Istvan Seri

Targeted Neonatal Echocardiography in the Neonatal Intensive Care Unit: Practice Guidelines and Recommendations for Training Writing group of the American Society of Echocardiography (ASE) in collaboration with the European Association of Echocardiography (EAE) and the Association for European Pediatric Cardiologists (AEPC)

Luc Mertens, MD, PhD, FASE, FESC, Istvan Seri, MD, PhD, HonD, Jan Marek, MD, PhD, FESC, Romaine Arlettaz, MD, Piers Barker, MD, FASE, Patrick McNamara, MD, MB, FRCPC, Anita J. Moon-Grady, MD, Patrick D. Coon, RDCS, FASE, Shahab Noori, MD, RDCS, John Simpson, MD, FRCP, FESC, Wyman W. Lai, MD, MPH, FASE, Toronto, Ontario, Canada; Los Angeles and San Francisco, California; London, United Kingdom; Zurich, Switzerland; Durham, North Carolina; Philadelphia, Pennsylvania; New York, New York

Effects of Low-Dose Dopamine Infusion on Cardiovascular and Renal Functions, Cerebral Blood Flow, and Plasma Catecholamine Levels in Sick Preterm Neonates

ABSTRACT: Effects of 2 and 4 μg/kg/min dopamine infusion on cardiovascular and renal functions, cerebral blood flow (CBF) and plasma catecholamine levels were studied in sick preterm neonates during the first four days of life. Preterm infants were found to have an enhanced responsiveness to the pressor effects of dopamine during this period. Comparison of the renal effects of 2 and 4 μg/kg/ min dopamine in 61 preterm infants indicate that 2 μg/kg/ min dopamine induces maximum diuresis and natriuresis during the first day of life provided that systemic blood pressure is within the predicted normal range. Although administration of 4 μg/kg/min dopamine induces further increases in blood pressure and glomerular filtration rate, urine output and sodium excretion remain similar to that on 2 μg/kg/min of the drug. These findings demonstrate that the direct tubular effects of dopamine play an important role in the diuretic and natriuretic action of the drug in the one-day old preterm infant. In five preterm neonates, changes in CBF transiently paralleled the dopamine-induced alterations in systemic blood pressure indicating that autoregulation of CBF is impaired but not completely ineffective in the one-day old preterm infant. In eight term neonates, increases in blood pressure had no effect on CBF. Measurements of plasma dopamine and norepinephrine levels in 14 preterm neonates and five children suggest that decreased metabolism of dopamine may contribute to the enhanced pressor responsiveness to dopamine in sick preterm infants. Based on these findings, we propose that dopamine should be started at 2 μg/kg/min in the hypotensive and/or oliguric preterm infant, and that the dose should be increased in a step-wise manner tailored to the cardiovascular and renal response to the patient.

Regional hemodynamic effects of dopamine in the sick preterm neonate

OBJECTIVE To study the effects of dopamine on renal, mesenteric, and cerebral blood flow in sick preterm neonates. STUDY DESIGN The pulsatility index was used to assess the dopamine-induced changes in renal, mesenteric, and cerebral blood flow by means of color Doppler ultrasonography in 23 nonhypotensive preterm neonates (birth weight: 981 +/- 314 g; postnatal age: <2 days). Dopamine was given at a dose of 6.1 +/- 3.0 microgram/kg per minute to combat oliguria, impaired peripheral perfusion, or both. Blood flow velocity measurements were made before and during dopamine administration, with each patient serving as his or her own control subject. RESULTS Dopamine significantly increased blood pressure and urine output. Dopamine decreased the pulsatility index in the renal artery (2.98 +/- 1.18 vs 1.68 +/- 0.45; P <.05) while the pulsatility index in the superior mesenteric and medial cerebral artery was not affected. Thus renal blood flow increased while mesenteric and cerebral blood flow remained unchanged during dopamine treatment. The increase in renal blood flow was independent of the blood pressure changes. CONCLUSIONS These findings suggest a functionally mature renal, but not mesenteric, vasodilatory dopaminergic response in the preterm neonate. The observations also indicate the lack of an effect of low- to medium-dose dopamine on cerebral hemodynamics in the nonhypotensive preterm neonate.

Targeted Neonatal Echocardiography in the Neonatal Intensive Care Unit: Practice Guidelines and Recommendations for Training

AAP : American Academy of Pediatrics AEPC : Association for European Paediatric Cardiology ASE : American Society of Echocardiography CDH : Congenital diaphragmatic hernia CHD : Congenital heart disease EAE : European Association of Echocardiography ECMO : Extracorporeal membrane oxygenation EF : Ejection fraction LV : Left ventricular MPI : Myocardial performance index mVCFc : Mean velocity of circumferential fiber shortening NICU : Neonatal intensive care unit PA : Pulmonary artery PDA : Patent ductus arteriosus RA : Right atrial RV : Right ventricular RVSp : Right ventricular systolic pressure SF : Shortening fraction SVC : Superior vena cava TEE : Transesophageal echocardiography TNE : Targeted neonatal echocardiography TVI : Time-velocity integral 2D : Two-dimensional VLBW : Very low birth weight The role of echocardiography in the neonatal intensive care unit (NICU) has changed over the past few years. Previously, nearly all echocardiographic studies in the NICU were performed by pediatric cardiologists to diagnose or monitor congenital heart disease (CHD) and to screen for patent ductus arteriosus (PDA). More recently, neonatologists have become interested in the echocardiographic assessment of hemodynamic instability in infants. The terms functional echocardiography and point-of-care echocardiography have been introduced to describe the use of echocardiography as an adjunct in the clinical assessment of the hemodynamic status in neonates.1–4 The increasing availability of echocardiography, with miniaturization of the technology, has resulted in more widespread use of echocardiography in NICUs around the world.5 Perhaps the most significant challenge for the application of so-called functional studies is that newborns in the NICU with hemodynamic instability are at a much higher risk for having underlying CHD. In addition, newborns in the NICU are unique in that they are in the process of …

Cardiovascular Effects of Sildenafil in Neonates and Infants with Congenital Diaphragmatic Hernia and Pulmonary Hypertension

Background: Pulmonary hypertension is a common problem in patients with congenital diaphragmatic hernia (CDH). In a subset of these patients, pulmonary hypertension persists despite optimized ventilatory management and supportive care. Sildenafil, a phosphodiestrase V inhibitor, has been used in the treatment of pulmonary hypertension in adults and children. Cardiovascular effects of sildenafil in patients with CDH and pulmonary hypertension are not known. Objective: To describe the changes in cardiovascular and respiratory parameters in newborn infants with CDH and persistent pulmonary hypertension refractory to inhaled nitric oxide (iNO) during the first 2 weeks of sildenafil administration. Methods: Retrospective data analysis of seven patients with CDH (birth weight = 2,573 ± 1,019 g; gestational age = 35.6 ± 4.3 weeks) receiving oral sildenafil for pulmonary hypertension refractory to iNO. Findings of serial echocardiograms and data on cardiovascular and respiratory status were assessed. Results: Right cardiac output increased and left cardiac output tended to increase 1.5–4 h after initiation of sildenafil and the increase was sustained throughout the study. Echocardiographic indices of pulmonary hypertension showed an apparent reduction in abnormally high pulmonary vascular resistance. Systemic blood pressure tended to decrease. Shortening fraction did not change. Ventilatory index and the need for iNO tended to decrease in the five surviving infants. Conclusions: These preliminary findings suggest that sildenafil may improve cardiac output by reducing pulmonary hypertension refractory to iNO in patients with CDH.

Hemodynamic Changes After Low-Dosage Hydrocortisone Administration in Vasopressor-Treated Preterm and Term Neonates

OBJECTIVE. We sought to investigate whether the increase in blood pressure and decrease in vasopressor support after hydrocortisone administration are associated with changes in systemic hemodynamics in neonates who receive high-dosage dopamine to maintain blood pressure at the lowest acceptable levels. METHODS. In this prospective, observational study, preterm and term neonates who required dopamine ≥15 μg/kg per minute to maintain minimum acceptable blood pressure received intravenous hydrocortisone 2 mg/kg followed by up to 4 doses of 1 mg/kg every 12 hours. Fifteen preterm and 5 term neonates without a patent ductus arteriosus composed the study population. Echocardiograms and vascular Doppler studies were performed immediately before the first dose of hydrocortisone and at 1, 2, 6 to 12, 24, and 48 hours thereafter. RESULTS. In the 15 preterm infants, during the first 12 hours of hydrocortisone treatment, the 28% increase in blood pressure paralleled that in the systemic vascular resistance without changes in stroke volume or cardiac output, whereas dopamine dosage decreased. By 24 hours, the dosage of dopamine continued to decrease, whereas stroke volume increased without additional changes in systemic vascular resistance. By 48 hours, dopamine dosage decreased by 72%; blood pressure and stroke volume increased by 31% and 33%, respectively; and systemic vascular resistance and cardiac output tended to be higher (14% and 21%, respectively) compared with baseline. Contractility, global myocardial function, and Doppler indices of blood flow in the middle cerebral and renal artery remained normal and unchanged. The findings in the 5 term infants showed a similar pattern for changes in cardiac function, systemic hemodynamics, and organ blood flow after hydrocortisone administration. CONCLUSIONS. In preterm and term neonates who require high-dosage dopamine to maintain blood pressure at the lowest acceptable levels, hydrocortisone improves blood pressure without compromising cardiac function, systemic perfusion, or cerebral and renal blood flow.

Changes in Cardiac Function and Cerebral Blood Flow in Relation to Peri/Intraventricular Hemorrhage in Extremely Preterm Infants

OBJECTIVE To investigate whether changes in cardiac function and cerebral blood flow (CBF) precede the occurrence of peri/intraventricular hemorrhage (P/IVH) in extremely preterm infants. STUDY DESIGN In this prospective observational study, 22 preterm infants (gestational age 25.9 ± 1.2 weeks; range 23-27 weeks) were monitored between 4 and 76 hours after birth. Cardiac function and changes in CBF and P/IVH were assessed by ultrasound every 12 hours. Changes in CBF were also followed by continuous monitoring of cerebral regional oxygen saturation (rSO2) and by calculating cerebral fractional oxygen extraction. RESULTS Five patients developed P/IVH (1 patient grade II and 4 patients grade IV). Whereas measures of cardiac function and CBF remained unchanged in neonates without P/IVH, patients with P/IVH tended to have lower left ventricular output and had lower left ventricle stroke volume and cerebral rSO2 and higher cerebral fractional oxygen extraction during the first 12 hours of the study. By 28 hours, these variables were similar in the 2 groups and myocardial performance index was lower and middle cerebral artery mean flow velocity higher in the P/IVH group. P/IVH was detected after these changes occurred. CONCLUSIONS Cardiac function and CBF remain stable in very preterm neonates who do not develop P/IVH during the first 3 postnatal days. In very preterm neonates developing P/IVH during this period, lower systemic perfusion and CBF followed by an increase in these variables precede the development of P/IVH. Monitoring cardiac function and cerebral rSO2 may identify infants at higher risk for developing P/IVH before the bleeding occurs.

Somatosensory lateralization in the newborn brain

Since the onset and early postnatal development of hemispheric lateralization in the human brain are unknown, we studied cortical activation induced by passive extension and flexion of the hand in neonates using functional magnetic resonance imaging (fMRI). In contrast to that seen in older age groups, somatosensory areas in the pre- and postcentral gyri of the neonate showed no significant hemispheric lateralization at term. Instead, our findings from independent left- and right-hand experiments suggest the presence of an emerging trend of contralateral lateralization of the somatosensory system at around term.

Functional MRI in neonates using neonatal head coil and MR compatible incubator.

Structural and functional magnetic resonance imaging of the newborn brain is a complex and challenging task. Term and preterm neonates require a controlled microenvironment and close monitoring during the MRI study to maintain respiratory and cardiovascular functions, body temperature, and fluid and electrolyte homeostasis. In addition, to minimize motion artifacts, most neonates also need to be sedated, which carries the risk of respiratory depression compromising the neonates ability to maintain appropriate ventilation and oxygenation during the procedure. Finally, because of their small head size, the use of the standard MR head coils results in suboptimal picture quality in the neonate. Thus, these limitations affect our ability to obtain both high quality structural and functional MRI studies. To overcome these difficulties, we have utilized an MR compatible incubator with a built-in radiofrequency head coil optimized for the neonatal brain volume. In this study we demonstrate that functional MRI and high-resolution structural MRI of the newborn brain can be achieved with this novel design. The use of this equipment offers potential for studying the development of the preterm and term neonatal brain and obtaining state-of-the-art, high-resolution structural and functional imaging in this most vulnerable patient population.

Systemic and cerebral hemodynamics during the transitional period after premature birth

Little is known about the effect on clinically relevant outcomes of the complex hemodynamic changes occurring during adaptation to extrauterine life in preterm neonates, particularly in very low birth weight neonates. As cardiovascular adaptation in this extremely vulnerable patient population is complicated by immaturity of all organ systems, especially that of the cardiorespiratory, central nervous, and endocrine systems, maladaptation has been suspected, but not necessarily proven, to contribute to mortality and long-term morbidities. This article describes recent advances in the understanding of hemodynamic changes in very low birth weight neonates during postnatal transition, and reviews the complex and developmentally regulated interaction between systemic and cerebral hemodynamics and the effect of this interaction on clinically relevant outcomes.