Surfactant Instillation Research Articles

Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) – Part II: In vivo Efficacy Testing in a Rabbit Surfactant Washout Model

PurposeSurfactant therapy incorporates liquid bolus instillation via endotracheal tube catheter and a mechanical ventilator in preterm neonates with respiratory distress syndrome (RDS). Aerosolized surfactants have generated interest and conflicting data on the efficacy of phospholipid (PL) dose requirements. We developed and characterized a synthetic lung surfactant excipient enhanced growth (SLS-EEG) dry powder aerosol product. In this study, we compare the in vivo performance of the new aerosol product with standard-of-care liquid instillation.MethodsJuvenile rabbits were sedated, anesthetized, intubated, and ventilated. Endogenous surfactant was depleted via whole lung lavage. Animals received either a standard dose of liquid Curosurf (200 mg PL/kg) instilled via a tracheal catheter, SLS-EEG powder aerosol (60 mg device loaded dose; equivalent to 24 mg PL/kg), or sham control. Gas exchange, lung compliance, and indices of disease severity were recorded every 30 min for 3.5 h and macro- and microscopy images were acquired at necropsy.ResultsWhile aerosol was administered at an approximately tenfold lower PL dose, both liquid-instilled and aerosol groups had similar, nearly complete recoveries of arterial oxygenation (PaO2; 96–100% recovery) and oxygenation index, and the aerosol group had superior recovery of compliance (P < 0.05). The SLS-EEG aerosol group showed less lung tissue injury, greater uniformity in lung aeration, and more homogenous surfactant distribution at the alveolar surfaces compared with liquid Curosurf.ConclusionsThe new dry powder aerosol SLS product (which includes the delivery strategy, formulation, and delivery system) has the potential to be a safe, effective, and economical alternative to the current clinical standard of liquid bolus surfactant instillation.

Heated and humidified high flow therapy (HHHFT) in extreme and very preterm neonates with respiratory distress syndrome (RDS): a retrospective cohort from a tertiary care setting in Pakistan

ObjectiveTo determine the role of heated humidified high flow therapy (HHHFT) as primary respiratory support in spontaneously breathing moderate-late, very and extreme preterm neonates with respiratory distress syndrome (RDS) at...

A multicentre neonatal interventional randomised controlled trial of nebulized surfactant for preterm infants with respiratory distress: Neo-INSPIRe trial protocol

IntroductionRespiratory distress syndrome in preterm infants is an important cause of morbidity and mortality. Less invasive methods of surfactant administration, along with the use of continuous positive airway pressure (CPAP), have improved outcomes of preterm infants. Aerosolized surfactant can be given without the need for airway instrumentation and may be employed in areas where these skills are scarce. Recent trials from high-resourced countries utilising aerosolized surfactant have had a low quality of evidence and varying outcomes.Methods and analysisThe Neo-INSPIRe trial is an unblinded, multicentre, randomised trial of a novel aerosolized surfactant drug/device combination. Inclusion criteria include preterm infants of 27–34+6 weeks’ gestational age who weigh 900-1999g and who require CPAP with a fraction of inspired oxygen (FiO2) of 0.25–0.35 in the first 2–24 h of age. Infants are randomised 1:1 to control (CPAP alone) or intervention (CPAP with aerosolized surfactant). The primary outcome is the need for intratracheal bolus surfactant instillation within 72 h of age. Secondary outcomes include the incidence of reaching failure criteria (persistent FiO2 of > 0.40, severe apnoea or severe work of breathing), the need for and duration of ventilation and respiratory support, bronchopulmonary dysplasia and selected co-morbidities of prematurity. Assuming a 40% relative risk reduction to reduce the proportion of infants requiring intratracheal bolus surfactant from 45 to 27%, the study will aim to enrol 232 infants for the study to have a power of 80% to detect a significant difference with a type 1 error of 0.05.Ethics and disseminationEthical approval has been granted by the relevant human research ethics committees at University of Cape Town (HREC 681/2022), University of the Witwatersrand HREC (221112) and Stellenbosch University (M23/02/004).Trial registrationPACTR202307490670785

Surfactant delivery strategies to prevent bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is one of the most devastating morbidities of preterm infants. Antenatal factors like growth restriction and inflammation are risk factors for its development. Use of oxygen and positive pressure ventilation, which are often necessary to treat respiratory distress syndrome (RDS), increase the risk for development of BPD. Continuous positive airway pressure (CPAP) as primary respiratory support allows for avoidance of positive pressure ventilation in many cases but may lead to a delay of surfactant administration which is a proven therapy for RDS. Several alternative surfactant delivery strategies, including nebulization of surfactant, pharyngeal instillation of surfactant, delivery of surfactant via supraglottic airway device or surfactant delivery via a thin endotracheal catheter have been described which allow for the benefit of surfactant therapy while on CPAP. This review reports available data and discusses the existing evidence of their value in preventing BPD as well as further research directions.

The Role of Bronchoscopy in the Management of Children With Cystic Fibrosis.

Currently, no consensus guidelines recommend routine bronchoscopy procedure in cystic fibrosis (CF), as no evidence is available concerning its use as either a diagnostic or therapeutic tool. Its efficacy is controversial, and no randomized controlled prospective trials are available to check its effectiveness. The aims of the present study were to evaluate the effectiveness of bronchoscopy as a diagnostic/therapeutic tool in CF children and adolescents; and to verify the effect of serial bronchoscopy on lung disease progression in subjects with CF not responding to a single procedure. Data of patients who received bronchoscopy at 2 Italian CF centers were collected. Bronchoalveolar lavage was performed during the procedure including airway clearance with mucolytics, inhaled antibiotics, and/or surfactant instillation. A total of 16 patients in center 1 and 17 in center 2 underwent, respectively, 28 and 23 bronchoscopic procedure in the study period. Five patients in each center underwent >1 procedure. All procedures were generally well tolerated. No patient required admission to the pediatric intensive therapy unit. In 19.6% of bronchoalveolar lavages, growth of Aspergillus fumigatus was evident, although not detected by sputum analyses. After the procedure, an increase in mean percent predicted forced expiratory volume in the 1 second >10% was observed, and a significant decrease in pulmonary exacerbations yearly was evident. Based on the results, we suggest bronchoscopy is not to be considered an obsolete tool, and it remains useful in CF management, although in selected cases. We encourage to support longitudinal observational studies to standardize the procedure, focusing on the choice of drugs to be instilled, modalities and timing of serial bronchoscopy and subsequent follow-up in selected severe clinical conditions.

Exogenous surfactant reduces inflammation and redox imbalance in rats under prone or supine mechanical ventilation.

Mechanical ventilation (MV) is a lifesaving therapy for patients with acute or chronic respiratory failure. Despite, it can also cause lung injury by inducing or worsening inflammatory responses and oxidative stress. Several clinical approaches have protective effects on the lungs, including the prone position and exogenous surfactant; however, few studies have evaluated the association between the two strategies, especially in individuals without previous lung injury. We tested the hypothesis that the effects of the homogenization in lung aeration caused by the prone position in association with the anti-inflammatory properties of exogenous surfactant pre-treatment could have a cumulative protective effect against ventilator-induced lung injury. Therefore, Wistar rats were divided into four experimental groups: Mechanical Ventilation in Supine Position (MVSP), Mechanical Ventilation in Prone position (MVPP), Mechanical Ventilation in Supine Position + surfactant (MVSPS), and Mechanical Ventilation in Prone Position + Surfactant (MVPPS). The intranasal instillation of a porcine surfactant (Curosurf®) was performed in the animals of MVSPS and MVPPS 1 h before the MV, all the rats were subjected to MV for 1 h. The prone position in association with surfactant decreased mRNA expression levels of pro-inflammatory cytokines in ventilated animals compared to the supine position; in addition, the NfκB was lower in MVPP, MVSPS and MVPPS when compared to MVSP. However, it had no effects on oxidative stress caused by MV. Pre-treatment with exogenous surfactant was more efficient in promoting lung protection than the prone position, as it also reduced oxidative damage in the lung parenchyma. Nevertheless, the surfactant did not cause additional improvements in most parameters that were also improved by the prone position. Our results indicate that the pre-treatment with exogenous surfactant, regardless of the position adopted in mechanical ventilation, preserves the original lung histoarchitecture, reduces redox imbalance, and reduces acute inflammatory responses caused by mechanical ventilation in healthy adult Wistar rats.

Changes in respiratory management and the impact on bronchopulmonary dysplasia.

Noninvasive respiratory support has reduced the need for mechanical ventilation and surfactant administration in very premature neonates. We sought to determine how the increased use of noninvasive ventilation and less surfactant instillation has impacted the development of bronchopulmonary dysplasia (BPD) using four currently used BPD definitions. This is a retrospective, single-center cohort study of neonates born at less than 28 weeks gestation between 2010 and 2018. A respiratory practice change (less surfactant and more noninvasive ventilation) occurred in 2014 following participation in the Surfactant Positive Airway Pressure and Pulse Oximetry trial. Therefore, patients were divided into two epochs to compare postnatal respiratory and clinical course and BPD outcomes across four currently relevant definitions (Vermont Oxford Network, National Institute of Child Health and Human Development, Canadian, andNeonatal Research Network). Clinical and demographic variables were similar between epochs. Despite significant differences in maternal and infant characteristics and clinical course, the incidence of BPD was not significantly different between the twoepochs regardless of the BPD definition utilized. There was a wide range in the incidence of BPD depending on the definition used. Despite decreased use of surfactant administration and invasive mechanical ventilation between the two epochs, the incidence of BPD did not change and there was wide variation depending on the definition used. A better understanding of the risk factors associated with BPD and a consensus definition is urgently needed to: 1) more accurately compare various studies, 2) help facilitate the conduct of clinical trials, and 3) enhance the development of novel therapeutic interventions to improve outcome.

Aerosol Delivery of Lung Surfactant and Nasal CPAP in the Treatment of Neonatal Respiratory Distress Syndrome.

After shifting away from invasive mechanical ventilation and intratracheal instillation of surfactant toward non-invasive ventilation with nasal CPAP and less invasive surfactant administration in order to prevent bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome, fully non-invasive surfactant nebulization is the next Holy Grail in neonatology. Here we review the characteristics of animal-derived (clinical) and new advanced synthetic lung surfactants and improvements in nebulization technology required to secure optimal lung deposition and effectivity of non-invasive lung surfactant administration. Studies in surfactant-deficient animals and preterm infants have demonstrated the safety and potential of non-invasive surfactant administration, but also provide new directions for the development of synthetic lung surfactant destined for aerosol delivery, implementation of breath-actuated nebulization and optimization of nasal CPAP, nebulizer circuit and nasal interface. Surfactant nebulization may offer a truly non-invasive option for surfactant delivery to preterm infants in the near future.

Preclinical Assessment of Nebulized Surfactant Delivered through Neonatal High Flow Nasal Cannula Respiratory Support.

High-flow nasal cannula (HFNC) is a non-invasive respiratory support (NRS) modality to treat premature infants with respiratory distress syndrome (RDS). The delivery of nebulized surfactant during NRS would represent a truly non-invasive method of surfactant administration and could reduce NRS failure rates. However, the delivery efficiency of nebulized surfactant during HFNC has not been evaluated in vitro or in animal models of respiratory distress. We, therefore, performed first a benchmark study to compare the surfactant lung dose delivered by commercially available neonatal nasal cannulas (NCs) and HFNC circuits commonly used in neonatal intensive care units. Then, the pulmonary effect of nebulized surfactant delivered via HFNC was investigated in spontaneously breathing rabbits with induced respiratory distress. The benchmark study revealed the surfactant lung dose to be relatively low for both types of NCs tested (Westmed NCs 0.5 ± 0.45%; Fisher & Paykel NCs 1.8 ± 1.9% of a nominal dose of 200 mg/kg of Poractant alfa). The modest lung doses achieved in the benchmark study are compatible with the lack of the effect of nebulized surfactant in vivo (400 mg/kg), where arterial oxygenation and lung mechanics did not improve and were significantly worse than the intratracheal instillation of surfactant. The results from the present study indicate a relatively low lung surfactant dose and negligible effect on pulmonary function in terms of arterial oxygenation and lung mechanics. This negligible effect can, for the greater part, be explained by the high impaction of aerosol particles in the ventilation circuit and upper airways due to the high air flows used during HFNC.

The exogenous surfactant pre-treatment attenuates ventilator-induced lung injury in adult rats

Mechanical ventilation is an essential supportive therapy in the treatment of critical patients, and it aims to maintain adequate gas exchange; however, it can also contribute to inflammation and oxidative stress, thus leading to lung injury. We tested the hypothesis that exogenous surfactant administration will be protective against ventilator-induced lung injury in adult healthy Wistar rats both because of its anti-inflammatory properties as well as its role in preventing alveolar collapse at end-expiration. Thus, the effect of intranasal instillation of a bovine exogenous surfactant was tested in Wistar rats submitted to mechanical ventilation. The animals were divided into four groups: (1) CONTROL; (2) SURFACTANT; (3) Mechanical ventilation (MV); (4) MV with pre-treatment with surfactant (MVSURFACTANT). The MV and MVSURFACTANT were submitted to MV with high tidal volume (12 mL/kg) for 1 h. After the experimental protocol, all animals were euthanized and the arterial blood, bronchoalveolar lavage fluid and lungs were collected for biochemical, immunoenzymatic assay, arterial blood gases, and morphometric analyzes. The Wistar rats that received exogenous surfactant (Survanta®) by intranasal instillation before MV demonstrated reduced levels of leukocytes, inflammatory biomarkers such as CCL2, IL-1, IL-6 and TNF-α. Furthermore, it prevented oxidative damage by reducing lipid peroxidation and protein carbonylation as well as histological pattern changes of pulmonary parenchyma. Our data indicate that exogenous surfactant attenuated lung inflammation and redox imbalance induced by mechanical ventilation in healthy adult rats suggesting a preventive effect on ventilator-induced lung injury.

A systematic review and meta-analysis of pulmonary surfactant combined with budesonide in the treatment of neonatal respiratory distress syndrome.

Neonatal respiratory distress syndrome (NRDS), if caused by a lack of pulmonary surfactant (PS), leads to progressive alveolar collapse. Glucocorticoids have anti-inflammatory and anti-allergic effects and can reduce bronchial and pulmonary edema. This research hopes to systematically evaluate the efficacy and safety of animal-derived PS combined with the glucocorticoid drug budesonide in the treatment of NRDS. Electronic databases (i.e., Wanfang, Weipu, CNKI, PubMed, Embase, Cochrane Library) were searched from inception until May 30th, 2021. Studies relevant to the treatment of pulmonary surfactant combined with budesonide in the treatment of neonatal respiratory distress syndrome were identified. Consequently, all the studies that met the inclusion criteria were considered qualified for screening. For the meta-analysis, all data were analyzed using RevMan 5.3 software. Furthermore, subgroup analysis was performed to evaluate the administration method of budesonide (nebulized inhalation, intratracheal instillation) combined with intratracheal instillation of pulmonary surfactant. A total of 10 articles were included in this study, involving 527 children. This meta-analysis suggests that the treatment of intratracheal infusion of pulmonary surfactant combined with budesonide therapy can effectively (I) reduce the time of mechanical ventilation (OR =-1.72,95% CI: -2.44 to -1.01, P<0.00001); (II) reduce the length of stay (OR =-5.17, 95% CI: -9.35 to -0.99, P=0.02); (III) reduce the incidence of bronchopulmonary dysplasia (BPD) (OR =0.52, 95% CI: 0.39-0.68, P<0.00001); and (IV) reduce the incidence of BPD (RR =0.73, 95% CI: 0.40-1.35, P=0.32). There was no significant difference in the incidence of retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), patent ductus arteriosus (PDA), or sepsis between the experimental group and the control group. The treatment of animal-derived pulmonary surfactant combined with budesonide can effectively shorten the hospital stay and reduce the time of invasive mechanical ventilation and the incidence of BPD. Meanwhile, it does not increase the risk of related complications or death. This approach can be applied clinically.

SAVING AND EARLY DICHARGE OF A NEONATE WITH SEVERE MECONIUM ASPIRATION SYNDROME

Animal experiments have shown the resolution of radiological infiltrates of meconium aspiration syndrome (MAS) after using surfactant lavage. Intra-tracheal instillation of surfactant, as well as surfactant lavage, is studied in MAS. However, INSURE (INtubation, administration of SURfactant, Extubation) is never reported to have been used for meconium aspiration syndrome although it is used as the standard method of delivery of surfactant for respiratory distress syndrome. This is a case report of the use of INSURE technique for severe Meconium Aspiration syndrome. The baby was born at term gestational age to a primigravida mother by C-section for fetal distress. The baby was vigorous with chest retractions. Hence baby was supported with delivery room Continuous positive airway pressure (CPAP) and shifted to Neonatal Intensive Care Unit (NICU). In NICU, the baby was stabilized and given surfactant using the INSURE technique. Subsequently, a Chest X-ray showed clearing of lung infiltrates and drastically reduced oxygen requirement of the baby and the baby was discharged early to home.

The Effect of Continuous PEEP Administration during Surfactant Instillation on Cerebral Hemodynamics in Intubated Preterm Infants: A NIRS Study.

There is an ongoing debate about the best and comfortable way to administer surfactant. We hypothesized that uninterrupted respiratory support and continuous PEEP implementation while instilling surfactant via endotracheal tube (ETT) with side port will result in higher regional cerebral tissue oxygenation (rcSO2) and the alterations in cerebral hemodynamics will be minimal. Preterm infants who required intubation in the delivery room and/or in the first 24 hours of life with gestational age <32 were enrolled. Patients were intubated either via conventional ETT or ETT with side port (Vygon) with appropriate sizes. Following neonatal intensive care unit admission a near-infrared spectroscopy (NIRS) probe was placed on the forehead and each infant was started to be monitored with NIRS. In conventional ETT group, patients separated from the ventilator while surfactant was instilled. In ETT with side port group, respiratory support was not interrupted during instillation. Heart rate, oxygen saturation, rcSO2, cerebral fractional tissue oxygen extraction (cFTOE), and blood pressures were recorded. A total of 46 infants were analyzed. Surfactant was instilled with conventional ETT in 23 and ETT with side port in 23 infants. Birth weights (1,037 ± 238 vs. 1,152 ± 277 g) and gestational ages (28 ± 2.3 vs. 29 ± 1.6 weeks) did not differ between groups. During instillation of surfactant, rcSO2 levels [61.5 (49-90) vs. 70 (48-85)] and cFTOE levels 0.28 (0.10-0.44) vs. 0.23 (0.03-0.44)] were similar (p = 0.58 and 0.82, respectively). Interruption of respiratory support during surfactant instillation did not significantly alter the cerebral tissue oxygenation. These results did not support our hypothesis and should be confirmed with further studies. · Monitoring intracerebral oxygenation changes during surfactant administration with NIRS is feasible.. · The surfactant administration method does not significantly alter the cerebral oxygenation.. · Surfactant administration itself rather than the method caused a transient drop in cerebral NIRS readings..

Is Less Invasive Surfactant Administration a Beneficial Method for Late Preterm Infants?

Late preterm infants (LPIs) have increased steadily in all newborns delivery and they are the largest patient group requiring admission to the neonatal intensive care unit. Surfactant treatment is frequently used in LPIs in case of respiratory distress, but the procedure and the timing of surfactant administration are not well-known. We aimed to evaluate the effect of surfactant administration techniques on pulmonary outcomes in LPIs with respiratory distress. In this retrospective study, we compared the effects of the less invasive surfactant administration (LISA) technique and conventional treatment on respiratory and other morbidities in LPIs who have respiratory difficulties. We named these two groups as the LISA group and the conventional group (CG). Comparison of the mechanical ventilation (MV) rates between the groups was the primary outcome of our study. There were 25 LPIs in each group. The duration of nasal continuous positive airway pressure (CPAP) and oxygenation were similar in both groups. The rate of MV and the duration of MV (P=0.004 and P=0.02) were lower in the LISA group. Also, the need for more than 1 dose of surfactant was higher in the MV requiring group, although it was not statistically significant between the groups (P=0.21). Using the LISA technique for surfactant instillation reduces any MV requirement. LISA is a very useful and reliable technique in experienced hands in LPIs as in very preterm infants.

Physiologic Effects of Instilled and Aerosolized Surfactant Using a Breath-Synchronized Nebulizer on Surfactant-Deficient Rabbits.

Surfactant administration incorporates liquid bolus instillation via endotracheal tube catheter and use of a mechanical ventilator. Aerosolized surfactant has generated interest and conflicting data related to dose requirements and efficacy. We hypothesized that aerosolized surfactant with a novel breath-actuated vibrating mesh nebulizer would have similar efficacy and safety as instilled surfactant. Juvenile rabbits (1.50 ± 0.20 kg, n = 17) were sedated, anesthetized, intubated, and surfactant was depleted via lung lavage on mechanical ventilation. Subjects were randomized to receive standard dose liquid instillation via catheter (n = 5); low dose surfactant (n = 5) and standard dose surfactant (n = 5) via aerosol; and descriptive controls (no treatment, n = 2). Peridosing events, disease severity and gas exchange, were recorded every 30 min for 3 h following surfactant administration. Direct-Instillation group had higher incidence for peridosing events than aerosol. Standard dose liquid and aerosol groups had greater PaO2 from pre-treatment baseline following surfactant (p < 0.05) with greater ventilation efficiency with aerosol (p < 0.05). Our study showed similar improvement in oxygenation response with greater ventilation efficiency with aerosol than liquid bolus administration at the same dose with fewer peridosing events. Breath-synchronized aerosol via nebulizer has potential as a safe, effective, and economical alternative to bolus liquid surfactant instillation.

Minimal invasive surfactant therapy in preterm infants with respiratory distress syndrome: a single-center experience.

Minimal invasive surfactant therapy (MIST) includes the tracheal instillation of surfactant via a thin catheter for the treatment of preterm infants with respiratory distress syndrome (RDS). We aimed to evaluate the impact of MIST compared to intubation, surfactant, extubation (INSURE) technique on respiratory outcomes. A prospectively recruited cohort of preterm infants ≤32 weeks with RDS was compared against a historical cohort of infants treated with INSURE. The primary outcome was the need for mechanical ventilation within 72 hours of age and secondary outcomes the overall need and duration of mechanical ventilation, the development of bronchopulmonary dysplasia, common morbidities, and survival. Thirty-six infants treated with MIST of 29.1±2.2 weeks' gestation and 1219±238 g birthweight compared against 37 infants of 28.8±2.3 weeks' gestation and 1195±336 g birthweight treated with INSURE. A lower proportion of infants treated with MIST required mechanical ventilation within 72 hours of age compared to those treated with INSURE (11% compared 32%, P=0.042). However, no significant differences were noted regarding the overall intubation incidence, bronchopulmonary dysplasia, other morbidities, or survival. In spontaneously breathing infants ≤32 weeks with RDS, the MIST technique was associated with a lower need for intubation within 72 hours of age, but otherwise with no significant differences regarding BPD or other neonatal morbidities.

Proposal of selective wedge instillation of pulmonary surfactant for COVID-19 pneumonia based on computational fluid dynamics simulation

BackgroundThe most important target cell of SARS-CoV-2 is Type II pneumocyte which produces and secretes pulmonary surfactant (PS) that prevents alveolar collapse. PS instillation therapy is dramatically effective for infant respiratory distress syndrome but has been clinically ineffective for ARDS. Nowadays, ARDS is regarded as non-cardiogenic pulmonary edema with vascular hyper-permeability regardless of direct relation to PS dysfunction. However, there is a possibility that this ineffectiveness of PS instillation for ARDS is caused by insufficient delivery. Then, we performed PS instillation simulation with realistic human airway models by the use of computational fluid dynamics, and investigated how instilled PS would move in the liquid layer covering the airway wall and reach to alveolar regions.MethodsTwo types of 3D human airway models were prepared: one was from the trachea to the lobular bronchi and the other was from a subsegmental bronchus to respiratory bronchioles. The thickness of the liquid layer covering the airway was assigned as 14 % of the inner radius of the airway segment. The liquid layer was assumed to be replaced by an instilled PS. The flow rate of the instilled PS was assigned a constant value, which was determined by the total amount and instillation time in clinical use. The PS concentration of the liquid layer during instillation was computed by solving the advective-diffusion equation.ResultsThe driving pressure from the trachea to respiratory bronchioles was calculated at 317 cmH2O, which is about 20 times of a standard value in conventional PS instillation method where the driving pressure was given by difference between inspiratory and end-expiratory pressures of a ventilator. It means that almost all PS does not reach the alveolar regions but moves to and fro within the airway according to the change in ventilator pressure. The driving pressure from subsegmental bronchus was calculated at 273 cm H2O, that is clinically possible by wedge instillation under bronchoscopic observation.ConclusionsThe simulation study has revealed that selective wedge instillation under bronchoscopic observation should be tried for COVID-19 pneumonia before the onset of ARDS. It will be also useful for preventing secondary lung fibrosis.

A single-center observational study on clinical features and outcomes of 21 SARS-CoV-2-infected neonates from India.

Coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an ongoing pandemic with significant morbidity and mortality. Neonates represent a vulnerable population, in which we have limited knowledge of its natural history, optimal management, and outcomes. In this retrospective observational study from a low-middle-income setting, clinical characteristics and outcomes of neonatal SARS-CoV-2 infection were evaluated. We report an incidence of 10.6% of SARS-CoV-2 infection (21 neonates), among a group of 198 neonates with suspected infection. Most of the SARS-CoV-2-infected neonates were term (80.9%) and none required any resuscitation. The infection was detected by a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV-2. Neonatal COVID-19 manifestations developed in one-third (33.3%) of the infected neonates. Most of them demonstrated the involvement of respiratory (33.3%) and gastrointestinal systems (4.8%). Laboratory parameters suggested multi-systemic involvement, with elevated creatine kinase (CK) (76.2%), creatine kinase-myocardial band (CK-MB) (76.2%), and lactate dehydrogenase (LDH) (71.4%) levels. Supportive treatment was given to infected neonates with intensive care required in six neonates (28.6%). This included four preterm and two term neonates, of which two received non-invasive and one received invasive ventilation with intra-tracheal surfactant instillation. IgM antibodies against COVID-19 were detected in one neonate. All neonates with COVID-19 improved and were successfully discharged.Conclusion: SARS-CoV-2 in neonates has a wide clinical spectrum. Further studies are needed which are adequately powered to completely understand the course of this infection in neonates, its implications not only in the neonatal period but also on long-term follow-up.What is Known:• SARS-CoV-2 infection has a predilection for all age groups but with limited literature on clinical profile, outcomes, and long-term follow-up in neonates.What is New:• SARS-CoV-2 infection in neonates has a wide clinical spectrum and displays a significant overlap with common neonatal conditions.• Most neonates with COVID-19 improved with supportive care, though a subset required intensive care, emphasizing the need for cautious monitoring and management.

Abdominal Neuroblastoma and Early Onset Acinetobacter Septicemia in a Newborn

Background: Neonatal sepsis is a leading cause of mortality and morbidity in the first month of life. The underlying risk factors for early-onset infection (in the first 3 days of life) are prematurity, low birth weight, maternal history of infection, difficult delivery, male gender, twin pregnancy, and congenital malformations. Acinetobacter is a nosocomial infection and rarely caused the early-onset-sepsis and meningitis. The most common neonatal tumor is neuroblastoma; however, it is not defined as a risk factor for early-onset sepsis. Case report: A 13-day-old newborn female was referred to our hospital due to ventriculitis, persistent meningitis, and an abdominal mass. She was a term neonate delivered by cesarean section from a mother with a nearly normal pregnancy with no complications, such as chorioamnionitis, prolonged rupture of membrane, urinary tract infection, preeclampsia, and diabetes. A fetal abdominal mass was detected on the left kidney in prenatal sonography. The patient was admitted to the Neonatal Intensive Care Unit in the first minutes of life because of respiratory distress and cyanosis. Subsequently, mechanical ventilation, endotracheal surfactant instillation, and antibiotic therapy were prescribed. Due to the deterioration of the general condition, fever, seizure, and hematuria on the third day, sepsis workup and changing the antibiotics were performed. Blood culture and cerebrospinal fluid (CSF) were positive for Acinetobacter baumannii. Persistent positive CSF culture led to the diagnosis of ventriculitis which was confirmed by brain computed tomography scan (CTS) and ventricular tap. The condition of the patient got better after intraventricular amikacin injection in addition to intravenous colistin and piperacillin. Postnatal sonography and CTS confirmed the abdominal neuroblastoma. Chemotherapy was initiated after the complete treatment of sepsis, meningitis, and ventriculitis. This case report presents a term and female neonate with early-onset neonatal sepsis and meningitis, caused by an unusual microorganism, and a prenatal history of abdominal neuroblastoma. Conclusion: By this case report, the clinicians are suggested to consider the Acinetobacter baumannii as the cause of fulminant sepsis and meningitis in a term neonate with no underlying risk factors for infection.  Keywords

Aerosolized Calfactant for Newborns With Respiratory Distress: A Randomized Trial.

Exogenous surfactants to treat respiratory distress syndrome (RDS) are approved for tracheal instillation only; this requires intubation, often followed by positive pressure ventilation to promote distribution. Aerosol delivery offers a safer alternative, but clinical studies have had mixed results. We hypothesized that efficient aerosolization of a surfactant with low viscosity, early in the course of RDS, could reduce the need for intubation and instillation of liquid surfactant. A prospective, multicenter, randomized, unblinded comparison trial of aerosolized calfactant (Infasurf) in newborns with signs of RDS that required noninvasive respiratory support. Calfactant was aerosolized by using a Solarys nebulizer modified with a pacifier adapter; 6 mL/kg (210 mg phospholipid/kg body weight) were delivered directly into the mouth. Infants in the aerosol group received up to 3 treatments, at least 4 hours apart. Infants in the control group received usual care, determined by providers. Infants were intubated and given instilled surfactant for persistent or worsening respiratory distress, at their providers' discretion. Among 22 NICUs, 457 infants were enrolled; gestation 23 to 41 (median 33) weeks and birth weight 595 to 4802 (median 1960) grams. In total, 230 infants were randomly assigned to aerosol; 225 received 334 treatments, starting at a median of 5 hours. The rates of intubation for surfactant instillation were 26% in the aerosol group and 50% in the usual care group (P < .0001). Respiratory outcomes up to 28 days of age were no different. In newborns with early, mild to moderate respiratory distress, aerosolized calfactant at a dose of 210 mg phospholipid/kg body weight reduced intubation and surfactant instillation by nearly one-half.