Department of Pediatrics, College of Medicine.
Department of Biostatistics, College of Public Health.
Pediatrics. 2024 Nov 1;154(5). doi: 10.1542/peds.2023-065610.
We sought to determine whether clonidine, a non-opioid α-2-adrenergic agonist, would effectively treat neonatal opioid withdrawal syndrome (NOWS).
This was an intention-to-treat randomized clinical trial. Enrollment criteria included prenatal opioid exposure, age ≤7 days, gestational age ≥35 weeks, no other medical condition, and need for pharmacotherapy. Primary outcomes were length of treatment and neurobehavioral performance.
A total of 1107 patients were screened for enrollment (645 ineligible, 91 parents or staff unavailable, 216 declined, 155 consented). Of 155 infants, 120 required treatment and were randomized to receive oral clonidine (n = 60) at 1 µg/kg/dose or morphine (n = 60), 0.06 mg/kg/dose, every 3 hours. Infants with no improvement had their doses increased by 25% of the initial dose every 12 to 24 hours. Those without improvement by the fourth dose increase, received adjunct therapy. Length of treatment did not differ between morphine and clonidine, with median (95% confidence interval [CI]) days, respectively, of 15 (13-17) and 17 (15-19), P = .48. More clonidine-treated infants (45%) needed adjunct therapy versus 10% in the morphine group, adjusted odds ratio (95% CI) = 8.85 (2.87-27.31). After treatment completion, the NICU Network Neurobehavioral Scales summary scores did not differ between clonidine-treated and morphine-treated infants.
Length of pharmacologic treatment and final neurobehavioral performance were not significantly different between the clonidine- and morphine-treated groups. Clonidine appears to be an effective non-opioid medication to treat NOWS. Future studies are needed to determine the optimal clonidine dosage for a quicker response and obviation of adjunct therapy.
我们旨在确定可乐定（一种非阿片类 α-2 肾上腺素能激动剂）是否能有效治疗新生儿阿片戒断综合征（NOWS）。
这是一项意向治疗的随机临床试验。纳入标准包括产前阿片类药物暴露、年龄≤7 天、胎龄≥35 周、无其他医疗状况和需要药物治疗。主要结局是治疗时间和神经行为表现。
共有 1107 名患者被筛选纳入（645 名不符合条件，91 名父母或工作人员无法联系，216 名拒绝，155 名同意）。在 155 名婴儿中，120 名需要治疗，被随机分为口服可乐定（n=60），剂量为 1μg/kg/剂量，或吗啡（n=60），剂量为 0.06mg/kg/剂量，每 3 小时一次。无改善的婴儿每 12 至 24 小时将剂量增加初始剂量的 25%。在第四次剂量增加后仍无改善的婴儿接受辅助治疗。吗啡和可乐定治疗的治疗时间无差异，中位数（95%置信区间）分别为 15（13-17）天和 17（15-19）天，P=0.48。更多接受可乐定治疗的婴儿（45%）需要辅助治疗，而接受吗啡治疗的婴儿为 10%，调整后的比值比（95%置信区间）为 8.85（2.87-27.31）。治疗完成后，接受可乐定和吗啡治疗的婴儿的新生儿重症监护病房神经行为量表总分无差异。
可乐定和吗啡治疗组的药物治疗时间和最终神经行为表现无显著差异。可乐定似乎是一种有效的非阿片类药物，可用于治疗 NOWS。需要进一步的研究来确定可乐定的最佳剂量，以获得更快的反应和避免辅助治疗。
