Identifying the precursor to oxytocin-induced uterine tachysystole by monitoring with uterine EMG

在美国，大约30%的女性（每年超过120万）在分娩过程中的某个时刻接受静脉注射催产素，以增加子宫收缩的频率和强度。催产素被归类为需要临床警惕的高度警惕药物。催产素通常是安全的，但当收缩过于频繁时，就会出现不良后果，这种情况被称为心动过速。心动过速与导致紧急剖宫产的胎儿窘迫（RR 2）、新生儿败血症（RR 2.0）、新生儿重症监护病房入院（RR 1.6）和胎儿结局下降（RR 1.5）相关。迄今为止，仅靠临床警惕还不足以降低这些与催产素相关的临床风险。个体对催产素的反应有明显的差异，一些患者在低剂量下会强烈收缩，而另一些患者则需要高剂量才能表现出轻微的收缩。如果没有一种可靠的、非侵入性的方法来监测催产素对子宫的影响，它仍然很难有效地管理。使用胎压测力法（toco）是评估分娩过程中收缩的标准方法，不幸的是，20%的患者出现了心动过速。这一高比率是产科实践中的一个严重差距。肌电图提供了一种评估子宫收缩的替代方法，因为肌肉收缩时会产生生物电信号。有趣的是，人们早就意识到子宫收缩之间也会产生生物电信号。这些信号是商业肌电系统中“假阳性收缩”报告的来源。然而，到目前为止，还没有人解释这些信号的来源、重要性或意义。在我们初步的子宫肌电图研究中，我们发现这些“宫缩之间”的信号在使用催产素时很突出。此外，随着子宫收缩模式接近心动过速，我们的分析表明，催产素相关的肌电图信号持续时间更长（2-3分钟），出现频率更高。在符合心动过速临床标准的受试者中，所有通道均可见到催产素相关信号，且持续时间更长（3 ~ 10分钟）。在这个一期SBIR项目中，我们将展示从原始数据中实时分离催产素相关信号的可行性（目的1）。在目标2中，我们将使用这些信号来分类子宫收缩：1)正常；2)早期催产素效应；3)心动过速前体；4) tachysystole。确定心动过速的前兆将使临床医生知道什么时候不建议额外的催产素输注并避免心动过速。这将缩小在催产素管理引产的实践差距。

Approximately 30% of all women in the US (over 1,200,000 annually) are exposed to IV oxytocin at some point during labor to increase the frequency and strength of uterine contractions. Oxytocin is classified as a high-alert medication requiring clinical vigilance. Oxytocin is generally safe, but adverse outcomes arise when contractions become too frequent, a condition called tachysystole. Tachysystole is associated with fetal distress resulting in emergency Cesarean delivery (RR 2), neonatal sepsis (RR 2.0), NICU admissions (RR 1.6) and depressed fetal outcomes (RR 1.5). To date, clinical vigilance alone has not sufficiently reduced these oxytocin-related clinical risks. There are marked variations of individual responses to oxytocin, with some patients contracting robustly at low doses, while others require high doses to express mild contractions. Without a reliable, non-invasive method to monitor the effects of oxytocin on the uterus, it remains difficult to effectively administer. The use of tocodynamometry (toco), the standard method of assessing contractions during labor, unfortunately results in 20% of patients experiencing tachysystole. This high rate is a serious gap in obstetrical practice. Electromyography offers an alternate method of assessing uterine contractions since bioelectrical signals are produced as the muscle contracts. Interestingly, it long been appreciated that uterine bioelectrical signals are also produced between contractions. These signals are the source of “false positive contraction” reporting in commercial EMG-based systems. However, to date there have been no explanations of the source, importance, or meaning of these signals. In our preliminary uterine EMG studies, we found these “between contractions” signals are prominent during oxytocin use. Furthermore, as the uterine contraction pattern approaches tachysystole, our analysis suggests that oxytocin-associated EMG signals last longer (2-3 minutes) and appear more frequently. In subjects that meet the clinical criteria of tachysystole, the oxytocin-associated signals are seen in all channels and persist even longer (3 to 10 minutes). In this Phase I SBIR project, we will show the feasibility of isolating the oxytocin-associated signals from raw data in real time (Aim 1). In Aim 2 we will use these signals to categorize the uterine contractions as 1) normal; 2) early oxytocin effects; 3) precursor to tachysystole; 4) tachysystole. Identifying the precursor to tachysystole will allow clinicians to know when additional oxytocin infusion is inadvisable and avoid tachysystole. This will close the gap in the practice of oxytocin management for induction of labor.