Following the first successful trial of surfactant replacement therapy for preterm infants with respiratory distress syndrome (RDS) by Fujiwara in 1980, several animal-derived natural surfactants and synthetic surfactants have been developed. Synthetic surfactants were designed to overcome limitations of natural surfactants such as cost, immune reactions, and infections elicited by animal proteins contained in natural surfactants. However, first-generation synthetic surfactants that are protein-free have failed to prove their superiority over natural surfactants because they lack surfactant protein (SP). Lucinactant, a second-generation synthetic surfactant containing the SP-B analog, was better or at least as effective as the natural surfactant, suggesting that lucinactant could act an alternative to natural surfactants. Lucinactant was approved by the U. S. Food and Drug Administration in March 2012 as the fifth surfactant to treat neonatal RDS. CHF5633, a second-generation synthetic surfactant containing SP-B and SP-C analogs, was effective and safe in a human multicenter cohort study for preterm infants. Many comparative studies of natural surfactants used worldwide have reported different efficacies for different preparations. However, these differences are believed to due to site variations, not actual differences. The more important thing than the composition of the surfactant in improving outcome is the timing and mode of administration of the surfactant. Novel synthetic surfactants containing synthetic phospholipid incorporated with SP-B and SP-C analogs will potentially represent alternatives to natural surfactants in the future, while improvement of treatment modalities with less-invasive or noninvasive methods of surfactant administration will be the most important task to be resolved.
Animals ; Cohort Studies ; Humans ; Infant, Newborn ; Infant, Premature ; Pulmonary Surfactants ; Surface-Active Agents ; United States Food and Drug Administration

OBJECTIVETo evaluate the clinical effect of endotracheal lavage with porcine pulmonary surfactant (PS) in term neonates with severe meconium aspiration syndrome (MAS).

METHODSA total of 136 full-term infants with severe MAS who were admitted to the neonatal intensive care unit between January 2010 and June 2013 were randomly and equally divided into PS lavage and PS injection groups. In the PS lavage group, patients were treated with endotracheal lavage using 3-5 mL of diluted PS (12 mg/mL) each time, and the PS injection group was given PS by intratracheal injection at the first dose of 200 mg/kg. Blood gas, oxygenation index (OI), and PaO2/FiO2 (P/F) of the two groups were evaluated before and 2, 12, 24, and 48 hours after the treatment, and the duration of mechanical ventilation, complication rate, and cure rate were compared between the two groups.

RESULTSCompared with the PS injection group, the PS lavage group had significantly higher PaO2 and P/F ration and significantly lower PaCO2 and OI at 12, 24, and 48 hours post-treatment (P<0.01), a significantly shorter duration of mechanical ventilation (P<0.01), a significantly smaller amount of PS (P<0.01), a significantly lower complication rate (P<0.05), and a significantly higher cure rate (97% vs 88%; P<0.05).

CONCLUSIONSCompared with the intratracheal injection of PS, endotracheal lavage with diluted PS in term neonates with severe MAS can increase ventilation and oxygenation efficiency, shorten the duration of mechanical ventilation, reduce the complication rate, and increase the cure rate, indicating that this method is a safe and effective therapeutic strategy.

Animals ; Humans ; Infant, Newborn ; Meconium Aspiration Syndrome ; drug therapy ; Pulmonary Surfactants ; administration & dosage ; Swine ; Therapeutic Irrigation ; Trachea

BACKGROUNDNeonatal respiratory distress syndrome (NRDS) is caused by a deficiency in pulmonary surfactant (PS) and is one of the main reasons of neonatal mortality. This study was conducted to evaluate the efficacy and safety of intra-amniotic administration of pulmonary surfactant for prophylaxis of NRDS.

METHODSForty-five pregnant women who were due for preterm delivery and whose fetuses' lungs proved immature were divided into two groups. Fifteen women (study group) were administered one dose of pulmonary surfactant injected into the amniotic cavity and delivered within several hours. Nothing was injected into the amniotic cavity of 30 women of the control group. The proportion of neonatal asphyxia, NRDS, mortality and the time in hospital were analyzed to determine if there was any difference between the two groups.

RESULTSThere was no significant difference between the two groups for neonatal asphyxia. Foam tests showed that higher proportion of neonates in the study group than in the control group (56.3% vs 13.3%, P < 0.05) had lung maturity. A greater number of control neonates (11/30, 32.3%) had NRDS, compared with the neonates given PS via the amniotic cavity before delivery (1/16, 6.3%, P < 0.05). The neonates in the study group spent nearly 10 days less in hospital than the control group [(32.4 +/- 7.6) days vs (42.0 +/- 15.7) days, P < 0.05], but the difference in mortality between the two groups was not statistically significant.

CONCLUSIONSIntra-amniotic administration of pulmonary surfactant can significantly reduce the proportion of NRDS and the time in hospital of preterm neonates. Whether this method can reduce the mortality of preterm neonates needs to be evaluated further. Intra-amniotic administration of pulmonary surfactant provides an additional effectual means for NRDS prophylaxis.

Amnion ; Female ; Humans ; Infant, Newborn ; Pulmonary Surfactants ; administration & dosage ; Respiratory Distress Syndrome, Newborn ; prevention & control ; Safety ; Treatment Outcome

OBJECTIVETo investigate the clinical epidemiological characteristics of neonatal respiratory failure in 1,108 neonates, and to provide a reference for improvement in clinical treatment and multicenter clinical studies.

METHODSThe clinical data of 1,108 neonates with respiratory failure were collected with questionnaires, and statistical analysis was performed for the epidemiological indices including primary diseases, clinical therapeutic methods, treatment outcome, and fatality.

RESULTSIn all the neonates with respiratory failure, the median gestational age was 37 weeks+1 day, the median birth weight was 2,600 g, the median age in days on admission to neonatal intensive care unit was 0.71 days (17 hours), and the boy/girl ratio was 3.1:1. The major primary diseases were respiratory distress syndrome (30.51%), pulmonary infection/sepsis (23.55%), and wet lung (13.18%). Of all the neonates, 48.64% received nasal continuous positive airway pressure (nCPAP), 12.81% received high-frequency oscillatory ventilation, 13.45% received pulmonary surfactant, and 8.66% received nitric oxide inhalation therapy. The fatality was 24.19%.

CONCLUSIONSThe major primary disease for neonatal respiratory failure is respiratory distress syndrome. Pulmonary surfactant, nCPAP, high-frequency oscillatory ventilation, and nitric oxide inhalation therapy are major therapeutic methods for neonatal respiratory failure, but neonatal respiratory failure still has a high fatality.

Female ; Humans ; Infant, Newborn ; Male ; Nitric Oxide ; administration & dosage ; Pulmonary Surfactants ; therapeutic use ; Respiration, Artificial ; Respiratory Insufficiency ; therapy

Acute respiratory distress syndrome (ARDS) is a heterogeneous syndrome that lacks definitive treatment. The cornerstone of management is sound intensive care treatment and early anticipatory ventilation support. A mechanical ventilation strategy aiming at optimal alveolar recruitment, judicious use of positive end-respiratory pressure (PEEP) and low tidal volumes (VT) remains the mainstay for managing this lung disease. Several treatments have been proposed in rescue settings, but confirmation is needed from large controlled clinical trials before they be recommended for routine care. Non-invasive ventilation (NIV) is suggested with a cautious approach and a strict selection of candidates for treatment. Mild and moderate cases can be efficiently treated by NIV, but this is contra-indicated with severe ARDS. The extra-corporeal carbon dioxide removal (ECCO2 R), used as an integrated tool with conventional ventilation, is playing a new role in adjusting respiratory acidosis and CO2. The proposed benefits of ECCO2 R over extra-corporeal membrane oxygenation (ECMO) consist in a reduction of artificial surface contact, avoidance of pump-related side effects and technical complications, as well as lower costs. The advantages and disadvantages of inhaled nitric oxide (iNO) are better recognized today and iNO is not recommended for ARDS and acute lung injury (ALI) in children and adults because iNO results in a transient improvement in oxygenation but does not reduce mortality, and may be harmful. Several trials have found no clinical benefit from various surfactant supplementation methods in adult patients with ARDS. However, studies which are still controversial have shown that surfactant supplementation can improve oxygenation and decrease mortality in pediatric and adolescent patients in specific conditions and, when applied in different modes and doses, also in neonatal respiratory distress syndrome (RDS) of preemies. Management of ARDS remains supportive, aimed at improving gas exchange and preventing complications. Progress in the treatment of ARDS must be addressed toward the new paradigm of the disease pathobiology to be applied to the disease definition and to predict the treatment outcome, also with the perspective to develop predictive and personalized medicine that highlights new and challenging opportunities in terms of benefit for patient's safety and doctor's responsibility, with further medico-legal implication.
Child ; Humans ; Nitric Oxide ; administration & dosage ; Noninvasive Ventilation ; Positive-Pressure Respiration ; Prone Position ; Pulmonary Atelectasis ; etiology ; Pulmonary Surfactants ; therapeutic use ; Respiratory Distress Syndrome, Adult ; therapy

We conducted a clinical trial to assess whether surfactant-TA given within the first six hours of life could improve oxygenation and reduce the ventilatory support in premature infants with hyaline membrane disease (HMD) during the first 24 hours of life. Eight premature infants with severe HMD requiring ventilation were treated, at a mean age of 2.72 hours, with a single intratracheal instillation of surfactant-TA (120 mg/kg). Arterial oxygenation improved dramatically as reflected by the increase of the a/A PO2 ratio and PaO2 to about 2 times the pretreatment values within 3 hours after surfactant treatment. And thus, oxygen concentrations (FiO2) could be reduced and remained significantly lower than pretreatment values during the first 24 hours after treatment. Infants given surfactant-TA required lower mean airway pressure (MAP) and had a significantly decreased ventilatory index (VI) during the first 24 hours after treatment, which reflect the decreased requirement for ventilatory support. Chest radiograph scores significantly improved within 24 hours after treatment compared with pretreatment scores. In this trial, we found that a single intratracheal dose of surfactant-TA given to infants with HMD resulted in improved respiratory status and radiographic findings during the first 24 hours after treatment.
Blood Gas Analysis/methods ; Clinical Trials ; Human ; Hyaline Membrane Disease/*drug therapy/radiography ; Infant, Newborn ; Oxygen/administration and dosage ; Pulmonary Surfactants/administration and dosage/*therapeutic use ; Respiration

We conducted a clinical trial to assess whether surfactant-TA given within the first six hours of life could improve oxygenation and reduce the ventilatory support in premature infants with hyaline membrane disease (HMD) during the first 24 hours of life. Eight premature infants with severe HMD requiring ventilation were treated, at a mean age of 2.72 hours, with a single intratracheal instillation of surfactant-TA (120 mg/kg). Arterial oxygenation improved dramatically as reflected by the increase of the a/A PO2 ratio and PaO2 to about 2 times the pretreatment values within 3 hours after surfactant treatment. And thus, oxygen concentrations (FiO2) could be reduced and remained significantly lower than pretreatment values during the first 24 hours after treatment. Infants given surfactant-TA required lower mean airway pressure (MAP) and had a significantly decreased ventilatory index (VI) during the first 24 hours after treatment, which reflect the decreased requirement for ventilatory support. Chest radiograph scores significantly improved within 24 hours after treatment compared with pretreatment scores. In this trial, we found that a single intratracheal dose of surfactant-TA given to infants with HMD resulted in improved respiratory status and radiographic findings during the first 24 hours after treatment.
Blood Gas Analysis/methods ; Clinical Trials ; Human ; Hyaline Membrane Disease/*drug therapy/radiography ; Infant, Newborn ; Oxygen/administration and dosage ; Pulmonary Surfactants/administration and dosage/*therapeutic use ; Respiration

OBJECTIVETo study the efficacy of different preparations of budesonide combined with pulmonary surfactant (PS) in improving blood gas levels and preventing bronchopulmonary dysplasia (BPD) in preterm infants with neonatal respiratory distress syndrome (NRDS).

METHODSA total of 184 preterm infants who developed NRDS within 4 hours after birth were randomly administered with PS + continuous inhalation of budesonide aerosol (continuous aerosol group), PS+budesonide solution (solution group), PS + single inhalation of budesonide aerosol (single aerosol group), and PS alone, with 46 neonates in each group. The changes in arterial blood gas levels, rate of invasive mechanical ventilation after treatment, time of assisted ventilation, rate of repeated use of PS, and the incidence of BPD were compared between the four groups.

RESULTSOn the 2nd to 4th day after treatment, pH, PCO2, and oxygenation index (FiO2/PaO2) showed significant differences among the four groups, and the continuous aerosol group showed the most improvements of all indicators, followed by the solution group, single aerosol group, and PS alone group. The continuous aerosol group had a significantly shorter time of assisted ventilation than the other three groups (P<0.05). The solution group had a significantly shorter time of assisted ventilation than the single aerosol and PS alone groups (P<0.05). The rate of invasive mechanical ventilation after treatment, rate of repeated use of PS, and incidence of BPD showed significant differences among the four groups (P<0.05), and the continuous aerosol group had the lowest rates, followed by the solution group.

CONCLUSIONSA combination of PS and continuous inhalation of budesonide aerosol has a better efficacy in the treatment of NRDS than a combination of PS and budesonide solution. The difference in reducing the incidence of BDP between the two administration methods awaits further investigation with a larger sample size.

Bronchopulmonary Dysplasia ; prevention & control ; Budesonide ; administration & dosage ; Drug Therapy, Combination ; Female ; Humans ; Infant, Newborn ; Male ; Pulmonary Surfactants ; administration & dosage ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn ; drug therapy

OBJECTIVETo study the clinical efficacy of porcine pulmonary surfactant (PS) combined with budesonide suspension intratracheal instillation in the treatment of neonatal meconium aspiration syndrome (MAS).

METHODSSeventy neonates with MAS were enrolled for a prospective study. The neonates were randomly assigned to PS alone treatment group and PS+budesonide treatment group (n=35 each). The PS alone treatment group was given PS (100 mg/kg) by intratracheal instillation. The treatment group was given budesonide suspension (0.25 mg/kg) combined with PS (100 mg/kg).

RESULTSThe rate of repeated use of PS in the PS+ budesonide group was significantly lower than that in the PS alone group 12 hours after treatment (p<0.05). The improvement of PaO/FiO, TcSaO, PaO, and PaCOin the PS+ budesonide group was significantly greater than that in the PS alone group 6, 12, and 24 hours after treatment (p<0.05). The chest X-ray examination showed that the pulmonary inflammation absorption in the PS+ budesonide group was significantly better than that in the PS alone group 48 hours after treatment (p<0.05). The incidence of complications in the PS+budesonide group was significantly lower than that in the PS alone group (p<0.05), and the average hospitalization duration was significantly shorter than that in the PS alone group (p<0.01).

CONCLUSIONSPS combined with budesonide suspension intratracheal instillation for the treatment of neonatal MAS is effective and superior to PS alone treatment.

Animals ; Budesonide ; administration & dosage ; Female ; Humans ; Infant, Newborn ; Length of Stay ; Male ; Meconium Aspiration Syndrome ; complications ; drug therapy ; Prospective Studies ; Pulmonary Surfactants ; administration & dosage ; Suspensions ; Swine ; Trachea

Bronchopulmonary Dysplasia ; prevention & control ; Continuous Positive Airway Pressure ; Humans ; Infant, Newborn ; Neuroprotective Agents ; pharmacology ; Nitric Oxide ; administration & dosage ; Pulmonary Surfactants ; administration & dosage ; Respiratory Distress Syndrome, Newborn ; therapy