【罂粟摘要】不同剂量卡贝缩宫素对拟在腰麻下行择期剖宫产的健康产妇心肌跨室壁复极离散度的影响：一项前瞻性随机临床试验
不同剂量卡贝缩宫素对拟在腰麻下行择期剖宫产的健康产妇心肌跨室壁复极离散度的影响：一项前瞻性随机临床试验
贵州医科大学 高鸿教授课题组
翻译：潘志军 编辑：佟睿 审校：曹莹
QT间期延长与尖端扭转型室性心动过速有关，但仍不能很好地预测药物的扭转性。心肌跨室壁复极离散度增加(TDR)是一个更可靠的预测指标，以T波峰值和结束之间的时间间隔(Tp-e)来衡量。卡贝缩宫素被推荐作为剖宫产(CD)产妇的宫缩剂，但其对Tp-e的影响尚不清楚。我们评估了不同剂量卡贝缩宫素对腰麻下择期CD期间Tp-e和Bazett校正的QT间期(QTc)的影响。
患者知情同意后，我们对50名择期CD健康产妇进行标准腰麻和输注去氧肾上腺素，并使用输液泵在1分钟内通过静脉注射(IV)随机泵注卡贝缩宫素50µg (C50组)或100µg (C100组)。在麻醉前、麻醉后5分钟、卡贝缩宫素给药后5分钟和10分钟获得12导联心电图 (ECG)。然后安排一位心脏病专家按照Emori标准进行测量QTc和Tp-e，他对ECG的分组和时间都不了解。主要结果是与基线值相比，C50和C100组之间以及每组内卡贝缩宫素后5分钟时Tp-e的变化。次要结果包括心律失常的发生、卡贝缩宫素后5分钟和10分钟的QTc变化、腰麻后与基线相比的组间和组内QTc和Tp-e的变化。
分析了41名平均年龄为39.0 ±0.7岁、体重为75.0 ±12.0kg产妇的数据。在组间，卡贝缩宫素给药后5分钟，C100组中的Tp-e比C50组长4.1毫秒（95%置信区间[CI]，0.8-7.5；P=0.01）。在组内，卡贝缩宫素给药后5分钟，C50组与基线相比没有显著增加Tp-e（平均差异[MD] 1.9毫秒；95% CI，-0.95 至4.81毫秒；P=0.42），但C100组显著增加（MD 5.1毫秒；95% CI，2.1–8.1；P=0.003）。卡贝缩宫素给药后5分钟和10分钟时，C50组和C100组的QTc显著增加（P都<0.001），无组间差异。本次研究均没有发生心律失常。
腰麻下健康产妇CD后给予C50 IV对Tp-e无影响，但C100对TP-e的延长作用最小。卡贝缩宫素给药后QTc的增加具有统计学意义，但没有明显的剂量依赖性效应。较高剂量下的最小Tp-e延长不太可能对TDR产生任何临床显著影响，因此诱发尖端扭转型室速的风险很低。
Natasha Clunies-Ross, Thomas M. Roston, James Taylor, et al. The Effect of Carbetocin Dose on Transmural Dispersion of Myocardial Repolarization in Healthy Parturients Scheduled for Elective Cesarean Delivery Under Spinal Anesthesia: A Prospective, Randomized Clinical Trial.[J]. (2021 Feb 1;132(2):485-492).
The Effect of Carbetocin Dose on Transmural Dispersion of Myocardial Repolarization in Healthy Parturients Scheduled for Elective Cesarean Delivery Under Spinal Anesthesia: A Prospective, Randomized Clinical Trial
Abstract
Background: QT interval prolongation is associated with torsade de pointes but remains a poor predictor of drug torsadogenicity. Increased transmural dispersion of myocardial repolarization (TDR), measured as the time interval between the peak and end of the T wave (Tp-e), is a more reliable predictor. Carbetocin is recommended as an uterotonic in patients undergoing cesarean delivery (CD), but its effect on Tp-e is unknown. We evaluated the effect of carbetocin dose on Tp-e and Bazett-corrected QT intervals (QTc) during elective CD under spinal anesthesia.
Methods: On patient consent, 50 healthy parturients undergoing elective CD with a standardized spinal anesthetic and phenylephrine infusion were randomized to receive an intravenous (IV) bolus of carbetocin 50 µg (C50) or 100 µg (C100) via an infusion pump over 1 minute. A 12-lead electrocardiogram (ECG) was obtained at baseline, 5 minutes after spinal anesthesia, then 5 and 10 minutes after carbetocin administration. A cardiologist blinded to group and timing of ECGs measured QTc and Tp-e using Emori’s criteria. Primary outcome was the change in Tp-e at 5 minutes after carbetocin administration between the C50 and C100 groups and within each group compared to baseline values. Secondary outcomes included occurrence of arrhythmias, changes in QTc at 5 and 10 minutes after carbetocin, changes in both QTc and Tp-e after spinal anesthesia compared to baseline between and within groups.
Results:Data from 41 parturients with a mean (standard deviation [SD]) age of 39.0 (0.7) years and weight of 75.0 (12.0) kg were analyzed. Between groups, at 5 minutes after carbetocin admin-istration, Tp-e in C100 was 4.1 milliseconds longer compared to C50 (95% confidence interval [CI], 0.8–7.5; P=0.01). Within groups, at 5 minutes after carbetocin administration, C50 did not significantly increase Tp-e compared to baseline (mean difference [MD] 1.9 milliseconds; 95% CI, −0.95 to 4.81 milliseconds; P=0.42) but C100 did (MD 5.1 milliseconds; 95% CI, 2.1–8.1;P=0.003). QTc increased significantly within C50 and C100 groups at 5 and 10 minutes after carbetocin administration (all P<0.001), with no between-group differences. There were no arrhythmias.
Conclusions:Tp-e was unaffected by C50 IV given after CD in healthy parturients under spinal anesthesia, but minimally prolonged by C100. The increase in QTc after carbetocin administration was statistically significant, but with no apparent dose-dependent effect. The minimal Tp-e prolongation at the higher dose is unlikely to have any clinically significant impact on TDR and therefore the risk of inducing torsade de pointes is low.