Surfactant replacement therapy for meconium aspiration syndrome. Multicenter study of surfactant (beractant) use in the treatment of term infants with severe respiratory failure. Survanta in Term Infants Study Group. Treatment of MAS with PPHN using combined therapy: SLL, bolus surfactant and iNO. Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. Treatment of severe meconium aspiration syndrome with porcine surfactant: a multicentre, randomized, controlled trial. A multicenter randomized, masked comparison trial of natural versus synthetic surfactant for the treatment of respiratory distress syndrome. Exogenous human surfactant for treatment of severe respiratory distress syndrome: a randomized prospective clinical trial. Early surfactant for neonates with mild to moderate respiratory distress syndrome: a multicenter, randomized trial. Endotracheal administration of surfactant in very low birth weight infants with respiratory distress syndrome.
The pathophysiology of meconium aspiration syndrome (MAS) is related not only to mechanical obstruction of the airways and chemical injury to the respiratory epithelium but also to surfactant inactivation by meconium. A randomized, controlled study was performed to determine whether high-dose surfactant therapy improves the pulmonary morbidity of term infants ventilated for MAS.
                Forty term infants receiving mechanical ventilation for MAS were enrolled in this trial, in which the infants in the study group (n = 20) received up to four doses of 150 mg (6 mL)/kg beractant (Survanta), instilled every 6 hours by continuous infusion for 20 minutes via a side hole endotracheal tube adapter, and the infants in the control group (n = 20) received 6 mL/kg air placebo.
                Mean arterial-to-alveolar PO2 ratio values increased from 0.09 to 0.11 at 1 and 6 hours with a concomitant slight decrease in oxygenation index values from 23.7 to 19.7 at 1 hour and 20.7 at 6 hours after the first dose of surfactant. Oxygenation improved cumulatively after the second and third dose of surfactant, with mean arterial-to-alveolar PO2 ratios and oxygenation indices of 0.18 and 12.1 at 6 hours after the second dose of surfactant and 0.31 and 5.9 at 6 hours after the third dose of surfactant, eliminating the need for a fourth dose in any infant in the study group. After three doses of surfactant, persistent pulmonary hypertension had resolved in all but one of the infants in the study group versus none of the infants in the control group. No air leaks developed in any of the 20 infants in the study group after surfactant therapy, and only 1 infant required extracorporeal membrane oxygenation. Air leaks developed in 5 of the 20 infants in the control group, and 6 underwent extracorporeal membrane oxygenation. The duration of mechanical ventilation, oxygen therapy, and admission was significantly shorter in the surfactant group than in the control group.
                Surfactant replacement therapy, if started within 6 hours after birth, improves oxygenation and reduces the incidence of air leaks, severity of pulmonary morbidity, and hospitalization time of term infants with MAS. The purpose of this study was to determine whether surfactant (beractant) administration to term newborns in respiratory failure and at risk for requiring extracorporeal membrane oxygenation (ECMO) treatment would significantly reduce the incidence of severe complications through 28 days of age and the need for ECMO.
                A multicenter (n = 44), randomized, double-blind, placebo-controlled trial was conducted. Infants weighing 2000 gm or more with gestational ages of 36 weeks or greater were stratified by diagnosis (meconium aspiration syndrome, sepsis, or idiopathic persistent pulmonary hypertension of the newborn) and oxygenation index (15 to 22, 23 to 30, 31 to 39) and then randomly assigned to receive four doses of beractant, 100 mg/kg (n = 167), or air placebo (n = 161) before ECMO treatment and four additional doses during ECMO, if ECMO was required. The incidence of untoward effects (including hemorrhagic, neurologic, pulmonary, renal, cardiovascular, infectious, metabolic, and technical complications) occurring before and after randomization and through 28 days of age or discharge were recorded.
                The two treatment groups were comparable in baseline parameters, including birth weight, sex, gestational age, oxygenation index, and primary diagnosis. There was no difference in the incidence of severe complications. The need for ECMO therapy was significantly less in the surfactant group than in the placebo group (p = 0.038); this effect was greatest within the lowest oxygenation index stratum (15 to 22; p = 0.013).
                Use of surfactant, particularly in the early phase of respiratory failure, significantly decreases the need for ECMO in the treatment of term newborns with respiratory failure, without increasing the risk of complications. The objective of the study was to compare the effectiveness of surfactant treatment either by bolus or surfactant lung lavage followed by inhaled nitric oxide (iNO) therapy in infants with meconium aspiration syndrome (MAS) complicated by persistent pulmonary hypertension (PPHN). In this study, thirteen infants with diagnosis of MAS and PPHN were first treated with conventional respiratory support. Then between 2 and 22h of life they were randomized either to bolus surfactant treatment (n=6) or surfactant lung lavage (SLL, n=7) treatment. Then all infants were treated with iNO therapy. The groups were compared with regard to their clinical course: changes in PaO(2), FiO(2), MAP, OI, A-a oxygen gradient, duration of iNO therapy, length of ventilation and hospitalization. Complications and mortality were also compared. The results showed that infants treated with SLL had significant improvements in oxygenation, decreases in MAP and A-a gradients. But there were no significant differences in duration of ventilation, iNO treatment, length of hospitalization or complications. In conclusion these data show no advantage of SLL therapy over bolus surfactant treatment in infants with MAS complicated by PPHN. To evaluate whether lung lavage with surfactant changes the duration of mechanical respiratory support or other outcomes in meconium aspiration syndrome (MAS).
                We conducted a randomized controlled trial that enrolled ventilated infants with MAS. Infants randomized to lavage received two 15-mL/kg aliquots of dilute bovine surfactant instilled into, and recovered from, the lung. Control subjects received standard care, which in both groups included high frequency ventilation, nitric oxide, and, where available, extracorporeal membrane oxygenation (ECMO).
                Sixty-six infants were randomized, with one ineligible infant excluded from analysis. Median duration of respiratory support was similar in infants who underwent lavage and control subjects (5.5 versus 6.0 days, P = .77). Requirement for high frequency ventilation and nitric oxide did not differ between the groups. Fewer infants who underwent lavage died or required ECMO: 10% (3/30) compared with 31% (11/35) in the control group (odds ratio, 0.24; 95% confidence interval, 0.060-0.97). Lavage transiently reduced oxygen saturation without substantial heart rate or blood pressure alterations. Mean airway pressure was more rapidly weaned in the lavage group after randomization.
                Lung lavage with dilute surfactant does not alter duration of respiratory support, but may reduce mortality, especially in units not offering ECMO.
                Copyright © 2011 Mosby, Inc. All rights reserved. A randomized, controlled clinical trial was performed in 19 Chinese neonatal intensive care units to evaluate the safety and efficacy of exogenous surfactant replacement therapy for severe meconium aspiration syndrome (MAS) in term and near-term neonates.
                Sixty-one term infants with severe MAS were randomly assigned to either a surfactant or a control group within 36 h after birth. The infants in the surfactant group (n=31) received an initial dose of porcine lung-derived surfactant (Curosurf) at 200 mg/kg, and repeated doses of 200, 100 and 100 mg/kg were given at 6-12 h intervals to a maximum of four doses if oxygenation index (OI) deteriorated by >2 from baseline. The primary outcomes were a reduction of OI to less than 10 and an increase of the pre-treatment a/A PO(2) ratio of 100% over baseline 24 h after surfactant treatment. The secondary outcomes were duration of mechanical ventilation, incidence of complications and survival to discharge from hospital.
                The general demographic characteristics of the study subjects were similar. There was a trend for surfactant-treated infants to have an improvement in arterial oxygenation compared to the control group. In comparison with the control group at 24 h, the surfactant group had a lower mean OI (8.1 vs 10.9), more infants with a 100% increase of a/A PO(2) (83% vs 48%, p<0.01) over baseline, and a larger area under the curve for PaO(2)/FiO(2) over baseline (3762+/-1877 vs 2715+/-1644 mmHg(.)h, p<0.05). Repeated measures of these parameters were also in favour of the surfactant group during 24 h to 3 and 7 d compared to the baseline (p<0.05). No differences were found in mean duration of mechanical ventilation, incidence of major complications and number of survivors between the two groups.
                Surfactant replacement therapy improved oxygenation in the study subjects, suggesting that surfactant may have a role in the treatment of severe MAS in term and near-term infants. 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 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. We studied the efficacy and safety of electively providing surfactant to preterm infants with mild to moderate respiratory distress syndrome (RDS) not requiring mechanical ventilation.
                A 5-center, randomized clinical trial was performed on 132 infants with RDS, birth weight >or=1250 grams, gestational age <or=36 weeks, postnatal age 4 to 24 hours, Fio(2) >or=40% for >or=1 hour, and no immediate need for intubation. Infants were randomly assigned to intubation, surfactant (Survanta, Ross Laboratories, Columbus, Ohio) administration, and expedited extubation (n=65) or expectant management (n=67) with subsequent intubation and surfactant treatment as clinically indicated. The primary outcome was duration of mechanical ventilation.
                Infants in the surfactant group had a median duration of mechanical ventilation of 2.2 hours compared with 0.0 hours for control infants, since only 29 of 67 control infants required mechanical ventilation (P=.001). Surfactant-treated infants were less likely to require subsequent mechanical ventilation for worsening respiratory disease (26% vs 43%, relative risk=0.60; 95% CI, 0.37, 0.99). There were no differences in secondary outcomes (duration of nasal continuous positive airway pressure, oxygen therapy, hospital stay, or adverse outcomes).
                Routine elective intubation for administration of surfactant to preterm infants >or=1250 grams with mild to moderate RDS is not recommended. This study was designed to evaluate whether the ventilatory maneuvers associated with surfactant replacement would, per se, influence oxygenation in newborn infants with severe respiratory distress syndrome. Eight patients (700 to 1400 g), all requiring mechanical ventilation with fraction of inspired oxygen greater than 0.6, were included in the trial; four were randomized to receive surfactant, and the others served as controls. Porcine surfactant (2 ml/kg; phospholipid concentration, 100 mg/ml) was instilled via a naso-endotracheal tube at end-expiration and dispersed into the lungs during a period of standardized "sighing" mediated by the ventilator: two prolonged ventilatory cycles (10 sec each) with an inspiration/expiration ratio of 4:1, followed by a 6-min ventilation with a frequency of 60 breath/min and an inspiration/expiration ratio of 4:1. Control babies received no surfactant but were otherwise subjected to the same ventilatory maneuvers. Surfactant-treated infants showed a rapid increase in transcutaneous oxygen associated with improved lung aeration in chest x-rays; the response was transient in three babies and persistent in one. No improvement was observed in control babies. We conclude that the beneficial effect of surfactant replacement cannot be attributed to the ventilatory maneuvers associated with the instillation procedure.
In infants with MAS, surfactant administration may reduce the severity of respiratory illness and decrease the number of infants with progressive respiratory failure requiring support with ECMO. The relative efficacy of surfactant therapy compared to, or in conjunction with, other approaches to treatment including inhaled nitric oxide, liquid ventilation, surfactant lavage and high frequency ventilation remains to be tested.