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Notes: Abstract We performed a multicenter prospective randomized controlled trial to determine the efficacy and safety of the surfactant preparation, Survanta (Abbott Laboratories, Chicago, USA), for 750–1750 g infants with idiopathic respiratory distress syndrome, (IRDS) receiving assisted ventilation with 40% or more oxygen. One hundred and six eligible infants from the eight participating centers were randomly assigned between March 1986 and June 1987 to receive either surfactant (100 mg phospholipid/kg, 4 ml/kg) or air (4 ml/kg) administered into the trachea within 8 h of brith (median time of treatment 6.2 h, range 3.2–9.1 h). The study was stopped before enrollment was completed at the request of the United States Food and Drug Administration when significant differences were observed in incidence of periventricular-intraventricular hemorrhage (PIH), between the surfactant treated and control infants. Surfactant treated infants had larger average increases in the arterial-alveolar oxygen ratio, (a/A ratio) (P〈0.0001), and larger average decreases in FiO2 (P〈0.0001) and mean airway pressure, (MAP) (P〈0.017) than controls over the 48 h following treatment. The magnitude of the differences between the surfactant and control groups were 0.19 (SE=0.03) for a/A ratio, −0.28 (SE=0.04) for FiO2 and −1.7 cm H2O (SE=0.70) for MAP. The clinical status on days 7 and 28 after treatment was classified using four predefined ordered categories: (1) no respiratory support; (2) supplemental O2 with or without continuous positive airway pressure (CPAP); (3) intermittent mandatory ventilation; and (4) death. There were no statistically significant differences in the status categories on days 7 or 28 between surfactant and control infants. There were no significant differences between the groups with respect to the incidence of patent ductus arteriosus, bronchopulmonary dysplasia, necrotizing entero-colitis, air leaks or death. There was a statistically significant difference between treated and control infants in the frequency and severity of periventricular-intraventricular hemorrhage (PIH) (Cochran-Mantel-Haenszelχ 2adj=6.36,P=0.01). Hemorrhages occurred in 59.6% of surfactant treated infants and 26.9% of controls. Severe hemorrhages (grades 3 or 4) occurred in 38.5% of surfactant treated infants and 15.4% of controls (χ 2adj=4.01,P=0.045). We conclude that the intratracheal administration of Survanta prior to 8 h of age to infants with IRDS receiving assisted ventilation with 40% or more oxygen results in a reduction in the severity of respiratory distress during the 48 h after therapy. Because of the difference in incidence of PIH between surfactant and control infants in this study, we recommend that future clinical trials of surfactant include more frequent prospective serial ultrasound evaluations for diagnosis of hemorrhage.

Notes: Abstract Surfactant therapy has been proven effective in the prevention and treatment of respiratory distress syndrome. Over 6,000 infants have been studied in randomized controlled trials. These studies have demonstrated that both prophylactic administration of surfactant and administration of surfactant to premature infants with established respiratory distress syndrome will decrease the risk of pneumothorax and decrease the risk of mortality. Currently, over 50% of very low birth weight infants in North America receive some sort of surfactant preparation. However, many questions remain regarding optimal usage of surfactant preparations. Recent randomized controlled trials have evaluated issues regarding surfactant dosage, treatment strategy, method of administration, and surfactant preparation. Initial doses in the range of 100–200 mg/kg with repeat doses to selected infants who relapse appears to be the best approach to therapy. Prophylactic surfactant therapy leads to a small but statistically significant reduction in the risk of pneumothorax and mortality. The clinical relevance of these advantages and the cost effectiveness of this care remains under debate. A variety of methods of administration have been used in randomized controlled trials. Trials which compare these methods of administration demonstrate the adequacy of currently tested bolus administration. However, other methods of administration, such as slow infusion of surfactant leads to uneven distribution of surfactant and poor response. Both synthetic surfactants and natural surfactant extracts have been proven effective in the care of these infants. However, randomized controlled trials which directly compare these two preparations demonstrate a small advantage to the use of natural surfactant extracts. Natural surfactant extracts improve initial ventilatory status and decrease the risk of pneumothorax. Surfactant replacement therapy has proven to be effective in the treatment of very low birth weight premature infants. Current clinical trials support the early institution of treatment either prophylactically or as soon as possible in intubated babies with signs of respiratory distress syndrome. Repeat treatment may be important in optimizing outcome due to surfactant inactivation. Currently available natural surfactant extracts improve early clinical outcome and decrease pneumothorax compared to the available synthetic preparations.

Notes: Abstract Surfactant therapy has been proven effective in the prevention and treatment of respiratory distress syndrome. Over 6,000 infants have been studied in randomized controlled trials. These studies have demonstrated that both prophylactic administration of surfactant and administration of surfactant to premature infants with established respiratory distress syndrome will decrease the risk of pneumothorax and decrease the risk of mortality. Currently, over 50% of very low birth weight infants in North America receive some sort of surfactant preparation. However, many questions remain regarding optimal usage of surfactant preparations. Recent randomized controlled trials have evaluated issues regarding surfactant dosage, treatment strategy, method of administration, and surfactant preparation. Initial doses in the range of 100–200 mg/kg with repeat doses to selected infants who relapse appears to be the best approach to therapy. Prophylactic surfactant therapy leads to a small but statistically significant reduction in the risk of pneumothorax and mortality. The clinical relevance of these advantages and the cost effectiveness of this care remains under debate. A variety of methods of administration have been used in randomized controlled trials. Trials which compare these methods of administration demonstrate the adequacy of currently tested bolus administration. However, other methods of administration, such as slow infusion of surfactant leads to uneven distribution of surfactant and poor response. Both synthetic surfactants and natural surfactant extracts have been proven effective in the care of these infants. However, randomized controlled trials which directly compare these two preparations demonstrate a small advantage to the use of natural surfactant extracts. Natural surfactant extracts improve initial ventilatory status and decrease the risk of pneumothorax. Surfactant replacement therapy has proven to be effective in the treatment of very low birth weight premature infants. Current clinical trials support the early institution of treatment either prophylactically or as soon as possible in intubated babies with signs of respiratory distress syndrome. Repeat treatment may be important in optimizing outcome due to surfactant inactivation. Currently available natural surfactant extracts improve early clinical outcome and decrease pneumothorax compared to the available synthetic preparations.