Robert J. Couser

Prophylaxis of Early Adrenal Insufficiency to Prevent Bronchopulmonary Dysplasia: A Multicenter Trial

Background. Infants developing bronchopulmonary dysplasia (BPD) show decreased cortisol response to adrenocorticotropic hormone. A pilot study of low-dose hydrocortisone therapy for prophylaxis of early adrenal insufficiency showed improved survival without BPD at 36 weeks’ postmenstrual age, particularly in infants exposed to histologic chorioamnionitis. Methods. Mechanically ventilated infants with birth weights of 500 to 999 g were enrolled into this multicenter, randomized, masked trial between 12 and 48 hours of life. Patients received placebo or hydrocortisone, 1 mg/kg per day for 12 days, then 0.5 mg/kg per day for 3 days. BPD at 36 weeks’ postmenstrual age was defined clinically (receiving supplemental oxygen) and physiologically (supplemental oxygen required for O2 saturation ≥90%). Results. Patient enrollment was stopped at 360 patients because of an increase in spontaneous gastrointestinal perforation in the hydrocortisone-treated group. Survival without BPD was similar, defined clinically or physiologically, as were mortality, head circumference, and weight at 36 weeks. For patients exposed to histologic chorioamnionitis (n = 149), hydrocortisone treatment significantly decreased mortality and increased survival without BPD, defined clinically or physiologically. After treatment, cortisol values and response to adrenocorticotropic hormone were similar between groups. Hydrocortisone-treated infants receiving indomethacin had more gastrointestinal perforations than placebo-treated infants receiving indomethacin, suggesting an interactive effect. Conclusions. Prophylaxis of early adrenal insufficiency did not improve survival without BPD in the overall study population; however, treatment of chorioamnionitis-exposed infants significantly decreased mortality and improved survival without BPD. Low-dose hydrocortisone therapy did not suppress adrenal function or compromise short-term growth. The combination of indomethacin and hydrocortisone should be avoided.

Survival and follow-up of infants born at 23 to 26 weeks of gestational age: Effects of surfactant therapy

Abstract Little information is available regarding the effect of surfactant on outcome for infants born at or before 26 weeks of gestation. We addressed this issue by reviewing records of 310 infants born at gestational ages of 23 through 26 weeks who were admitted to our nursery from 1986, when surfactant was introduced, through 1990. Surfactant was administered to 154 infants (5 during a single-dose prevention study, 25 during a multiple-dose prevention study, 124 while receiving a Food and Drug Administration treatment investigational new drug); 156 infants were not treated with surfactant. Seventy-three percent of the treated infants survived, compared with 55% of the nontreated infants. Increased survival occurred at all gestational ages between 23 and 26 weeks but were greatest in infants born at 23 and 24 weeks. At follow-up, no differences in neurologic outcome were detected between surfactant-treated and nontreated infants. We conclude that surfactant use in extremely premature infants improves survival rates without increasing the proportion of impaired survivors. (J P EDIATR 1994;124: 119-24)

Effects of exogenous surfactant therapy on dynamic compliance during mechanical breathing in preterm infants with hyaline membrane disease

In a prospective, randomized, controlled clinical trial, the immediate and the longitudinal effects of exogenous surfactant therapy on pulmonary mechanics were evaluated in extremely premature infants during mechanical respiration. Ninety-four infants weighing between 600 and 1250 gm received either exogenous surfactant or sham (air) therapy in the delivery room and up to three additional doses in the first 48 hours of life if they were ventilator-dependent, had fractional inspiratory oxygen requirements greater than or equal to 0.30, and radiographic findings consistent with hyaline membrane disease. Each infant underwent pulmonary mechanics assessment (dynamic compliance, total pulmonary resistance, tidal volume) immediately before and 1 hour after each dose, and at 24, 48, and 72 hours and 7 days of age. There were no significant differences in dynamic compliance, total pulmonary resistance, and tidal volume in the surfactant (n = 47) and control (n = 47) groups before and 1 hour after each dose. However, dynamic compliance was 50% greater in the surfactant group at 24 hours of age (p less than or equal to 0.009); this difference steadily increased to 94% at 7 days of age (p less than or equal to 0.009). Oxygenation, assessed by the ratio of alveolar to arterial oxygen pressure, was significantly greater in the surfactant group during the first 72 hours of life; the greatest difference was noted at 24 hours (p less than or equal to 0.001). Mean airway pressure requirements in the surfactant group were significantly less than in the control group at all times during the first week. We conclude that exogenous surfactant therapy, administered at birth and during the first 48 hours of life in extremely premature infants with hyaline membrane disease, improves dynamic compliance and gas exchange during mechanical breathing.

Effectiveness of dexamethasone in preventing extubation failure in preterm infants at increased risk for airway edema

We studied 50 preterm infants who had multiple or traumatic endotracheal intubations, or whose duration of endotracheal intubation was > or = to 14 days, and who were considered at high risk for airway edema. These infants were enrolled in a prospective, randomized, controlled clinical trial to assess whether prophylactic dexamethasone therapy would be effective in the prevention of postextubation stridor and respiratory distress. At study entry, both groups had similar weights, postnatal ages, methylxanthine use, ventilator settings, blood gas values, and pulmonary function test results (dynamic compliance, total respiratory resistance, tidal volume, peak-to-peak transpulmonary pressure, minute ventilation, and peak inspiratory and expiratory flow rates). Patients underwent blood gas studies, physical examinations, and pulmonary function testing at baseline (4 hours before extubation) and again 2 to 4 hours and 18 to 24 hours after extubation. Twenty-seven infants received dexamethasone, 0.25 mg/kg per dose, at baseline, and then every 8 hours for a total of three doses; 23 infants received saline solution at corresponding times. Eighteen to twenty-four hours after extubation, total pulmonary resistance increased by 225% from baseline in the control group compared with 33% in the dexamethasone group (p < 0.006), and the dexamethasone group had a greater tidal volume, a greater dynamic compliance, and a lower arterial carbon dioxide pressure. Of 23 control infants, 10 had postextubation stridor compared with 2 of 27 dexamethasone-treated patients (p < 0.006). Of the 23 control patients, 4 required reintubation compared with none of the treated group (p < 0.05). We conclude that the prophylactic use of corticosteroids for the prevention of postextubation stridor and respiratory distress is efficacious in low birth weight, high-risk preterm infants.

Prophylactic indomethacin therapy in the first twenty-four hours of life for the prevention of patent ductus arteriosus in preterm infants treated prophylactically with surfactant in the delivery room

OBJECTIVE To determine whether a course of low-dose indomethacin therapy, when initiated within 24 hours of birth, would decrease ductal shunting in premature infants who received prophylactic surfactant in the delivery room. DESIGN Ninety infants, with birth weights of 600 to 1250 gm, were entered into a prospective, randomized, controlled trial to receive either indomethacin, 0.1 mg/kg per dose, or placebo less than 24 hours and again every 24 hours for six doses. Echocardiography was performed on day 1 before treatment and on day 7, 24 hours after treatment. A hemodynamically significant patent ductus arteriosus (PDA) was confirmed with an out-of-study echocardiogram, and the nonresponders were treated with standard indomethacin or ligation. RESULTS Forty-three infants received indomethacin (birth weight, 915 +/- 209 gm; gestational age, 26.4 +/- 1.6 weeks; 25 boys), and 47 received placebo (birth weight, 879 +/- 202 gm; gestational age, 26.4 +/- 1.8 weeks; 22 boys) (P = not significant). Of 90 infants, 77 (86%) had a PDA by echocardiogram on the first day of life before study treatment; 84% of these PDAs were moderate or large in size in the indomethacin-treated group compared with 93% in the placebo group. Nine of forty indomethacin-treated infants (21%) were study-dose nonresponders compared with 22 (47%) of 47 placebo-treated infants (p < 0.018). There were no significant differences between both groups in any of the long-term outcome variables, including intraventricular hemorrhage, duration of oxygen therapy, endotracheal intubation, duration of stay in neonatal intensive care unit, time to regain birth weight or reach full caloric intake, incidence of bronchopulmonary dysplasia, and survival. No significant differences were noted in the incidence of oliguria, elevated plasma creatinine concentration, thrombocytopenia, pulmonary hemorrhage, or necrotizing enterocolitis. CONCLUSION The prophylactic use of low doses of indomethacin, when initiated in the first 24 hours of life in low birth weight infants who receive prophylactic surfactant in the delivery room, decreases the incidence of left-to-right shunting at the level of the ductus arteriosus.

Long-term follow-up of premature infants treated with prophylactic, intratracheal recombinant human CuZn superoxide dismutase.

OBJECTIVE:To examine the long-term effects of treatment with recombinant human CuZn superoxide dismutase (rhSOD) in infants enrolled previously in two placebo-controlled trials.STUDY DESIGN:Records for 46 (88%) infants were examined, with 19 infants having received either single or multiple intratracheal (i.t.) doses of placebo, 12 having received a single i.t. dose of rhSOD, and 15 having received multiple i.t. doses of rhSOD. Mean age at follow-up was 28 months corrected age. Records were examined for neurologic dysfunction, developmental delay, and any significant medical disorders.RESULTS:Four placebo infants (21%) had evidence of neurodevelopmental abnormalities and four infants developed asthma. Four single-dose rhSOD infants (33%) had neurodevelopmental abnormalities and two infants developed asthma. One multiple-dose rhSOD infant had evidence ofneurodevelopmental abnormalities and one developed asthma. No other differences were found between the placebo and rhSOD groups.CONCLUSION: Preliminary data suggest that rhSOD is safe and not associated with any long-term adverse effects. Further results will depend on the results of multicenter trials of rhSOD in preterm infants.

Effects of surfactant therapy on outcome of infants with birth weights of 600 to 750 grams

Replacement therapy with exogenous surfactant has been studied for both prevention and treatment of respiratory distress syndrome. Although reports demonstrate improved survival rates for surfactant-treated infants with RDS, the impact of this therapy on outcome of extremely low birth weight infants is unknown. TM Previous studies have not reported outcome after surfactant treatment for the subset of premature infants who are born at ELBWs and who are at the highest risk for complications of prematurity. We report the outcome of infants born with birth weights between 600 and 750 gm who underwent prospective random selection to receive either surfactant or placebo as part of a multidose prevention study.

The Effects of Multiple Doses of Recombinant Human CuZn Superoxide Dismutase (rhSOD) in Premature Infants with Respiratory Distress Syndrome (RDS)

The Effects of Multiple Doses of Recombinant Human CuZn Superoxide Dismutase (rhSOD) in Premature Infants with Respiratory Distress Syndrome (RDS)

Long Term Follow-up of Premature Infants Treated with Prophylactic, Intratracheal Recombinant Human CuZn Superoxide Dismutase (rhSOD) |[diams]| 1211

Long Term Follow-up of Premature Infants Treated with Prophylactic, Intratracheal Recombinant Human CuZn Superoxide Dismutase (rhSOD) ♦ 1211

Indomethacin (INC) Pharmacokinetics in Extremely Premature Infants who Receive Prophylactic (P) ICN in the First 24H of Life for Prevention of Patent Ductus Arteriosus (PDA) |[bull]| 991

Indomethacin (INC) Pharmacokinetics in Extremely Premature Infants who Receive Prophylactic (P) ICN in the First 24H of Life for Prevention of Patent Ductus Arteriosus (PDA) • 991