Video laryngoscopy-assisted less-invasive surfactant administration quality improvement initiative.

OBJECTIVE: To describe the use of quality improvement methodology in transitioning from delivery of surfactant by INSURE (INtubation-SURfactant administration-Extubation) to video laryngoscope-assisted LISA (less-invasive surfactant administration) for infants with respiratory distress syndrome (RDS) receiving non-invasive ventilatory support. SETTING: Two large neonatal intensive care units (NICUs) at Northwell Health (New Hyde Park, New York, USA). STUDY POPULATION: Infants with RDS receiving continuous positive airway pressure in the NICU and eligible for surfactant administration. RESULTS: LISA was initiated in our NICUs in January 2021, after extensive guideline development, education programmes, hands-on training and provider credentialing. Our Specific, Measurable, Achievable, Relevant and Timely aim was to deliver surfactant by LISA for 65% of total doses by 31 December 2021. This goal was achieved within 1 month of go-live. In total, 115 infants received at least one dose of surfactant during the year. Of those, 79 (69%) received it via LISA and 36 (31%) via INSURE. Two Plan-Do-Study-Act cycles contributed to improved adherence to guidelines on timely surfactant administration and both written and video documentation. CONCLUSIONS: Safe and effective introduction of LISA with the use of video laryngoscopy is achievable with careful planning, clear clinical guidelines, adequate hands-on training and comprehensive safety and quality control.

Does every newborn need an imaging study after a fall? Case series and literature review.

OBJECTIVE: This study examines the clinical and radiographic information from neonates who sustained a newborn fall (NF) to identify risk factors for the NF and the presence of skull fracture and intracranial bleed. In addition, published articles will be reviewed to provide data to assist in the evidence-based management of mothers after delivery and neonates after NF. STUDY DESIGN: This is a retrospective chart review of neonates who sustained a NF in a level 4 NICU between 2016 and 2019. Results of imaging reports, maternal and neonatal clinical information, physical examination after fall, mode of delivery, time of day of fall, time between delivery and fall, feeding regimen, and maternal in hospital opioid use were recorded. Published reports containing imaging results and the incidence of skull fracture after NF were obtained by searching Pub Med from 2000 to 2019. MAIN OUTCOME MEASURES: The main outcome of this study is to determine the presence and location of fractures and intracranial hemorrhage after a NF. Secondary outcome includes identification of clinical factors associated with the NF and presence of fractures. Student's t-test was used for statistical comparisons. RESULTS: Twenty-one neonates sustained a NF and 83% were imaged by cranial CT. Skull fractures were identified by CT in 53% of neonates and ∼1/3 of infants had small intracranial hemorrhage. All infants were clinically stable and no neonate required neurosurgical intervention. Most NFs (73%) occurred between midnight and 8 AM and were associated with maternal sleeping while holding the infant. CONCLUSIONS: Mothers should have increased monitoring and support especially the days after delivery from 11 PM to 9 AM to assess for maternal exhaustion and to prevent NFs regardless of opioid use. When indicated, low-dose rapid sequence CT scan rather than X-ray is preferred for evaluation of the neonate after a fall.

A Quality Improvement Project to Standardize Surfactant Delivery in the Era of Noninvasive Ventilation.

INTRODUCTION: Continuous positive airway pressure (CPAP) and surfactant both improve outcomes for premature infants with respiratory distress syndrome. However, prolonged trials of CPAP, as well as observation periods after intubation, may delay the administration of surfactant. Late surfactant treatment likely increases the incidence of bronchopulmonary dysplasia, which leads to significant morbidity and healthcare utilization. METHODS: We aimed to decrease time from meeting standard criteria (start of a continuous run of FiO2 > 40% or PaCO2 > 65 for >90 min) to intubation, and from intubation to surfactant administration, for infants <1,500 g or younger than 32 weeks gestation. Retrospective data collection from the electronic medical record assessed those process measures as the primary endpoints. Balancing measures were the adverse outcomes of asymmetric lung disease, the inappropriate position of the endotracheal tube, or pneumothorax on the first x-ray (within 24 h) after surfactant. RESULTS: Mean time to intubation for infants 28-32 weeks gestation decreased from 321 to 81 minutes in response to a literature review for physicians and free-text orders for notification. Time to intubation for infants younger than 28 weeks gestation did not change. Administration of surfactant within 1 hour of intubation improved from 78% to 100% after a program for trainees and coordination with radiology. There were no adverse occurrences. CONCLUSIONS: Educational interventions and targeted process change can successfully implement standard criteria for intubation and surfactant administration for premature infants. Determination of an acceptable range of evidence-based practice is essential for the engagement of medical staff. Timely intubation and surfactant may decrease bronchopulmonary dysplasia.

Correction: MIF inhibition enhances pulmonary angiogenesis and lung development in congenital diaphragmatic hernia.

In the original version of this article, the name of the author "Kamesh Ayasolla" was incorrectly given as "Kamesh Ayyasola". This has now been corrected to "Kamesh Ayasolla" in both the PDF and HTML versions of the article.

MIF inhibition enhances pulmonary angiogenesis and lung development in congenital diaphragmatic hernia.

BACKGROUND: Congenital diaphragmatic hernia (CDH) is a complex birth anomaly with significant mortality and morbidity. Lung hypoplasia and persistent pulmonary hypertension (PPHN) limit survival in CDH. Macrophage migration inhibitory factor (MIF), a key regulator of innate immunity, is involved in hypoxia-induced vascular remodeling and PPHN. We hypothesized that antenatal inhibition of MIF in CDH fetuses, would reduce vascular remodeling, and improve angiogenesis and lung development. METHODS: Pregnant rats were randomized into three groups: Control, nitrofen, and nitrofen + ISO-92. Lung volumes of pups were measured by CT scanning. Right ventricular systolic pressure (RVSP) and vascular wall thickness (VWT) were measured together with MIF concentration, angiogenesis markers, lung morphometry, and histology. RESULTS: Prenatal treatment with ISO-92, an MIF inhibitor, improved normalization of static lung volume, lung volume-to-body weight ratio, decreased alveolar septal thickness, RVSP and VWT and improved radial alveolar count as compared to the non-treated group. Expression of MIF was unaffected by ISO-92; however, ISO-92 increased p-eNOS and VEGF activities and reduced arginase 1, 2 and Sflt-1. CONCLUSION: Prenatal inhibition of MIF activity in CDH rat model improves angiogenesis and lung development. This selective intervention may be a future therapeutic strategy to reduce the morbidity and mortality of this devastating condition.

The use of less invasive surfactant administration (LISA) in the United States with review of the literature.

BACKGROUND: The majority of extremely low gestational age neonates undergo intubation for surfactant therapy. Less invasive surfactant administration (LISA) uses a thin catheter inserted into the trachea to deliver the surfactant. During the procedure, the infant is breathing spontaneously while supported with continuous positive airway pressure. Although LISA is widely adapted in Europe and Australia, the rate of LISA use in the United States is unknown. STUDY DESIGN: The aim of this study is to evaluate the use of LISA in the US. A web-based survey was distributed via SurveyMonkey to 2550 neonatologists from AAP's SoNPM mailing list. RESULTS: Of the 472 neonatologists who answered the survey, 15% used LISA either as a part of routine care (8%) or as part of research (7%). CONCLUSION: Unlike several regions of Europe, LISA is not widely used in the US. Future studies should address ambiguities regarding infant selection, procedure training and "roadblocks" to its broader application.

The superiority of point of care ultrasound in localizing central venous line tip position over time.

The primary objective was to study agreement between X-rays and point of care ultrasound (POC-US) in determining central venous line (CVL) tip position. The secondary objective was to examine malposition rates over time using POC-US. Fifty-six neonates were enrolled who had a CVL placed. Initial X-rays and POC-US were obtained. POC-US was performed daily thereafter for the total of 6 days. US video clips were acquired in four standard echocardiographic views: subcostal, four-chamber, and short- and long-axis parasternal views. Gwet's agreement coefficient (AC1) for agreement measured inter-rater reliability of X-rays and POC-US (correct position/malposition). A generalized linear mixed model for binary clustered data estimated malposition rate over time. All analyses were conducted using SAS version 9.4 and Agree Stat. The study included 108 "pairs" of X-rays and POC-US images. Agreement coefficient (AC1), with respect to correct position/malposition of CVL tip, was high AC1 = 0.872 (UVC-AC1 = 0.814, PICC-AC1 = 0.94). Among birth weight (BW) < 1000 g, 1000-1499 g, and BW > 1500 g, AC1 values were 0.922, 0.774, and 0.873, respectively. CVL tip malposition rate decreased over time.Conclusions: Agreement between POC-US and X-rays for CVL tip position was high, with the highest in BW < 1000 g. The data suggest that POC-US can be used for initial confirmation and follow up of CVL tip position. What is Known • X-ray is currently the gold standard for localizing central venous line (CVL) tip position. • Malposition of CVL tip can lead to life-threatening complications. What is New • POC-US is superior to X-ray as it can follow CVL tip position over time, detecting malpositioned lines, adjusting them in a timely manner thus preventing complications. • Standardizing CVL placement, X-ray acquisition, POC-US acquisition with four views with video clips and ultrasound operator training increases accuracy and thus agreement between X-ray and POC-US. • UVC tip is more likely to be malpositoned than PICC tip. Malposition of UVC tip using POC-US decreased over time due to shrinking of the umbilical cord in the first 48 of life.

Role of EC-SOD overexpression in preserving pulmonary angiogenesis inhibited by oxidative stress.

UNLABELLED: Angiogenesis is one of the most important processes for normal lung development. Oxidative stress can impair the pulmonary angiogenesis, leading to chronic lung disease or Bronchopulmonary dysplasia (BPD). OBJECTIVE: To investigate the protective effects of EC-SOD overexpression on pulmonary angiogenesis on neonates following exposure to acute hyperoxia. DESIGN/METHODS: Transgenic (TG) and wild-type (WT) neonatal mice (10 mice per group) were exposed either to air (control group) or 95% O(2) for 7 days starting at birth. After exposure, all animals were sacrificed. ROS concentration was measured in lung homogenates using OxiSelect ROS assay kit. Mean vascular density (MVD) was measured using anti CD34 staining. RNA was extracted and the angiogenesis markers, VEGF, VEGFR1 and VEGFR2 and PECAM-1 were analyzed by RT-q PCR. VGEF protein was measured using Western blots. Endothelial progenitor cells (EPCs) was assayed by flow cytometer. RESULTS: There was a significant reduction of ROS in TG hyperoxic neonate group (156±14.2) compared to WT hyperoxic animals (255±35.1). Evaluation of MVD, using anti-CD34, showed marked significant increase of MVD in the TG group following hyperoxic exposure (85±12) in comparison to the WT hyperoxic group (62±8.4), (P<0.05). Among the hyperoxic groups, both RNA and protein of VEGF expression were significantly reduced in the WT animals compared to the TG group (P<0.05). The same trend was found in VEGFR 1 and 2 which were significantly reduced in WT group compared to the TG group (P<0.05). There was no significant difference between hyperoxia TG and control group (P>0.05). PECAM expression was significantly reduced in both hyperoxic compared to normoxic groups (P<0.05). EPC's showed significant reduction in WT hyperoxic group compared to others (P>0.05). CONCLUSIONS: EC-SOD plays a key role in preserving angiogenesis by scavenging free radicals which has an inhibitory effect on angiogenesis process in neonatal mice lung following exposure to hyperoxia.

Effect of gestational age on cord blood plasma copper, zinc, magnesium and albumin.

BACKGROUND: The transport of essential trace elements from mother to fetus varies throughout gestation, and the role of transport proteins in the neonate and the mother may change during pregnancy. Magnesium, often used as tocolytic agent, may reach the fetus and appear in cord blood at higher than normal concentrations. AIMS: To determine cord blood plasma zinc, copper and magnesium concentrations, as well as plasma albumin in premature and full-term newborns, and correlate these values with those of maternal blood plasma at birth. Also, to examine whether cord blood plasma concentration of these elements varies with gestational age. SUBJECTS: The 35 mother-infant pairs included: 11 in the 38-42-week gestational age (GA), 9 in the 34-37-week GA, 11 in the 29-33-week GA group and 4 in the 24-28-week GA. Magnesium for tocolysis was given to five of the mothers in the 29-33-week GA cohort and two of the women giving birth at 24-28-week GA. RESULTS: Trend analysis showed that while cord plasma zinc decreased with GA at birth, the reverse was observed for copper. There were no differences with GA either in maternal plasma zinc or copper. However, maternal ceruloplasmin tended to decrease with GA (P=0.0174). Maternal and cord blood plasma magnesium exhibited a strong correlation (r=0.942, P<0.001), as well as between cord plasma magnesium and zinc (r=0.448, P<0.01). CONCLUSIONS: While the vigorous mother-to-fetus uphill zinc transfer is clear throughout the last trimester, copper remains in cord blood plasma at much lower concentrations than in the mother, suggesting that prematurity may place the newborn infant at a greater risk than the term infant to copper deficiency. This situation, together with a reduced synthesis in the fetus of the transport protein ceruloplasmin, creates another potential challenge in the nutritional support of the premature infant.

Zinc supplementation in oral rehydration solutions: experimental assessment and mechanisms of action.

BACKGROUND: Zinc deficiency is associated with chronic diarrhea. This condition is generally linked to an overproduction of nitric oxide (NO), which induces secretion and cellular damage as a free radical. Use of oral rehydration solutions (ORS) is an important part of diarrhea treatment, especially early in infancy and for patients with cholera. The presence of zinc in an ORS could be a positive factor in recovery from diarrheal disease. OBJECTIVE: This study was undertaken to determine whether zinc added to an ORS could regulate the synthesis of NO metabolites in the lumen of zinc deficient rat intestine, acting as a gastrointestinal protector and thus accelerating normalization of intestinal function and zinc status. METHODS: The effects of zinc on NO metabolism were studied in young male rats fed a zinc deficient diet for three weeks to mimic the condition of patients with recurrent diarrheal episodes. During the fourth week of the zinc deficient feedings, experimental diarrhea was induced using cathartics (magnesium citrate plus phenolphthalein) that exacerbate NO production. A standard ORS with or without 1 mM zinc was given to the rats for the last two days. A control group received a zinc sufficient diet. Rats were killed at each stage. Intestinal nitric oxide synthase (NOS) was assayed, cecal fluid contents were analyzed for nitrates and nitrites, intestinal histology was examined, and activation of nuclear factor NF-kappaB DNA binding activity was determined. RESULTS: Rats fed the zinc-deficient diet for three weeks gained less weight than rats fed a normal zinc content diet and had a lower plasma zinc than controls (51.6 +/- 5.4 [n = 101 vs. 143.6 +/- 7.2 microg/dL [n = 11], p < 0.05). Recovery with ORS+Zn resulted in a higher plasma zinc than with the ORS-Zn (ORS+Zn: 186.5 +/- 12.2; ORS-Zn: 57.5 +/- 6.6 microg/dL, p < 0.05). The zinc-deficient diet did not alter mucosal NOS, as compared to the values of rats fed a normal diet. However, those animals which received five days of cathartic fluids had a small intestinal NOS higher than that of all other groups. Either ORS+Zn or ORS-Zn normalized NOS activity, regardless of cathartic treatment. The rats fed the zinc deficient diet had generally a higher content of NO metabolites in the cecum than rats fed a normal diet. After recovery with either type of ORS, rats given the cathartic remained with higher cecal NO metabolite concentrations than rats that had no induced diarrhea. After recovery with ORS+Zn, intestinal villi showed significant expansion of the lamina propria, an indication of greater absorption of fluid, while with ORS-Zn this was not present. Small intestinal homogenates of rats recovering with ORS+Zn had a decreased NF-kappaB DNA binding activity than tissues from rats consuming ORS-Zn. CONCLUSIONS: The results are consistent with the hypothesis that addition of Zn to an ORS may contribute to improving the physiologic status of the small intestine and potentially reduce the risks of recurrent diarrhea episodes.