Eddie Kwan

Sensitive fused-silica capillary gas chromatographic assay using electron-capture detection for indomethacin in ovine fetal fluids

A sensitive gas chromatographic (GC) method with electron-capture detection (ECD) has been developed to quantitate indomethacin (IND) in plasma, urine, amniotic, and tracheal fluids obtained from the pregnant sheep model. IND and the internal standard, alpha-methylindomethacin (alpha-Me-IND) are extracted by a simple liquid-liquid extraction procedure using ethyl acetate and derivatized with N-methyl-N-(tert.-butyldimethyl-silyl)trifluoroacetamide (MTBSTFA) at 60 degrees C for 50 min. The limit of quantitation (LOQ) is 1 ng/ml with a C.V. < 10% and signal-to-noise ratio > 10. Recoveries from all fluids were greater than 80%. Calibration curves were linear over the range of 1-32 ng/ml with a coefficient of determination (r2) > 0.999. Inter- and intra-day coefficients of variation were < 10% at concentrations of 2-32 ng/ml, and < 20% at the LOQ. Applicability of the developed method is demonstrated for a pharmacokinetic study of IND samples collected following long-term infusion of IND in a chronically instrumented ovine fetus.

Clearance and disposition of indometacin in chronically instrumented fetal lambs following a 3-day continuous intravenous infusion.

Indometacin is used in pregnancy for the treatment of premature labour, but there are limited data on the disposition of the drug in the fetus. In order to elucidate fetal indometacin pharmacokinetics at plasma levels and duration comparable with those occurring with use of the drug for tocolysis in humans, indometacin was administered at doses of 1.9 (low dose, LD; n = 5) or 7.5 (high dose, HD; n = 9) μg min−1 to steady state over a 3‐day period in chronically instrumented fetal lambs. Indometacin concentrations in biological fluid samples were analysed by a sensitive capillary gas chromatography‐electron capture detection method. The mean steady‐state fetal arterial plasma indometacin concentrations were 68.6 ± 16.5 ng mL−1 in the LD infusion and 230.3 ± 28.8 ng mL−1 in the HD infusion. Indometacin concentrations in amniotic fluid were ∼10% of those in fetal plasma, and below assay detection limits in tracheal fluid. Total body clearance (TBC) in the LD and HD infusions were not different and the overall mean was 11.3 ± 1.2 mL min−1 kg−1. In the 11 experiments where paired fetal arterial and umbilical venous samples were collected, the extraction of indometacin across the placenta averaged only 5.2 ± 1.1%, indicating low placental permeability to the drug in sheep. However, fetal placental clearance (CLpl) of indometacin (10.0 ± 2.5 mL min−1 kg−1, n = 10) averaged 115.1± 41.2% of TBC in these animals and the calculated value for fetal non‐placental clearance (0.6 ± 2.8 mL min−1 kg−1) was not significantly different from zero. Fetal renal clearance of intact indometacin (3.8 ± 1.1 μL min−1 kg−1; n = 12) was also very low. However, treatment of fetal urine with glucuronidase indicated the presence of glucuronide conjugates and these comprised 69.9 ± 8.2% of the total drug concentration (i.e. intact + conjugated) in urine. Thus, the fetal lamb appears to be able to glucuronidate indometacin, but the contribution of this and other non‐placental routes to overall fetal elimination of the drug appear minimal. CLpl of the drug is also low owing to the physicochemical properties of indometacin (high polarity) and the permeability characteristics of the sheep placenta.

A Randomized Controlled Trial of the Use of Oral Glucose with or without Gentle Facilitated Tucking of Infants during Neonatal Echocardiography

Objective To compare the effect of oral glucose given with or without facilitated tucking (FT), versus placebo (water) to facilitate image acquisition during a targeted neonatal echocardiography (TNE). Design Factorial, double blind, randomized controlled trial. Setting Tertiary neonatal intensive care unit (NICU). Patients Infants born between 26 and 42 weeks of gestation (GA). Interventions One of four treatment groups: oral water (placebo), oral glucose (25%), facilitated tucking with oral water or facilitated tucking with oral glucose, during a single, structured TNE. All infants received a soother. Main Outcome Measure Change in Behavioral Indicators of Infant Pain (BIIP) scores. Results 104 preterm infants were randomized (mean ± SD GA: 33.4 ± 3.5 weeks). BIIP scores remained low during the echocardiography scan (median, [IQ range]: 0, [0 to 1]). There were no differences in the level of agitation of infants amongst the treatment groups, with estimated reductions in mean BIIP relative to control of 0.27 (95%CI -0.40 to 0.94) with use of oral glucose and .04 (-0.63 to 0.70) with facilitated tucking. There were also no differences between treatment groups in the quality and duration of the echocardiography scans. Conclusions In stable infants in the NICU, a TNE can be performed with minimal disruption in a majority of cases, simply by providing a soother. The use of 25% glucose water in this context did not provide further benefit in reducing agitation and improving image acquisition. Clinical Trial Registration Clinical Trials.gov: NCT01253889

Outcomes of Respiratory Syncytial Virus Immunoprophylaxis in Infants Using an Abbreviated Dosing Regimen of Palivizumab.

intelligence. If βbreak indicates a statistically significant upward shift in a carefully calibrated estimation model, which also includes all plausible and available environmental controls, there is strong evidence that the resulting partial regression coefficient of duration of breastfeeding is still not reflecting pure nutritional effects. The pattern shown in this study also helps explain why studies comparing children who have ever been breastfed and those who have never been breastfed find no difference in intelligence.6

Respiratory syncytial virus-neutralizing serum antibody titers in infants following palivizumab prophylaxis with an abbreviated dosing regimen

Background Monthly injections of palivizumab during the respiratory syncytial virus (RSV) season in at-risk infants reduces RSV-associated hospitalizations. However, the additive effect of naturally acquired immunity remains unclear. The objective of this study was to assess total neutralizing serum antibodies (NAb) against RSV in at-risk infants who had received an abbreviated course of palivizumab prophylaxis. Methods Serum samples were collected from infants enrolled in the RSV Immunoprophylaxis Program in British Columbia, Canada over 2 consecutive RSV seasons (2013 to 2015). Infants in this program had received an abbreviated course of palivizumab in accordance with the provincial guidelines. Data were compared to adults and infants less than 12 months of age who did not receive palivizumab. Anti-RSV NAb titers were measured using an RSV microneutralization assay. Findings Infants who received palivizumab had anti-RSV NAb titers at the end of the RSV season that persisted beyond what is expected from the pharmacokinetics of palivizumab alone. Moreover, 54% of the control infants who did not receive palivizumab and all tested adults had protective anti-RSV NAb titers. Conclusions Based on our observations, we hypothesize that naturally acquired NAb provide additive protection, which may significantly reduce the need for additional doses of palivizumab in infants at risk of severe RSV infections.

Low plasma magnesium is associated with impaired brain metabolism in neonates with hypoxic-ischaemic encephalopathy

To determine the association between lowest plasma magnesium concentration and brain metabolism, and whether magnetic resonance imaging brain injury patterns moderated the association in hypoxic‐ischemic encephalopathy.

Oral glucose during targeted neonatal echocardiography: is it useful?

Targeted neonatal echocardiography (TNE) is widely used in the cardiovascular management of sick infants in neonatal intensive care unit (NICU).1 TNE should only be performed by operators who possess the knowledge and skills to acquire high-quality images in a structured manner, in order to formulate a diagnosis and medical recommendation. Suboptimal image quality due to agitation of the infant during a TNE may prolong scan time and result in errors in measurements and interpretation, leading to incorrect medical decisions. Oral glucose solutions are recommended to reduce procedure-related stress in infants.2 However, there are no data supporting this intervention in the context of the conductance of TNE. Anecdotally, many neonatologist sonographers across the globe have adopted the routine use of oral glucose to reduce agitation and facilitate image acquisition during a TNE, despite a lack of supporting scientific evidence. To determine whether oral glucose is effective in reducing agitation during a TNE, 104 infants born between 26 …

Oral glucose during targeted neonatal echocardiography: is it useful?: Table 1

Targeted neonatal echocardiography (TNE) is widely used in the cardiovascular management of sick infants in neonatal intensive care unit (NICU).1 TNE should only be performed by operators who possess the knowledge and skills to acquire high-quality images in a structured manner, in order to formulate a diagnosis and medical recommendation. Suboptimal image quality due to agitation of the infant during a TNE may prolong scan time and result in errors in measurements and interpretation, leading to incorrect medical decisions. Oral glucose solutions are recommended to reduce procedure-related stress in infants.2 However, there are no data supporting this intervention in the context of the conductance of TNE. Anecdotally, many neonatologist sonographers across the globe have adopted the routine use of oral glucose to reduce agitation and facilitate image acquisition during a TNE, despite a lack of supporting scientific evidence. To determine whether oral glucose is effective in reducing agitation during a TNE, 104 infants born between 26 …

Oral glucose during targeted neonatal echocardiography

Targeted neonatal echocardiography (TNE) is widely used in the cardiovascular management of sick infants in neonatal intensive care unit (NICU).1 TNE should only be performed by operators who possess the knowledge and skills to acquire high-quality images in a structured manner, in order to formulate a diagnosis and medical recommendation. Suboptimal image quality due to agitation of the infant during a TNE may prolong scan time and result in errors in measurements and interpretation, leading to incorrect medical decisions. Oral glucose solutions are recommended to reduce procedure-related stress in infants.2 However, there are no data supporting this intervention in the context of the conductance of TNE. Anecdotally, many neonatologist sonographers across the globe have adopted the routine use of oral glucose to reduce agitation and facilitate image acquisition during a TNE, despite a lack of supporting scientific evidence. To determine whether oral glucose is effective in reducing agitation during a TNE, 104 infants born between 26 …