Prevention of chronic lung disease in preterm infants by early postnatal dexamethasone therapy. Comparative efficacy of exosurf and survanta surfactants on early clinical course of respiratory distress syndrome and complications of prematurity. Prevention of bronchopulmonary dysplasia by administration of bovine superoxide dismutase in preterm infants with respiratory distress syndrome. Failure of early postnatal dexamethasone to prevent chronic lung disease in infants with respiratory distress syndrome. Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. [The second phase clinical observation of anti-radiation effect by superoxide dismutase]. Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. Clinical Inhaled Nitric Oxide Research Group. A double-blind randomised controlled trial of continuous oxygen therapy for compromised fetuses. Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial.
Recent studies suggest that early dexamethasone therapy may lessen the pulmonary inflammation in preterm infants with respiratory distress syndrome (RDS). To investigate whether early (<12 hr) postnatal dexamethasone therapy would reduce the incidence of chronic lung disease (CLD), a randomized, double-blind, controlled trial was conducted in 40 infants (birth weights from 500 to 1,999 gm) who had severe RDS and required mechanical ventilation within 6 hr of birth. All infants received one dose of Survanta before they were randomly assigned to control (saline placebo) or dexamethasone-treated groups (0.5 mg/kg/d for 1 week, then tapered over 3 weeks). Sequential analysis was performed with the end point of assessment being the presence or absence of CLD on postnatal Day 28. Statistical significance favoring dexamethasone was reached when 12 consecutive pairs in which one infant had CLD and the other did not have CLD showed that ten pairs favored dexamethasone and two pairs favored control treatment. Among the survivors, 12/15 were extubated in the dexamethasone group and 9/16 in the control group at the end of study. Infants in the treated group had transient hyperglycemia and hypertension. There was no difference between the groups in mortality and in incidence of sepsis or intraventricular hemorrhage. We conclude that early postnatal dexamethasone therapy is potentially effective in the lessening of CLD in preterm infants. To substantiate our result, large randomized controlled trials are needed and warranted. To determine the comparative efficacy of Exosurf Neonatal and Survanta surfactants on the early course of respiratory distress syndrome (RDS), arterial blood gases, ventilatory support, outcome morbidity rate, and complications of prematurity and RDS.
                Medical records from 203 premature newborn infants undergoing mechanical ventilation for respiratory distress syndrome, and who received up to four rescue doses of either Exosurf or Survanta, were retrospectively reviewed.
                All groups were comparable for birth weight and gestational age. Although the two randomized groups were similar in severity of RDS based on fraction of inspired oxygen (FIO2) and ventilatory support, a significantly greater improvement in respiratory function as evidenced by FIO2, mean airway pressure, alveolar-arterial partial pressure of oxygen difference, and oxygen index, was observed in the Survanta group from 12 hours (p < 0.05) through 48 hours (p < 0.01). Comparison of outcome morbidity rate by gestational age showed a higher occurrence of retinopathy of prematurity (p < 0.02) among the older infants (28 to 32 weeks) who were treated with Exosurf.
                Survanta exerted a significantly faster response in the early clinical course of RDS compared with Exosurf. However, no difference in the impact on eventual respiratory outcome was observed. We therefore conclude that both surfactants are effective for the treatment of RDS. The effectiveness of bovine superoxide dismutase (SOD) in the prevention of bronchopulmonary dysplasia was evaluated in a prospective double-blind controlled study in 45 neonates (mean gestational age 28.7 weeks, mean weight 1154 gm) with severe respiratory distress syndrome. All were ventilator dependent with FiO2 greater than or equal to 0.7 at 24 hours of age. Either bovine SOD (0.25 mg/kg) or saline solution was administered subcutaneously every 12 hours according to random selection until patients could be maintained in room air without ventilatory or continuous positive airway pressure (CPAP) support. SOD levels were detected in all patients given treatment. Mean peak values at 4 hours after dose ranged from 0.15 micrograms/ml (dose 1) to 0.45 micrograms/ml (dose 10). The drug was well tolerated, and no side effects were detected. Among the 31 survivors (SOD 14, placebo 17) radiologic evidence of BPD was significantly less in patients given SOD (3/14 vs 12/17, P = 0.008). Clinical signs of bronchopulmonary dysplasia (wheezing, pneumonia) were less in patients given SOD (3/14 vs 11/17, P = 0.019). Patients given SOD required fewer days of CPAP (P less than 0.003). There were no differences in days of O2 therapy, intermittent positive pressure breathing, or incidence and severity of patent ductus arteriosus or intraventricular hemorrhage. This preliminary study suggests that SOD may be helpful in reducing the severity of bronchopulmonary dysplasia in infants with respiratory distress syndrome. To study the effect of early postnatal dexamethasone (days 1-3) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome.
                A multicentre, randomised, placebo controlled, blinded study was carried out in 18 neonatal intensive care units in Israel. The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life. The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days, duration of ventilation or oxygen therapy, need for subsequent steroids for established chronic lung disease and incidence of major morbidities.
                The study consisted of 248 infants (dexamethasone n = 132; placebo n = 116). No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants (dexamethasone 44%, placebo 67%; P = 0.001). Gastrointestinal haemorrhage, hypertension, and hyperglycaemia were more common in treated infants, but no life threatening complications, such as gastrointestinal perforation, were encountered.
                These data do no support the routine use of early postnatal steroids, but may justify further study in a selected, high risk group of infants. In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD. Multiple center randomized controlled double blind clinical trait was conducted to evaluate the anti-radiotherapy effect by SOD (produced by Hunan Biochemical Work) in 159 patients. Injection of 4000U SOD immediately after receiving radiotherapy significantly reduced the occurrence rate of skin, oral mucosal, pelvic visceral and systematic adverse reaction, only the reduction of leukopenia did not reach the statistical significant level. No adverse effect of SOD injection was observed. The results suggest that SOD is a safe and effective agent to attenuate the radiotherapy reactions. Inhaled nitric oxide improves gas exchange in neonates, but the efficacy of low-dose inhaled nitric oxide in reducing the need for extracorporeal membrane oxygenation has not been established.
                We conducted a clinical trial to determine whether low-dose inhaled nitric oxide would reduce the use of extracorporeal membrane oxygenation in neonates with pulmonary hypertension who were born after 34 weeks' gestation, were 4 days old or younger, required assisted ventilation, and had hypoxemic respiratory failure as defined by an oxygenation index of 25 or higher. The neonates who received nitric oxide were treated with 20 ppm for a maximum of 24 hours, followed by 5 ppm for no more than 96 hours. The primary end point of the study was the use of extracorporeal membrane oxygenation.
                Of 248 neonates enrolled, 126 were randomly assigned to the nitric oxide group and 122 to the control group. Extracorporeal membrane oxygenation was used in 78 neonates in the control group (64 percent) and in 48 neonates in the nitric oxide group (38 percent) (P=0.001). The 30-day mortality rate in the two groups was similar (8 percent in the control group and 7 percent in the nitric oxide group). Chronic lung disease developed less often in neonates treated with nitric oxide than in those in the control group (7 percent vs. 20 percent, P=0.02). The efficacy of nitric oxide was independent of the base-line oxygenation index and the primary pulmonary diagnosis.
                Inhaled nitric oxide reduces the extent to which extracorporeal membrane oxygenation is needed in neonates with hypoxemic respiratory failure and pulmonary hypertension. To investigate the effect of chronic oxygen therapy in fetuses with absent end diastolic flow in the umbilical artery assessed by doppler analysis at 24-30 weeks of gestation.
                A double-blind, randomised control trial was performed with patients blindly allocated to receive humidified oxygen or humidified air.
                A tertiary referral hospital in South Africa.
                Thirty-two women who presented between 24 and 30 weeks of gestation with a confirmed finding of absent end diastolic flow in the umbilical artery.
                After randomisation patients were allocated to receive a 40% mixture of humidified oxygen or humidified air from uniform coloured gas cylinders which were marked either 'a' or 'b' All women received betamethasone from 27 weeks of gestation on a weekly basis. Cardiotocographs were used from 28 weeks of gestation; after 28 weeks of gestation an amniocentesis was considered to confirm fetal maturity. Women were expected to breath the allocated gas continuously apart from meals and visits to the toilet.
                Survival of the fetus was the main outcome measure with secondary outcome measures documenting improvement in the fetal condition in utero.
                There were 16 women randomised to receive oxygen and 16 to receive air. There were nine survivors in the oxygen group (56.3%) and six in the air group (37.5%) (relative risk 1.5, 95% confidence interval 0.7-3.2). There was a nonsignificant increase in mean birthweight in the oxygen group (858.3 grammes vs 774.4 grammes) and a nonsignificant increase in mean duration of treatment in the oxygen group (12.8 days vs 10.4 days).
                This study did not demonstrate that chronic oxygen therapy provides any benefits to compromised fetuses between 24 and 30 weeks of gestation. Larger studies with sufficient power are necessary to assess whether oxygen therapy can reduce perinatal mortality by a clinically useful amount in this group of patients. Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease.
                We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age.
                The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%).
                Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.
Based on currently available published trials, there is insufficient evidence to draw firm conclusions about the efficacy of superoxide dismutase in preventing chronic lung disease of prematurity. Data from a small number of treated infants suggest that it is well tolerated and has no serious adverse effects.