Individual variations in fentanyl pharmacokinetics and pharmacodynamics in preterm infants.

AIM: Fentanyl pharmacokinetics and pharmacodynamics are lacking in preterm infants. Our aim was to study these and their relation with a new formulation of fentanyl 5 µg/mL for procedural pain. METHODS: Preterm infants were given 0.5 (n = 20, median gestational age 26.5; range 23.3-34.1 weeks) and 2 µg/kg (n = 8, 27.4; 25.3-30.7 weeks) fentanyl, respectively, before skin-breaking procedures or tracheal intubation. Blood samples were collected after ten minutes, two, four, eight and 24 hours. Physiologic parameters were monitored and pain scores assessed. RESULTS: The median fentanyl concentrations were 0.18, 0.15, 0.15 and 0.57, 0.37, 0.35 ng/mL at 15-31 minutes, two and four hours and the half-lives were 1.6 to 20.5 or 4.1 to 32.6 hours for the low- and high-dose groups, respectively. A significant correlation was seen between weight at study inclusion and half-life (Spearman's r = -0.9, p < 0.001), volume of distribution (r = -0.8, p < 0.01) and clearance (r = -0.9, p < 0.01) in the low-dose group (n = 9). Pain assessment results were not correlated to pharmacokinetic variables. Fentanyl was well tolerated. CONCLUSION: The inter-individual variation of fentanyl pharmacokinetics is large in preterm infants, and the dose of 0.5 µg/kg seems not effective for skin-breaking procedures.

Deformation imaging and rotational mechanics in neonates: a guide to image acquisition, measurement, interpretation, and reference values.

Advances in neonatal cardiac imaging permit a more comprehensive assessment of myocardial performance in neonates that could not be previously obtained with conventional imaging. Myocardial deformation analysis is an emerging quantitative echocardiographic technique to characterize global and regional ventricular function in neonates. Cardiac strain is a measure of tissue deformation and strain rate is the rate at which deformation occurs. These measurements are obtained in neonates using tissue Doppler imaging (TDI) or two-dimensional speckle tracking echocardiography (STE). There is an expanding body of literature describing longitudinal reference ranges and maturational patterns of strain values in term and preterm infants. A thorough understanding of deformation principles, the technical aspects, and clinical applicability is a prerequisite for its routine clinical use in neonates. This review explains the fundamental concepts of deformation imaging in the term and preterm population, describes in a comparative manner the two major deformation imaging methods, provides a practical guide to the acquisition and interpretation of data, and discusses their recognized and developing clinical applications in neonates.

Application of Neonatologist Performed Echocardiography in the assessment and management of persistent pulmonary hypertension of the newborn.

Pulmonary hypertension contributes to morbidity and mortality in both the term newborn infant, referred to as persistent pulmonary hypertension of the newborn (PPHN), and the premature infant, in the setting of abnormal pulmonary vasculature development and arrested growth. In the term infant, PPHN is characterized by the failure of the physiological postnatal decrease in pulmonary vascular resistance that results in impaired oxygenation, right ventricular failure, and pulmonary-to-systemic shunting. The pulmonary vasculature is either maladapted, maldeveloped, or underdeveloped. In the premature infant, the mechanisms are similar in that the early onset pulmonary hypertension (PH) is due to pulmonary vascular immaturity and its underdevelopment, while late onset PH is due to the maladaptation of the pulmonary circulation that is seen with severe bronchopulmonary dysplasia. This may lead to cor-pulmonale if left undiagnosed and untreated. Neonatologist performed echocardiography (NPE) should be considered in any preterm or term neonate that presents with risk factors suggesting PPHN. In this review, we discuss the risk factors for PPHN in term and preterm infants, the etiologies, and the pathophysiological mechanisms as they relate to growth and development of the pulmonary vasculature. We explore the applications of NPE techniques that aid in the correct diagnostic and pathophysiological assessment of the most common neonatal etiologies of PPHN and provide guidelines for using these techniques to optimize the management of the neonate with PPHN.

Tissue Doppler velocity imaging and event timings in neonates: a guide to image acquisition, measurement, interpretation, and reference values.

Neonatologists can use echocardiography for real-time assessment of the hemodynamic state of neonates to support clinical decision-making. There is a large body of evidence showing the shortcomings of conventional echocardiographic indices in neonates. Newer imaging modalities have evolved. Tissue Doppler imaging is a new technique that can provide measurements of myocardial movement and timing of myocardial events and may overcome some of the shortcomings of conventional techniques. The high time resolution and its ability to assess left and right cardiac function make tissue Doppler a favorable technique for assessing heart function in neonates. The aim of this review is to provide an up-to-date overview of tissue Doppler techniques for the assessment of cardiac function in the neonatal context, with focus on measurements from the atrioventricular (AV) plane. We discuss basic concepts, protocol for assessment, feasibility, and limitations, and we report reference values and give examples of its use in neonates.

Preterm Birth Is Associated with Altered Myocardial Function in Infancy.

BACKGROUND: Preterm birth has been associated with myocardial remodeling and accelerated cardiovascular ageing in later life, but the underlying mechanisms are unknown. The investigators used echocardiography to undertake a sequential analysis of myocardial function in preterm infants. METHODS: This study evaluated the cardiac performance of 25 very preterm infants (born at a gestational age of 26-30 weeks), at birth, 3 months (term-equivalent age), and 6 months later (3 months of corrected age). Speckle-tracking echocardiography was used to determine myocardial function, assessing the magnitude of myocardial deformation as longitudinal strain, deformation rate (strain rate), and velocity in both ventricles during systole and diastole. The results were compared with those in 30 infants born at term investigated at birth and at 3 months of age. RESULTS: At term-equivalent age, the speckle-tracking estimates were similar in both groups. Three months later, very preterm infants exhibited significantly lower left ventricular mean free wall longitudinal strain (-20.0% vs -22.0%, P = .010) and lower left ventricular early diastolic (median, -7.37 vs -10.9 cm/sec, P = .003) and late diastolic (median, -5.11 vs -6.95 cm/sec, P = .009) myocardial velocities than infants born at term. There were no statistically significant group differences in right ventricular or interventricular septal measurements. Conventional echocardiographic variables did not differ significantly between the two groups at any age. CONCLUSIONS: Very preterm infants develop altered left ventricular myocardial function 6 months after birth. Follow-up examinations are needed to determine the implications for cardiovascular health in the growing number of children surviving very preterm birth.

Transition from fetal to neonatal life: changes in cardiac function assessed by speckle-tracking echocardiography.

OBJECTIVE: Assessment of cardiac function by speckle-tracking (2D-S) echocardiography in the transitional period from fetal to neonatal life in a healthy population. METHODS: Ultrasound assessment of cardiac function of 30 healthy fetuses at the gestational age of 28 weeks, and follow-up after birth using 2-D strain derived novel parameters such as longitudinal strain (S), strain rate (SR), tissue velocities, MPI- and E/E'-index, E/A- and E'/A'-rate of both right (RV) and left ventricles (LV) and interventricular septum (IVS) and comparison to conventionally measured cardiac stroke volume (SV), cardiac output (CO) and ejection fraction (EF). RESULTS: Ultrasound 2D-S performance and analysis were technically feasible and reproducible in all 30 fetuses and in the neonatal period. In fetuses, tissue velocities and SR measurements were homogenous for all regions of interest in both ventricles, and strain increased from apex to base and was significantly higher in the RV compared to LV. All calculated indices were almost identical for RV and LV. After birth, strain and strain rate exhibited significantly lower values, and systolic tissue velocities were higher in comparison to fetal values in both chambers and in all regions of interest. CONCLUSION: Speckle-tracking echocardiography is a feasible and reproducible technique in analyzing both fetal and newborn cardiac functions. Therefore, it might be useful in clinical routine examinations and give new insights in transitional physiology.

Relative intima-media thickening after preterm birth.

AIM: Preterm infants are at increased risk of early arterial growth arrest and cardiovascular mortality. We assessed intima-media thickness (IMT) - an early marker of accelerated vascular ageing - in very preterm infants. METHODS: Longitudinal cohort study of 21 very preterm and 29 term infants, all with appropriate birthweights. Intima-media thickness was assessed by M-Mode ultrasound of the aorta and carotid arteries at three occasions during a 6-month period corresponding to the third trimester of pregnancy and ending 3 months after term equivalent age. RESULTS: No differences in absolute aortic or carotid IMT were found. However, in relation to vessel lumen diameter, the IMT switched from being narrower in preterm infants, compared with foetuses at 28 weeks of gestation, to being significantly thicker in both the aorta and carotid artery in older infants born preterm, compared with term controls of equivalent postmenstrual age. Although the aortic and carotid artery diameters increased significantly with postnatal age, IMT did not. CONCLUSION: In relation to vessel diameter, subjects born preterm show thicker intima-media in the great arteries than infants born at term. It remains to be established whether this relative intima-media thickening persists and may be a risk marker for future cardiovascular disease.

Giant fibroma in the left ventricle of an infant: imaging findings in magnetic resonance imaging, echocardiography and angiography.

The diagnosis of a rare case of giant intraventricular fibroma in an infant by MRI in comparison with other imaging modalities, such as echocardiography and angiography, is discussed. For preoperative planning only MRI showed the myocardial infiltration. The myocardial blood supply of the tumor could be evaluated qualitatively by contrast-enhanced MRI, but the direct visualization of the distally located branches could only be assessed by coronary angiography. Magnetic resonance coronary angiography using the navigator technique failed to depict the distal part of the coronaries. The obstruction of the left ventricle outflow tract could be assessed and quantified by all imaging modalities.