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Miracles, like London buses, just seem to come along. The truth is, there are no miracles, just lots of hard work behind the scenes, minds open to opportunity, serendipity, and possibly a little luck. In my time as a pediatric respiratory physician, I have borne witness to remarkable advances in treatment that have changed patients' fortunes overnight. Examples of these include artificial surfactant replacement for premature newborns, conjugate Haemophilus influenzae type b vaccination, propranolol for infants with subglottic haemangiomas, mandibular distraction for babies with micrognathia, cystic fibrosis transmembrane conductance regulator modulators therapy for patients with cystic fibrosis, and antisense oligonucleotide therapy for infants with spinal muscular atrophy. There are lessons to be learned from reflection upon these life-transforming treatments, and perhaps it is a good time just to pause and wonder.

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 physiopathol­ogy.

Miracles, like London buses, just seem to come along. The truth is, there are no miracles, just lots of hard work behind the scenes, minds open to opportunity, serendipity and possibly a little luck. In my time as a paediatric respiratory physician, I have born witness to remarkable advances in treatment that have changed patients’ fortunes overnight. Examples of these include artificial surfactant replacement for premature newborns, conjugate haemophilus influenzae type b vaccination, propranolol for infants with subglottic haemangiomas, mandibular distraction for babies with micrognathia, cystic fibrosis transmembrane conductance regulator modulators therapy for patients with cystic fibrosis and antisense oligonucleotide therapy for infants with spinal muscular atrophy. There are lessons to be learned from reflection upon these life transforming treatments, and perhaps it is a good time just to pause and wonder.

Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in preterm infants due to primary surfactant deficiency. Surfactant replacement has greatly improved the short and long term prognosis of RDS but its administration criteria remain uncertain. Lung ultrasound has been recently shown as a non-invasive, repeatable, bedside tool to estimate parenchymal aeration using a semiquantitative score (LUS). The objective of this systematic review and meta-analysis is to evaluate the accuracy of LUS, assessed on the first day of life, to predict surfactant replacement. Methods will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) guidelines and the protocol has been registered in PROSPERO database (registration number: CRD42021247888). Primary outcome: in a population of preterm infants, LUS will be compared in neonates who received surfactant replacement versus those who did not. Secondary outcome will be the accuracy of lung ultrasound score to predict the need for ≥ 2 doses of surfactant.

Exogenous surfactant replacement is the most effective evidence-based therapy for respiratory distress syndrome in preterm infants. The mode of administration has evolved in the last decade towards less invasive techniques that aim to effectively provide an adequate dose of surfactant, while allowing spontaneous respiration to continue, and with the support of continuous positive airway pressure. Surfactant delivery via aerosolisation, pharyngeal instillation, and laryngeal mask are being actively pursued in research, but have not yet been adopted to any significant degree in clinical practice. Surfactant administration via thin catheter, on the other hand, is becoming more widely used in neonatal intensive care units worldwide and is now an acknowledged alternative to the standard mode of surfactant delivery. Different devices, including nasogastric tubes, vascular catheters, and purpose-built surfactant instillation catheters are used. We present here a contemporary review of surfactant administration via thin catheter, in a practical guide format that reflects the individual and collective scientific opinions of the clinicians who participated in formulating the guide.

Objective Semiquantitative lung ultrasound improves the timeliness of surfactant replacement, but its financial consequences are unknown. We aim to investigate if the ultrasound-guided surfactant administration influences the general costs of surfactant therapy for preterm neonates affected by respiratory distress syndrome. Study design This is a pharmacoeconomic, retrospective, and before-and-after study investigating the impact of ultrasound-guided surfactant replacement (echography-guided Surfactant THERapy [ESTHER]) on pharmaceutical expenditure within the ESTHER initiative. Data extracted from the institutional official database hosted by the hospital administration for financial management were used for the analysis. We analyzed the number of surfactant administrations in neonates of gestational age ≤326/7 weeks, and the number of surfactant vials used from January 1, 2014 to June 30, 2014 (i.e., during the period of standard surfactant administration policy) and from July 1, 2016 to December 31, 2018 (that is during ESTHER policy). Results ESTHER did not modify surfactant use, as proportion of treated neonates with RDS receiving at least one surfactant dose (Standard: 21.3% vs. ESTHER: 20.9%; p = 0.876) or as proportion of used vials over the total number of vials opened for neonates of any gestational age (Standard: 37% vs. ESTHER: 35%; p = 0.509). Conclusion Ultrasound-guided surfactant replacement using a semiquantitative lung ultrasound score in preterm infants with RDS does not change the global use of surfactant and the related expenditure. Key points · ESTHER is able to increase the timeliness of surfactant replacement.. · The ultrasound-guided surfactant administration does not increase the cost of surfactant therapy.. · The ultrasound-guided surfactant administration does not change the global surfactant utilization..

The reviews of this paper are available via the supplemental material section.

* Abbreviations: HMD: : hyaline membrane disease NIH: : National Institutes of Health UCLA: : University of California, Los Angeles Mary Ellen Avery, MD. Photograph kindly provided by Rosalind S. Brown, MD. How do the lungs of newborns support their first breaths, and why do some infants develop respiratory distress? This crucial research question emerged in the 1950s and was investigated by numerous physicians and scientists, including the American pediatrician Mary Ellen Avery, who devoted her career to the regulation of infant respiration. In a 1964 lecture, Avery drew a distinction between the intrauterine and extrauterine environments stating that “It is clearly at birth that regular rhythmic respiration begins. Something is turned on, something must be different just after birth from the way it was before, and this something must be essential to the regulation of respiration.”(1) Although Avery was a physician by training and not a scientist, research played a significant role in her career and led to her prominence as one of the investigational leaders of respiratory distress syndrome, which was known as hyaline membrane disease (HMD) during the time of Avery’s research. Avery focused on the role of surfactant, specifically its deficiency in HMD, challenging the accepted view at the time that HMD was caused by an obstruction in the lungs due to the aspiration of hyaline membranes. (2)(3)(4) Avery’s act of shifting the understanding of HMD from an obstructive disease to one of a biochemical deficiency was all the more striking given her role as a pediatrician and not a formally trained laboratory scientist. Biographers have estimated that her findings on HMD and their subsequent translation to treatment in the form of surfactant replacement have saved the lives of more than 800,000 infants. (2) The discovery of surfactant deficiency as the cause of HMD in 1959 not only challenged the accepted understanding of the disease at the time, but …

Objective To improve time of surfactant administration with a surfactant replacement protocol based on semiquantitative lung ultrasound score (LUS) thresholds. Study design Quality improvement (QI), prospective, before-after, pilot study. In a 6-month period surfactant replacement was based only on inspired oxygen fraction (FiO2) thresholds. In the second 6-month period, surfactant was given when either the FiO2 or LUS exceeded the limits. The main QI measures were the proportion of neonates receiving surfactant within the first 3 hours of life and maximal FiO2 reached before surfactant replacement. Secondary QI measures were the duration of respiratory support and ventilator-free days. Data were also collected for 1 year after the study to verify sustainability. Results Echography-guided Surfactant THERapy (ESTHER) increased the proportion of neonates receiving surfactant within the first 3 hours of life (71.4%-90%; P Conclusions ESTHER improved the timeliness of surfactant administration and secondary QI indicators related to surfactant replacement.

Extracorporeal membrane oxygenation (ECMO) continues to be an important rescue therapy for newborns with a variety of causes of cardio-respiratory failure unresponsive to high-frequency ventilation, surfactant replacement, and inhaled nitric oxide. There are approximately 800 neonatal respiratory ECMO cases reported annually to the Extracorporeal Life Support Organization; venoarterial ECMO has been used in approximately 72% with a cumulative survival of 71% and venovenous has been used in 28% with a survival of 84%. Congenital diaphragmatic hernia is now the most common indication for ECMO. This article reviews the development of the two types of extracorporeal support, venoarterial and venovenous ECMO, and discusses the advantages of each method, the current selection criteria, the procedure, and the clinical management of neonates on ECMO.

Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report updated recommendations of a European Panel of expert neonatologists who developed consensus guidelines after critical examination of the most up-to-date evidence in 2007 and 2010. This second update of the guidelines is based upon published evidence up to the end of 2012. Strong evidence exists for the role of antenatal steroids in RDS prevention, but it is still not clear if the benefit of repeated courses on respiratory outcomes outweighs the risk of adverse outcomes in the short and long term. Many practices involved in preterm neonatal stabilization at birth are not evidence based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in the management of RDS but the best preparation, optimal dose and timing of administration at different gestations is not completely clear. In addition, use of very early continuous positive airway pressure (CPAP) has altered the indications for prophylactic surfactant administration. Respiratory support in the form of mechanical ventilation may be lifesaving but can cause lung injury, and protocols should be directed at avoiding mechanical ventilation where possible by using non-invasive respiratory support such as CPAP. For babies with RDS to have best outcomes, it is essential that they have optimal supportive care, including maintenance of normal body temperature, proper fluid management, good nutritional support, appropriate management of the ductus arteriosus and support of the circulation to maintain adequate tissue perfusion. Copyright (c) 2013 S. Karger AG, Basel

Despite remarkable improvements in survival of extremely premature infants, the burden of BPD among survivors remains a frustrating problem for parents and caregivers. Advances, such as antenatal steroids and surfactant replacement, which have dramatically improved survival, have not reduced BPD among survivors. Other advances that have significantly improved the combined outcome of death or BPD, such as vitamin A and avoidance of mechanical ventilation, have had smaller magnitude effects on the outcome of BPD alone. Postnatal steroids have a clear beneficial effect on BPD, but the optimal preparation, dose, and timing for maximizing benefit and minimizing harm have yet to be determined. This persistent burden of BPD among the most immature survivors remains a challenge for the NRN and other researchers in neonatal medicine.

Surfactant deficiency was identified as the cause of respiratory distress syndrome (RDS) as long ago as 1959. Trials of surfactant replacement in the 1960s were unsuccessful because the preparations used contained only phospholipids and they were administered inefficiently by nebulization. In the 1970s Bengt Robertson and Göran Enhörning showed that natural surfactant, containing both phospholipids and proteins, could ameliorate the signs of RDS in immature rabbits. In the 1980s Bengt Robertson and Tore Curstedt developed a porcine surfactant, Curosurf® (named after their surnames), which was effective in immature animals and was used in a pilot clinical trial beginning in 1983. Subsequent randomized clinical trials were planned a year later by Bengt Robertson, Tore Curstedt and Henry Halliday, and the first trial was begun in 1985. This showed that Curosurf reduced pulmonary air leaks and neonatal mortality in preterm infants with severe RDS. A second trial, coordinated by Christian Speer, demonstrated that multiple doses of Curosurf were more effective than a single dose. Subsequent trials conducted by the Collaborative European Multicenter Study Group, which included among others Guilio Bevilacqua, Janna Koppe, Ola Saugstad, Nils Svenningsen and Jean-Pierre Relier, showed that early treatment was more effective than later administration and that infants treated at birth had similar neurodevelopmental status to untreated controls at a corrected age of 2 years. Members of the Collaborative European Multicenter Study Group in Denmark and Sweden performed studies to demonstrate the benefits of a combination of surfactant treatment and early continuous positive airway pressure. Curosurf has also been compared with several synthetic and natural surfactants, and at a dose of 200 mg/kg Curosurf has been shown to be superior to either Survanta® or Curosurf used at a dose of 100 mg/kg. Recently, new-generation synthetic surfactants containing both phospholipids and proteins have been developed. After preclinical testing, CHF5633 (developed by Tore Curstedt and Jan Johansson in collaboration with Chiesi Farmaceutici) has undergone a preliminary first study in humans under the guidance of Christian Speer. If effective, this new surfactant preparation could revolutionize the treatment of preterm infants worldwide as it could be made consistently and safely in almost unlimited quantities. This story of a porcine surfactant preparation has been truly remarkable, and many thousands of preterm babies worldwide are now alive and well because of it.

Clinical trials have evaluated the overall efficacy of surfactant therapy, as well as the relative efficacy of different surfactant preparations, the optimal timing of administration and the optimal dosage. Surfactant therapy leads to significant clinical improvement in infants at risk for, or having, respiratory distress syndrome (RDS). Clinical trials that compared the effects of synthetic or animal-derived surfactant preparations to placebo or no therapy demonstrate that surfactant therapy lead to rapid improvement in oxygenation, decreased ventilator support, decreased risk of pneumothorax, and mortality. Earlier treatment, prophylactic treatment of infants at high risk of developing RDS, and selective re-treatment leads to improved clinical outcome as well. Currently available animal-derived surfactants are superior to non-protein-containing synthetic surfactants. Ongoing evaluation will determine if important differences in animal-derived products are noted. Future trials will evaluate third-generation surfactant products and further refine what constitutes optimal use of surfactant.

PURPOSE OF REVIEW: This paper aims to provide a condensed review of the most essential and current research findings in the field of acute lung injury over the past year. RECENT FINDINGS: We review the most recent important findings in both laboratory-based and clinical research in the field of acute lung injury. Significant advances have been made in the past year with respect to our understanding of the pathogenesis of acute lung injury, and how key pathological events relate to prognosis, outcomes, and the promise of new potential therapeutic interventions. In particular, significant advances have been made in our understanding of the prognostic roles of neutrophil recruitment and clearance, fibrinogenesis, inflammatory cytokines, alveolar fluid clearance, and endothelial injury and activation. Paramount studies have provided greater skepticism over the efficacy of prone positioning and the currently available surfactant replacement therapies. In addition, new research has fostered an improved appreciation of the long-term sequelae of acute lung injury. SUMMARY: Recent advances in our understanding of the pathogenesis of acute lung injury have provided the promise of exciting potential interventions to modify intravascular and extravascular fibrinogenesis, neutrophil activation and clearance, and alveolar fluid clearance. Our new understanding of prolonged disability and post-traumatic stress in acute lung injury survivors will ultimately change the standard for how these patients are managed in the intensive care unit and followed beyond their hospital stay.

Bengt Robertson, a Swedish pediatric pathologist, teamed up with his countryman Goran Enhorning, an obstetrician, in the 1960s and 1970s to conduct seminal basic research on surfactant replacement in animal models of respiratory distress syndrome (RDS). This research formed the foundation for the very successful randomized clinical trials of natural surfactant replacement for RDS in the 1980s and 1990s. Bengt Robertson was born in Stockholm in 1935, just 6 years after another Swede, Kurt van Neergaard, first demonstrated the importance of pulmonary surfactant for normal lung function. (1) Robertson was educated at Sodra Latins Gymnasium in Stockholm and graduated from high school in 1953 before studying medicine at the Karolinska Institutet. He graduated as MD in 1960, and in 1968, he successfully defended his PhD thesis entitled “The intrapulmonary arterial pattern in normal infancy and in transposition of the great arteries” at the Karolinska Institutet in Stockholm. In 1970, he was appointed as a Consultant in Pediatric Pathology at St. Goran's Hospital in Stockholm, and from 1974, he was Director of the Division for Experimental Perinatal Pathology in the Department of Women and Child Health at the Karolinska Institutet. At least two unsuccessful trials of surfactant replacement for RDS in preterm neonates were completed in the 1960s. (2)(3) The surfactant used in these trials was dipalmitoylphosphatidylcholine, and it was administered by aerosolization. Robertson and Enhorning reasoned that natural surfactant administered by direct instillation into the lungs would be …

To investigate if bronchoalveolar lavage leads to increased alveolar and physiologic deadspace or a deadspace/ tidal volume ratio and if surfactant replacement restores the lung to its prelavage condition.Prospective, animal cohort study.An animal laboratory in a university medical center.Seven adult rabbits receiving artificial ventilation.Our single-breath CO2 analysis station contained the following equipment: pneumotachometer Ventrak 1550, a mainstream capnometer Capnogard 1265, a signal processor, and computer software. Repeated bronchoalveolar lavage was performed in seven adult rabbits to simulate acute respiratory distress syndrome. Surfactant therapy was administered after bronchoalveolar lavage induced a 20% reduction in baseline arterial PO2. The calculated parameters of alveolar and physiologic deadspace and the deadspace/tidal volume ratio were derived from the single-breath CO2 plot by Ventrak 1550 in combination with the Capnogard 1265. The arterial end-tidal Pco2 difference, the alveolar-arterial PO2 difference, and the arterial/alveolar PO2 ratio were obtained by capnography and arterial blood gas analysis. Measurements of these parameters were performed before bronchoalveolar lavage, during bronchoalveolar lavage, and after surfactant application.The alveolar and physiologic deadspace and the deadspace/tidal volume ratio were significantly higher in lavaged animals. After application of natural surfactant, these parameters were significantly reduced but the baseline values could not be reached. Bronchoalveolar lavage led to a significant fall in the arterial/alveolar PO2 ratio, which increased after surfactant therapy. There was a negative correlation between the arterial/alveolar PO2 ratio and the deadspace/tidal volume ratio. The alveolar and physiologic deadspace and the deadspace/tidal volume ratio correlated with the arterial end-tidal Pco2 difference. The best correlation was obtained between the arterial end-tidal Pco2 difference and the alveolar deadspace/tidal volume ratio (r = 0.98).Bronchoalveolar lavage elevates the alveolar and physiologic deadspace and the deadspace/tidal volume ratios and is combined with a fall in the arterial/alveolar PO2 ratio. Surfactant treatment improves the gas exchange but does not restore the lung to its prebronchoalveolar lavage condition, which indicates that the exogenous surfactant affects only partly the recruitment of the atelectatic areas.

AIM To determine whether abnormal transvascular protein flux can be measured with positron emission tomography (PET) in neonates with respiratory distress syndrome (RDS). METHODS Fourteen infants with normal gas exchange (non-RDS group) underwent one PET measurement and 12 infants with RDS (the RDS group) underwent two measurements of protein flux, as determined by the pulmonary transcapillary escape rate for 68 Gallium labelled transferrin (PTCER). RESULTS The mean PTCER for the RDS infants (132 ± 39 10 -4 /min) was significantly greater than that for infants without RDS (75 ± 27 10 -4 /min). PTCER did not change between measurements in the infants with RDS, including five who received and responded to surfactant replacement between the two scans. CONCLUSIONS Increased transvascular flux of large molecular weight proteins complicates RDS in preterm infants. PET provides a tool with which to evaluate the processes that contribute to pulmonary dysfunction in neonates.

Lung surfactant is crucial for optimal pulmonary function throughout life. An absence or deficiency of surfactant can affect the surfactant pool leading to respiratory distress. Even if the coupling between surfactant dysfunction and the underlying disease is not always well understood, using exogenous surfactants as replacement is usually a standard therapeutic option in respiratory distress. Exogenous surfactants have been extensively studied in animal models and clinical trials. The present article provides an update on the evolution of surfactant therapy, types of surfactant treatment, and development of newer-generation surfactants. The differences in the performance between various surfactants are highlighted and advanced research that has been conducted so far in developing the optimal delivery of surfactant is discussed.

Surfactant replacement in preterm infants with respiratory distress syndrome (RDS) has been a major therapeutic breakthrough and the most intensively studied intervention in neonatal medicine. Surfactant whether given prophylactically in the delivery room or in babies with established RDS reduces the severity of RDS, the incidence of air leaks and pneumothorax and, most importantly, neonatal death. Many randomized controlled trials have explored different strategies to optimize the effect of surfactant administration and have further improved neonatal outcome. Whenever indicated, surfactant should be administered as early as possible in the course of the RDS.

Objective. To study the effect of a single dose of exogenous bovine surfactant on oxygen and ventilatory requirements of neonates with early chronic lung disease. Study design. Prospective pilot study. Setting. Three regional neonatal intensive care units. Methods. Infants 7 to 30 days old with birth weights less than 1500 g were eligible if they required a fraction of inspired oxygen (FIO2) of more than 0.4, had stable ventilatory requirements for 24 hours before study entry, and showed diffuse haziness on chest radiographs. Those with patent ductus arteriosus or active infection or those receiving steroid therapy were excluded. After treatment with the surfactant, differences in FIO2 and the ventilator efficiency index were analyzed using the Wilcoxon signed rank test. Results. Ten patients were recruited. Median values (range): birth weight, 693 g (530 to 1100 g); gestation, 25 weeks (24 to 27 weeks); and postnatal age at study entry, 13 days (9 to 30 days). The FIO2 decreased significantly between 0 and 1 hour after surfactant administration, from a median (range) of 0.67 (0.47 to 0.88) to 0.39 (0.28 to 0.63). This effect was sustained for 24 hours (median FIO2, 0.36). Although the FIO2 subsequently increased to 0.49 (range, 0.35 to 0.88) at 72 hours, it was significantly lower than that entry before the study. There was a trend toward an increase in the ventilator efficiency index at 24 and 48 hours. Conclusions. A single dose of surfactant is effective in reducing oxygen requirements in neonates with early chronic lung disease. Surfactant replacement may be useful adjunctive therapy in these neonates.

Respiratory distress syndrome (RDS) is a leading cause of morbidity and mortality in premature neonates. This syndrome is caused by a lack of endogenous surfactant production in the lungs. Surfactant replacement was established as a safe and effective treatment in the 1990s and has become the standard of care for these infants. Surfactant products are either protein-free synthetic phospholipid compounds or animal-derived lung preparations. Currently, about 90,000 infants a year receive treatment with one of the commercially available animal-derived surfactants. Lucinactant (Surfaxin®) is a new synthetic surfactant with a pulmonary surfactant-associated protein B mimic that recently received FDA approval. The clinical trials that have been performed, although underpowered, may indicate that lucinactant is superior to phospholipid synthetic surfactant preparations and at least as effective as animal-derived surfactants in reducing morbidity and mortality from RDS. This review summarizes the current clinical knowledge about lucinactant.

A meta-analysis of the literature is carried out in order to present the current knowledge of ARDS in childhood (0-15 years). This might be helpful for planning controlled studies on new therapeutic measures (e.g. surfactant replacement, antioxidants, extracorporeal gas exchange). By means of Medline all available publications were taken into account referring to minimal criteria defined before. There were 4 studies (50 patients) and 48 individual case-reports (48 patients). Most often ARDS was caused by infection (21 resp. 30%), aspiration (12 resp. 23%) and trauma (10 resp. 23%). Therapeutically high respiration pressures and toxic oxygen tensions were applied generally (average maximum PEEP: 14.7 resp. 15.8 cm H2O; average maximum PIP: 59.6 resp. 61.9 cm H2O; FiO2 > 0.5 for an average of 10.1 resp. 10.4 days). The most frequent complications were barotrauma (43.8 resp. 78%), infection (60.4%) and multiorgan failure (66.7%). Mortality rate was 31.3 resp. 52%. So also in childhood almost every second case is fatal. Especially multiorgan failure as well as high levels of FiO2 and PEEP indicate bad prognosis at an early stage. Therefore it is necessary and justified to perform clinical trials on therapeutic agents successfully tested in animal studies before.

Despite recent advances in the perinatal management of neonatal respiratory distress syndrome (RDS), controversies still exist. We report the updated recommendations of a European panel of expert neonatologists who had developed consensus guidelines after critical examination of the most up-to-date evidence in 2007. These updated guidelines are based upon published evidence up to the end of 2009. Strong evidence exists for the role of a single course of antenatal steroids in RDS prevention, but the potential benefit and long-term safety of repeated courses are unclear. Many practices involved in preterm neonatal stabilisation at birth are not evidence-based, including oxygen administration and positive pressure lung inflation, and they may at times be harmful. Surfactant replacement therapy is crucial in the management of RDS, but the best preparation, optimal dose and timing of administration at different gestations is not always clear. Respiratory support in the form of mechanical ventilation may also be lifesaving, but can cause lung injury, and protocols should be directed at avoiding mechanical ventilation where possible by using nasal continuous positive airways pressure or nasal ventilation. For babies with RDS to have best outcomes, it is essential that they have optimal supportive care, including maintenance of a normal body temperature, proper fluid management, good nutritional support, management of the ductus arteriosus and support of the circulation to maintain adequate tissue perfusion.

In this issue of Critical Care, Lu and colleagues [1] report signifi cant and prolonged lung reaeration after intratracheal bolus instillation of porcine-derived surfactant. In this substudy of a larger randomized controlled trial of patients with acute lung injury [2], the investigators elegantly demonstrate increased volumes of gas in poorly and non-aerated lung of patients who were treated with surfactant as compared with patients who received routine care. Do these encouraging fi ndings truly support the rationale for exogenous surfactant replacement as an indication for lung reaeration in patients with acute lung injury? Th is can be questioned. First, intratracheal bolus instillation of surfactant required recruitment maneuvers. Indeed, larger tidal volumes (TVs) and higher levels of positive end-expiratory pressure (PEEP) were used for as long as 30 minutes after instillation of surfactant to each lung. Th e instillation procedure per se could be (solely) responsible for increased volumes of gas in poorly and non-aerated lung. In addition, bolus instillation of surfactant resulted in temporarily severe hypoxemia in more than half of the patients treated with surfactant [2]. Th ough not reported in the original study or the present study, rescue therapies such as prone ventilation, repeated recruitment maneuvers, and higher levels of PEEP could have been used more intensively in these patients. Th ese rescue maneuvers, in response to surfactant instillation-induced hypoxemia, could also be responsible for the fi ndings by Lu and colleagues [1].

Massive milk aspiration during infant feeding is a severe event causing respiratory distress, asphyxia and sudden death.1 To date, only experimental models have shown that administration of exogenous surfactant is a successful treatment for acute lung injury induced by acidified formula, or human breast milk, aspiration.2 3 We describe a case of massive milk aspiration successfully treated with surfactant administration in a very low birthweight infant. A 1180 g male infant of 30 weeks’ gestation was delivered by caesarean section due to variable decelerations in cardio-tocographic readings. The infant’s Apgar scores were 8 and 9 at 1 and 5 min, respectively. …

New therapies are being developed to improve survival of low-birth-weight infants, especially those weighing less than 1000 g. The most exciting new development is the use of surfactant replacement therapy for treatment of respiratory distress syndrome. This therapy results in less severe acute lung disease and has decreased mortality from respiratory distress syndrome. As more infants survive, consideration of long-term sequelae including chronic lung disease and neurologic outcome are of paramount importance. This review covers strategies for prevention and treatment of respiratory distress syndrome (including surfactant replacement). New and evolving treatments for amelioration of chronic lung disease and issues in neurologic outcome for the low-birth-weight infant (including prevention of intraventricular hemorrhage) are addressed.