Corrected QT Interval and Methadone Dose and Concentrations in Pregnant and Postpartum Women
Corrected QT Interval and Methadone Dose and Concentrations in Pregnant and Postpartum Women
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DOI：
10.4088/jcp.16m11318
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发表时间：
2017-09-01
影响因子：
5.3
通讯作者：
Wisner, Katherine L.
中科院分区：
文献类型：
--
作者：
Bogen, Debra L.;Hanusa, Barbara H.;Wisner, Katherine L.
背景：美沙酮是妊娠期间阿片类药物依赖的标准治疗方法；然而，其对母亲校正的QT间期(QTC)的影响尚未得到评估。我们在孕妇、产后妇女和新生儿中研究了美沙酮剂量与对映体特定血浆浓度和QTC之间的关系。我们评估了QTC筛查指南对孕妇和婴儿的相关性。方法：从2006年到2008年，在单一治疗方案中，对接受阿片类药物依赖治疗的妇女在怀孕期间、产后和脐血中的美沙酮浓度进行了测定。在母亲体内美沙酮浓度达到峰值时和婴儿出生后48小时内采集心电图(ECG)。结果：孕期美沙酮平均日剂量(SD)为94.2 mg，产后日均美沙酮剂量为112.5(46.6)mg。孕晚期美沙酮剂量和R-美沙酮浓度与QTc值呈正相关(P<0.05)，而S-美沙酮、R-美沙酮/S-美沙酮浓度和总美沙酮浓度与QTc值无相关性。产后QTc值与剂量或对映体浓度无明显相关性。婴儿QTC与产妇分娩时的剂量或对映体特定的脐带美沙酮浓度无关。孕妇和产后妇女QTC和Gt；分别为13%和17%，婴儿为19%。结论：妊娠晚期QTC与剂量和R-美沙酮浓度相关。然而，在怀孕期间和怀孕后，QT间期延长在女性中很常见。鉴于QTC>；450ms的发生率相对较高，对于孕妇和产后妇女来说，在美沙酮开始使用前后进行心电图检查是可取的。
Background: Methadone is a standard treatment for opioid dependence in pregnancy; however, its impact on maternal corrected QT interval (QTc) has not been evaluated. We studied the association between methadone dose and enantiomer-specific plasma concentrations and QTc among pregnant and postpartum women and newborns. We assessed the relevance of QTc screening guidelines for pregnant women and infants.Methods: From 2006 to 2008, plasma methadone concentrations were measured during pregnancy, postpartum, and in cord blood in women treated for opioid dependence at a single treatment program. Electrocardiograms (ECGs) were obtained at peak methadone concentrations in mothers and within 48 hours of birth for infants. Pearson correlations were performed at each time point for QTc and R-methadone, S-methadone, and total methadone concentrations and ratio of R-methadone/S-methadone concentrations.Results: Mean (SD) daily methadone dose for the 25 women was 94.2 (39.1) mg during pregnancy and 112.5 (46.6) mg postpartum. During the third trimester, higher methadone dose and R-methadone concentration correlated with longer QTc (Pearson r = 0.67, P < .001 and Pearson r = 0.49, P = .02, respectively), while S-methadone concentration, R-methadone/S-methadone concentration ratio, and total methadone concentration did not. Postpartum, QTc did not significantly correlate with dose or enantiomer concentrations. Infant QTc did not correlate with maternal dose at delivery or enantiomer-specific cord methadone concentrations. In pregnant and postpartum women, 13% and 17%, respectively, had QTc >= 450 ms, as did 19% of infants.Conclusions: QTc correlated with dose and R-methadone concentration during the third trimester. However, longer QTc was common among women during and after pregnancy. Given the relatively high rate of QTc > 450 ms, an ECG before and after methadone initiation is advisable for pregnant and postpartum women.