Hemodynamic evaluation in preterm infants using ultrasonic cardiac output monitor (USCOM).

We aimed to establish reference ranges for USCOM parameters in preterm infants, determine factors that affect cardiac output, and evaluate the measurement repeatability. This retro-prospective study was performed at Fondazione IRCCS San Gerardo dei Tintori, Monza, Italy. We included infants below 32 weeks of gestational age (GA) and/or 1500 g of birth weight (BW). We excluded infants with congenital heart diseases or hemodynamic instability. Measurements were performed at 3 ± 1, 7 ± 2, and 14 ± 2 postnatal days. We analyzed 204 measurements from 92 patients (median GA = 30.57 weeks, BW = 1360 g). The mean (SD) cardiac output (CO) was 278 (55) ml/min/kg, cardiac index (CI) was 3.1 (0.5) L/min/m2, and systemic vascular resistance (SVRI) was 1292 (294) d*s*cm-5/m2. CO presented a negative correlation with postmenstrual age (PMA), while SVRI presented a positive correlation with PMA. The repeatability coefficient was 31 ml/kg/min (12%).  Conclusion: This is the first study describing reference values for USCOM parameters in hemodynamically stable preterm infants and factors affecting their variability. Further studies to investigate the usefulness of USCOM for the longitudinal assessment of patients at risk for cardiovascular instability or monitoring the response to therapies are warranted. What is Known: • The ultrasonic cardiac output monitoring (USCOM) has been widely used on adult and pediatric patients and reference ranges for cardiac output (CO) by USCOM have been established in term infants. What is New: • We established reference values for USCOM parameters in very preterm and very-low-birth-weight infants; the reference ranges for CO by USCOM in the study population were 198-405 ml/kg/min. • CO normalized by body weight presented a significant negative correlation with postmenstrual age (PMA); systemic vascular resistance index presented a significant positive correlation with PMA.

The effect of breathing on ductus arteriosus blood flow directly after birth.

Spontaneous breathing at birth influences ductus arteriosus (DA) flow. This study quantifies the effect of breathing on DA shunting directly after birth. In healthy term infants born by elective cesarean section, simultaneous measurements of DA shunting and tidal volumes during spontaneous breathing were performed at 2-5, 5-8, and 10-13 min after birth. Eight infants with a mean (SD) gestational age of 40 (1) weeks and 3216 (616) grams were studied. Inspiratory tidal volume was 5.8 (3.3-7.7), 5.7 (4.0-7.1), and 5.2 (4.3-6.1) mL/kg at 2-5, 5-8, and 10-13 min. The velocity time integral of left-to-right shunting significantly increased during inspiration when compared to expiration (8.4 (5.2) vs. 3.7 (2.3) cm, 8.9 (4.4) vs. 5.6 (3.4) cm, and 14.0 (6.7) vs. 8.4 (6.9) cm; all p < 0.0001) at 2-5, 5-8, and 10-13 min, respectively. In contrast, right-to-left shunting was not different between inspiration and expiration at 2-5 and 10-13 min (11.1 (2.4) vs. 11.1 (2.6) cm and 10.7 (2.3) vs. 10.6 (3.0) cm; p > 0.05), but there was a small increase at 5-8 min (12.1 (2.4) vs. 10.8 (2.9) cm; p = 0.001) during expiration. CONCLUSION: Directly after birth, ductal shunting is influenced by breathing effort, predominantly with an increase in left-to-right shunt due to inspiration. What is Known: • Spontaneous breathing at birth influences ductus arteriosus flow and pulmonary blood flow. • Crying causes a significant increase in left-to-right ductus arteriosus shunting. What is New: • Left-to-right ductus arteriosus shunting increases during inspiration compared to expiration. • Breathing is important for ductal shunting and contributes to pulmonary blood flow.

Guidelines and Recommendations for Targeted Neonatal Echocardiography and Cardiac Point-of-Care Ultrasound in the Neonatal Intensive Care Unit: An Update from the American Society of Echocardiography.

Targeted neonatal echocardiography (TNE) involves the use of comprehensive echocardiography to appraise cardiovascular physiology and neonatal hemodynamics to enhance diagnostic and therapeutic precision in the neonatal intensive care unit. Since the last publication of guidelines for TNE in 2011, the field has matured through the development of formalized neonatal hemodynamics fellowships, clinical programs, and the expansion of scientific knowledge to further enhance clinical care. The most common indications for TNE include adjudication of hemodynamic significance of a patent ductus arteriosus, evaluation of acute and chronic pulmonary hypertension, evaluation of right and left ventricular systolic and/or diastolic function, and screening for pericardial effusions and/or malpositioned central catheters. Neonatal cardiac point-of-care ultrasound (cPOCUS) is a limited cardiovascular evaluation which may include line tip evaluation, identification of pericardial effusion and differentiation of hypovolemia from severe impairment in myocardial contractility in the hemodynamically unstable neonate. This document is the product of an American Society of Echocardiography task force composed of representatives from neonatology-hemodynamics, pediatric cardiology, pediatric cardiac sonography, and neonatology-cPOCUS. This document provides (1) guidance on the purpose and rationale for both TNE and cPOCUS, (2) an overview of the components of a standard TNE and cPOCUS evaluation, (3) disease and/or clinical scenario-based indications for TNE, (4) training and competency-based evaluative requirements for both TNE and cPOCUS, and (5) components of quality assurance. The writing group would like to acknowledge the contributions of Dr. Regan Giesinger who sadly passed during the final revisions phase of these guidelines. Her contributions to the field of neonatal hemodynamics were immense.

Role of Perfusion Index and Pulse Variability Index in the Assessment of Neonatal Hemodynamics: A Systematic Review.

Hemodynamic monitoring of neonates is crucial because neonates are easily and acutely susceptible to hemodynamic disturbances. As such, non-invasive monitoring of hemodynamics is preferable. It has been postulated that non-invasive pulse oximetry determines the perfusion index and pulse variability index and provides accurate measurements to predict hemodynamic changes in preterm or term infants. Equally, numerous studies have investigated the efficacy of perfusion and pulse variability indices in monitoring neonatal hemodynamics. The aim of this study was to systematically review studies that have delved into the role of perfusion and pulse variability indices in the assessment of neonatal hemodynamics. The study collected data from 2010-2023 using the patient, intervention, comparison, outcome (PICO) search strategy using the databases PubMed, Scopus, and Excerpta Medica database (Embase). A total of 616 articles were evaluated based on their appropriateness and relevance; we included seven studies. As per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted a systematic review. Our study concluded that these indices were effective in measuring hemodynamics.

Comparison of Cardiac Output Measurement by Electrical Velocimetry with Echocardiography in Extremely Low Birth Weight Neonates.

INTRODUCTION: Electrical velocimetry (EV) offers a noninvasive tool for continuous cardiac output (CO) measurements which might facilitate hemodynamic monitoring and targeted therapy in low birth neonates, in whom other methods of CO measurement are not practicably feasible. METHODS: This prospective observational study compared simultaneous cardiac output measurements by electrical velocimetry (COEV) with transthoracic echocardiography (COTTE) in extremely low birth weight (ELBW) neonates in the neonatal intensive care unit (NICU). Echocardiography was performed by 1 single examiner. Data were analyzed by Bland-Altman analysis and independent-samples analysis of variance. A mean percentage error (MPE) of <30% and limits of agreement (LOA) up to ±30% were considered clinically acceptable. RESULTS: Thirty-eight ELBW neonates were studied and yielded 85 pairs of COEV and COTTE measurements. Bland-Altman analysis showed an overall bias (the mean difference) and LOA of -126 and -305 to +52 mL min-1, respectively, and an MPE of 66%. Patients with patent ductus arteriosus had a higher bias with LOA and MPE of -166.8, -370.7 to +37 mL min-1, and 69%, respectively. The overall true precision was 58%. CONCLUSION: This study showed high bias and lack of agreement between EV and TTE for measurement of CO in ELBW infants in NICU, limiting applicability of EV to monitor absolute values.

Evaluation of hemodynamics in healthy term neonates using ultrasonic cardiac output monitor.

BACKGROUND: Transition from intrauterine to extrauterine life is a critical phase during which several changes occur in cardiovascular system. In clinical practice, it is important to have a method that allows an easy, rapid and precise evaluation of hemodynamic status of a newborn for clinical management. We here propose a rapid, broadly applicable method to monitor cardiovascular function using ultrasonic cardiac output monitoring (USCOM). METHODS: We here present data obtained from a cohort of healthy term newborns (n = 43) born by programmed cesarean section at Fondazione MBBM, Ospedale San Gerardo. Measurements were performed during the first hour of life, then at 6 + 2, at 12-24, and 48 h of life. We performed a screening echocardiography to identify a patent duct at 24 h and, if patent, it was repeated at 48 h of life. RESULTS: We show that physiologically, during the first 48 h of life, blood pressure and systemic vascular resistance gradually increase, while there is a concomitant reduction in stroke volume, cardiac output, and cardiac index. The presence of patent ductus arteriosus significantly reduces cardiac output (p = 0.006) and stroke volume (p = 0.023). Furthermore, newborns born at 37 weeks of gestational age display significantly lower cardiac output (p < 0.001), cardiac index (p = 0.045) and stroke volume (p < 0.001) compared to newborns born at 38 and ≥ 39 weeks. Finally, birth-weight (whether adequate, small or large for gestational age) significantly affects blood pressure (p = 0.0349), stroke volume (p < 0.0001), cardiac output (p < 0.0001) and cardiac index (p = 0.0004). In particular, LGA infants display a transient increase in cardiac index, cardiac output and stroke volume up to 24 h of life; showing a different behavior from AGA and SGA infants. CONCLUSIONS: Compared to previous studies, we expanded measurements to longer time-points and we analyzed the impact of commonly used clinical variables on hemodynamics during transition phase thus making our data clinically applicable in daily routine. We calculate reference values for each population, which can be of clinical relevance for quick bedside evaluation in neonatal intensive care unit.

Management of Neonatal Hypotension and Shock.

The current standard approach to manage circulatory insufficiency is inappropriately simple and clear: respond to low blood pressure to achieve higher values. However, the evidence for this is limited affecting all steps within the process: assessment, decision making, therapeutic options, and treatment effects. We have to overcome the 'one size fits all' approach and respect the dynamic physiologic transition from fetal to neonatal life in the context of complex underlying conditions. Caregivers need to individualize their approaches to individual circumstances. This paper will review various clinical scenarios, including managing transitional low blood pressure, to circulatory impairment involving different pathologies such as hypoxia-ischemia and sepsis. We will highlight the current evidence and set potential goals for future development in these areas. We hope to encourage caregivers to question the current standards and to support urgently needed research in this overlooked but crucial field of neonatal intensive care.

High-Dose Cannabidiol Induced Hypotension after Global Hypoxia-Ischemia in Piglets.

BACKGROUND: Cannabidiol (CBD) is considered a promising neuroprotectant after perinatal hypoxia-ischemia (HI). We have previously studied the effects of CBD 1 mg/kg in the early phase after global HI in piglets. In contrast to prior studies, we found no evidence of neuroprotection and hypothesized that higher doses might be required to demonstrate efficacy in this animal model. OBJECTIVE: To assess the safety and potential neuroprotective effects of high-dose CBD. METHODS: Anesthetized newborn piglets underwent global HI by ventilation with 8% O2 until the point of severe metabolic acidosis (base excess -20 mmol/L) and/or hypotension (mean arterial blood pressure ≤20 mm Hg). Piglets were randomized to intravenous treatment with vehicle (n = 9) or CBD (n = 13). The starting dose, CBD 50 mg/kg, was reduced if adverse effects occurred. The piglets were euthanized 9.5 h after HI and tissue was collected for analysis. RESULTS: CBD 50 mg/kg (n = 4) induced significant hypotension in 2 out of 4 piglets, and 1 out of 4 piglets suffered a fatal cardiac arrest. CBD 25 mg/kg (n = 4) induced significant hypotension in 1 out of 4 piglets, while 10 mg/kg (n = 5) was well tolerated. A significant negative correlation between the plasma concentration of CBD and hypotension during drug infusion was observed (p < 0.005). Neuroprotective effects were evaluated in piglets that did not display significant hypotension (n = 9) and CBD did not alter the degree of neuronal damage as measured by a neuropathology score, levels of the astrocytic marker S100B in CSF, magnetic resonance spectroscopy markers (Lac/NAA and Glu/NAA ratios), or plasma troponin T. CONCLUSIONS: High-dose CBD can induce severe hypotension and did not offer neuroprotection in the early phase after global HI in piglets.

Ventilator-induced pulse pressure variation in neonates.

During positive pressure ventilation, arterial pressure variations, like the pulse pressure variation (PPV), are observed in neonates. However, the frequency of the PPV does not always correspond with the respiratory rate. It is hypothesized that PPV is caused by cardiopulmonary interaction, but that this mismatch is related to the low respiratory rate/heart rate ratio. Therefore, the goal of this study is to investigate the relation between PPV and ventilation in neonates. A prospective observational cross-sectional study was carried out in a third-level neonatal intensive care unit in a university hospital. Neonates on synchronized intermittent mandatory ventilation (SIMV) or high-frequency ventilation (HFV) participated in the study. The arterial blood pressure was continuously monitored in 20 neonates on SIMV and 10 neonates on HFV. In neonates on SIMV the CO2 waveform and neonates on HFV the thorax impedance waveform were continuously monitored and defined as the respiratory signal. Correlation and coherence between the respiratory signal and pulse pressure were determined. The correlation between the respiratory signal and pulse pressure was -0.64 ± 0.18 and 0.55 ± 0.16 and coherence at the respiratory frequency was 0.95 ± 0.11 and 0.76 ± 0.4 for SIMV and HFV, respectively. The arterial pressure variations observed in neonates on SIMV or HFV are related to cardiopulmonary interaction. Despite this relation, it is not likely that PPV will reliably predict fluid responsiveness in neonates due to physiological aliasing.