Non-invasive Monitoring of hemodynamic status in preterm infants:a prospective comparison of 3 different approaches including feasibility, reproducibility and association to relevant clinical short term outcome

背景：了解新生儿血流动力学是新生儿护理和神经保护的关键。尽管进行了数十年的研究，但对于如何持续监测极早产儿的血流动力学仍存在不确定性。血流主要取决于两个关键因素：血压(BP)和血管阻力(以及新生儿分流的存在)。目前仍然普遍的做法是只关注血压，从而忽视新生儿可能存在的复杂和动态(病理)生理学。因此，在低血压的婴儿中，在全身血管阻力低的情况下，血流(从而氧气输送)或其替代参数心输出量仍然是正常的。无创性心输出量(CO)监测、脑局部氧合(近红外光谱，NIRS)和搏动指数监测(PI，脉搏血氧仪)可能有可能为常规的血压和心率血流动力学监测提供额外信息。方法：我们打算对在科克大学妇产医院出生的100名早产儿(2016年近8000名婴儿的出生率)和32周的出生后48小时内进行前瞻性观察试验。本研究由两部分组成：1.可行性和可重复性：1.确保使用心电图仪(Osypka Medical，柏林，德国)监测CO是安全可靠的(20例婴儿)。(主要研究)通过无创血流动力学监测预测循环衰竭(另外80名婴儿)。结果变量：可行性：出生后48小时内通过心电测量和PI分析连续记录CO至少24小时的婴儿比例。重复性：联合监测和超声心动图(即左心输出量)。主要研究：循环衰竭预测因变量：不良结局(是/否)，独立变量：临床怀疑婴儿血流动力学受损的开始时间和比例(如肤色、毛细血管再充盈时间和GT；3S)、实验室参数(即乳酸酸中毒)、BP、PI分析、NIRS或CO测量及其组合。目的：本研究的主要目的是确定不同的连续血流动力学监测方法对早产儿出生48小时内血流动力学的影响，并建立无创血流动力学监测方法。这些数据可能导致对动脉低血压和允许性低血压的更准确的定义，从而为基于证据的算法评估早产儿的血流动力学状态提供数据。

Background:Understanding neonatal hemodynamics is key to neonatal care and neuroprotection. Despite decades of research, uncertainty continues as to how to continuously monitor hemodynamics in extremely preterm infants. Blood flow is mainly dependent on two key factors: blood pressure (BP) and vascular resistance (and the presence of neonatal shunts). It is still common practice to focus only on BP, thus neglecting the complex and dynamic (patho)physiology that may be present in newborn infants. Thus, in infants with low blood pressure, flow (and hence oxygen delivery) or its surrogate parameter cardiac output, can still be normal in cases of low systemic vascular resistance. Non-invasive cardiac output (CO) monitoring, cerebral regional oxygenation (Near-infrared spectroscopy, NIRS) and pulsatility index monitoring (PI, pulse oxymetry) may have the potential to support routine hemodynamic monitoring of BP and heart rate with additional information.Methods: We intend to perform a prospective observational trial in 100 preterm infants born at Cork University Maternity Hospital (birth rate of almost 8000 babies in 2016) <32 weeks’ gestation during the first 48 postnatal hours. This study consists of 2 parts:1. feasibility and reproducibility: to ensure CO monitoring using electrical cardiometry (Osypka Medical, Berlin, Germany) is safe and reliable (20 infants).2. (main study) prediction of circulatory failure by non-invasive hemodynamic monitoring (80 additional infants).Outcome Variables:For feasibility:The proportion of infants in whom a continuous recording of CO by electrical cardiometry and PI analysis was obtained for at least 24 hours during the first 48 hours after birth.For reproducibility:CO-monitoring and echocardiography (i.e. left ventricular output).Main study: Prediction of circulatory failureDependent variable: Adverse outcome (Yes/No), where an adverse outcome is defined as a cranial ultrasound abnormality or death within 7 days of birth.Independent variables: Onset and proportion of time infants are suspected to have impaired hemodynamics as defined by clinical suspicion (i.e. skin colour, capillary refill time>3s), laboratory parameters (i.e. lactic acidosis), BP, PI analysis, NIRS or CO measures and combination of these measures.Aim:The principle objective of this study is to determine the impact of different continuous hemodynamic monitoring methods and to establish non-invasive hemodynamic monitoring methods in preterm infants within 48 hours of birth. These data may result in more precise definitions of arterial hypotension and permissive hypotension, thus providing data for an evidence based algorithm to assess hemodynamic status in preterm infants.