The Provo multicenter early high-frequency oscillatory ventilation trial: improved pulmonary and clinical outcome in respiratory distress syndrome. Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. Surfactant replacement therapy for meconium aspiration syndrome. Patient-initiated, pressure-regulated, volume-controlled ventilation compared with intermittent mandatory ventilation in neonates: a prospective, randomised study. Use of surfactant for prophylaxis versus rescue treatment of respiratory distress syndrome: experience from an Italian-Bulgarian trial. Pilot study of nebulized surfactant therapy for neonatal respiratory distress syndrome. Early versus delayed surfactant administration in extremely premature neonates with respiratory distress syndrome ventilated by high-frequency oscillatory ventilation. Prevention of neonatal respiratory distress syndrome by tracheal instillation of surfactant: a randomized clinical trial. Combined hormonal therapy for the prevention of respiratory distress syndrome and its consequences.
To compare the hospital course and clinical outcome of preterm infants with respiratory distress syndrome treated with surfactant and managed with high-frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CV) as their primary mode of ventilator support.
                A prospective randomized clinical trial.
                Three community-based level III neonatal intensive care units.
                A total of 125 neonates who were 35 weeks or less estimated gestation requiring intubation and assisted ventilation for respiratory distress syndrome with arterial to alveolar oxygen ratio less than .50.
                Patients were randomized to continue CV (61 patients) or be changed to HFOV (64 patients) after exogenous surfactant administration (100 mg/kg). HFOV was used in a strategy to promote lung recruitment and maintain lung volume. Protocol respiratory care guidelines were followed; otherwise routine care was provided by each neonatal intensive care unit.
                No differences were noted in demographic features between the two study groups. The study population birth weight was 1.51 +/- .47 kg (mean +/- SD), gestational age was 30.9 +/- 2.5 weeks, and study entry age was 2 to 3 hours. Patients randomized to HFOV demonstrated the following significant findings compared with CV-treated patients: vasopressor support was less intensive; surfactant redosing was not as frequent; oxygenation improved more rapidly and remained higher during the first 7 days; fewer infants required prolonged supplemental oxygen or ventilator support; treatment failure was reduced; more patients survived without chronic lung disease at 30 days; need for continuous supplemental oxygen at discharge was less; frequency of necrotizing enterocolitis illness was lower; there were fewer abnormal hearing tests; and hospital costs were decreased. No differences were seen between the two study groups in the frequency or severity of patent ductus arteriosus, air leak, retinopathy of prematurity, or intraventricular hemorrhage. Length of hospital stay and survival to discharge were similar for HFOV- and CV-treated infants.
                When used early with a lung recruitment strategy, HFOV after surfactant replacement resulted in clinical outcomes consistent with a reduction in both acute and chronic lung injury. Benefit was evident for preterm infants both less than or equal to 1 kg and more than 1 kg. In addition, early HFOV treatment may have had a more global effect on patient health throughout the hospitalization, resulting in reduced morbidity and decreased health care cost. 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. 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. To compare the effects of patient-initiated, pressure-regulated, volume-controlled ventilation (PRVC) with pressure-preset intermittent mandatory ventilation (IMV) in neonates with respiratory failure.
                Randomised, prospective study.
                Intensive care unit (14 beds) in a 300-bed paediatric teaching hospital.
                60 neonates with respiratory distress syndrome (RDS) or congenital pneumonia, weighing < 2500 g and requiring mechanical ventilation.
                Ventilatory support until extubation via either IMV (n = 30) or PRVC (n = 27). In PRVC, the tidal volume (VT) was preset and pressure-controlled breaths delivered with peak inspiratory pressure values adapted to achieve the preset VT.
                Main outcome measures were duration of ventilation and incidence of bronchopulmonary dysplasia (BPD). Pulmonary air leaks and intraventricular haemorrhage (IVH) were considered major adverse effects. Demographic data, ventilation parameters and arterial/alveolar oxygen tension ratio were similar at randomisation. Duration of ventilation and incidence of BPD were not decreased by the use of PRVC. Air leaks occurred in 3 neonates in the PRVC group and in 7 babies treated with IMV (NS). The incidence of IVH grade > II was lower in babies treated with PRVC (p < 0.05). In a subgroup of neonates weighing < 1000 g, the duration of ventilation and incidence of hypotension were reduced in the PRVC group (p < 0.05).
                Patient-initiated, pressure-regulated, volume-controlled ventilation can be safely used in neonates and may contribute to a lower incidence of complications. To show if surfactant applied in different social-sanitary realities as prophylaxis of respiratory distress syndrome (RDS) is equally useful and able to reduce mortality and incidence of 3-4 radiological grade RDS.
                Two neonatal intensive care units (NICU) in Italy, one NICU in Bulgaria and one NICU in Romania were involved in a randomized controlled clinical trial of prophylaxis vs rescue treatment of RDS. Babies with gestational age 26-30 wks were randomized before birth to prophylaxis in the delivery-room with 200 mg/kg of porcine surfactant (prophylaxis) or to routine assistance (control). Subsequently the babies developing RDS requiring mechanical ventilation and fraction of inspired oxygen (FiO2) > or = 0.4 to maintain PaO2 about 50 mmHg were allowed to be treated rescue with 200 mg/kg of the same surfactant. To reach end-points of reducing mortality by 40% and incidence of radiological grade 3-4 RDS a total number of 174 patients were required.
                Due to logistic, practical and social-political problems the study was interrupted after enrollment of 93 babies (61 in Italy and 32 in Bulgaria). The Romanian centre did not start the study because it was impossible in the scheduled times to equip it for mechanical ventilation of the newborn infants. Analysis done on an intention to treat basis did not show significant reductions of mortality and 3-4 radiological grade RDS, even if there was a trend towards a reduction in the babies given prophylaxis. A significantly lower number of babies given prophylaxis required a subsequent rescue treatment compared to controls (p < 0.001). There was no difference in other complications such as intraventricular haemorrhage, air-leak syndromes and infections between prophylaxis and control infants. As regards pulmonary gas exchange, the PaO2/FiO2 ratio was significantly improved in the babies given prophylaxis for the first 12 hours of life vs the controls.
                Even if the study was terminated before term, the analysis of the data shows that prophylaxis with surfactant is equally effective in different social-clinical conditions to improve pulmonary gas-exchange, especially in the first critical hours of life of premature babies. Thirty-four spontaneously breathing newborns with respiratory distress syndrome (RDS) requiring nasal continuous positive airway pressure (CPAP) and an arterial-to-alveolar oxygen tension ratio (a/A PO2) of 0.15-0.22 were randomized to treatment with nebulized surfactant (Curosurf) or to serve as controls. All children were first supported by nasal CPAP according to normal clinical routines. Surfactant was administered using a modified Aiolos nebulizer, and a total of 480 mg was aerosolized in each case. The control group received no nebulized material, but had the same CPAP support. Acid-base status and a/A PO2 were determined at regular intervals before, during and after surfactant administration. Both groups included in the study were similar with regard to gestational age, birthweight, steroids given before birth, sex and Apgar scores as well as a/A PO2 when entering the study. There were no significant differences between the groups in a/A PO2 1-12 h after randomization, number of infants needing mechanical ventilation, time on ventilator or CPAP. Two children in the treated group developed bronchopulmonary dysplasia. No side effects of the surfactant therapy were noted. No beneficial effects of aerosolized surfactant were demonstrated in our trial, contrary to data from animal experiments. This finding probably reflects differences in administration techniques. Our findings do not justify large clinical trials with the same protocol. Further work is needed to optimize delivery of aerosolized surfactant to the neonatal lung in clinical practice. To determine whether early surfactant administration is superior to selective delayed treatment in terms of improving survival and/or reducing chronic lung disease in extremely premature neonates with respiratory distress syndrome (RDS) treated by high-frequency oscillatory ventilation (HFOV).
                Prospective randomized clinical trial.
                Tertiary neonatal intensive care unit (NICU) in the Perinatology Center of Prague.
                Forty-three extremely premature infants who needed artificial ventilation within 3 h after delivery.
                Patients were randomly assigned to either early ( n=21) or delayed (n=22) administration of surfactant. All were ventilated by HFOV as the primary mode of ventilation using the high volume strategy aimed at optimizing lung volume. Curosurf at a dose of 100 mg/kg was given as a single bolus via the endotracheal tube within 1 min immediately after intubation in the early group (EARL), or during HFOV only when defined criteria were reached in the delayed (DEL) group.
                No differences were noted in demographic data between the two groups. Fewer infants randomized to the EARL group required oxygen use or died at 36 weeks (combined outcome 29% vs 64%, p=0.021), and there was a lower incidence of any intraventricular hemorrhage in this group (43 vs 82%, p=0.008).
                When compared to delayed dosing, early administration of surfactant followed by HFOV facilitates and accelerates respiratory stabilization during the acute phase of severe RDS, may reduce the incidence of chronic lung disease or death and may positively influence the incidence of severe intracranial pathology in extremely premature infants with primary surfactant insufficiency. With a randomized clinical trial, the possibility was assessed that a tracheal instillation of pulmonary surfactant prior to the first breath might prevent the development of some of the signs of neonatal respiratory distress syndrome. Of the 72 infants in the trial, all born at a gestational age of less than 30 weeks, 39 received 3 or 4 mL of surfactant, prepared from the lipids extracted from calf lung lavage. The treatment resulted in a significantly improved gas exchange during the first 72 hours of life. On the average, the arterial/alveolar PO2 ratio was 0.15 higher for the treated infants, and only about half as much extra oxygen had to be supplied. The respiratory support (peak inspiratory pressure X frequency) could be lowered significantly. Pulmonary interstitial emphysema occurred in 13 of the 33 control infants, but in only three of the 39 treated infants. Six of the control infants died in the neonatal period, but only one treated infant died. It is concluded that surfactant supplementation prior to the first breath is feasible and is of value as protection against the respiratory distress syndrome and the negative effects of hypoxia and ventilatory support. In performing this meta-analysis, we have attempted to use comparable data, but there are limitations to the information that is available at present. Some studies reported results for all patients entered, whereas others reported only optimally treated patients (Table 2). Many of the trials have not yet been published in final form and subjected to peer review. In addition, all the studies reported here were conducted before the widespread use of surfactant therapy. It is unclear whether the benefit of antenatal TRH and steroid therapy on end points such as death or BPD would persist if surfactant was also used. (Surfactant has, however, little impact on the percentage of survivors with BPD, perhaps because sicker infants survive with this treatment and go on to develop BPD.) Studies comparing antenatal TRH plus steroid plus postnatal surfactant to antenatal steroid plus postnatal surfactant are clearly required, and are in progress in a number of centers around the world. Because of these limitations, the routine use of antenatal TRH plus steroid cannot be currently recommended. However, the apparent benefits of this therapy in terms of RDS, death, and CLD that have been reported here do suggest that it might be used in selected situations. An example is threatened delivery of a very premature infant with an immature amniotic fluid pulmonary maturation profile. These infants are at risk for RDS and CLD, even if antenatal steroid and postnatal surfactant therapy is used.(ABSTRACT TRUNCATED AT 250 WORDS)
Caution should be exercised in applying these results to modern neonatal intensive care, because the studies included in this review were conducted prior to the introduction of antenatal steroids, post natal surfactant and the use of synchronised modes of ventilatory support. Most of the participants had single pathology (HMD) and no studies examined the effects of IT on newborns ventilated for other reasons such as meconium aspiration and congenital heart disease (lungs with normal compliance). However, the increased rates of air leaks and deaths using long ITs are clinically important; thus, infants with poorly compliant lungs should be ventilated with a short IT.