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 explore the clinical efficacy of intratracheal instillation of pulmonary surfactant (PS) combined with budesonide for preventing bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW) infants.

METHODSThirty VLBW infants with gestational age <32 weeks who developed neonatal respiratory distress syndrome (NRDS) (grade III-IV) suffering from intrauterine infection were randomly assigned into a PS + budesonide group and a PS alone group. The changes were compared between the two groups in arterial blood gas indexes, oxygenation index (OI), duration of mechanical ventilation, duration of oxygen supplementation, incidence of BPD, mortality rate at 36 weeks corrected gestational age and incidences of other complications except BPD.

RESULTSCompared with the PS alone group, the PS+budesonide group had a lower incidence of BPD, shorter duration of mechanical ventilation and oxygen supplementation (P<0.05). On the 2nd to 6th day after treatment, the PS+budesonide group had higher pH value of arterial blood gas and OI and lower carbon dioxide partial pressure compared with the PS alone group (P<0.05). There were no significant differences in the mortality rate at 36 weeks corrected gestational age and the incidences of other complications except BPD between the two groups (P>0.05).

CONCLUSIONSIntratracheal instillation of PS combined with budesonide can effectively reduce the incidence of BPD in VLBW premature infants with severe NRDS.

Bronchopulmonary Dysplasia ; prevention & control ; Budesonide ; administration & dosage ; Female ; Humans ; Infant, Newborn ; Infant, Very Low Birth Weight ; Male ; Pulmonary Surfactants ; administration & dosage ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn ; drug therapy

To treat respiratory distress syndrome, surfactant is currently delivered via less invasive surfactant administration (LISA) or INtubation SURfactant Extubation (INSURE). The aim of this study was to compare the effect of the two delivery methods of surfactant on cerebral autoregulation. Near infrared spectroscopy monitoring was carried out to detect cerebral oxygen saturation (ScO), and the mean arterial blood pressure (MABP) was simultaneously recorded. Of 44 preterm infants included, the surfactant was administrated to 22 via LISA and 22 via INSURE. The clinical characteristics, treatments and outcomes of the infants showed no significant differences between the two groups. The correlation coefficient of ScOand MABP (r) 5 min before administration was similar in the two groups. During surfactant administration, rincreased in both groups (0.44±0.10 to 0.54±0.12 in LISA, 0.45±0.11 to 0.69±0.09 in INSURE). In the first and second 5 min after instillation, rwas not significantly different from baseline in the LISA group, but increased in the first 5 min after instillation (0.59±0.13, P=0.000 compared with the baseline in the same group) and recovered in the second 5 min after instillation (0.48±0.10, P=0.321) in the INSURE group. There were significant differences in the change rates of rbetween the two groups during and after surfactant administration. Our results suggest that cerebral autoregulation may be affected transiently by surfactant administration. The effect duration of LISA is shorter than that of INSURE (<5 min in LISA vs. 5-10 min in INSURE).
Administration, Intranasal ; adverse effects ; Brain ; metabolism ; Female ; Homeostasis ; Humans ; Infant, Newborn ; Infant, Premature ; Intubation ; adverse effects ; Male ; Oxygen Consumption ; Pulmonary Surfactants ; administration & dosage ; therapeutic use ; Respiratory Distress Syndrome, Newborn ; drug therapy ; therapy

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 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

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

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.
Biological Products/administration & dosage/*therapeutic use ; Birth Weight ; Bronchopulmonary Dysplasia/drug therapy ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Phospholipids/administration & dosage/*therapeutic use ; Pulmonary Surfactants/administration & dosage/*therapeutic use ; Republic of Korea ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn/*drug therapy ; Retrospective Studies ; Risk ; Treatment Outcome ; Ventilator Weaning

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.
Biological Products/administration & dosage/*therapeutic use ; Birth Weight ; Bronchopulmonary Dysplasia/drug therapy ; Female ; Gestational Age ; Humans ; Infant, Newborn ; Infant, Premature ; Male ; Phospholipids/administration & dosage/*therapeutic use ; Pulmonary Surfactants/administration & dosage/*therapeutic use ; Republic of Korea ; Respiration, Artificial ; Respiratory Distress Syndrome, Newborn/*drug therapy ; Retrospective Studies ; Risk ; Treatment Outcome ; Ventilator Weaning

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

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