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。尽管经过数十年的研究，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）。仍然普遍的做法是只关注血压，从而忽略了新生儿可能存在的复杂和动态（病理）生理。因此，对于低血压的婴儿，在全身血管阻力低的情况下，流量（以及由此产生的氧输送）或其替代参数心输出量仍可正常。无创心输出量（CO）监测、脑区域氧合（近红外光谱，NIRS）和脉搏指数监测（PI，脉搏血氧仪）可能具有支持常规血流动力学监测血压和心率的附加信息的潜力。方法：我们打算在科克大学妇产医院出生的100名早产儿（2016年出生率近8000名）中进行一项前瞻性观察试验，这些早产儿在出生后48小时内妊娠<32周。本研究主要包括两个部分：1.研究内容；可行性和可重复性：确保使用心电测量法（Osypka Medical，柏林，德国）进行CO监测安全可靠（20名婴儿）。（主要研究）通过无创血流动力学监测预测循环衰竭（新增80例婴儿）。结果变量：可行性：在出生后48小时内，通过心电测量和PI分析连续记录至少24小时CO的婴儿比例。为了再现性：co监测和超声心动图（即左心室输出量）。主要研究：循环衰竭预测因变量：不良结果（是/否），其中不良结果定义为出生后7天内颅内超声异常或死亡。自变量：根据临床怀疑（即肤色、毛细血管再充血时间bbb3s）、实验室参数（即乳酸性酸中毒）、BP、PI分析、NIRS或CO测量以及这些测量的组合来定义，婴儿怀疑有血流动力学受损的发病和时间比例。目的：本研究的主要目的是确定不同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，建立无创血流动力学监测方法。这些数据可能导致更精确的动脉性低血压和允许性低血压的定义，从而为评估早产儿血流动力学状态的基于证据的算法提供数据。

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.