Cerebral electrical activity in extremely preterm infants is affected by various factors including blood gas and circulatory parameters.To investigate whether continuously measured invasive mean arterial blood pressure (BP) is associated with electroencephalographic (EEG) discontinuity in extremely preterm infants.This prospective observational study examined 51 newborn infants born <29 weeks gestation in the first 3 days after birth. A single channel of raw EEG was used to quantify discontinuity. Mean BP was acquired using continuous invasive measurement and Doppler ultrasound was used to measure left ventricular output (LVO) and common carotid artery blood flow (CCAF).Median gestation and birthweight were 25.6 weeks and 760 g, respectively. Mean discontinuity reduced significantly between days 1 and 3. EEG discontinuity was significantly related to gestation, pH and BP. LVO and CCAF were not associated with EEG discontinuity.Continuously measured invasive mean arterial BP was found to have a negative relationship with EEG discontinuity; increasing BP was associated with lower EEG discontinuity. This did not appear to be mediated by surrogates of systemic or cerebral blood flow. Infants receiving inotropic support had significantly increased EEG discontinuity on the first day after birth.
Objective This study aimed to examine the variation between clinician-recorded and continuously downloaded invasive blood pressure (BP). Study Design Prospective study where invasive BP data were downloaded every 10 seconds for the first week of life. Hourly clinician-recorded BP was recorded. Agreement between the two methods were examined. Results A total of 1,180 BP measurements were examined from 42 preterm infants with a mean (standard deviation [SD]) gestation and birthweight of 25.7 weeks (1.4) and 802 g (177) respectively. The mean (SD) bias was −0.11 mm Hg (3.17), but the 95% limits of agreement (LOA) varied between −6.3 and +6.1 mm Hg. Inotrope usage was significantly higher for BP measurements that fell in the 5% outliers when compared with those that fell within the 95% LOA (62.7 vs. 44.6%, p = 0.006). Conclusion Clinicians showed no systematic bias to over- or underrecord BP, but some of the greatest differences were found in infants receiving inotropes. Key Points
Objective To examine the feasibility of a trial allocating different blood pressure (BP) intervention levels for treatment in extremely preterm infants. Design Three-arm open randomised controlled trial performed between February 2013 and April 2015. Setting Single tertiary level neonatal intensive care unit. Patients Infants born <29 weeks’ gestation were eligible to participate, if parents consented and they did not have a major congenital malformation. Interventions Infants were randomised to different levels of mean arterial BP at which they received cardiovascular support: active (<30 mm Hg), moderate (<gestational age mm Hg) or permissive (signs of poor perfusion or <19 mm Hg). Once this threshold was breached, all were managed using the same treatment guideline. BP profiles were downloaded continuously; cardiac output and carotid blood flow were measured at 1 day and 3 days, and amplitude integrated EEG was recorded during the first week. Cranial ultrasound scans were reviewed blind to study allocation. Main outcome measure Inotrope usage and achieved BP. Results Of 134 cases screened, 60 were enrolled, with mean gestation 25.8 weeks (SD 1.5) and birth weight 817 g (SD 190). Invasively measured BP on the first day and inotrope usage were highest in the active and lowest in the permissive arms. There were no differences in haemodynamic or EEG variables or in clinical complications. Predefined cranial ultrasound findings did not differ significantly; no infants in the active arm had parenchymal brain lesions. Conclusion The BP threshold used to trigger treatment affects the achieved BP and inotrope usage, and it was possible to explore these effects using this study design. Trial registration number ISRCTN83507686 .
Background: Diameter forms an integral part of blood flow measurement. This study aimed to explore different three-dimensional (3D) printed materials to develop flow phantom models of the carotid artery in preterm newborn infants and to investigate best materials for diameter measurement validation. Methods: We produced a 3D printed Doppler flow phantom model with vessel lumen diameter of 2.0 mm with varying vessel characteristics using data from 21 preterm infants (right carotid vessel lumen diameter, wall thickness, blood flow measurements using Doppler ultrasound and distance of the carotid artery from skin surface) examined for research or clinical purposes. Flow phantom vessel lumen diameters were measured by a single operator blinded to flow phantom diameter. Results: 15 diameter measurements were performed. Ultrasound measured vessel lumen diameter measurements resulted in underestimation of the true lumen diameter. The measured mean (SD, range) diameter was 0.163 (0.105, 0-0.420) mm. This study found that difference in vessel lumen diameter measurements were least with the hybrid material (FLXA9895-DM) with shore value of 95 in matte finish. Vessel wall thickness was systematically overestimated in the majority of the measurements {Anterior wall thickness, mean(SD, range) 0.145(0.081, 0.020–0.300) mm and posterior wall thickness, mean(SD, range) 0.103(0.117, minus 0.100–0.370) mm}. Conclusion: We successfully produced a 3D printed flow phantom model of the carotid artery in preterm infants with varying vessel characteristics and identified flow phantoms that produced the least difference in ultrasound measured vessel lumen diameter measurements. Researchers and clinicians can use this information for further studies involving ultrasound diameter measurements.
Diameter form an integral part of blood flow measurement. This study aimed to explore different three-dimensional (3D) printed materials to develop flow phantom models of the carotid artery in preterm newborn infants and to investigate ideal diameter measurement points using ultrasound that reflected accurate lumen diameter measurement.
Cerebral blood flow measurements data using Doppler ultrasound of the right common carotid artery from 21 randomly selected preterm infants were used to produce a 3D printed Doppler flow phantom model with three different vessel diameters. Diameters were measured by multiple observers blinded to phantom vessel characteristics and each other’s measurements. 9 measurement points were studied. Agreement between observers, inter and intra observer reliability and coefficient of variation (CoV) was examined.
Of the 63 diameter measurements, 45 (71%) were performed on flow phantoms with vessel diameter of 0.196 cm. Bland-Altman plots revealed that measurement performed using leading edge to centre (mean bias 1.8% {95%LOA -4.1% to 7.7%}) and centre to trailing edge (mean bias 1.1% {95%LOA -5.4% to 7.8%}) resulted in the most accurate lumen diameter measurements. Inter and intra-observer reliability was excellent. The mean CoV for inter observer measurements was 1.7% and intra observer measurements was 1.6% and 1.8% for each observer.
We successfully produced a 3D printed flow phantom model of the carotid artery in preterm infants and identified two measurement methods that result in reliable and accurate lumen diameter measurement. Researchers and clinicians can use this information for further studies involving ultrasound diameter measurements in small calibre vessels.
Anomalous pulmonary venous drainage is a rare cause of congenital heart disease with varied clinical presentation. Symptoms can differ depending on the degree of venous obstruction. An 8-day-old term baby presented with tachypnea and was subsequently found to have an unobstructed infracardiac total anomalous pulmonary venous drainage. She underwent an uneventful surgical repair. The diagnosis of total anomalous pulmonary venous drainage can be delayed or missed, and a high index of suspicion is necessary.
Cerebral blood flow is increasingly monitored in preterm infants. Doppler ultrasound of the carotid artery is a widely available method but is operator dependent. Our aim was to design and produce a realistic flow phantom model of the carotid artery of preterm infants.Data from cerebral blood flow measurements using Doppler ultrasound of the right common carotid artery from 21 premature newborn infants were used to produce a Doppler flow phantom model with three different vessel diameters. Vessel diameter, continuous and pulsatile flow volume measurements were performed by two blinded observers (with more than eight and 20 years of experience).Vessel diameter measurements using the phantom were underestimated by 7%. Continuous flow volume measurements were overestimated by 7% by both observers (observer 1 mean difference 1.5 ± 1.96 SD -3.3 to 6.3 ml/min versus observer 2, 1.9 ± 1.96 SD -3.6 to 7.4 ml/min). Pulsatile flow measurements were overestimated by 12.6% by observer 1 (2.7 ± 1.96 SD -0.6 to 5.9 ml/min) and by 7.8% by observer 2 (1.7 ± 1.96 SD -1.6 to 4.9 ml/min). There was good interobserver and intraobserver reliability for the majority of measurements using continuous and pulsatile flow.It is feasible to produce a realistic flow phantom model of the neonatal carotid artery of preterm infants. Diameter measurements were underestimated and flow measurements were overestimated. These errors fell within acceptable limits for in vivo measurements. If these limitations were related to materials, this could be explored using a wall-less model. The flow phantom could be utilised for research and training clinicians in measuring cerebral blood flow using the carotid artery in this vulnerable group of infants.
Severe acute respiratory syndrome coronavirus 2 infections are uncommon in newborn infants. This report describes possible in utero transmission of the B.1.1.7 (alpha) variant in a preterm infant born at 31 weeks' gestational age who presented with severe respiratory disease. The infant was treated with high-frequency oscillatory ventilation, antiviral medications, and corticosteroids and transitioned to noninvasive respiratory support on day 33. By day 63, she was off positive pressure support and breathing room air and she was discharged from the hospital on day 70. She demonstrated normal growth and development at a 6-month follow-up visit. Placental histopathology revealed placentitis characterized by loss of intervillous spaces resulting from fibrin deposition and inflammatory cell infiltration. Optimum management strategies for treating infants with severe acute respiratory syndrome coronavirus 2 infection have yet to be determined.
Vancomycin is a commonly used antimicrobial to treat hospital acquired infections in neonates. Although both intermittent and continuous dosing regimens are used, there is limited data on population pharmacokinetics (PK) for continuous vancomycin usage to inform correct dosing.
Aim
To determine the population PK parameters of vancomycin in neonatal patients with a wide range of gestational ages and birth weights receiving different dosing regimens.
Methods
Data were collected prospectively from 56 newborns who were receiving vancomycin for late onset sepsis (32 on continuous infusion and 24 on intermittent dosage) following approval from Barts Health Clinical Effectiveness Unit. Peak and trough vancomycin concentrations were collected from infants on intermittent dosage, and random levels for continuous infusion. An enzymatic assay on the COBAS 702 platform was used to measure vancomycin (linear range 1.7–80 μg/ml). Population PK analysis was performed by simultaneously modelling both intermittent and continuous infusion data using nonlinear mixed-effects modelling (NONMEM 7.3).
Results
There were 183 vancomycin samples available for analysis (n = 81 from the intermittent group, and n = 102 from infants on continuous infusion). The median (range) postnatal age at baseline was 26 (1–156) days; and gestational age 29 (23.7–41.9) weeks. The final model that provided the best fit to the data was a 1-compartment model. Allometric weight scaling and postmenstrual age (PMA) driven sigmoidal maturation function were included a priori and no further covariate provided a significant improvement in the model fit. The model was internally evaluated using basic diagnostic plots and a visual predictive check, which indicated that the model is able to describe the data and had good predictive power. The final parameter estimates (mean (relative standard error)) of clearance (CL) and volume of distribution (V) were 5.6 L/h/70 kg (5.3%) and 40.0 L/70 kg (9.3%), respectively. For a typical infant from the studied population (weight=1.7 kg, PMA=35.7 weeks), CL was 0.10 L/h, and V was 0.97 L.
Conclusions
A population PK model was developed for both intermittent and continuous vancomycin dosage newborns and was shown to have good descriptive and predictive properties. This model will be used to develop a new dosing scheme which will then be prospectively evaluated.
The aim of this study was to perform flow volume measurements with Doppler ultrasound using novel 3D printed flow phantom models of carotid artery in preterm infants with varying characteristics.
Clinical data from cerebral blood flow measurements using Doppler ultrasound of the right common carotid artery from premature newborn infants were used to produce a 3D printed Doppler flow phantom model with three different vessel diameters; 0.158 cm, 0.196 cm and 0.244 cm. Leading edge to centre was used to measure vessel diameter. Two observers performed flow volume measurements using continuous and pulsatile flow. Agreement between observers was examined using Bland-Altman plots.
24 measurements were performed. 18 (75%) measurements were performed using continuous flow. Pulsatile flow measurements were performed on lumen diameter of 0.244 cm only using physiological rates. Bland-Altman analysis for continuous flow measurements for observer 1 and 2 were -0.007 (95%LOA -4.3 to 4.3) ml/min and 3.2 (95%LOA -2.7 to 9.1) ml/min. Bias for pulsatile flow measurements for observer 1 and 2 were 1.5 (95%LOA -0.8 to 3.8) ml/min and 4.6 (0.7 to 8.5) ml/min respectively. Inter and intra-observer reliability was excellent for majority of measurements. The mean coefficient of variation for inter observer diameter measurements was 1.2% and intra observer measurements were between 1.5% to 3.9% for both observers.
Flow volume measurements performed using 3D printed materials resulted in realistic echogenicities mimicking biological tissues. Validity and reliability studies, within and between, observers showed acceptable results. Researchers and clinicians can use this model for further training and simulation.
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