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

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

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

OBJECTIVETo investigate the clinical effect of combination therapy with high-frequency oscillation ventilation (HFOV), pulmonary surfactant (PS) and inhaled nitric oxide (iNO) in the treatment of neonatal hypoxemic respiratory failure (HRF).

METHODSA total of 116 neonates with HRF were studied, and they were randomly divided into two groups: triple therapy (n=58) and dual therapy (n=58). The triple therapy group received HFOV, PS, and iNO, while the dual therapy group received HFOV and iNO. Blood gas values, PaO2/FiO2 (P/F), oxygenation index (OI), and pulmonary arterial pressure (PA) were determined before treatment and after 24 and 48 hours of treatment. Among the neonates with different P/F ratios and OI values and with or without persistent pulmonary hypertension of the newborn (PPHN), the treatment outcomes of two groups were compared.

RESULTSThe durations of mechanical ventilation and iNO therapy in the triple therapy group were significantly shorter than in the dual therapy group (P<0.01). After 24 and 48 hours of treatment, the triple therapy group had significantly improve PaO2 and PaCO2 compared with the dual therapy group (P<0.01). After 24 and 48 hours of treatment, the neonates with PPHN in the triple therapy group had significantly decreased PA compared with the dual therapy group (P<0.01). In the cases with a P/F ratio of ≤50, the triple group had a significantly higher cure rate than the dual therapy group (P<0.05). In both groups, the P/F ratios of the neonates who died were significantly lower than those of survivors (P<0.01). In the cases with an OI of ≥40, the triple group had a significantly higher cure rate than the dual therapy group (P<0.05). In both groups, the OI values of the neonates who died were significantly higher than those of survivors (P<0.01). In neonates with PPHN, the triple group had a significantly higher cure rate than the dual therapy group (P<0.05). The triple therapy group had a significantly shorter length of hospital stay (P<0.01) and a significantly higher cure rate (P<0.05) compared with the dual therapy group. There were no significant differences in complications between the two groups (P>0.05). No severe side effect was found during the treatment in either group.

CONCLUSIONSTriple therapy with HFOV, PS and iNO is a more effective treatment for neonatal HRF compared with the dual therapy with HFOV and iNO. The triple therapy can significantly improve oxygenation and survival rate, providing a new treatment for the neonates with HRF, especially the critical cases who suffer severe lung disease with PPHN and have a P/F ratio of ≤50 or an OI of ≥40.

Administration, Inhalation ; Female ; High-Frequency Ventilation ; Humans ; Hypoxia ; complications ; Infant, Newborn ; Length of Stay ; Male ; Nitric Oxide ; administration & dosage ; Oxygen ; blood ; Prognosis ; Pulmonary Surfactants ; therapeutic use ; Respiratory Insufficiency ; therapy

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

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 evaluate dose response of inhaled nitric oxide (iNO) for surfactant-treated rabbits with meconium aspiration-induced acute lung injury (ALI) and hypoxemic respiratory failure (HRF), and variation of measured iNO by continuous NO delivery in pressure support ventilation (PSV).

METHODSAdult rabbits (2.0 - 3.5 kg, n = 33) were randomized to receive intratracheal meconium instillation for 30 min and subjected to following treatment (n = 6 - 8). There were 4 groups: Control (C); NO, iNO at 1, 10, 20 and 40 x 10(-6) each for 60 min at 30 min interval of disconnection; Surf, intratracheal instillation of porcine lung surfactant phospholipids (100 mg/kg); SNO, both iNO and surfactant as in the NO and Surf groups; and a normal group (N), which did not undergo meconium aspiration but received sham deliveries of normal saline. All the animals were treated with PSV for 6 h. iNO levels at different input and sampling sites in the NO and SNO groups were detected by on-line chemiluminescent technique. The blood gas and lung mechanics were measured during the experiments every 2 h.

RESULTS(1) Meconium aspiration induced ALI and severe HRF (PaO(2)/FiO(2) < 200 mmHg) and depressed dynamic compliance of respiratory system (Cdyn) and airway resistance (Raw). In both Surf and NO groups modestly improved oxygenation was observed. In the SNO, values for PaO(2)/FiO(2) were improved from (185 +/- 39) mmHg at baseline to (301 +/- 123) mmHg at 6 h, while moderate or transient improvement was observed in both Surf and NO groups. Cdyn and Raw were only improved for short time in the Surf, NO and SNO groups. iNO had a mild response at 1 x 10(-6) to good response at 10 and 20 x 10(-6), but no further improvement occurred at 40 x 10(-6). The response of iNO in NO group was relatively transient compared to the SNO group. (2) When iNO was connected to the ventilator circuit, the connected site should be placed before humidifier to minimize fluctuation of iNO concentration, and sampling site for iNO monitoring should be placed adequately to eliminate artifact.

CONCLUSIONSiNO synergistically improved surfactant effects on oxygenation and lung mechanics. Continuous supply of iNO with non-continuous flow ventilator provided stable NO within accepted target range with least variation.

Administration, Inhalation ; Animals ; Drug Therapy, Combination ; Female ; Humans ; Infant, Newborn ; Lung ; drug effects ; pathology ; physiopathology ; Male ; Meconium ; Meconium Aspiration Syndrome ; complications ; Nitric Oxide ; administration & dosage ; therapeutic use ; Phospholipids ; therapeutic use ; Pulmonary Surfactants ; therapeutic use ; Pulmonary Ventilation ; Rabbits ; Random Allocation ; Respiratory Distress Syndrome, Adult ; etiology ; therapy ; Treatment Outcome