Agthe Alexander G, Kim George R, Mathias Kay B, Hendrix Craig W, Chavez-Valdez Raul, Jansson Lauren, Lewis Tamorah R, Yaster Myron, Gauda Estelle B
Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Pediatrics. 2009 May;123(5):e849-56. doi: 10.1542/peds.2008-0978. Epub 2009 Apr 27.
To determine if oral clonidine would reduce the duration of opioid detoxification for neonatal abstinence syndrome.
Infants with intrauterine exposure to methadone or heroin and neonatal abstinence syndrome (2 consecutive modified Finnegan scores of > or =9) were enrolled at 2 hospitals during 2002-2005 and followed until final hospital discharge. All enrolled infants (80) received oral diluted tincture of opium according to a standardized algorithm and were randomly assigned to receive oral clonidine (1 microg/kg every 4 hours) (40 infants) or placebo (40 infants). Primary outcome was duration of opioid therapy. Secondary outcomes included the amount of opium required to control symptoms, number of treatment failures, and differences in blood pressure, heart rate, and oxygen saturation.
The median length of therapy was 27% shorter in the clonidine group (11 [95% confidence interval: 8-15 days]) than in the placebo group (15 days [95% confidence interval: 12-17 days]). In the clonidine group, 7 infants required restarting opium after initial discontinuation versus none in the placebo group, with the total length of treatment/observation remaining significantly less in the clonidine group. Higher dosages of opium were required by 40% of the infants in the placebo group versus 20% in the clonidine group. Treatment failures occurred in 12.5% of the infants in the placebo group versus none in the clonidine group. Hypertension, hypotension, bradycardia, or desaturations did not occur in either group. Three infants in the clonidine group died as a result of myocarditis, sudden infant death syndrome, and homicide, all after hospital discharge and before 6 months of age.
In this randomized, double-blind trial, adding clonidine to standard opioid therapy for detoxification from in utero exposure to methadone or heroin reduced the duration of pharmacotherapy for neonatal abstinence without causing short-term adverse cardiovascular outcomes. A larger trial is indicated to determine long-term safety.
确定口服可乐定是否会缩短新生儿戒断综合征的阿片类药物脱毒持续时间。
2002年至2005年期间，在两家医院招募了宫内暴露于美沙酮或海洛因且患有新生儿戒断综合征（连续两次改良芬尼根评分≥9分）的婴儿，并随访至最终出院。所有入选婴儿（80例）均按照标准化方案接受口服稀释鸦片酊治疗，并随机分为接受口服可乐定（每4小时1μg/kg）（40例婴儿）或安慰剂（40例婴儿）。主要结局是阿片类药物治疗的持续时间。次要结局包括控制症状所需的鸦片量、治疗失败的次数以及血压、心率和血氧饱和度的差异。
可乐定组的中位治疗时长（11天[95%置信区间：8 - 15天]）比安慰剂组（15天[95%置信区间：12 - 17天]）短27%。在可乐定组中，7例婴儿在最初停用鸦片后需要重新开始使用，而安慰剂组中无此情况，可乐定组的总治疗/观察时长仍显著较短。安慰剂组40%的婴儿需要更高剂量的鸦片，而可乐定组为20%。安慰剂组12.5%的婴儿出现治疗失败，而可乐定组无此情况。两组均未出现高血压、低血压、心动过缓或血氧饱和度降低。可乐定组有3例婴儿分别因心肌炎、婴儿猝死综合征和他杀死亡，均在出院后且未满6个月龄时。
在这项随机双盲试验中，在标准阿片类药物治疗中添加可乐定用于宫内暴露于美沙酮或海洛因的脱毒治疗，可缩短新生儿戒断的药物治疗持续时间，且未导致短期不良心血管结局。需要进行更大规模的试验来确定长期安全性。
