±0. 8） , （2. 9 ± 1.3） in 29 000 while （3.9 ± 1.9） , （4. 9±2.4） and （5. 1 ± 1.6） in 43 000, which was not different from that before the treatment. Conclusions Biofeedback and DDAVP are both effective therapies for PNE in children. Biofeedback is helpful in correcting voiding dysfunction and DDAVP can increase AQP2 protein in the urine. With higher effective rate within four month, biofeedback is strongly recommended. However better treatment outcome needs a multidiseiplinary team of nephrologists, urologists and therapists.