Surfactant Utilization Evaluation in a Major Teaching Hospital in West of Iran: An Observational, Prospective Study

Background: The respiratory distress syndrome (RDS) is a common pulmonary disorder that usually occurs as a result of preterm labor and is associated with lack of surfactant. The aim of this study was to evaluate the pattern of surfactant prescription in Alzahra teaching hospital in Tabriz, Iran. Methods: This drug use evaluation (DUE) study was conducted in the neonatal intensive care unit (NICU) of Al-Zahra Hospital, Tabriz, Iran. The demographic and clinical data collection was performed using clinical records of patients. The pattern of surfactant replacement therapy was evaluated and compared with the European Consensus Guideline on the management of respiratory distress syndrome in 2016. Results: A total of 252 premature infants who received surfactant between August 2017 and March 2018 were included. 80.8% of neonates were born by cesarean section. The most used surfactant was Curosurf®, which was used in 82.1% of cases. Only 34.9% of the infants received within 8 hours of birth. Moreover, 79% of infants received the standard dose of surfactant, while 9.5 % and 11.5% were given high and low doses of surfactant, respectively. Conclusion: The pattern of surfactant replacement therapy was not completely according to the guidelines, particularly regarding the time of administration. Considering the importance of dose and timely administration of surfactant, providing strategies to decrease these errors are important.

Late surfactant replacement therapy and its efficacy on severe bronchopulmonary dysplasia in National Children Hospital

Bronchopulmonary dysplasia (BPD) is a chronic lung disease that is most commonly seen in premature infants who require prolonged mechanical ventilation and oxygen therapy. 75% of intubated infants have episodes of dysfunctional surfactants associated with lower levels of surfactant proteins. This study aims to evaluate the effectiveness of late surfactant therapy in treating BPD in premature infants. Nineteen preterm infants diagnosed with severe BPD requiring mechanic ventilation, according to Jobe and Bancalari, were treated with surfactant (Poractant alpha 100mg/kg intra-tracheal). Patients were observed for change in oxygen requirement before and at 1-h, 6-h, 12-h, 24-h, and 48-h after treatment. There were 13 boys and 6 girls; boy to girl ratio was 2.16/1. The mean gestation age was 28.3 ± 2 weeks; the mean birth weight was 1134.7 ± 314 gram. There was an increase in SpO2 (saturation of peripheral oxygen), PaO2 (the partial pressure of oxygen in arterial blood) and reduction in FiO2 (fraction of inspired oxygen), PaCO2 (the partial pressure of carbon dioxide in arterial blood), OI (oxygen index), MAP (mean airway pressure) and AaDO2 (Alveolar-to-arterial oxygen gradient) after surfactant (p < 0.05). Conclusion: In patients with severe BPD, late surfactant therapy has shown initial benefits in lung functions and reducing oxygen requirement.

Clinical case of severe coronavirus infection in a 6-month-old child

Nowadays, the creation of treatment protocols for young children with COVID-19 is especially relevant, as some issues of pathogenesis and genetic determinism of severe lung damage are still unclear. COVID-19-induced respiratory distress syndrome is a predictable severe complication that requires early diagnosis and proper treatment. Given the pathogenetic mechanism of lung damage in COVID-19, surfactant replacement therapy may be useful in the treatment of this cohort of patients. Clinical case. A clinical case of severe coronavirus infection caused by SARS-CoV-2 in a 6-month-old child is presented. The course of the disease was accompanied by severe damage to the lung parenchyma with the development of acute respiratory distress. The examination of the patient confirmed the genetic determinism of severe COVID-19, polymorphic risk alleles of the genes GSTM1, GSTP1, SFTP-B. The child's treatment included not only long-term mechanical ventilation, but also surfactant replacement therapy. The child recovered and was discharged without signs of respiratory failure. Conclusions. This clinical case demonstrates the association of genetic polymorphism with severe virus-induced lung damage. Because severe respiratory failure in COVID-19 is likely to be due to the development of acute respiratory distress syndrome, administration of exogenous surfactant should be considered as a possible treatment option. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: COVID-19, children, virus-induced respiratory distress syndrome, gene polymorphism, surfactant administration.

Pulmonary surfactant: a unique biomaterial with life-saving therapeutic applications.

: Pulmonary surfactant is a complex lipoprotein mixture secreted into the alveolar lumen by type 2 pneumocytes, which is composed by tens of different lipids (approximately 90% of its entire mass) and surfactant proteins (approximately 10% of the mass). It is crucially involved in maintaining lung homeostasis by reducing the values of alveolar liquid surface tension close to zero at end-expiration, thereby avoiding the alveolar collapse, and assembling a chemical and physical barrier against inhaled pathogens. A deficient amount of surfactant or its functional inactivation is directly linked to a wide range of lung pathologies, including the neonatal respiratory distress syndrome. This paper reviews the main biophysical concepts of surfactant activity and its inactivation mechanisms, and describes the past, present and future roles of surfactant replacement therapy, focusing on the exogenous surfactant preparations marketed worldwide and new formulations under development. The closing section describes the pulmonary surfactant in the context of drug delivery. Thanks to its peculiar composition, biocompatibility, and alveolar spreading capability, the surfactant may work not only as a shuttle to the branched anatomy of the lung for other drugs but also as a modulator for their release, opening to innovative therapeutic avenues for the treatment of several respiratory diseases.

A Randomized Clinical Trial of Intratracheal Administration of Surfactant and Budesonide Combination in Comparison to Surfactant for Prevention of Bronchopulmonary Dysplasia

Objectives: Bronchopulmonary dysplasia (BPD) remains a major problem in preterm infants occurring in up to 50% of infants born at < 28 weeks gestational age. Inflammation plays an important role in the pathogenesis of BPD. This study was conducted to evaluate the efficacy of intratracheal budesonide administration in combination with a surfactant in preventing BPD in preterm infants. Methods: In a randomized clinical trial, 128 preterm infants at < 30 weeks gestational age and weighing < 1500 g at birth were studied. All had respiratory distress syndrome (RDS) and needed surfactant replacement therapy. They were randomly allocated into two groups; surfactant group (n = 64) and surfactant + budesonide group (n = 64). Neonates in the surfactant group received intratracheal Curosurf 200 mg/ kg/dose. Patients in the surfactant + budesonide group were treated with intratracheal instillation of a mixed suspension of budesonide 0.25 mg/kg and Curosurf 200 mg/kg/ dose. Neonates were followed untill discharge for the primary outcome which was BPD and secondary outcomes including sepsis, patent ductus arteriosus (PDA), retinopathy of prematurity (ROP), and necrotizing enterocolitis (NEC). Results: The mean gestational age and birth weight of the studied neonates were 28.3±1.6 weeks and 1072.0±180.0 g, respectively. The demographic characteristics and RDS score were similar in the two groups. BPD occurred in 24 (37.5%) neonates in the surfactant + budesonide group and 38 (59.4%) neonates in surfactant group, p = 0.040. Hospital stay was 29.7±19.2 days (median = 30 days) in the surfactant group and 23.3±18.1 days (median = 20 days) in the surfactant + budesonide group, p = 0.050. The rates of sepsis, PDA, ROP, and NEC were not significantly different in the two groups. Conclusions: The use of budesonide in addition to surfactant for rescue therapy of RDS in preterm infants decreases the incidence of BPD and duration of respiratory support significantly. Large adequately powered clinical trials with long-term safety assessments are needed to confirm our findings before its routine use can be recommended.

The Miracles of Surfactant: Less Invasive Surfactant Administration, Nebulization, and Carrier of Topical Drugs

Surfactant replacement therapy (SRT) has long become the standard of care in the treatment of neonatal respiratory distress syndrome (RDS), significantly decreasing acute pulmonary morbidity and mortality in preterm infants. For decades, this beneficial replacement therapy has been administered via endotracheal tube. Despite significantly improving the outcome of RDS, however, the burden of bronchopulmonary dysplasia remains, in particular, in very immature preterm infants. Acknowledging the direct relationship between exposure to and duration of invasive mechanical ventilation and chronic lung disease, the latter has been gradually replaced by noninvasive ventilation strategies in neonatal RDS. This replacement is strongly related to the demand for similarly noninvasive modes of surfactant administration. Alternative techniques in spontaneously breathing infants have evolved, including less invasive techniques using thin catheters (less invasive surfactant administration and minimally invasive surfactant treatment) as well as nebulization of surfactant, although the latter is not ready for clinical application yet. In addition, given their therapeutic delivery to the lungs and subsequent alveolar distribution, surfactant preparations represent an attractive vehicle for pulmonary deposition of drugs in preterm infants. Further improvement of SRT and expansion of the field of application of lung surfactant may hold additional benefits, especially in the treatment of the most immature preterm infants.

The efficacy of intra-tracheal budesonide with surfactant in treatment of respiratory distress syndrome and prevention of bronchopulmonary dysplasia

Background: Premature birth is an important issue in developed and developing countries. Surfactant replacement therapy of respiratory distress syndrome (RDS) causes a change in the normal pattern of the disease and increases the likelihood of survival of more premature newborns with chronic pulmonary damage. The purpose of this study was to investigate the effects of budesonide and surfactant on the treatment of respiratory distress syndrome and the prevention of bronchopulmonary dysplasia. Methods: In a randomized clinical trial, 128 preterm infants less than 1250 g or gestational age of 26-30 weeks that were admitted to Al-Zahra Hospital from 2017 to 2018 with RDS and needed surfactant replacement therapy were enrolled. They were randomly allocated into two groups. In one group (group Surfactant), the surfactant was administered intratracheally 2.5 cc/kg and in the second group (group Surfactant + Budesonide), budesonide was administered 0.25 mg/kg in addition to the intratracheal surfactant. The primary outcome was bronchopulmonary dysplasia and the secondary outcome was complications of prematurity. Results: In this study 128 neonates including 48 (60.9%) boys and 50 (39.1%) girls were studied. The mean gestational ages of studied neonates were 28.32±1.60 weeks. The mean duration of mechanical ventilation, continuous positive airway pressure (CPAP), high flow nasal cannulae (HFNC), and need for supplemental oxygen were significantly shorter in the group that received surfactant and budesonide combination. The required FiO2 at four hours after surfactant treatment was significantly lower in group Surfactant + Budesonide than the Surfactant group (p = 0.01). In the group Surfactant, 38 neonates (59.4%) and in group S+B, 24 cases (37.5%) developed bronchopulmonary dysplasia (BPD), (p = 0.04). The mortality rate was 15 neonates that 6 cases were in group S+B (p =0.29). Conclusion: In our study, using surfactant with budesonide combination in comparison with surfactant alone is associated with less respiratory support and BPD rate. Future studies with a larger number of patients before routine use of surfactant and budesonide combination is recommended.

Evidence for the Management of Bronchopulmonary Dysplasia in Very Preterm Infants

Background: Very preterm birth often results in the development of bronchopulmonary dysplasia (BPD) with an inverse correlation of gestational age and birthweight. This very preterm population is especially exposed to interventions, which affect the development of BPD. Objective: The goal of our review is to summarize the evidence on these daily procedures and provide evidence-based recommendations for the management of BPD. Methods: We conducted a systematic literature research using MEDLINE/PubMed on antenatal corticosteroids, surfactant-replacement therapy, caffeine, ventilation strategies, postnatal corticosteroids, inhaled nitric oxide, inhaled bronchodilators, macrolides, patent ductus arteriosus, fluid management, vitamin A, treatment of pulmonary hypertension and stem cell therapy. Results: Evidence provided by meta-analyses, systematic reviews, randomized controlled trials (RCTs) and large observational studies are summarized as a narrative review. Discussion: There is strong evidence for the use of antenatal corticosteroids, surfactant-replacement therapy, especially in combination with noninvasive ventilation strategies, caffeine and lung-protective ventilation strategies. A more differentiated approach has to be applied to corticosteroid treatment, the management of patent ductus arteriosus (PDA), fluid-intake and vitamin A supplementation, as well as the treatment of BPD-associated pulmonary hypertension. There is no evidence for the routine use of inhaled bronchodilators and prophylactic inhaled nitric oxide. Stem cell therapy is promising, but should be used in RCTs only.

A comparison of LISA versus insure: A single center experience

BACKGROUND: Less invasive surfactant replacement therapy (SRT) methods have been linked to better respiratory outcomes. The primary aim of this study was to determine if Less Invasive Surfactant Administration (LISA) altered the rate of bronchopulmonary dysplasia (BPD) in preterm infants. Secondary objectives were to determine if LISA compared to Intubation Surfactant Extubation (InSurE) resulted in different respiratory outcomes and hospital course. METHODS: In this retrospective chart review, outcomes were compared in two preterm infant groups (25–32 weeks gestation). Infants in Group 1 received surfactant replacement therapy (SRT) via InSurE method, while infants in Group 2 received SRT via LISA method. RESULTS: Regardless of SRT method utilized, there were no significant differences in rates of BPD between the two groups in infants born at 25–32 weeks gestation (30.6% vs 33.3% ; P = 0.47). CONCLUSIONS: Despite using LISA method rather than InSurE for SRT, premature infants continue to be at high risk for BPD. LISA shows promise as a safe, noninvasive SRT alternative to invasive methods like InSurE.