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Notes: Abstract A 3-month-old girl presented with anorexia, failure to thrive and drowsiness. She was mildly icteric with hepatomegaly and peripheral oedema. Disordered liver function tests were associated with the biopsy appearances of a giant cell hepatitis and with a Fanconi syndrome. At the age of 16 weeks she collapsed with profound hypoglycaemia. Fasting also provoked hypoglycaemia with lactic acidaemia. She became increasingly irritable and hypotonic and, although initially liver and renal function improved, she deteriorated and died of hepatocellular failure and septicaemia. A post-mortem revealed massive fatty degeneration of the liver. The activity of phosphoenolpyruvate carboxykinase in her cultured skin fibroblasts was 16% of controls. Her brother died at the age of 4 weeks of sudden infant death syndrome.

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.