European Journal of Cardiovascular Medicine

Shock is an acute, complex state of circulatory dysfunction which results in insufficient oxygen and nutrient delivery to tissues relative to their metabolic demand leading to cellular dysfunction that may eventually cause cell death. Initially shock may be compensated with reduction in blood supply to skin, muscle, and splanchnic vessels and adequate blood flow to vital organs. This may then be followed by an uncompensated phase when signs of poor perfusion are accompanied by hypotension.  Sepsis is a major cause of morbidity and death in the neonatal period, affecting 1– 8 per 1,000 of all neonates.1 International paediatric sepsis consensus statement defines septic shock as cardiovascular organ dysfunction in presence of sepsis.2 When sepsis is associated with cardiovascular dysfunction leading to septic shock, survival is further compromised.3

In premature neonates, extremely low systemic perfusion can occur with normal blood pressure (BP). The diagnosis and management of shock in the new-born presents many challenges to neonatologists. The determination of the adequacy of overall circulatory well-being remains predominantly subjective, and there are no validated clinical scoring systems available. Despite its many limitations, mean arterial blood pressure remains the most commonly used marker for circulatory compromise. Reliance on mean blood pressure values alone to determine circulatory well-being is an overly simplistic approach to a much more complex problem. A normal blood pressure does not equate to normal end-organ blood flow. There has been a recent move in other areas of medicine to incorporating multimodal monitoring in the management of complex clinical problems, such as neurocritical care. Multimodal monitoring provides the opportunity to overcome some of the shortcomings of each monitoring technique and ultimately achieves more accuracy in determining appropriate interventions. Echocardiography represents an objective tool to assist with the assessment of shock in the newborn infant.4

Functional echocardiography is rational and non-invasive, and may have a very important part to play in the overall assessment and management of newborn shock. It is non-invasive, readily available, performed at the bedside, and provides information in real time, making it an ideal tool to evaluate hemodynamic state and to acquire physiological and anatomical information in critically-ill patients.5-7 this practice is well established in adults and paediatric cardiac intensive care units.  Echocardiography though being used by the neonatologists in many neonatal intensive care units (NICU) across the world.  However, there remains a significant variation in the clinical practice of the neonatologist performing echocardiography.8 Despite its increasing popularity and use in the neonatal clinical practice, there is a very limited established structured training or accreditation process specifically designed for the neonatologists to acquire skills in targeted or functional echocardiography. The aim of this study will be to assess the correlation of functional echocardiography with clinical parameters in term neonates with septic shock.

This study was conducted with the aim to assess correlation of functional echocardiography with clinical parameters in neonates with septic shock. The primary objective was to assess the correlation of functional echocardiography with clinical parameters in neonates with septic shock. The secondary objectives were to study the impact of fluid resuscitation on outcome based on echocardiography and to assess the mortality outcomes based on echocardiography.

This was a Single centric Prospective cross-sectional type of study. It was conducted in the Department of Neonatology (NICU), GMC Aurangabad. Sample size was calculated using the formula, n=Z*Z(pq)/d*d, which came out to be 138. Written Informed Consent of the parents was taken before inclusion in the study. Study population included all the newborns in NICU, GMCH, Aurangabad who developed septic shock as diagnosed by signs and symptoms of sepsis and confirmed by clinical and lab parameters. Neonates with diagnosed or suspected congenital and/ or cardiac mal-formation, those diagnosed with shock of etiology other than septic shock and those already on inotropic support were excluded from the study.

After obtaining the Informed Consent and fulfilment of the inclusion criteria, detailed base line information of maternal and neonatal variables was recorded including number of antenatal visits (booked pregnancy defined as ≥4 and unbooked as < 4 antenatal visits),9 gestational age at delivery, mode of delivery, Weight of the newborn was recorded immediately after delivery. Clinically, shock was diagnosed in any neonate as having tachycardia (HR> 160/min using multipara monitor and verified using the stethoscope), prolonged CFT (≥4s),10 hypotension was considered when mean BP < 5th centile for gestational age, weight, and postnatal age).11 Other clinical parameter like core to periphery temperature difference, along with lab. Investigations like CBC, CRP, Blood culture, ABG was carried out.

Septic shock was managed initially by two normal saline boluses, 10mL/kg each, given over 30 minutes. If signs of septic shock persisted, vasoactive drugs were instituted. Echocardiography was performed at baseline during the infusion of saline bolus but before starting vasoactive drugs.12 Repeat assessments were performed 2 hour after starting infusion of vasoactive drugs, after increased dose inotrope/ after deterioration and after complete stabilization.

Baby was enrolled in the study if septic screen or blood culture came out to be positive. Functional echocardiography was performed in supine position using standard views as recommended by American society of echocardiography. Cardiac output (CO) was estimated by Teichholz formula using M-mode echocardiogram.13,14 Fractional Shortening (FS) and Ejection Fraction (EF) was assessed in parasternal long axis view and was machine calculated.  cIVC was visualised in subcostal long axis view at M mode. The maximum (Dmax) and minimum (Dmin) diameter of the Inferior vena cava (IVC) was measured by M-mode imaging at 1.5 to 2 cm from its confluence to the right atrium perpendicular to the long axis of the IVC at end-expiration and end-inspiration over a single ventilatory cycle.15 Diameters were measured in triplicate and the obtained values were averaged. Left Ventricular Output (Aortic VTI and Aortic diameter) was evaluated in Parasternal long axis view/ Apical 5 chamber view using M mode/ Pulse doppler by

(3.14 x Aortic diameter in cm x Aortic VTI) x HR

4 x birth weight in kg

The physiological information gained by bedside functional echocardiography aided in making a logical choice of medications depending upon the underlying physiology and the desired hemodynamic effects. For example, patients with shock warranted use of vasopressor therapy while patients with impaired cardiac function needed more inotropic therapy.16 All the data collected from patient was compiled in a Microsoft office Excel for analysis. Pearson’s correlation test was used to flag the significant correlations with p<0.05.

The gestational age of the neonates ranged from 27 to 41 weeks, with a mean of 33.08 ± 3.17 weeks. The most frequent blood culture finding was K. pneumoniae (24.29%). Total Leukocyte Count was lower than normal in 70% neonates. Pearson’s correlation test was used to assess the correlation of the hemodynamic parameters with cardiac function at the time of diagnosis, after resuscitation with inotropes at 2 hours, and after stabilization.  

depict the distribution of neonates according to post-conception risk factors. The most frequent post-conception risk factors were premature rupture of membranes (39.29%), and pregnancy induced hypertension (27.86%).

depict the distribution of neonates according to mode of delivery. The most frequent mode of delivery was vaginal (65%) followed by LCSC (23.57%) and assisted (11.43%).

depict the distribution of neonates according to indications of LSCS. The most frequent indication of LSCS was fetal distress (36.67%), and abruption placenta (13

depict the distribution of neonates according to presentation at delivery. The most frequent presentation at delivery was vertex (87.14%) followed by breech (10.71%) and shoulder (2.14%).

depict the distribution of neonates according to course of labor. The most frequent course of labor was uneventful (87.14%) followed by prolonged 2nd stage (7.86%).

depict the distribution of neonates according to events during labor. The most frequent event during labor was leaking PV > 24 hours (5.71%) followed by uterine tenderness (2.14%).

depict the distribution of neonates according to inotropic support. The most frequent inotropic support used was Dobutamine (61.43%) followed by Dobutamine + Adrenaline (35.71%) and Dobutamine + Dopamine (2.86%).

depict the distribution of neonates according to days of inotropic support. Most of the neonates required inotropic support for 1 day (60%) followed by 2 days (31.43%) and 3 days (8.57%). The mean days of inotropic support was 1.4 ± 0.55.

depict the distribution of neonates according to number of boluses required. Most of the neonates required 1 bolus (67.5%) followed by 2 boluses (32.5%). The mean number of boluses required was 1.33 ± 0.47.

This was a novel study focusing on the correlation between functional echocardiography with clinical parameters in neonatal septic shock at different clinical intervals. 2D echo is non-invasive, portable and can give real time analysis of physiological information, which in conjunction with clinical assessment, can help in guiding targeted specific therapy. Studies have shown that clinical management may change in 30–60% cases in response to echocardiography. The hemodynamic response to sepsis is not characterized well among the neonates & early recognition and aggressive supportive therapy of sepsis-associated myocardial dysfunction are important to reduce morbidity and mortality among the neonates.16

In our study, on diagnosis of shock, HR negatively correlated with FS and EF. In a study of cardiac function affection in neonatal sepsis showed that, there is an element of myocardial depression in septic shock as an adaptive event that tends to reduce energy expenditure eventually preventing the activities of cell death pathways.17 Their study had shown that EF/FS are significantly affected in patients with septic shock followed by improvement of these parameters with resolution of sepsis. Findings of the above study were confirmed by study conducted on assessment of myocardial function by TDI in neonatal sepsis. It showed that patients suffering from volume resuscitation sepsis experience myocardial dysfunction despite that results in increased LVEDV and decreased EF.17 A study conducted on early onset sepsis in neonate & its association with high heart rate revealed that early onset of neonatal sepsis have been associated with increased HR. Increased HR at the onset of shock compensated for decreased stroke volume.18

After 2 hours post inotrope and fluid resuscitation, HR had positive correlation with cIVC and inverse correlation with FS and LVO. Mean BP significantly and positively correlated FS, EF, and LVO. While CFT significantly and inversely correlated FS, EF, and LVO. In neonates with septic shock, treated with inotropes, cIVC, had moderate positive correlation with HR which was similar to the study, however their correlation did not achieve statistical significance due to smaller sample size.19 We hypothesize that this correlation was due to increased capillary permeability in babies with septic shock with relative intravascular volume loss & hence decreased preload with compensatory tachycardia to maintain cardiac output (CO=SV*HR). A similar study had noted that cIVC, FS, EF, CO were significantly lower in babies with septic shock as compared to controls.19 However, they had shown moderate to strong negative correlation with MBP in septic shock possibly due to preserved myocardial function in that population. After an increased dose of inotrope, the MBP showed significant positive correlation with FS.

Cross sectional observational study providing real time hemodynamic status of the enrolled neonates by using functional echocardiography at different point of time, contributed to the management of septic shock in these babies. Inclusion of only inborn infants and non-invasive arterial blood gas measurements were the limitations. Preload assessment of the heart is crucial in management, but it can be affected by multiple factors such as changing lung compliance and presence of mechanical ventilation. FS can be affected by regional wall motion abnormalities. EF measurements is affected by preload afterload and limited motion of IVS A left-to-right (LtR) ductal shunt will increase LVO and thereby overestimate the amount of blood that actually reaches the systemic circulation, since LVO = SBF + ductal LtR flow.

Neonatal shock continues to be a major challenge. Neonatal hemodynamic assessment is rather complex and should encompass more than solely monitoring heart rate, blood pressure, and other inaccurate clinical variables. Functional echocardiography aids in the clinical evaluation of neonatal shock and aids in monitoring the effectiveness of treatment

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