الفهرس 
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Abstract
A patent ductus arteriosus (PDA) in the first three days of life is a normal physiologic remnant in healthy term neonates. Conversely, a PDA in preterm neonates causes significant clinical sequelae as a result from left to right shunting. It is widely recognized that a hemodynamically significant PDA is known to contribute to increased morbidity and mortality. The increase in pulmonary blood flow in the setting of prematurity leads to pulmonary edema, noncompliant lungs, and worsening of respiratory status. Other sequelae of a hemodynamically significant PDA include intraventricular hemorrhage, necrotizing enterocolitis, congestive heart failure, and failure to thrive. Echocardiography is often used to evaluate hemodynamic significance of PDA. In general, pharmacological closure of PDA is less successful in infants with ductal diameter >2mm. Lower ductal maximum velocity, which is usually associated with a larger PDA or higher pulmonary pressure, is another predictor of treatment failure. An increase in left ventricular cardiac output (CO) has been positively correlated with significant ductal shunting and PDA severity. The underlying reason is that a PDA with significant left-to-right flow may lead to a compensatory increase in CO in order to maintain systemic blood flow. Indeed, following closure of ductus after pharmacological therapy or surgical ligation, cardiac output normalizes accordingly. The use of echocardiography to gather meaningful hemodynamic data often necessitates serial assessments that can be tedious and effortful. Electrical cardiometry (EC) is a non-invasive, impedance-based monitor that provides absolute cardiac output estimates in clinical practice. Unlike echocardiography, EC is simple to apply, continuous in measurements and not operator-dependent. The principle of Electrical cardiometry (EC) is based on applying a high frequency, very low-magnitude current across the chest via topical electrodes distributes mainly to blood. Hence, pulsatile changes in thoracic blood volume will cause changes in electrical thoracic impedance. The changes in impedance during systole are proportional to cardiac output. Electrical cardiometry can be useful in trending hemodynamic changes in the clinical setting as hemodynamic reference by EC for neonates without PDA and without invasive ventilation support has been established, and COEC is positively correlated with gestational age (GA) and weight. In addition, EC was used to monitor the effects of ductal ligation on COEC, which revealed an initial decline in COEC followed by recovery. This work aimed to monitor hemodynamic alternations during pharmacological closure of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates. This was a Prospective observational study was that was conducted in neonatal intensive care unit (NICU) of Tanta University Hospital (TUH) on eighty preterm neonates with left-to-right patent ductus arteriosus with gestational age between 28 weeks and 35 weeks. The study started from October 2019 to April 2020; the patients were subdivided into 2 main groups: 1) group I: included 40 preterm neonates with hemodynamically significant left-to-right PDA (hsPDA). They were furtherly subdivided according to their response to the pharmacological treatment of (hsPDA) with five days’ course of (intravenous paracetamol) into 2 subgroups: group IA included 20 responders preterm neonates and group IB included 20 nonresponders preterm neonates 2) group II: include forty hemodynamically stable preterm neonates as a control group either completely free by routine echocardiography or with hemodynamically stable left-to-right PDA. Inclusion criteria: Preterm neonates with GA between 28 weeks and 35 weeks admitted to NICU during first week of life. Exclusion criteria: ▪ Neonates with major cardiac abnormalities (except for the presence of PDA or PFO) or aortic arch anomalies. ▪ Neonates with right-to-left or bidirectional shunting PDA. ▪ Neonates in need for hemodynamic support ▪ Neonates in need for high frequency ventilation. ▪ Neonates with persistent pulmonary hypertension ▪ Neonates with chromosomal anomaly. ▪ Neonates with major complications such as intraventricular hemorrhage (IVH) or necrotizing enterocolitis (NEC). ▪ Neonates with poor renal function (serum creatinine >1.8mg/dl or oliguria <1ml/kg/hr.). Methods All patients were subjected to: A. Thorough history taking which included: Peri-natal history including: • Maternal obstetric and medical history. • Family history. Natal history of labor and delivery. B. Full clinical examination: • Assessment of the gestational age (GA) at birth by the modified New Ballard score and physical examination. • Anthropometric and vital measurement • Cardiac examination: heart sounds and presence of any murmur. • Chest examination C. Transthoracic echocardiography (TTE): • Serial echocardiography were performed in relation to pharmacological treatment: within an hour prior the start of treatment (baseline), 24h after starting treatment regimen (during treatment), and 24h after treatment completion. • Echocardiographic parameters of the PDA were assessed, which included ductal size and shunt direction, maximum flow velocity, and left atrium to aortic root ratio (LA/Ao) and left ventricular fractional shortening (FS). D. Electrical Cardiometry (EC): • Hemodynamics were assessed using the ICON ® hemodynamic monitor (ICON Cardiotronics, Inc., La Jolla, CA 92307; Osypka Medical GmbH, Berlin, and Germany, model C3, Serial no: 1817406) • Four skin electrodes (iElectrical Cardiometry Skin Sensors; Osypka Medical) were applied over the forehead, left lower neck, left midaxillary line at the level of xiphoid process and lateral aspect of left thigh. • EC was placed at least 1h prior the start of treatment and kept in situ until 24h after completing treatment • Hemodynamic parameters recorded by EC, included: 1) Stroke volume (SV) 2) Heart rate 3) Cardiac output (CO) 4) Stroke volume variation 5) Index of contractility (ICON) 6) Thorathic fluid content 7) Systemic vascular resistance (SVR) E. Laboratory investigations: CBC. C-Reactive protein (CRP). Renal function tests (RFTs) Serum electrolytes level: sodium, potassium, calcium Blood gases (ABG/CBG) F. Radiological investigations: Chest X-Ray Transcranial US The study revealed that: • There was no significant difference in all the demographic and anthropometric measurements among the studied groups. • The gestational age ranged from 31 to 33 in the three groups. The gestational age was slightly lower in responders group compared to groups non-responders and control groups • The diastolic blood pressure was significantly higher in control group compared to group I (cases). There was no difference in diastolic pressure between responders and non-responders groups. • The baseline measurements obtained by echocardiography for the studied groups: • The ductal size was largest in non-responders, followed by responders, and then control group, with significant differences between all groups. • The LA/Ao was highest in non-responders, followed by responders, then control group. Significant differences existed between group I (cases) and control group. However, the difference between responders and non-responders groups was not significant • As regards the FS measurements, the three groups were comparable with no significant differences among them The baseline measurements obtained by EC for the studied groups: • The SV and CO values were highest in non-responders group IB, followed by responders subgroup IA, then control group II. There were significant differences among all the groups on post hoc pairwise comparisons. • The SVR measurements were highest in control group II, followed by responders subgroup IA, then non-responders subgroup IB. Significant differences were detected on pairwise comparisons between groups IA and IB, groups IA and II, and groups IB and II. • The measurements of HR, SVV, ICON and TFC were comparable among the three groups, with no statistically significant differences. The EC follow up data in responders group IA showed: • The SV and CO measurements showed a significant decrease after starting treatment from the baseline values. After completion of treatment, there was a significant increase in the measurements after starting treatment. Meanwhile, the levels after completing treatment were still significantly lower than the baseline measurements. • The SVR measurement showed a significant increase after starting treatment from the baseline values. After completion of treatment, there was a significant decrease from the measurements after starting treatment. Meanwhile, the levels after completing treatment were still significantly higher than the baseline measurements. The EC follow up data in no-responders subgroup IB showed: • The SV measurements showed a slight non-significant decrease after starting treatment from the baseline values. After completion of treatment, there was a significant increase from both the baseline and after starting treatment. • The CO measurement showed a significant decrease after starting treatment from the baseline values. After completion of treatment, there was a significant increase in the measurements after starting treatment which was significantly higher than the baseline measurements also. • The SVR measurement showed a slight increase after starting treatment from the baseline values. After completion of treatment, there was a significant decrease from the measurements of baseline level and after starting treatment. There were significant differences between the studied groups regarding the Chest X-Ray findings at the time of recruitment (p<0.001). The findings in the studied groups were in the form of cardiomegaly (30%, 20%, 5%, respectively), lung congestion (40%, 35%, 12.5%, respectively), and mild (5%, 20%, 52.5%, respectively), moderate (10%, 25%, 30%), and severe RDs (15%, 0%, 0%). Regarding the correlations between EC data at baseline and (demographic, anthropometric and echo data) in responders subgroup IA: Summary 116 • There were no observed significant associations between CO data at baseline and Ductal size or LA/Ao. • The SVR showed a significant positive weak association with LA/Ao. Otherwise, there were no observed significant associations. Regarding the correlations between EC data 24hr after treatment was completed and (demographic, anthropometric and echo data) in responders subgroup IA, there were no observed significant associations between SVR and other variables. Concerning non-responders subgroup IIB, the correlations between EC data at baseline and 24hr after treatment completed, there were no observed significant associations between SVR and other variables.