Carpenter Ryan J, Kouyoumjian Shaghig, Moromisato David Y, Lieu Phuong, Amirnovin Rambod
J Pediatr Pharmacol Ther. 2020 Jan-Feb;25(1):31-38. doi: 10.5863/1551-6776-25.1.31.
Postoperative fluid overload is ubiquitous in neonates and infants following operative intervention for congenital heart defects; ineffective diuresis is associated with poor outcomes. Diuresis with furosemide is widely used, yet there is often resistance at higher doses. In theory, furosemide resistance may be overcome with chlorothiazide; however, its efficacy is unclear, especially in lower doses and in this population. We hypothesized the addition of lower-dose, intravenous chlorothiazide following surgery in patients on high-dose furosemide would induce meaningful diuresis with minimal side effects.
This was a retrospective, cohort study. Postoperative infants younger than 6 months, receiving high-dose furosemide, and given lower-dose chlorothiazide (1-2 mg/kg every 6-12 hours) were identified. Diuretic doses, urine output, fluid balance, vasoactive-inotropic scores, total fluid intake, and electrolyte levels were recorded.
There were 73 patients included. The addition of lower-dose chlorothiazide was associated with a significant increase in urine output (3.8 ± 0.18 vs 5.6 ± 0.27 mL/kg/hr, p < 0.001), more negative fluid balance (16.1 ± 4.2 vs -25.0 ± 6.3 mL/kg/day, p < 0.001), and marginal changes in electrolytes. Multivariate analysis was performed, demonstrating that increased urine output and more negative fluid balance were independently associated with addition of chlorothiazide. Subgroup analysis of 21 patients without a change in furosemide dose demonstrated the addition of chlorothiazide significantly increased urine output (p = 0.03) and reduced fluid balance (p < 0.01), further validating the adjunct effects of chlorothiazide.
Lower-dose, intravenous chlorothiazide is an effective adjunct treatment in postoperative neonates and infants younger than 6 months following cardiothoracic surgery.
先天性心脏病手术干预后的新生儿和婴儿术后液体超负荷情况普遍存在;利尿无效与不良预后相关。呋塞米利尿被广泛应用,但高剂量时常常出现耐药。理论上,氢氯噻嗪可克服呋塞米耐药;然而,其疗效尚不清楚,尤其是低剂量时以及在该人群中的疗效。我们假设,在接受高剂量呋塞米治疗的患者术后加用低剂量静脉注射氢氯噻嗪会诱导显著利尿且副作用最小。
这是一项回顾性队列研究。纳入术后6个月以下、接受高剂量呋塞米且给予低剂量氢氯噻嗪(每6 - 12小时1 - 2 mg/kg)的婴儿。记录利尿剂量、尿量、液体平衡、血管活性-正性肌力评分、总液体摄入量和电解质水平。
共纳入73例患者。加用低剂量氢氯噻嗪与尿量显著增加(3.8±0.18 vs 5.6±0.27 mL/kg/小时,p<0.001)、液体平衡更负(16.1±4.2 vs -25.0±6.3 mL/kg/天,p<0.001)以及电解质的轻微变化相关。进行多因素分析,结果表明尿量增加和液体平衡更负与加用氢氯噻嗪独立相关。对21例呋塞米剂量未改变的患者进行亚组分析,结果表明加用氢氯噻嗪显著增加了尿量(p = 0.03)并降低了液体平衡(p<0.01),进一步证实了氢氯噻嗪的辅助作用。
低剂量静脉注射氢氯噻嗪是心胸外科手术后6个月以下新生儿和婴儿术后的一种有效辅助治疗方法。