Critical care of severe bronchiolitis during shortage of ICU resources.

Large seasonal outbreaks of bronchiolitis put pressure on healthcare systems and particularly on intensive care units (ICUs). ICU admission is necessary to provide respiratory support to the severest cases, otherwise bronchiolitis can result in substantial mortality. ICU resources are often insufficient and there is scant evidence to guide the ICU clinical management. Most available studies do not cover the ICU-admitted cases and do not consider the associated public health issues. We review this topic through a multidisciplinary approach from both the clinical and public health perspectives, with an analysis based on pathophysiology and cost-effectiveness. We suggest ways to optimise respiratory care, minimise ICU stay, "protect" ICU beds and, whenever possible, make them available for other critically ill children. We also provide guidance on how to prepare ICUs to work under stressful conditions due to outbreaks and to reduce the risk of nosocomial cross-contamination, particularly in ICUs caring for high-risk children. Funding: None.

Nasopharyngeal SARS-CoV-2 load and perinatal outcomes after maternal infection diagnosed close to delivery.

BACKGROUND: The occurrence of COVID-19 during the pregnancy can cause several negative maternal and neonatal outcomes. Nasopharyngeal viral load is associated with inflammatory markers and might influence the disease severity in non-pregnant patients, but there are no data about the relationship between viral load and perinatal outcomes in pregnant patients. OBJECTIVE: To investigate the hypothesis that nasopharyngeal SARS-CoV-2 load (estimated with real-time polymerase chain reaction delta cycle (ΔCt), measured in hospital clinical laboratories) is associated with perinatal outcomes, when COVID-19 is diagnosed in the third trimester of pregnancy. STUDY DESIGN: International, retrospective, observational, multi-center, cohort study enrolling 390 women (393 neonates, three pairs of twins), analyzed with multivariate generalized linear models with skewed distributions (gamma) and identity link. The analyses were conducted for the whole population and then followed by a subgroup analysis according to the clinical severity of maternal COVID-19. RESULTS: The estimated viral load in maternal nasopharynx is not significantly associated with gestational age at birth (adjusted B: -0.008 (95%CI: -0.04; 0.02); p = 0.889), birth weight (adjusted B: 4.29 (95%CI: -25; 35); p = 0.889), weight Z-score (adjusted B: -0.01 (95%CI: -0.03; 1); p = 0.336), 5' Apgar scores (adjusted B: -0. -9.8e-4 (95%CI: -0.01; 0.01); p = 0.889), prematurity (adjusted OR: -0.97 (95%CI: 0.93; 1.03); p = 0.766) and the small for gestational age status (adjusted OR: 1.03 (95%CI: 0.99; 1.07); p = 0.351). Similar results were obtained in subgroup analyses according to COVID-19 clinical severity. CONCLUSIONS: The estimated maternal nasopharyngeal viral load in pregnant women affected by COVID-19 during the third trimester is not associated with main perinatal outcomes.

Continuous Venovenous Hemofiltration Performed by Neonatologists With Cardio-Renal Pediatric Dialysis Emergency Machine to Treat Fluid Overload During Multiple Organ Dysfunction Syndrome: A Case Series.

OBJECTIVES: A new device is available for neonates needing extracorporeal renal replacement therapy. We reviewed the use of this device (in continuous venovenous hemofiltration [CVVH] mode) in term or preterm neonates affected by multiple organ dysfunction syndrome (MODS) with fluid overload. DESIGN: Case series. SETTING: Academic specialized referral neonatal ICU (NICU) with expertise on advanced life support and monitoring. PATIENTS: Neonates with MODS and fluid overload despite conventional treatments and receiving at least one CVVH session. INTERVENTION: CVVH with the Cardio-Renal Pediatric Dialysis Emergency Machine. MEASUREMENTS AND MAIN RESULTS: Ten (three preterm) neonates were treated using 18 consecutive CVVH sessions. All patients were in life-threatening conditions and successfully completed the CVVH treatments, which almost always lasted 24 hr/session, without major side effects. Three neonates survived and were successfully discharged from hospital with normal follow-up. CVVH reduced fluid overload (before versus after represented as a weight percentage: 23.5% [12-34%] vs 14.6% [8.2-24.1%]; p = 0.006) and lactate (before versus after: 4.6 [2.9-12.1] vs 2.9 mmol/L [2.3-5.5 mmol/L]; p = 0.001). CVVH also improved the Pa o2 to Fio2 (before vs after: 188 mm Hg [118-253 mm Hg] vs 240 mm Hg [161-309 mm Hg]; p = 0.003) and oxygenation index (before vs after: 5.9 [3.8-14.6] vs 4 [2.9-11]; p = 0.002). The average cost of CVVH in these patients was minor (≈3%) in comparison with the median total cost of NICU care per patient. CONCLUSIONS: We have provided CVVH to critically ill term and preterm neonates with MODS. CVVH improved fluid overload and oxygenation. The cost of CVVH was minimal compared with the overall cost of neonatal intensive care.

Evolution of Ultrasound-Assessed Lung Aeration and Gas Exchange in Respiratory Distress Syndrome and Transient Tachypnea of the Neonate.

OBJECTIVE: To use clinical, lung ultrasound, and gas exchange data to clarify the evolution of lung aeration and function in neonates with respiratory distress syndrome (RDS) and transient tachypnea of the neonate (TTN), the most common types of neonatal respiratory failure. STUDY DESIGN: In this prospective observational cohort study, lung aeration and function were measured with a semiquantitative lung ultrasound score (LUS) and transcutaneous blood gas measurement performed at 1 hour (time point 0), 6 hours (time point 1), 12 hours (time point 2), 24 hours (time point 3) and 72 hours (time point 4) of life. Endogenous surfactant was estimated using lamellar body count (LBC). LUS, oxygenation index (OI), oxygen saturation index (OSI), and transcutaneous pressure of carbon dioxide (PtcCO2) were the primary outcomes. All results were adjusted for gestational age. RESULTS: Sixty-nine neonates were enrolled in the RDS cohort, and 58 neonates were enrolled in the TTN cohort. LUS improved over time (within-subjects, P < .001) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001). Oxygenation improved over time (within-subjects, P = .011 for OI, P < .001 for OSI) but was worse for the RDS cohort than for the TTN cohort at all time points (between-subjects, P < .001 for OI and OSI). PtcCO2 improved over time (within-subjects, P < .001) and was similar in the RDS and TTN cohorts at all time points. Results were unchanged after adjustment for gestational age. LBC was associated with RDS (ß = -0.2 [95% CI, -0.004 to -0.0001]; P = .037) and LUS (ß = -3 [95% CI, -5.5 to -0.5]; P = .019). CONCLUSIONS: For the first 72 hours of life, the RDS cohort had worse lung aeration and oxygenation compared with the TTN cohort at all time points. CO2 clearance did not differ between the cohorts, whereas both lung aeration and function improved in the first 72 hours of life.

The intracavitary ECG method for tip location of ultrasound-guided centrally inserted central catheter in neonates.

BACKGROUND: The correct position of the tip of a central venous access device is important in all patients, and especially in neonates. The traditional method of tip location (approximated intra-procedural length estimation + post procedural chest X-ray) is currently considered inaccurate and not cost-effective by most recent guidelines, which recommend the adoption of tip location by intracavitary electrocardiography (IC-ECG) whenever possible. METHODS: This study prospectively investigated the applicability, the feasibility, the accuracy, and the safety IC-ECG for tip location in neonates requiring insertion of ultrasound-guided centrally inserted central venous catheters (CICCs) with caliber 3Fr or more. All catheter tip locations were verified using simultaneously both IC-ECG and ultrasound-based tip location, using the Neo-ECHOTIP protocol. RESULTS: A total of 105 neonates were enrolled. The applicability of IC-ECG was 100% since a P wave was evident on the surface ECG of all neonates recruited for the study. The feasibility was also 100% since an increase of the P-wave was detected in all cases. The accuracy was also 100%, since a perfect match between IC-ECG based tip location and ultrasound-based tip location was found. There were no adverse events directly or indirectly related to the IC-ECG technique; no arrhythmias occurred. CONCLUSIONS: When applied to ultrasound guided CICCs, tip location by IC-ECG is applicable and feasible in neonates, and it is safe and accurate.

Rapid Superficial Vein Assessment (RaSuVA): A pre-procedural systematic evaluation of superficial veins to optimize venous catheterization in neonates.

BACKGROUND: Placement of peripheral intra-venous cannulas and epicutaneo-caval catheters is routinely performed in in Neonatal Intensive Care Unit (NICU), and both devices require visible superficial veins easy to cannulate. NICU patients are intrinsically characterized by poor and fragile vein asset, so that puncture and cannulation of superficial veins is often a challenge even for trained clinicians and cannulation frequently results in a stressful, painful, difficult procedure. METHODS AND RESULTS: Rapid Superficial Vein Assessment is meant to offer a systematic pre-procedural evaluation of all superficial veins of the newborn, so to allow a rational choice of the best insertion site, tailored on the single patient, and optimized for the specific type of venous access device. The superficial veins are examined systematically, both with and without NIR technology, exploring seven skin areas in the following order: (1) medial malleolus, (2) lateral malleolus, (3) retro-popliteal fossa, (4) back of the hand and wrist, (5) antecubital fossa, (6) anterior scalp surface, and (7) posterior scalp surface. CONCLUSIONS: The aim of the protocol is to increase the first attempt success rate and reduce the duration of the procedure, the number of attempts for single patient and possibly to limit complications, stress, and pain in neonates.

Use of cyanoacrylate glue for the sutureless securement of epicutaneo-caval catheters in neonates.

INTRODUCTION: Epicutaneo-caval catheters (ECC) are pivotal for drug and fluid infusion in neonates. Given the intrinsic importance of the catheter for the patients' health and the need to avoid stressful and painful procedures on premature or critically ill newborns with fragile and poor vein asset, it is clearly necessary an accurate bundle for ECC insertion and management to avoid complications that may lead to non-elective ECC removal. Among others, dislodgment is an acknowledged complication, and conventionally adopted fixing devices seem alone unsatisfying in relation to ECC securement. OBJECT: To evaluate the usefulness of medical Cyanoacrylate Glue (CG) as a solution to strengthen conventional ECC securement. METHODS: Since the use of CG has become part of our ECC insertion bundle in 2018, the present study compares all term and preterm neonates admitted in our NICU in 2018 who required an ECC for any cause (92 cases) with an historical cohort formed by all neonates who required an ECC in 2017 (80 patients). RESULTS: CG added to usual securement devices is effective in reducing ECC accidental dislodgment. Moreover, it is easy and safe to apply and remove, limits bleeding and oozing at the puncture site, and may also be an effective antimicrobial mechanical barrier.

Securement of central venous catheters by subcutaneously anchored suturless devices in neonates.

BACKGROUND: Accidental dislodgement of central venous catheters is a frequent complication in NICU and it often requires catheter replacement. Subcutaneously anchored sutureless devices (SAS) have been recently introduced in clinical practice for securement of different types of central catheters, but they have never been used in neonates. We evaluated safety and efficacy of SAS in neonates. METHODS: All neonates who required central venous catheters inserted via ultrasound-guided cannulation during 12 months of clinical practice in our NICU. We adopted SAS for securement of all central venous catheters inserted in neonates via ultrasound guided cannulation either of the brachio-cephalic vein (centrally inserted central catheters: CICC) or the femoral vein (femorally inserted central catheters: FICC). Results: seventy-two central catheters were inserted in 70 preterm and term neonates (3-4 Fr power injectable polyurethane catheters; 62 CICC + 10 FICC) and they were all secured with SAS. Mean postmenstrual age at the time of insertion was 31 weeks and mean weight was 1400 g. SAS was easy to place in all cases. The median duration of the line was 6 weeks. No accidental dislodgement of CICC or FICC was recorded. All SAS but one were left in place until elective removal of the catheter. In all patients, SAS removal was easy and uneventful, and it did not require any sedation or local anesthesia. Conclusions: SAS was effective in preventing accidental catheter dislodgement in 100% of cases. Complications during insertion, maintenance and removal were negligible.

Meta-Analysis of Lung Ultrasound Scores for Early Prediction of Bronchopulmonary Dysplasia.

Rationale: Lung ultrasound scores (LUS) might be useful in monitoring neonates with chronic pulmonary insufficiency of prematurity and in predicting bronchopulmonary dysplasia (BPD). Given their ease of use, accuracy, and lack of invasiveness, LUS have been the subject of several recent studies. Objectives: We sought to clarify whether LUS provide an accurate and early (within the first 2 wk of life) prediction of BPD in preterm infants of gestational age ⩽32 weeks. Methods: This was a systematic review and diagnostic accuracy meta-analysis following PRISMA-P (Preferred Reporting Items for Systematic review and Meta-Analysis Protocols), PRISMA (Preferred Reporting Items for Systematic review and Meta-Analysis), and QUADAS (QUAlity of Diagnostic Accuracy Studies) guidelines. Studies designed to predict BPD in the first 2 weeks of life using LUS were selected. A classical LUS (calculated for 6 chest areas) and its extended version (eLUS, 10 chest areas) were tested. Results: Seven studies (1,027 neonates) were meta-analyzed. LUS and eLUS showed good diagnostic accuracy in predicting BPD at 7 and 14 days of life (area under the curve, 0.85-0.87; pooled sensitivity, 70-80%; pooled specificity, 80-87%). The diagnostic accuracy of LUS and eLUS did not differ at any time point (area under the curve difference always P > 0.05). Repeating the analyses without outliers or with moderate to severe BPD as the outcome yielded similar results. Meta-regressions showed that prenatal steroid prophylaxis and sex were not significant effect confounders. Conclusions: LUS are accurate for early prediction of BPD and moderate to severe BPD, in an average population of preterm infants ⩽32 weeks' gestation. The diagnostic accuracy is similar for LUS and eLUS, so the use of the simpler score should be advocated. Registration: PROSPERO CRD42021233010.

Noninvasive Ventilation in a Pediatric Trauma Center: A Cohort Study.

OBJECTIVE: To determine whether non-invasive ventilation (NIV) can avoid the need for tracheal intubation and/or reduce the duration of invasive ventilation (IMV) in previously intubated patients admitted to the pediatric intensive care unit (PICU) and developing acute hypoxemic respiratory failure (AHRF) after major traumatic injury. STUDY DESIGN: A single center observational cohort study. SETTING: Pediatric ICU in a University Hospital (tertiary referral Pediatric Trauma Centre). POPULATION: During the 48-month study period, 276 patients (median age 6.4 years) with trauma were admitted to PICU; among 86 of them, who suffered from AHRF and received ventilation (IMV and/or NIV) for more than 12 hrs, 32 patients (median age 8.5 years) were treated with NIV. INCLUSION/EXCLUSION CRITERIA: Inclusion criteria: at least 12 hours of NIV; exclusion criteria: patients with facial trauma or congenital malformations; patients receiving IMV <12 hours or perioperative ventilation. MEASUREMENTS AND RESULTS: Among NIV patients, 27 (84,3%) were previously on IMV, while 5 (15,6%) could be managed exclusively with NIV. In patients with post-extubation respiratory distress, NIV was successful in 88.4% of cases. Before starting NIV, P/F ratio was 242.7 ± 71. After 8 hours of NIV treatment, a significant oxygenation improvement (PaO2/FiO2 = 354.3 ± 81; p = 0.0002) was found, with no significant changes in carbon dioxide levels. A trend toward increasing ventilation-free time has been evidenced; NIV resulted feasible and generally well tolerated. CONCLUSIONS: AHRF in trauma patients is multifactorial and may be due to many reasons, such as lung contusion, aspiration of blood or gastric contents. Systemic inflammatory response and transfusions may also contribute to hypoxia. Our pilot study strongly suggests that NIV can be applied in post-traumatic AHRF: it may successfully reduce the time of both invasive ventilation and deep sedation. Further data from controlled studies are needed to assess the advantage of NIV in pediatric trauma.

Neonatal Life-Threatening Nonoliguric Hyperkalemia Under Therapeutic Hypothermia.

To illustrate our experience with two cases of neonatal life-threatening hyperkalemia during therapeutic hypothermia (TH) despite a normal acid-base status, urine output, and preserved renal function. Clinical cases are presented from Pediatric Intensive Care Unit (PICU) admission to the onset of the hyperkalemia, with related complications and after resolution. Similar cases were not retrieved from a critical review of pertinent literature. Severe hyperkalemia pathophysiology and risk factors have been debated. Two full-term adequate for weight female neonates were admitted to PICU because of perinatal asphyxia who underwent TH. Prenatal history was completely uneventful, nor hereditary genetic conditions were reported; moreover, long-term follow-up ruled out any metabolic or renal disease. Despite an accurate evaluation of previous clinical series and literature on TH and perinatal asphyxia, these hyperkalemic episodes remain unexplained. The hypoxic-ischemic insult may affect multiple organs, mainly central nervous system, heart, lung, and kidneys; acute muscle breakdown and consequent rising of myoglobin may also have a precipitating role in acute kidney failure (AKF) and hyperkalemia. Electrolyte imbalance is a possible finding as a consequence of combined cell injury and AKF. In contrast, an isolated severe hyperkalemia is exceedingly rare in nonoliguric neonates.

Personalized Medicine for the Management of RDS in Preterm Neonates.

Continuous positive airway pressure and surfactant represent the first- and second-line treatment for respiratory distress syndrome in preterm neonates, as European and American guidelines, since 2013 and 2014, respectively, started to recommend surfactant replacement only when continuous positive airway pressure fails. These recommendations, however, are not personalized to the individual physiopathology. Simple clinical algorithms may have improved the diffusion of neonatal care, but complex medical issues can hardly be addressed with simple solutions. The treatment of respiratory distress syndrome is a complex matter and can be only optimized with personalization. We performed a review of tools to individualize the management of respiratory distress syndrome based on physiopathology and actual patients' need, according to precision medicine principles. Advanced oxygenation metrics, lung ultrasound, electrical impedance tomography, and both quantitative and qualitative surfactant assays were examined. When these techniques were investigated with diagnostic accuracy studies, reliability measures have been meta-analysed. Amongst all these tools, quantitative lung ultrasound seems the more developed for the widespread use and has a higher diagnostic accuracy (meta-analytical AUC = 0.952 [95% CI: 0.951-0.953]). Surfactant adsorption (AUC = 0.840 [95% CI: 0.824-0.856]) and stable microbubble test (AUC = 0.800 [95% CI: 0.788-0.812]) also have good reliability, but need further industrial development. We advocate for a more accurate characterization and a personalized approach of respiratory distress syndrome. With the above-described currently available tools, it should be possible to personalize the treatment of respiratory distress syndrome according to physiopathol-ogy.

Umbilical Venous Catheter Update: A Narrative Review Including Ultrasound and Training.

The umbilical venous catheter (UVC) is one of the most commonly used central lines in neonates. It can be easily inserted soon after birth providing stable intravenous access in infants requiring advanced resuscitation in the delivery room or needing medications, fluids, and parenteral nutrition during the 1st days of life. Resident training is crucial for UVC placement. The use of simulators allows trainees to gain practical experience and confidence in performing the procedure without risks for patients. UVCs are easy to insert, however when the procedure is performed without the use of ultrasound, there is a quite high risk, up to 40%, of non-central position. Ultrasound-guided UVC tip location is a simple and learnable technique and therefore should be widespread among all physicians. The feasibility of targeted training on the use of point-of-care ultrasound (POCUS) for UVC placement in the neonatal intensive care unit (NICU) among neonatal medical staff has been demonstrated. Conversely, UVC-related complications are very common and can sometimes be life-threatening. Despite UVCs being used by neonatologists for over 60 years, there are still no standard guidelines for assessment or monitoring of tip location, securement, management, or dwell time. This review article is an overview of the current knowledge and evidence available in the literature about UVCs. Our aim is to provide precise and updated recommendations on the use of this central line.

Extrapulmonary Surfactant Therapy: Review of Available Data and Research/Development Issues.

Since the discovery of surfactant, a large amount of knowledge has been accumulated about its biology and pharmacology. Surfactant is the cornerstone of neonatal respiratory critical care, but its proteins and phospholipids are produced in various tissues and organs, with possible roles only partially similar to that played in the alveoli. As surfactant research is focused mainly on its respiratory applications, knowledge about the possible role of surfactant in extrapulmonary disorders has never been summarized. Here we aim to comprehensively review the data about surfactant biology and pharmacology in organs other than the lung, especially focusing in the more promising surfactant extrapulmonary roles. We also review any preclinical or clinical data available about the therapeutic use of surfactant in these contexts. We offer a summary of knowledge and research/development milestones, as possible useful guidance for researchers of multidisciplinary background.

Subcutaneously Anchored Sutureless Device for Securement of Chest Tubes in Neonates with Pleural Effusion: Three Case Reports.

We report the clinical cases of three neonates, all of them premature, requiring the placement of a chest tube for drainage of a massive pleural effusion. In all three patients, the chest tube was secured using a new subcutaneously anchored sutureless system. This new securement device was easy to insert and to remove, and highly effective in preventing dislodgment. Also, it was not associated to any undesired effect: no sign of pain and/or discomfort and no skin inflammation. The securement device proved to be comfortable and harmless even in fragile patients as neonates, including the frailest ones, the premature. To our best knowledge, this is the first report describing the use of such a device for this purpose.

Gut and Lung Microbiota in Preterm Infants: Immunological Modulation and Implication in Neonatal Outcomes.

In recent years, an aberrant gastrointestinal colonization has been found to be associated with an higher risk for postnatal sepsis, necrotizing enterocolitis (NEC) and growth impairment in preterm infants. As a consequence, the reasons of intestinal dysbiosis in this population of newborns have increasingly become an object of interest. The presence of a link between the gut and lung microbiome's development (gut-lung axis) is emerging, and more data show as a gut-brain cross talking mediated by an inflammatory milieu, may affect the immunity system and influence neonatal outcomes. A revision of the studies which examined gut and lung microbiota in preterm infants and a qualitative analysis of data about characteristic patterns and related outcomes in terms of risk of growing impairment, Necrotizing Enterocolitis (NEC), Bronchopulmonary Dysplasia (BPD), and sepsis have been performed. Microbiota take part in the establishment of the gut barrier and many data suggest its immune-modulator role. Furthermore, the development of the gut and lung microbiome (gut-lung axis) appear to be connected and able to lead to abnormal inflammatory responses which have a key role in the pathogenesis of BPD. Dysbiosis and the gut predominance of facultative anaerobes appear to be crucial to the pathogenesis and subsequently to the prevention of such diseases.