Higashi Kouji, Murakami Tomoaki, Ishikawa Yuichi, Itoi Toshiyuki, Ohuchi Hideo, Kodama Yoshihiko, Honda Takashi, Masutani Satoshi, Yamazawa Hirokuni, Senzaki Hideaki, Ishikawa Shiro
Department of Cardiology, Chiba Children's Hospital, Japanese Society of PEdiatric Circulation and Hemodynamics, Japan; Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
Department of Cardiology, Chiba Children's Hospital, Japanese Society of PEdiatric Circulation and Hemodynamics, Japan; Japanese Society of PEdiatric Circulation and Hemodynamics, Japan.
Int J Cardiol. 2016 Feb 15;205:37-42. doi: 10.1016/j.ijcard.2015.12.003. Epub 2015 Dec 15.
Tolvaptan, a vasopressin V2-receptor antagonist, has been reported to improve congestion in adult patients with heart failure. However, it has not been fully clarified whether tolvaptan is also effective and safe for pediatric patients as well as adult.
This trial was a multicenter, retrospective, observational study, and was led by the Japanese Society of PEdiatric Circulation and Hemodynamics (J-SPECH). Thirty-four pediatric patients who received tolvaptan to treat congestive heart failure were enrolled in this study.
An increment in the urinary volume and decrease in the body weight from baseline were significant at day 1 (+106.7 ± 241.5%, p = 0.008 and -2.30 ± 4.17%, p = 0.01), day 3 (+113.5 ± 261.9%, p = 0.02 and -2.30 ± 4.17%, p = 0.01), week 1 (+56.3 ± 163.5%, p = 0.01 and -1.55 ± 4.09%, p = 0.03) and month 1 (+91.1 ± 171.6%, p = 0.01 and -2.95 ± 5.98, p = 0.03). The significant predictive factors in responders, who was defined as patients who achieved an increase in the urinary volume at day 1, were older age (p = 0.03), larger body weight before exacerbation (p = 0.04), higher weight at one day before the first administration of tolvaptan (p = 0.03), higher aspartate aminotransferase levels (p = 0.03) and higher urinary osmolality levels (p = 0.03). A logistic regression analysis showed that the urinary osmolality was the only significant predictive factor for responders to tolvaptan. Adverse drug reactions were observed in 7 patients (20.6%). Six patients had thirst and a dry month, and 1 had a mild increase in the alanine aminotransferase and aspartate aminotransferase.
Tolvaptan can be effectively and safely administered in pediatric patients. Because the kidneys in neonates and infants are resistant to arginine vasopressin, the efficacy of tolvaptan may be less effective compared to older children.
托伐普坦是一种血管加压素V2受体拮抗剂，据报道可改善成年心力衰竭患者的充血症状。然而，托伐普坦对儿科患者是否也有效且安全尚未完全阐明。
本试验是一项多中心、回顾性观察研究，由日本儿科学循环与血液动力学学会（J-SPECH）牵头。本研究纳入了34例接受托伐普坦治疗充血性心力衰竭的儿科患者。
在第1天（尿量增加+106.7±241.5%，p = 0.008；体重下降-2.30±4.17%，p = 0.01）、第3天（尿量增加+113.5±261.9%，p = 0.02；体重下降-2.30±4.17%，p = 0.01）、第1周（尿量增加+56.3±163.5%，p = 0.01；体重下降-1.55±4.09%，p = 0.03）和第1个月（尿量增加+91.1±171.6%，p = 0.01；体重下降-2.95±5.98，p = 0.03）时，尿量较基线增加及体重较基线下降均具有显著性。将第1天尿量增加的患者定义为有反应者，其显著预测因素为年龄较大（p = 0.03）、病情加重前体重较大（p = 0.04）、首次服用托伐普坦前一天体重较高（p = 0.03）、天冬氨酸转氨酶水平较高（p = 0.03）和尿渗透压水平较高（p = 0.03）。逻辑回归分析显示，尿渗透压是托伐普坦有反应者的唯一显著预测因素。7例患者（20.6%）观察到药物不良反应。6例患者有口渴和口干，1例患者丙氨酸转氨酶和天冬氨酸转氨酶轻度升高。
托伐普坦可在儿科患者中有效且安全地使用。由于新生儿和婴儿的肾脏对精氨酸血管加压素耐药，与大龄儿童相比，托伐普坦的疗效可能较差。
