RESUMEN
A randomized, double-blind, placebo-controlled trial was performed in 13 hospitals in Canada to assess whether two rescue doses of a synthetic surfactant (Exosurf Neonatal) would reduce mortality and morbidity rates in neonates with respiratory distress syndrome who weighed from 750 to 1249 gm. As part of the original trial design, double-blind follow-up evaluations were performed at 1-year adjusted age. A total of 118 patients who received air placebo and 114 patients who received synthetic surfactant were evaluated at 1 year. Growth and development in the two groups were equivalent. Scores on the Bayley Scales of Infant Development were within the normal range for both groups (mental development index, 90 +/- 22 vs 92 +/- 22; psychomotor development index, 81 +/- 19 vs 87 +/- 22 for the air placebo and synthetic surfactant groups, respectively). However, in both groups the proportion of infants with any impairment (air placebo group, 43 of 118 (36%); synthetic surfactant group, 41 of 114 (36%) and severe impairment (air placebo group, 29 of 118 (25%); synthetic surfactant group, 21 of 114 (18%)) was substantial. We conclude that two rescue doses of synthetic surfactant in infants with RDS who weighed 750 to 1249 gm had no detrimental effect on developmental outcome or late morbidity. No long-term benefits to 12-months corrected age were observed with the use of surfactant in this weight class. Larger studies or meta-analyses of existing trials will be required to determine if there are any late outcome advantages associated with rescue use of synthetic surfactant in infants weighing 700 to 1249 gm.
Asunto(s)
Alcoholes Grasos/administración & dosificación , Recién Nacido de Bajo Peso , Recien Nacido Prematuro , Fosforilcolina , Polietilenglicoles/administración & dosificación , Surfactantes Pulmonares/administración & dosificación , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Aire , Desarrollo Infantil , Método Doble Ciego , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Estado de Salud , Humanos , Recién Nacido , Masculino , Enfermedades del Sistema Nervioso/epidemiología , Desempeño Psicomotor , Retinopatía de la Prematuridad/epidemiologíaRESUMEN
In a multicenter, double-masked, placebo-controlled rescue trial conducted at 12 Canadian hospitals, two 5 ml/kg doses of a synthetic surfactant or air placebo were administered to 224 infants with birth weights of 500 to 749 gm who had established respiratory distress syndrome and an arterial/alveolar oxygen tension ratio of less than 0.22. The first dose was given between 2 and 24 hours of age; the second dose was given 12 hours later to the infants continuing to receive mechanical ventilation. Infants were stratified at study entry by birth weight and gender. Infants receiving synthetic surfactant showed significant improvements in alveolar-arterial oxygen tension gradient, arterial/alveolar oxygen tension ratio, and oxygen and ventilator requirements through day 7. In the group randomized to synthetic surfactant, significant improvements were seen in oxygen requirements at the first time point measured (2 hours; p = 0.02), in the alveolar-arterial oxygen tension gradient by the second time point measured (6 hours; p = 0.03), and in mean airway pressure after 6 hours. Overall mortality at 28 days was not significantly different in the two groups (50% vs 46%, air placebo group vs synthetic surfactant group; p = 0.586). Similarly, neither the incidence of bronchopulmonary dysplasia (37% vs 30%, air placebo group vs synthetic surfactant group; p = 0.089) nor the incidence of survival without BPD through 28 days (17% vs 26%, respectively; p = 0.070) was significantly different in the two groups. No significant differences in the incidence of safety-related outcomes or in adverse effects such as apnea or pulmonary hemorrhage were noted. These findings indicate that rescue therapy with synthetic surfactant results in physiologic improvements in very tiny premature infants, but improvements in overall mortality or other complications of respiratory distress syndrome were not documented in the sample evaluated.
Asunto(s)
Alcoholes Grasos/administración & dosificación , Recién Nacido de Bajo Peso , Fosforilcolina , Polietilenglicoles/administración & dosificación , Surfactantes Pulmonares/administración & dosificación , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Aire , Método Doble Ciego , Combinación de Medicamentos , Alcoholes Grasos/efectos adversos , Femenino , Humanos , Recién Nacido , Masculino , Polietilenglicoles/efectos adversos , Estudios Prospectivos , Surfactantes Pulmonares/efectos adversos , Síndrome de Dificultad Respiratoria del Recién Nacido/complicaciones , Síndrome de Dificultad Respiratoria del Recién Nacido/mortalidad , Tasa de SupervivenciaRESUMEN
In an across study analysis of five multicenter, placebo-controlled trials of the synthetic surfactant, Exosurf Neonatal in infants weighing at least 700 gm, the incidence of clinical pulmonary hemorrhage was 1.9% in treated infants and 1.0% in control infants. To investigate whether a similar increase was also present histologically at postmortem examination, a blinded retrospective review of all autopsy reports from infants dying during these five trials was conducted. Pulmonary hemorrhage was present in 55% of 159 infants undergoing autopsy; the incidence was not different in infants treated with surfactant or air placebo. Birth weight was inversely related to the incidence of pulmonary hemorrhage in both groups. Pulmonary pathologic findings significantly associated with pulmonary hemorrhage included pulmonary interstitial emphysema and necrotizing laryngotracheitis in both groups. In the surfactant group, patent ductus arteriosus, intraventricular hemorrhage, and pneumothorax were significantly more frequent among those who developed pulmonary hemorrhage. In contrast to clinical diagnosis, pathologic diagnosis of pulmonary hemorrhage at autopsy was not more common in infants treated with Exosurf Neonatal.
Asunto(s)
Alcoholes Grasos/uso terapéutico , Hemorragia/epidemiología , Enfermedades del Prematuro/epidemiología , Enfermedades Pulmonares/epidemiología , Fosforilcolina , Polietilenglicoles/uso terapéutico , Surfactantes Pulmonares/uso terapéutico , Autopsia , Método Doble Ciego , Combinación de Medicamentos , Alcoholes Grasos/efectos adversos , Hemorragia/etiología , Hemorragia/patología , Humanos , Incidencia , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/etiología , Enfermedades del Prematuro/patología , Enfermedades Pulmonares/etiología , Enfermedades Pulmonares/patología , Polietilenglicoles/efectos adversos , Surfactantes Pulmonares/efectos adversos , Síndrome de Dificultad Respiratoria del Recién Nacido/prevención & controlRESUMEN
Ten preterm infants (birth weight 0.970 to 2.495 kg) with apnea due to periodic breathing (apneic interval = 5 to 10 seconds) or with "serious apnea" (greater than or equal to 20 seconds) were studied before and after the administration of theophylline. We determined the incidence of apnea, respiratory minute volume, alveolar gases, arterial gases and pH, "specific" compliance, functional residual capacity, and work of breathing. Theophylline decreased the incidence of apnea (P less than .05), increased respiratory minute volume (P less than 0.001), decreased (PACO2 (and PaCO2 P less than 0.001), increased the slope of the CO2 response curve (P less than 0.02) with a significant shift to the left (P less than 0.02). These findings suggest that the decreased incidence of apnea after theophylline is associated with an increase in alveolar ventilation and increased sensitivity to CO2 with a pronounced shift of the CO2 response curve to the left. These data are consistent with the idea that apnea is a reflection of a depressed respiratory system.