Chest compressions superimposed with sustained inflation during neonatal cardiopulmonary resuscitation: are we ready for a clinical trial?

Neonates requiring cardiopulmonary resuscitation (CPR) are at risk of mortality and neurodevelopmental injury. Poor outcomes following the need for chest compressions (CCs) in the delivery room prompt the critical need for improvements in resuscitation strategies. This article explores a technique of CPR which involves CCs with sustained inflation (CC+SI). Unique features of CC+SI include (1) improved tidal volume delivery, (2) passive ventilation during compressions, (3) uninterrupted compressions and (4) improved stability of cerebral blood flow during resuscitation. CC+SI has been shown in animal studies to have improved time to return of spontaneous circulation and reduced mortality without significant increase in markers of inflammation and injury in the lung and brain, compared with standard CPR. The mechanics of CCs, rate of compressions, ventilation strategies and compression-to-ventilation ratios are detailed here. A large randomised controlled trial comparing CC+SI versus the current 3:1 compression-to-ventilation ratio is needed, given the growing evidence of its potential benefits.

Positive Pressure Ventilation in Preterm Infants in the Delivery Room: A Review of Current Practices, Challenges, and Emerging Technologies.

BACKGROUND: A major proportion of preterm neonates require positive pressure ventilation (PPV) immediately after delivery. PPV may be administered through a face mask (FM) or nasal prongs. Current literature indicates that either of these are associated with similar outcomes. SUMMARY: Nonetheless, FM remains the most utilized and the best choice. However, most available FM sizes are too large for extremely preterm infants, which leads to mask leak and ineffective PPV. Challenges to providing effective PPV include poor respiratory drive, complaint chest wall, weak thoracic muscle, delayed liquid clearance, and surfactant deficiency in preterm infants. Mask leak, airway obstruction, poor technique, and inappropriate size are correctable causes of ineffective PPV. Visual assessment of chest rise is often used to assess the efficacy of PPV. However, its accuracy is debatable. Though end tidal CO2 may adjudge the effectiveness of PPV, clinical studies are limited. The compliance of a preterm lung is highly dynamic. The inflating pressure set on T-piece is constant throughout the resuscitation, but the lung volume and dynamics changes with every breath. This leads to huge fluctuations of tidal volume delivery and can trigger inflammatory cascade in preterm infants leading to brain and lung injury. Respiratory function monitoring in the delivery room has potential for guiding and optimizing delivery room resuscitation. This is, however, limited by high costs, complex information that is difficult to interpret during resuscitation, and absence of clinical trials. KEY MESSAGES: This review summarizes the existing literature on PPV in preterm infants, the various aspects related to it such as the pathophysiology, interfaces, devices utilized to deliver it, appropriate technique, emerging technologies, and future directions.

Early Echocardiographic Predictors of Eventual Need for Patent Ductus Arteriosus Treatment: A Retrospective Study.

OBJECTIVE: Hemodynamically significant patent ductus arteriosus (hsPDA) in preterm neonates is associated with end-organ injury including intraventricular hemorrhage. Early treatment may reduce morbidities but may result in overtreatment. This study aimed to examine the association between commonly obtained echocardiographic markers within the first 12 hours of life and eventual treatment of an hsPDA. STUDY DESIGN: Patients with <32 weeks' gestational age had blinded echocardiograms done within the first 12 hours of life as part of research protocols. Subsequent treatment of the patent ductus arteriosus (PDA) was determined by the clinical team independent of echocardiogram results. t-tests and chi-square tests were done for continuous data and categorical outcomes. A receiver operating curve was created to optimize cutoff values. RESULTS: Among 199 neonates studied (mean time of echocardiogram 6.7 h after birth), those needing PDA treatment had higher left ventricular output (LVO), right ventricular output (RVO), and superior vena cava (SVC) flow (p-values 0.007, 0.044, and 0.012, respectively). Cutoffs for predicting PDA treatment were LVO > 204 mL/kg/min (63% sensitivity, 66% specificity), RVO > 221 mL/kg/min or SVC flow > 99 mL/kg/min (sensitivities 70 and 43%, specificities 48 and 73%, respectively). CONCLUSION: Preterm neonates with higher markers of cardiac output in the first 12 hours of birth later required PDA treatment. These data are the first to use standard cardiac output measures in the first 12 hours of life to predict the need for future PDA treatment. Further prospective studies will need to be performed to corroborate these associations between echocardiographic markers and clinical outcomes/morbidities. KEY POINTS: · Early diagnosis of hsPDA may prevent severe morbidity and death.. · There are echocardiographic markers beyond duct size and flow direction that may aid early diagnosis.. · Cardiac output markers within the first 12 hours of life may predict need for treatment of hsPDA..

Umbilical cord milking-benefits and risks.

The most common methods for providing additional placental blood to a newborn are delayed cord clamping (DCC) and umbilical cord milking (UCM). However, DCC carries the potential risk of hypothermia due to extended exposure to the cold environment in the operating room or delivery room, as well as a delay in performing resuscitation. As an alternative, umbilical cord milking (UCM) and delayed cord clamping with resuscitation (DCC-R) have been studied, as they allow for immediate resuscitation after birth. Given the relative ease of performing UCM compared to DCC-R, UCM is being strongly considered as a practical option in non-vigorous term and near-term neonates, as well as preterm neonates requiring immediate respiratory support. However, the safety profile of UCM, particularly in premature newborns, remains a concern. This review will highlight the currently known benefits and risks of umbilical cord milking and explore ongoing studies.

A newborn's "life line" - A review of umbilical cord management strategies.

Literature supporting various umbilical management strategies have increased substantially over the past decade. Delayed cord clamping and umbilical cord milking are increasing embraced by obstetricians and neonatologists, and multiple international governing bodies now endorse these practices. This review summarizes the benefits and limitations of the different umbilical cord management strategies for term, near-term, and preterm neonates. Additional studies are underway to elucidate the safety profile of these practices, long term outcomes, and variations within these strategies that could potentially augment the benefits.

Cardiopulmonary Resuscitation with an Intact Umbilical Cord.

The body of literature supporting different umbilical management strategies has increased over the past decade as the role of cord management in neonatal transition is realized. Multiple international governing bodies endorse delayed cord clamping, and this practice is now widely accepted by obstetricians and neonatologists. Although term and preterm neonates benefit in some ways from delayed cord clamping, additional research on variations in this practice, including resuscitation with an intact cord, aim to find the optimal cord management practice that reduces mortality and major morbidities.

Optimizing respiratory management in preterm infants: a review of adjuvant pharmacotherapies.

Adjuvant respiratory therapies in preterm neonates aim to reduce long-term morbidities and mortality. Commonly utilized therapies include caffeine, systemic glucocorticosteroids, inhaled steroids, inhaled bronchodilators, and diuretics. This review discusses the available literature that supports some of these practices and points out where clinical practices are not corroborated by evidence. Therapies with no proven clinical benefit must be weighed against potential adverse effects.

Improving Accuracy of Handoff by Implementing an Electronic Health Record-generated Tool: An Improvement Project in an Academic Neonatal Intensive Care Unit.

BACKGROUND: Written patient handoffs are susceptible to errors or incompleteness. The accuracy is dependent on the person inputting the information. Thus, handoff printouts generated by electronic health records (EHR) with automation reduces the risk of transcription errors and improves consistency in format. This single-center quality improvement project aims to increase the accuracy of handoff printouts with an EHR-generated handoff tool. METHODS: This project used a plan-do-study-act methodology. Participants included registered nurses, neonatal nurse practitioners, neonatal hospitalists, pediatric residents, neonatal fellows, and neonatologists. The goals were to (1) increase accuracy of information to 80%, (2) reduce verbal handoff time by 20%, (3) reduce the frequency of incorrectly listed medications below 20%, and (4) improve user satisfaction by 1 point (on a 5-point Likert scale) over 6 months. Baseline assessment included a survey and a review of handoff reports 4 months before transitioning to the new handoff tool. We created a new handoff tool using EHR autogenerated phrases (Epic SmartPhrases) and autopopulated fields for pertinent Neonatal Intensive Care Unit patient data. RESULTS: After the unit-wide implementation of the new tool, the accuracy of 16 patient data points increased from 51% to 97%, while the frequency of patients with incorrectly listed medications decreased from 51% to 0%. Handoff time remained unchanged, while a 5-question user satisfaction survey showed an increase on the Likert scale. CONCLUSIONS: We demonstrated that handoff printouts generated by EHR have fewer inaccuracies than manually scripted versions and do not add to the time required to give verbal handoff.

Management and outcomes of pediatric septic thrombophlebitis: a case series.

Septic thrombophlebitis is a potentially life-threatening condition. Pediatric hematologists are often consulted to provide recommendations regarding anticoagulation management. We conducted a ten-year retrospective, single-center study of hospitalized pediatric patients who were treated for septic thrombophlebitis. Our primary outcome was resolution of thrombophlebitis. Twenty-eight patients were included in the study. Eighty-nine percent of patients received both antibiotic and anticoagulation therapy. The median durations of intravenous and total antibiotic therapy were 47.5 days (range 14-120) and 65 days (range 14-281), respectively, and median duration of anticoagulation therapy was 92 days (range 41-268). Resolution of thrombosis defined by magnetic resonance imaging, computed tomography, or ultrasound imaging was documented in 16 of 28 (57%) patients. Despite the high rate of persistent thrombosis, there was a low risk of relapse of infection in cases where antibiotic and/or anticoagulation was discontinued prior to complete resolution of the thrombus. Further research is needed to determine if duration of antibiotic and/or anticoagulation treatment can be shortened.

Erythrocyte-Coated Nanoparticles Block Cytotoxic Effects of Group B Streptococcus ß-Hemolysin/Cytolysin.

Group B Streptococcus (GBS) emerged as a leading cause of invasive infectious disease in neonates in the 1970s, but has recently been identified as an escalating public health threat in non-pregnant adults, particularly those of advanced aged or underlying medical conditions. GBS infection can rapidly develop into life-threatening disease despite prompt administration of effective antibiotics and initiation of state-of-the-art intensive care protocols and technologies due to deleterious bacterial virulence factors, such as the GBS pore-forming toxin ß-hemolysin/cytolysin (ß-H/C). ß-H/C is known to have noxious effects on a wide range of host cells and tissues, including lung epithelial cell injury, blood brain barrier weakening, and immune cell apoptosis. Neonatal and adult survivors of GBS infection are at a high risk for substantial long-term health issues and neurologic disabilities due to perturbations in organ systems caused by bacterial- and host- mediated inflammatory stressors. Previously engineered anti-virulence inhibitors, such as monoclonal antibodies and small molecular inhibitors, generally require customized design for each different pathogenic toxin and do not target deleterious host pro-inflammatory responses that may cause organ injury, septic shock, or death. By simply wrapping donor red blood cells (RBCs) around polymeric cores, we have created biomimetic "nanosponges." Because nanoparticles retain the same repertoire of cell membrane receptors as their host cell, they offer non-specific and all-purpose toxin decoy strategies with a broad ability to sequester and neutralize various bacterial toxins and host pro-inflammatory chemokines and cytokines to attenuate the course of infectious disease. This proof-of-concept study successfully demonstrated that intervention with nanosponges reduced the hemolytic activity of live GBS and stabilized ß-H/C in a dose-dependent manner. Nanosponge treatment also decreased lung epithelial and macrophage cell death following exposure to live GBS bacteria and stabilized ß-H/C, improved neutrophil killing of GBS, and diminished GBS-induced macrophage IL-1ß production. Our results, therefore, suggest biomimetic nanosponges provide a titratable detoxification therapy that may provide a first-in-class treatment option for GBS infection by sequestering and inhibiting ß-H/C activity.

Through Thick and Thin: The In Vitro Effects of Thickeners on Infant Feed Viscosity.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common problem in neonates, and current modalities for thickening human milk produce inconsistent outcomes. The objective of this in vitro study is to measure the viscosity effect of different thickening strategies. METHODS: We thickened donor human milk (DHM) and formula using various thickeners: starch-based thickeners (SBT; Thick It, rice cereal), and gum-based thickeners (GBT; xanthan gum: Simply Thick, Thicken Up Clear; carob gum: GelMix). We also assessed formula with added starches marketed for reflux, including Similac Spit Up (SSU) and Enfamil AR (EAR). The viscosity of each sample was measured over time using a rotary viscometer. Additional variables, including acidity, temperature, and the addition of human milk fortifier, were tested. RESULTS: Formula can be effectively thickened with all tested thickeners, but the viscosities of thickened formula increase over time. On the other hand, DHM does not effectively thicken with SBT. Autoclaving DHM inactivates digestive enzymes, thus allowing SBT to successfully thicken autoclaved DHM. GBT effectively thickened both DHM and formula but reached higher viscosities than intended based on manufacturer recommendations. Adding acid to xanthan-gum thickened DHM resulted in phase separation and formation of solid precipitant. CONCLUSIONS: Current thickening strategies of preterm infant feeding produces highly variable results in final feed viscosity. The unpredictable properties of gum-based thickeners raise questions about their safety profile. Objective measures of liquid viscosity and careful consideration of acidity and time are recommended for adequate comparisons of thickening regimens. Human milk continues to be the most challenging feed type to thicken.