Search

OBJECTIVES To reduce transfers to the neonatal intensive care unit (NICU) for neonates with opioid withdrawal while also reducing length of stay and pharmacologic intervention, and maintaining standards of safety. PATIENTS AND METHODS This was a single-center quality-improvement (QI) initiative in a free-standing maternity hospital comparing outcomes for neonatal opioid withdrawal syndrome (NOWS) before and after a series of QI bundles in infants >36 weeks' gestation age (GA). We compared outcomes to our preintervention period (January, 2013 to December, 2013; n = 42) with outcomes postintervention cycle 1 (October, 2016 to September, 2017; n = 126), and postintervention cycle 2 (November, 2017 to October, 2018; n = 160). Cycle 1 included organizing a multidisciplinary task force who focused on emphasis on nonpharmacologic and dyad-centered care, and also standardized pharmacologic management. Cycle 2 reflects the transition to a functional assessment tool and as-needed morphine administration on the postpartum floor. RESULTS Transfer to the NICU for management of NOWS dropped from 71.4% before the quality improvement project down to 5.6% (P

Cardiac intervention remains controversial in patients with trisomy 13 and 18 and little is known about factors that may affect outcomes. The goal of this study was to evaluate preoperative factors and surgical approach with respect to outcomes in these patients. Patients with congenital heart disease and trisomy 13 or 18 presenting to our institution from 2004 through 2015 were retrospectively reviewed. Patients were grouped into complete intervention, palliated intervention, and non-intervention. Pre-intervention variables, timing and type of intervention, post-intervention outcomes, and survival were recorded and comparisons were made between the groups. Of 34 patients, 18 cardiac interventions were performed. Complete repair was performed in 11(61%) and palliation in 7(39%). Median age for complete repair was 9.2 vs. 1.7 months in palliated patients (p

Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant. A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period. For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO2 × mean airway pressure), SP-B content (+75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment. Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant.

We describe a method to measure protein synthesis and catabolism in humans without prior purification and use the method to measure the turnover of surfactant protein-B (SP-B). SP-B, a lung-specific, hydrophobic protein essential for fetal-neonatal respiratory transition, is present in only picomolar quantities in tracheal aspirate samples and difficult to isolate for dynamic turnover studies using traditional in vivo tracer techniques. Using infusion of [5,5,5-(2)H(3)] leucine and a targeted proteomics method, we measured both the quantity and kinetics of SP-B tryptic peptides in tracheal aspirate samples of symptomatic newborn infants. The fractional synthetic rate (FSR) of SP-B measured using the most abundant proteolytic fragment, a 10 amino acid peptide from the carboxy-terminus of proSP-B (SPTGEWLPR), from the circulating leucine pool was 0.035 +/- 0.005 h(-1), and the fractional catabolic rate was 0.044 +/- 0.003 h(-1). This technique permits high-throughput and sensitive measurement of turnover of low abundance proteins with minimal sample preparation.

Objective To measure the intrapharyngeal pressure (IPP) generated by high-flow nasal cannula (HFNC) at varying flow rates up to 5 l min(-1). Study design We studied 14 infants on HFNC or NCPAP using IPP manometry to measure the IPP generated at flows of 1, 2, 3, 4 and 5 l min(-1). Result On average flow rates of 1, 2, 3, 4 and 5 l min(-1) generated an IPP (cm of H(2)O) of 1.70+/-0.34, 1.75+/-0.2, 2.62+/-0.28, 3.78+/-0.44 and 4.84+/-0.51 respectively. Conclusion HFNC delivers significant IPP and is potentially a well-tolerated and viable option to provide CPAP at flows of > or = 3 min(-1) in infants with respiratory distress.

Objectives To use stable isotopically labeled precursors of pulmonary surfactant phospholipids to measure precursor utilization and surfactant turnover in premature infants who required mechanical ventilation at birth, 2 weeks, and >4 weeks of age. Study design Infants of ≤28 weeks' gestation received simultaneous 24-hour intravenous infusions of [1,2,3,4- 13 C 4 ] palmitate and [1- 13 C 1 ] acetate at birth, 2 weeks, and ≥4 weeks of life. Disaturated phospholipids were extracted from sequential tracheal aspirate samples obtained over a period of 2 weeks. Fractional catabolic rate (a measure of total turnover) and the fractional synthetic rates from plasma palmitate and de novo synthesis (acetate) were measured. Results The fractional catabolic rate increased from 25.3% ± 7.0% per day at birth to 53.8% ± 14.4% per day at 4 weeks ( P = .001). The combined contribution from plasma palmitate and de novo synthesis to total synthesis increased from 44.2% ± 19.8% at birth to 85.2% ± 32.8% at 4 weeks ( P = .03). Conclusions Total surfactant turnover increased in premature infants with evolving bronchopulmonary dysplasia. The increasing contributions from acetate and plasma palmitate suggest a decrease in surfactant phospholipid recycling.

We compared kinetic indices of pulmonary surfactant metabolism in premature infants (n = 41) with respect to i) tracer ([1-(13)C1]acetate, [U-(13)C6]glucose, and [1,2,3,4-(13)C4] palmitate), ii) phospholipid (PL) pool (total PLs or disaturated PLs), or iii) instrumentation [gas chromatography/mass spectrometry (GC/MS) or GC-combustion-isotope ratio mass spectometry (GC-C-IRMS)]. Tracer incorporation was measured in PLs extracted from serial tracheal aspirates after a 24 h tracer infusion. The fractional catabolic rate (FCR), representing the total fractional turnover from all sources of surfactant production, was independent of tracer. The fractional synthesis rate of surfactant PL from plasma palmitate was significantly higher than that from palmitate synthesized de novo from acetate, and these two sources of palmitate together accounted for only half of the total surfactant production in preterm infants. [U-(13)C6]glucose showed significant recycling of the (13)C label in intermediary metabolism, distinguishable by GC-MS but not by GC-C-IRMS, resulting in a slower apparent FCR when GC-C-IRMS was used. The extracted PL pool did not affect the surfactant metabolic indices. We suggest that FCR should be used as a primary measure of surfactant turnover kinetics and that tracers labeling both de novo synthesis (acetate and glucose) and preformed pathways (plasma palmitate) can be used to partition the fractional contribution of each pathway to total production.

Studies using stable isotopically labeled glucose and palmitate as precursors of pulmonary surfactant synthesis have demonstrated slow surfactant turnover in premature infants with respiratory distress syndrome (RDS). However, only limited data about surfactant turnover are available for term infants. Because acetate is a direct precursor of de novo synthesized surfactant fatty acid, we measured [1-13C1]acetate incorporation into surfactant of term infants without respiratory dysfunction (control group), preterm infants with RDS, and term infants with primary respiratory failure to determine whether stable isotopically labeled acetate would yield similar results to previous studies of preterm infants with RDS and, furthermore, would distinguish normal from abnormal surfactant turnover. Despite similar amounts of phospholipids and acetate precursor enrichment, the control group had higher fractional synthetic rate and shorter half-life of clearance than preterm infants with RDS, (fractional synthetic rate, 15.4 +/- 2.4 versus 2.2 +/- 0.4%/d, p < 0.001; half-life of clearance, 27 +/- 3 versus 105 +/- 11 h, p < 0.001). Term infants with severe respiratory failure had a lower fractional synthetic rate than those with mild disease (2.9 +/- 0.6 versus 13.8 +/- 3.5%/d, p = 0.014) and a reduced amount of phospholipids recovered from tracheal aspirates (54 +/- 17 versus 300 +/- 28 nmol, severe versus mild disease, respectively, p < 0.001). The amount of phospholipids in tracheal aspirates correlated inversely with disease severity, (r = -0.75, p = 0.01). We conclude that normal surfactant turnover in term infants is faster than in preterm infants with RDS. Surfactant turnover in term infants with severe respiratory failure is similar to that of preterm infants with RDS, suggesting either delayed maturity of the surfactant system or disruption from the underlying disease process.

Many extremely low gestational age neonates (≤ 28 wk, ELGANS) continue to require intubation and mechanical ventilation beyond the first week of life and many experience episodes of dysfunctional surfactant associated with low surfactant protein B content and clinically significant respiratory decompensations (Pediatr Res 2004;56:918-26). We hypothesized that booster surfactant treatment (booster) given during week 2-3 to these infants is safe and improves pulmonary outcome. Infants were enrolled in one of two booster pilot trials. ELGANS requiring ventilation at 7 to 10 days of life received one to two doses of “prophylactic” surfactant (Infasurf®, 3 mL/kg) 1 week apart. In a separate “Rescue” pilot trial, ventilated ELGANS at 5 to 21 days of life with respiratory decompensation received two doses of Infasurf over 12 to 24 hours. Tracheal aspirate (TA) samples were analyzed for minimum surface tension (STmin) in a pulsating bubble surfactometer and for concentrations of cytokines, growth factors, and chemokines. Clinical data including respiratory severity score (SS = mean airway press × FiO2) were collected. Twenty-six infants have been enrolled in the ongoing pilot trials. Mean GA and BW were 25.5 ± 1.3 week and 718.3 ± 151.8 g, respectively. Surfactant instillation was tolerated by infants in both trials. Changes in SS, as an index of initial clinical response, are shown as the number of infants with lower SS score/number with same SS score/number with higher SS score compared to the pr-treatment value (mean and range SS): Following treatment, there was an initial decrease in STmin for most infants, indicating improved function. Analysis of concentrations of IL-1α, IL-1β, IL-6, IL-8, TNFα, IL-10, RANTES, MIP-1α, TGF-β1, and VEGF after treatment revealed no significant changes as compared with pretreatment. These preliminary results support the safety of booster surfactant administration in ventilated ELGANS beyond 7 days of age and indicate a favorable initial response in respiratory status. This therapy will be tested for safety and prevention of bronchopulmonary dysplasia in a multicenter, randomized, controlled trial.

Empirical force-field calculations have shown that the co-ordination geometry 1 of bleomycin (BLM) binding to cobalt proposed by Umezawa and that, 2, proposed by Hilbers is sterically possible. In the calculations it was found that changing the charge on the metal ion has a significant effect on the BLM conformation, however the differences in conformation between the two binding geometries are much larger than those due to charge differences. Based on BLM–DNA docking studies, it is suggested that both the bithiazole tail and the metal-binding region of BLM with binding geometry 2 could be interacting with the minor groove of DNA.