Real-Time Ultrasound Guidance for Umbilical Venous Cannulation in Neonates With Congenital Heart Disease.

OBJECTIVES: Umbilical venous cannulation is the favored approach to perinatal central access worldwide but has a failure rate of 25-50% and the insertion technique has not evolved in decades. Improving the success of this procedure would have broad implications, particularly where peripherally inserted central catheters are not easily obtained and in neonates with congenital heart disease, in whom umbilical access facilitates administration of inotropes and blood products while sparing vessels essential for later cardiac interventions. We sought to use real-time, point-of-care ultrasound to achieve central umbilical venous access in patients for whom conventional, blind placement techniques had failed. DESIGN: Multicenter case series, March 2019-May 2021. SETTING: Cardiac and neonatal ICUs at three tertiary care children's hospitals. PATIENTS: We identified 32 neonates with congenital heart disease, who had failed umbilical venous cannulation using traditional, blind techniques. INTERVENTIONS: Real-time ultrasound guidance and liver pressure were used to replace malpositioned catheters and achieve successful placement at the inferior cavoatrial junction. MEASUREMENTS AND MAIN RESULTS: In 32 patients with failed prior umbilical venous catheter placement, real-time ultrasound guidance was used to successfully "rescue" the line and achieve central position in 23 (72%). Twenty of 25 attempts (80%) performed in the first 48 hours of life were successful, and three of seven attempts (43%) performed later. Twenty-four patients (75%) were on prostaglandin infusion at the time of the procedure. We did not identify an association between patient weight or gestational age and successful placement. CONCLUSIONS: Ultrasound guidance has become standard of care for percutaneous central venous access but is a new and emerging technique for umbilical vessel catheterization. In this early experience, we report that point-of-care ultrasound, together with liver pressure, can be used to markedly improve success of placement. This represents a significant advance in this core neonatal procedure.

Inhaled Nitric Oxide Is Associated with Improved Oxygenation in a Subpopulation of Infants with Congenital Diaphragmatic Hernia and Pulmonary Hypertension.

OBJECTIVES: To determine which patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PH) benefit from inhaled nitric oxide (iNO) treatment by comparing characteristics and outcomes of iNO responders to nonresponders. STUDY DESIGN: We performed a retrospective chart review of infants with CDH treated at our center between 2011 and 2016. In a subset of patients, iNO was initiated for hypoxemia or echocardiographic evidence of extrapulmonary right to left shunting. Initial post-treatment blood gases were reviewed, and patients were classified as responders (increased PaO2 >20 mm Hg) or nonresponders. Baseline characteristics, echocardiograms and outcomes were compared between groups with Fisher exact tests and Mann-Whitney t tests, as appropriate. RESULTS: During the study period, 95 of 131 patients with CDH (73%) were treated with iNO. All patients with pretreatment echocardiograms (n = 90) had echocardiographic evidence of PH. Thirty-eight (40%) patients met treatment response criteria. Responders had significant improvements in PaO2 (51 ± 3 vs 123 ± 7 mm Hg, P < .01), alveolar-arterial gradient (422 ± 30 vs 327 ± 27 mm Hg, P < .01), and PaO2 to FiO2 ratio (82 ± 10 vs 199 ± 15 mm Hg, P < .01). Nonresponders were more likely to have left ventricular systolic dysfunction (27% vs 8%, P = .03) on echocardiogram. Responders were less likely to require extracorporeal membrane support (50 vs 24%, P = .02). CONCLUSIONS: iNO treatment is associated with improved oxygenation and reduced need for ECMO in a subpopulation of patients with CDH with PH and normal left ventricular systolic function.

Trends in transcatheter and operative closure of patent ductus arteriosus in neonatal intensive care units: Analysis of data from the Pediatric Health Information Systems Database.

BACKGROUND: The risks and benefits of pharmacologic treatment and operative closure of patent ductus arteriosus (O-PDA) in premature infants remain controversial. Recent series have demonstrated the feasibility of transcatheter PDA closure (TC-PDA) in increasingly small infants. The effect of this change on practice has not been evaluated. METHODS: A multicenter observational study of infants treated in neonatal intensive care units in hospitals contributing data to the Pediatric Health Information Systems Database from January 2007 to December 2017 was performed to study trends in the propensities for (1) mechanical closure of PDA and (2) TC-PDA versus O-PDA, as well as interhospital variation in practice. RESULTS: A total of 6,214 subjects at 44 hospitals were studied (5% TC-PDA). Subject median gestational age was 25 weeks (interquartile range: 24-27 weeks). Median age at closure was 24 days (interquartile range: 14-36 days). The proportion of all neonatal intensive care unit patients undergoing either O-PDA or TC-PDA decreased (3.1% in 2007 and 0.7% in 2017, P < .001), whereas the proportion in which TC-PDA was used increased significantly (0.1% in 2007 to 29.0% in 2017). Case-mix-adjusted multivariable models similarly demonstrated increasing propensity to pursue TC-PDA (odds ratio [OR] 1.66 per year, P < .001) with acceleration of the trend after 2014 (OR 2.46 per year, P < .001) as well as significant practice variation (P < .001, median OR 4.6) across the study period. CONCLUSIONS: In the face of decreasing closure of PDA, the use of TC-PDA increased dramatically with significant practice variability. This demonstrates that there is equipoise for potential clinical trials.

US-guided placement and tip position confirmation for lower-extremity central venous access in neonates and infants with comparison versus conventional insertion.

PURPOSE: To describe experience with the use of ultrasound (US)-guided placement and tip position confirmation for direct saphenous and single-incision tunneled femoral noncuffed central venous catheters (CVCs) placed in neonates and infants at the bedside. MATERIALS AND METHODS: A retrospective review of the interventional radiology (IR) database and electronic medical records was performed for 68 neonates and infants who received a CVC at the bedside and for 70 age- and weight-matched patients with CVCs placed in the IR suite between 2007 and 2012. Technical success, complications, and outcomes of CVCs placed at the bedside were compared with those in an age- and weight-matched sample of children with CVCs placed in the IR suite. RESULTS: A total of 150 primary insertions were performed, with a technical success rate of 100%. Total catheter lives for CVCs placed at the bedside and in the IR suite were 2,030 catheter-days (mean, 27.1 d) and 2,043 catheter-days (mean, 27.2 d), respectively. No significant difference was appreciated between intraprocedural complications, mechanical complications (bedside, 1.53 per 100 catheter-days; IR, 1.76 per 100 catheter-days), or infectious complications (bedside, 0.39 per 100 catheter-days; IR, 0.34 per 100 catheter-days) between groups. CONCLUSIONS: US-guided placement and tip position confirmation of lower-extremity CVCs at bedside for critically ill neonates and infants is a safe and feasible method for central venous access, with similar complications and catheter outcomes in comparison with CVCs placed by using fluoroscopic guidance in the IR suite.

Regoaling: a conceptual model of how parents of children with serious illness change medical care goals.

BACKGROUND: Parents of seriously ill children participate in making difficult medical decisions for their child. In some cases, parents face situations where their initial goals, such as curing the condition, may have become exceedingly unlikely. While some parents continue to pursue these goals, others relinquish their initial goals and generate new goals such as maintaining the child's quality of life. We call this process of transitioning from one set of goals to another regoaling. DISCUSSION: Regoaling involves factors that either promote or inhibit the regoaling process, including disengagement from goals, reengagement in new goals, positive and negative affect, and hopeful thinking. We examine these factors in the context of parental decision making for a seriously ill child, presenting a dynamic conceptual model of regoaling. This model highlights four research questions that will be empirically tested in an ongoing longitudinal study of medical decision making among parents of children with serious illness. Additionally, we consider potential clinical implications of regoaling for the practice of pediatric palliative care. SUMMARY: The psychosocial model of regoaling by parents of children with a serious illness predicts that parents who experience both positive and negative affect and hopeful patterns of thought will be more likely to relinquish one set of goals and pursue a new set of goals. A greater understanding of how parents undergo this transition may enable clinicians to better support them through this difficult process.

The artificial placenta and EXTEND technologies: one of these things is not like the other.

The so called "Artificial Placenta" and "Artificial Womb" (EXTEND) technologies share a common goal of improving outcomes for extreme premature infants. Beyond that goal, they are very dissimilar and, in our view, differ sufficiently in their technology, intervention strategy, demonstrated physiology, and risk profiles that bundling them together for consideration of the ethical challenges in designing first in human trials is misguided. In this response to the commentary by Kukora and colleagues, we will provide our perspective on these differences, and how they impact ethical clinical study design for first-in-human trials of safety/feasibility, and subsequently efficacy of the two technologies.

Individualising care in severe bronchopulmonary dysplasia: a series of N-of-1 trials comparing transpyloric and gastric feeding.

OBJECTIVE: Compare rates of hypoxaemia during transpyloric and gastric feedings in very preterm infants with severe bronchopulmonary dysplasia. DESIGN: N-of-1 multiple crossover trials with individual patient and pooled data analyses. SETTING: Level IV intensive care nursery. PATIENTS: Infants receiving positive airway pressure between 36 and 55 weeks postmenstrual age were enrolled between December 2014-July 2016. INTERVENTION: N-of-1 trial consisting of two blocks, each with a 4-day gastric and 4-day transpyloric feeding period assigned in random order. MAIN OUTCOME MEASURES: The primary outcome was the frequency of daily intermittent hypoxaemic events (SpO2 ≤80% lasting 10-180 s). Secondary outcomes included the daily proportion of time with an SpO2 ≤80% and mean daily fraction of inspired oxygen. RESULTS: Of 15 infants, 13 completed the trial and 2 stopped early for transient worsening in respiratory status during gastric feedings. In the intention-to-treat analyses, transpyloric feedings resulted in increased rates of intermittent hypoxaemia in five infants, greater time per day in hypoxaemia in three infants and more supplemental oxygen use in three infants. One infant received more supplemental oxygen during gastric feedings. The remaining study outcomes were similar between the feeding routes in all other infants. Pooling all data, transpyloric feedings resulted in a higher frequency of intermittent hypoxaemic events (median 7.5/day (IQR 1-23.5) vs 3/day (1-11); adjusted incidence rate ratio 1.8, 95% CI 1.3 to 2.5) and a greater proportion of daily hypoxaemia time (median 0.8% (IQR 0.1-2.3) vs 0.4% (0.07-1.8); adjusted mean difference 1.6, 95% CI 1.1 to 2.5). CONCLUSIONS: Transpyloric compared with gastric feedings modestly increased rates of hypoxaemia among study participants. TRIAL REGISTRATION NUMBER: NCT02142621.

Initiating resuscitation before umbilical cord clamping in infants with congenital diaphragmatic hernia: a pilot feasibility trial.

BACKGROUND: Infants with congenital diaphragmatic hernia (CDH) often experience hypoxaemia with acidosis immediately after birth. The traditional approach in the delivery room is immediate cord clamping followed by intubation. Initiating resuscitation prior to umbilical cord clamping (UCC) may support this transition. OBJECTIVES: To establish the safety and feasibility of intubation and ventilation prior to UCC for infants with CDH. To compare short-term outcomes between trial participants and matched controls treated with immediate cord clamping before intubation and ventilation. DESIGN: Single-arm, single-site trial of infants with CDH and gestational age ≥36 weeks. Infants were placed on a trolley immediately after birth and underwent intubation and ventilation, with UCC performed after qualitative CO2 detection. The primary feasibility endpoint was successful intubation prior to UCC. Prespecified safety and physiological outcomes were compared with historical controls matched for prognostic variables using standard bivariate tests. RESULTS: Of 20 enrolled infants, all were placed on the trolley, and 17 (85%) infants were intubated before UCC. The first haemoglobin and mean blood pressure at 1 hour of life were significantly higher in trial participants than controls. There were no significant differences between groups for subsequent blood pressure values, vasoactive medications, inhaled nitric oxide or extracorporeal membrane oxygenation. Blood gas and oxygenation index values did not differ between groups at any point. CONCLUSIONS: Intubation and ventilation prior to UCC is safe and feasible among infants with CDH. The impact of this approach on clinically relevant outcomes deserves investigation in a randomised trial.

A Proposed Model for Perinatal Palliative Care.

Perinatal palliative care allows for an active partnership among a pregnant woman, her family, and her multidisciplinary treatment team and addresses her specialized medical care, emotional, social, and familial needs when a life-limiting fetal diagnosis is confirmed. The purpose of this article is to highlight the multidisciplinary care model used within a perinatal palliative care program. A case study provides a unique perspective on support needed for parents who anticipate that their newborn may die before or shortly after birth.

Anti-gastroesophageal reflux surgery in infants with severe bronchopulmonary dysplasia.

Gastroesophageal reflux may exacerbate lung disease in infants with bronchopulmonary dysplasia (BPD). Anti-reflux surgery may therefore reduce the severity of this disease in some infants. We report a retrospective series of 22 infants with severe BPD who underwent anti-reflux surgery. Our experience indicates that these procedures can be safely performed in this population and that early post-operative initiation of gastric feeds is well tolerated. Modest post-operative reductions in required oxygen and median respiratory rate were observed.

Pulmonary and systemic nitric oxide metabolites in a baboon model of neonatal chronic lung disease.

We report on developmental changes of pulmonary and systemic nitric oxide (NO) metabolites in a baboon model of chronic lung disease with or without exposure to inhaled NO. The plasma levels of nitrite and nitrate, staining for S-nitrosothiols and 3-nitrotyrosine in the large airways, increased between 125 d and 140 d of gestation (term 185 d) in animals developing in utero. The developmental increase in NO-mediated protein modifications was not interrupted by delivery at 125 d of gestation and mechanical ventilation for 14 d, whereas plasma nitrite and nitrate levels increased in this model. Exposure to inhaled NO resulted in a further increase in plasma nitrite and nitrate and an increase in plasma S-nitrosothiol without altering lung NO synthase expression. These data demonstrate a developmental progression in levels of pulmonary NO metabolites that parallel known maturational increases in total NO synthase activity in the lung. Despite known suppression of total pulmonary NO synthase activity in the chronic lung disease model, pulmonary and systemic NO metabolite levels are higher than in the developmental control animals. Thus, a deficiency in NO production and biological function in the premature baboon was not apparent by the detection and quantification of these surrogate markers of NO production.

Biological significance of nitric oxide-mediated protein modifications.

Nitric oxide (NO), despite an apparently simple diatomic structure, has a wide variety of functions in both physiology and pathology and within every major organ system. It has become an increasingly important scientific challenge to decipher how this wide range of activity is achieved. To this end a number of investigators have begun to explore how NO-mediated posttranslational modifications of proteins may represent mechanisms of cellular signaling. These modifications include: 1). binding to metal centers; 2). nitrosylation of thiol and amine groups; 3). nitration of tyrosine, tryptophan, amine, carboxylic acid, and phenylalanine groups; and 4). oxidation of thiols (both cysteine and methionine residues) and tyrosine. However, two particular modifications have recently received much attention, nitrosylation of thiols to produce S-nitrosothiol and nitration of tyrosine residues to produce nitrotyrosine. It is the purpose of this review to examine the possibility that these modifications may play a role in NO-mediated signaling.