Surfactant administration by transient intubation in infants 29 to 35 weeks' gestation with respiratory distress syndrome decreases the likelihood of later mechanical ventilation: a randomized controlled trial. Early extubation and nasal continuous positive airway pressure after surfactant treatment for respiratory distress syndrome among preterm infants <30 weeks' gestation. Surfactant replacement therapy for severe neonatal respiratory distress syndrome: an international randomized clinical trial. Collaborative European Multicenter Study Group. A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome. Randomized trial comparing 3 approaches to the initial respiratory management of preterm neonates. Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial. A controlled trial of human surfactant replacement therapy for severe respiratory distress syndrome in very low birth weight infants. A prospective randomized, controlled trial comparing synchronized nasal intermittent positive pressure ventilation versus nasal continuous positive airway pressure as modes of extubation. Bovine surfactant replacement therapy in neonates of less than 30 weeks' gestation: a randomized controlled trial of prophylaxis versus treatment.
To assess, among premature infants with early respiratory distress syndrome (RDS), the effect of one dose of intratracheally administered surfactant followed by extubation to nasal continuous positive airway pressure (NCPAP) on subsequent mechanical ventilation (MV), when compared with NCPAP alone.
                Randomized, blinded trial in infants 29 to 35 weeks' gestation with mild-to-moderate RDS requiring supplemental oxygen and NCPAP. Infants were randomized to intubation, surfactant treatment, and immediate extubation (surfactant group N=52), or to no intervention (control group N=53). All infants were subsequently managed with NCPAP.
                Need for later MV was 70% in the control group and 50% in the surfactant group. Surfactant group subjects had lower inspired oxygen fraction (FiO(2)) after study intervention and were less likely to require subsequent surfactant. Overall surfactant use, duration of O(2) therapy, length of stay, and bronchopulmonary dysplasia were unaffected.
                Among premature infants with mild-to-moderate RDS, transient intubation for surfactant administration reduces later MV.
                Journal of Perinatology (2005) 25, 703-708. doi:10.1038/sj.jp.7211381; published online 15 September 2005. To test the hypothesis that preterm infants with infant respiratory distress syndrome who are treated with nasal continuous positive airway pressure (NCPAP) and surfactant administration followed by immediate extubation and NCPAP application (SURF-NCPAP group) demonstrate less need for mechanical ventilation (MV), compared with infants who receive MV after surfactant administration (SURF-MV group).
                A prospective randomized study was conducted, in which infants <30 weeks' gestation were randomized to the SURF-NCPAP group or the SURF-MV group.
                At 7 days of life, no patient in the SURF-NCPAP group but 6 patients (43%) in the SURF-MV group still were undergoing MV. The duration of oxygen therapy, NCPAP, and MV, the need for a second dose of surfactant, and the length of stay in the intensive care unit were significantly greater in the SURF-MV group.
                The immediate reinstitution of NCPAP after surfactant administration for infants with infant respiratory distress syndrome is safe and beneficial, as indicated by the lesser need for MV and the briefer requirement for respiratory supports, compared with the institution of MV after surfactant treatment. Moreover, this strategy contributed to reducing the need for surfactant treatment and reducing the time and costs involved in keeping the infants in the neonatal intensive care unit. In a randomized multicenter trial, involving the collaboration of eight European neonatal intensive care units, the efficacy of replacement therapy with a new surfactant preparation (Curosurf) was tested in 146 patients with severe neonatal respiratory distress syndrome. Criteria for entry included birth weight 700 to 2,000 g, age when treated two to 15 hours, and requirement of artificial ventilation with FiO2 greater than or equal to 0.6. The babies were treated with a single large dose of surfactant (200 mg/kg) at a median age of nine hours (range two to 15 hours). Average FiO2 before treatment was the same (0.80) for both surfactant-treated patients and control patients. Babies receiving surfactant showed, within five minutes, a dramatic improvement of oxygenation as reflected by a nearly threefold increase of the PaO2/FiO2 ratio. Six hours after randomization, the PaO2/FiO2 ratio still showed a 98% improvement in surfactant-treated patients compared with controls (P less than .001), and statistically significant differences in favor of the treated babies persisted until 48 hours after randomization, when surviving control infants began to recover. Treatment with surfactant decreased neonatal (less than or equal to 28 days) mortality from 51% to 31% (P less than .05). Compared with control babies, the surfactant-treated group also had a decreased incidence of pulmonary interstitial emphysema (23% v 39%; P less than .05) and pneumothorax (18% v 35%; P less than .05). The percentage of survivors without bronchopulmonary dysplasia in the treated group was more than twice that of the control group (55% v 26%; P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS) To compare the efficacy and safety of two surfactant preparations in the treatment of respiratory distress syndrome (RDS).
                We conducted a randomized, masked comparison trial at 21 centers. Infants with RDS who were undergoing mechanical ventilation were eligible for treatment with two doses of either a synthetic (Exosurf) or natural (Infasurf) surfactant if the ratio of arterial to alveolar partial pressure of oxygen was less than or equal to 0.22. Crossover treatment was allowed within 96 hours of age if severe respiratory failure (defined as two consecutive arterial/alveolar oxygen tension ratios < or = 0.10) persisted after two doses of the randomly assigned surfactant. Four primary outcome measures of efficacy (the incidence of pulmonary air leak (< or = 7 days); the severity of RDS; the incidence of death from RDS; and the incidence of survival without bronchopulmonary dysplasia (BPD) at 28 days after birth) were compared by means of linear regression techniques.
                The primary analysis of efficacy was performed in 1033 eligible infants and an analysis of safety outcomes in the 1126 infants who received study surfactant. Preentry demographic characteristics and respiratory status were similar for the two treatment groups, except for a small but significant difference in mean gestational age (0.5 week) that favored the infasurf treatment group. Pulmonary air leak (< or = 7 days) occurred in 21% of Exosurf- and 11% of infasurf-treated infants (adjusted relative risk, 0.53; 95% confidence interval, 0.40 to 0.71; p < or = 0.0001). During the 72 hours after the initial surfactant treatment, the average fraction of inspired oxygen (+/-SEM) was 0.47 +/- 0.01 for Exosurf- and 0.39 +/- 0.01 for infasurf-treated infants (difference, 0.08; 95% confidence interval, 0.06 to 0.10; p < 0.0001); the average mean airway pressure (+/-SEM) was 8.6 +/- 0.1 cm H2O; for Exosurf- and 7.2 +/- 0.1 cm H2O for Infasurf-treated infants (difference, 1.4 cm H2O; 95% confidence interval, 1.0 to 1.8 cm H2O; p < 0.0001). The incidences of RDS-related death, total respiratory death, death to discharge, and survival without bronchopulmonary dysplasia at 28 days after birth did not differ. The number of days of more than 30% inspired oxygen and of assisted ventilation, but not the duration of hospitalization, were significantly lower in Infasurf-treated infants.
                Compared with Exosurf, Infasurf provided more effective therapy for RDS as assessed by significant reductions in the severity of respiratory disease and in the incidence of air leak complications. We designed a multicenter randomized trial to compare 3 approaches to the initial respiratory management of preterm neonates: prophylactic surfactant followed by a period of mechanical ventilation (prophylactic surfactant [PS]); prophylactic surfactant with rapid extubation to bubble nasal continuous positive airway pressure (intubate-surfactant-extubate [ISX]) or initial management with bubble continuous positive airway pressure and selective surfactant treatment (nCPAP).
                Neonates born at 26 0/7 to 29 6/7 weeks' gestation were enrolled at participating Vermont Oxford Network centers and randomly assigned to PS, ISX, or nCPAP groups before delivery. Primary outcome was the incidence of death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age.
                648 infants enrolled at 27 centers. The study was halted before the desired sample size was reached because of declining enrollment. When compared with the PS group, the relative risk of BPD or death was 0.78 (95% confidence interval: 0.59-1.03) for the ISX group and 0.83 (95% confidence interval: 0.64-1.09) for the nCPAP group. There were no statistically significant differences in mortality or other complications of prematurity. In the nCPAP group, 48% were managed without intubation and ventilation, and 54% without surfactant treatment.
                Preterm neonates were initially managed with either nCPAP or PS with rapid extubation to nCPAP had similar clinical outcomes to those treated with PS followed by a period of mechanical ventilation. An approach that uses early nCPAP leads to a reduction in the number of infants who are intubated and given surfactant. We performed a randomized, prospective clinical trial comparing intratracheal administration of human surfactant with conventional treatment with intermittent mandatory mechanical ventilation alone for treatment of severe respiratory distress syndrome in preterm infants of less than 30 weeks gestation. Twenty-two infants (mean gestational age 27.0 weeks, mean birth weight 987 gm) were given surfactant, and 23 infants (mean gestational age 27.2 week, mean birth weight 1055 gm) received intermittent mandatory ventilation. Infants given surfactant required less FiO2 during the first week, had lower mean airway pressure during the first 48 hours, and had improved ventilatory index and a/A PO2 ratio. Death or the occurrence of bronchopulmonary dysplasia was significantly less among infants given surfactant (P = 0.019). Pneumothorax, pulmonary interstitial emphysema, and need for FiO2 greater than or equal to 0.3 for greater than 30 days was significantly less in the surfactant group. This trial confirms the efficacy of treatment with human surfactant in preterm infants with severe respiratory distress syndrome. In a randomized, controlled study, human surfactant derived from amniotic fluid was administered within 12 hours of birth to infants with severe respiratory distress syndrome who were born at 24 to 32 weeks of gestation weighing less than or equal to 1500 gm. A second dose of surfactant was given to patients in the treatment group if they met ventilator requirements indicating relapse or lack of response to the initial dose. No significant improvement was observed in mortality rate (9/28 vs 15/31) or incidence of bronchopulmonary dysplasia (5/28 vs 3/31) when surfactant-treated infants were compared with control subjects, although there was a significant reduction in initial respirator and inspired oxygen requirements and the arterial/alveolar oxygen ratio improved. In addition, there was a significant reduction in pulmonary air leak in treated infants (10/28 vs 20/31; p less than 0.05). Retreatment was associated with an attenuated ventilatory response and with a higher mortality rate (7/14) than that of infants who did not require a second dose (2/14; p = 0.05), indicating a more severe form of disease. Multiple discriminant analysis, including eight independent variables, revealed that increasing birth weight, earlier age at surfactant treatment, and female gender were significantly associated with survival. These data suggest that early surfactant treatment may reduce mortality rates in very low birth weight infants with severe respiratory distress syndrome, as well as reduce ventilator requirements and the incidence of pulmonary air leaks. To determine whether synchronized nasal intermittent positive pressure ventilation (SNIPPV) would decrease extubation failure compared with nasal continuous positive airway pressure (NCPAP) in preterm infants being ventilated for respiratory distress syndrome (RDS).
                Infants who were </=34 weeks' gestational age and who were ventilated for RDS were randomized to either SNIPPV or NCPAP after extubation. The criteria for extubation were peak inspiratory pressure of </=16 cm H(2)O, positive end expiratory pressure of </=5 cm H(2)O, intermittent mandatory ventilation rate of 15 to 25, and fraction of inspired oxygen </=0.35. Pulmonary function tests (PFT) were obtained before extubation. After extubation, blood gases were monitored for a minimum of 72 hours. Success was defined as remaining in the selected mode of treatment or demonstrating improvement (switching to oxyhood/nasal cannula/room air) by 72 hours.
                Thirty-two (94%) of 34 infants were extubated successfully with the use of SNIPPV versus 18 (60%) of 30 with the use of NCPAP (P <.01). There was no difference in apnea/bradycardia episodes in the 2 groups during the 72-hour study period. Among 55 infants who had PFT, 80% (8 of 10) with dynamic lung compliance of >/=0.5 mL/kg/cm H(2)O and expiratory airway resistance of </=70 cm H(2)O/L/s were extubated successfully. In infants with poor lung function (dynamic lung compliance: <0.5 mL/kg/cm H(2)O; expiratory airway resistance: >70 cm H(2)O/L/s), successful extubation was seen in 93% (27 of 29) in the SNIPPV group and 60% (15 of 25) in the NCPAP group. When weight was controlled for at the time of extubation, the odds of success in the SNIPPV group were 21.1 times higher (95% confidence interval: 3.4, 130.1) than that of the NCPAP group.
                SNIPPV is more effective than NCPAP in weaning infants with RDS from the ventilator. PFT may be useful in predicting successful extubation. The influence of the timing of surfactant replacement therapy for the treatment of neonatal respiratory distress syndrome was evaluated in a study of 182 neonates of less than 30 weeks' gestation who were randomly assigned prior to delivery to one of three study groups: control (dummy instillation of air given at birth), early surfactant (surfactant given at birth), or late surfactant (surfactant given at less than 6 hours of age). Subjects in the late surfactant group could avoid treatment if they had a clear chest roentgenogram and required no supplemental oxygen at a mean airway pressure of less than 7 cm of water. All treated neonates were eligible to receive up to three additional doses during the first 5 days of life. The three groups were comparable with respect to birth weight, gestational age, and other perinatal parameters with the exception of a lower cord arterial pH and 1-minute Apgar score in the early surfactant group. Of the 60 neonates randomly assigned to late treatment, 29 (48%) were deemed surfactant sufficient and thereby avoided treatment; the other 31 received their first dose at a mean age of 2.9 hours. There was a significant improvement in gas exchange during the first week of life in both surfactant groups compared with the control group, reflected by differences in fraction of inspired oxygen, arterial/alveolar PO2, and ventilation index (peak pressure x rate on the ventilator) (P less than .001). Surfactant therapy also resulted in a lower incidence of pulmonary air leak and severe chronic lung disease (defined as requirement for respiratory support beyond 36 weeks post-conceptional age). There were no differences between early and late surfactant groups in any of these parameters. The only statistically significant difference between the surfactant groups was that the early group had a higher incidence of mild chronic lung disease (respiratory support beyond 28 days of age) than the late treatment group (P less than .005). Neonates in the late treatment group were extubated earlier and had a shorter neonatal intensive care unit stay than control neonates (P less than .05), whereas those in the early group were not significantly different from control neonates in these parameters. It is concluded that replacement therapy with bovine lung surfactant extract in neonates of less than 30 weeks' gestation results in decreased oxygen and ventilatory requirements during the first week of life and a lower incidence of pulmonary air leak and severe chronic lung disease.(ABSTRACT TRUNCATED AT 400 WORDS)
Early surfactant replacement therapy with extubation to NCPAP compared with later selective surfactant replacement and continued mechanical ventilation with extubation from low ventilator support is associated with less need mechanical ventilation, lower incidence of BPD and fewer air leak syndromes. A lower treatment threshold (FIO2 < 0.45) confers greater advantage in reducing the incidences of airleak syndromes and BPD; moreover a higher treatment threshold (FIO2 at study > 0.45) was associated with increased risk of PDA. These data suggest that treatment with surfactant by transient intubation using a low treatment threshold (FIO2 < 0.45) is preferable to later, selective surfactant therapy by transient intubation using a higher threshold for study entry (FIO2 > 0.45) or at the time of respiratory failure and initiation of mechanical ventilation.