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儿童水肿和低钠血症疾病的血管加压素受体拮抗剂:系统文献综述。

Vaptans for oedematous and hyponatraemic disorders in childhood: A systematic literature review.

机构信息

Pediatric Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzona, Switzerland.

Family Medicine, Faculty of Biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland.

出版信息

Br J Clin Pharmacol. 2022 Oct;88(10):4474-4480. doi: 10.1111/bcp.15367. Epub 2022 May 12.

Abstract

AIMS

The aim of this study was to systematically review the use of vaptans (nonpeptide vasopressin receptor antagonists) in children.

METHODS

Through a database search (Web of Science, the National Library of Medicine, Excerpta Medica), we identified case series and case reports and extracted clinical and laboratory data.

RESULTS

Twenty-six articles, published since 2008, reported on 226 patients. Among 115 children with hyponatraemic (n = 63) and oedematous disorders (n = 52), a 48 hour course of tolvaptan with an initial dose of 0.38 ± 0.27 mg/kg was administered in 106 cases, while intravenous conivaptan was reported in nine cases. An increase (P < .02) in urine output was shown in both oedematous (from 3.2 ± 2.0 to 5.3 ± 6.7 mL/kg/day) and hyponatraemic (from 3.0 ± 1.5 to 4.4 ± 2.3 mL/kg/day) patients. In these latter, sodium increased from 125 ± 6 to 133 ± 6 mmol/L (P < .0001). The increase in sodium level correlated with its basal value, but not with the administered vaptan dose. Among 111 children undergoing cardiac surgery, after tolvaptan 0.21 ± 0.01 mg/kg/day, mostly combined with conventional diuretics, an increase in diuresis by 41 ± 4% was seen within 24 hours (P < .0001). Similarly, a single add-on dose of tolvaptan 0.45 mg/kg allowed a reduced additional intravenous furosemide administration (0.26 ± 0.23 vs 0.62 ± 0.48 mg/kg, P < .005). Side effects were rarely reported, and included excessive thirst and xerostomia in seven, skin rash in one and elevated aminotransferases in one patient(s).

CONCLUSION

Vaptans appear to be safe for oedematous and hyponatraemic disorders also in children. Although they increase diuresis and natraemia, no superiority to traditional diuretics and sodium supplements has been demonstrated. Reported side effects are rare and non-serious.

摘要

目的

本研究旨在系统回顾血管加压素受体拮抗剂(非肽类血管加压素受体拮抗剂)在儿童中的应用。

方法

通过数据库检索(Web of Science、美国国立医学图书馆、荷兰医学文摘),我们确定了病例系列和病例报告,并提取了临床和实验室数据。

结果

2008 年以来,26 篇文章报道了 226 例患者。在 115 例低钠血症(n=63)和水肿性疾病(n=52)患儿中,106 例给予托伐普坦 48 小时疗程,初始剂量为 0.38±0.27mg/kg,9 例给予静脉注射康昔普坦。水肿(从 3.2±2.0 至 5.3±6.7 mL/kg/天)和低钠血症(从 3.0±1.5 至 4.4±2.3 mL/kg/天)患儿的尿量均增加(P<.02)。在这些患儿中,钠从 125±6mmol/L 增加到 133±6mmol/L(P<.0001)。钠水平的升高与基础值相关,但与给予的血管加压素受体拮抗剂剂量无关。在 111 例行心脏手术的患儿中,托伐普坦 0.21±0.01mg/kg/天,大多与常规利尿剂联合应用,24 小时内利尿增加 41±4%(P<.0001)。同样,单次给予托伐普坦 0.45mg/kg 可减少额外静脉注射呋塞米的用量(0.26±0.23 与 0.62±0.48mg/kg,P<.005)。不良反应罕见,7 例出现口渴和口干,1 例出现皮疹,1 例出现氨基转移酶升高。

结论

血管加压素受体拮抗剂在儿童水肿和低钠血症中似乎是安全的。虽然它们增加了尿量和血钠,但与传统利尿剂和钠补充剂相比,并没有显示出优越性。报告的不良反应罕见且不严重。

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