RESUMEN
OBJECTIVE: To determine whether the group B streptococcal (GBS) polysaccharide exotoxin CM101, which induces a complement-activated cytokine-driven inflammatory response, is present in body fluids of infants with GBS disease. STUDY DESIGN: With a sandwich enzyme-linked immunosorbent assay, CM101 was measured in plasma, urine, and cerebrospinal fluid from newborn infants who were evaluated for possible infection and from older infants with culture-confirmed GBS disease. RESULTS: Urine from 11 newborn infants with culture-confirmed early-onset disease contained large amounts of CM101 (1.0 to 5.5 mg/48 h). Plasma concentrations were 62.6 +/- 10.5 microg/mL in these infants and were 69.0 +/- 21.2 microg/mL in 4 older infants with late-onset disease. Plasma CM101 concentrations did not correlate with indexes of illness severity, leukocyte counts, or interleukin-6 or interleukin-8 plasma concentrations. CM101 was present in cerebrospinal fluid of 5 infants with meningitis (8.4 +/- 1.6 microg/mL). CM101 was not found in control samples. CM101 isolated from urine had molecular weight and sugar composition similar to those obtained from GBS culture media, and they both elicited a comparable pathophysiologic response when infused intravenously in lambs. CONCLUSIONS: CM101 is present in infants with GBS disease, and it appears to be the same as CM101 obtained from GBS culture media.
Asunto(s)
Toxinas Bacterianas/aislamiento & purificación , Polisacáridos Bacterianos/aislamiento & purificación , Sepsis/microbiología , Infecciones Estreptocócicas/microbiología , Animales , Toxinas Bacterianas/metabolismo , Líquidos Corporales/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Lactante , Recién Nacido , Interleucina-6/sangre , Interleucina-8/sangre , Recuento de Leucocitos , Polisacáridos Bacterianos/metabolismo , Sepsis/metabolismo , Sepsis/fisiopatología , Ovinos , Infecciones Estreptocócicas/metabolismo , Infecciones Estreptocócicas/fisiopatología , Streptococcus agalactiae/clasificación , Streptococcus agalactiae/metabolismoRESUMEN
In a multicenter, double-blind, placebo-controlled trial that enrolled 215 premature infants with birth weights of 500 to 699 gm, 106 infants were treated prophylactically with a single 5 ml/kg dose of synthetic surfactant and 109 infants were given an equivalent dose of air placebo shortly after birth. In each group, 40 children survived infancy: 36 children in the air placebo group and 30 children in the synthetic surfactant group were available for follow-up. Weight, height, and head circumference measurements were similar for both groups at 1-year adjusted age. Infants who received synthetic surfactant at birth had statistically similar Bayley Scales of Infant Development scores (mental developmental index, 92 vs 83; psychomotor developmental index, 87 vs 82) compared with controls. Mild to moderate impairments in the synthetic surfactant group were 7% versus 29% in the control group; these differences were not statistically significant. The incidence of retinopathy of prematurity, the number of hospital readmissions, the need for surgery after day 28, evidence of chronic lung disease, the need for respiratory support at 1-year adjusted age, and the incidence of allergies were also not different between the two groups. However, the proportion of infants surviving without impairment was modestly higher in the synthetic surfactant group (8%, air placebo group; 23%, synthetic surfactant group). The findings from this small study indicate that infants weighing 500 to 699 gm who receive a single prophylactic dose of synthetic surfactant at birth have neurodevelopmental outcomes at least equivalent to those of infants given air placebo at 1-year follow-up.
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/prevención & control , Aire , Desarrollo Infantil , Método Doble Ciego , Combinación de Medicamentos , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Recién Nacido , Enfermedades Pulmonares/epidemiología , Masculino , Examen Neurológico , Desempeño Psicomotor , Retinopatía de la Prematuridad/epidemiologíaRESUMEN
To determine the effect of analgesia and paralysis on lung volume and oxygenation in premature infants supported by mechanical ventilation because of hyaline membrane disease, functional residual capacity (FRC), and arterial/alveolar oxygen tension ratio were measured in nine premature infants with hyaline membrane disease before and after the administration of morphine sulfate and pancuronium bromide. Without a change of positive end-expiratory pressure, ventilator rate and peak inspiratory pressure were increased before the first set of measurements to minimize the contribution of the infants' own respiratory effort to total ventilation. These ventilator settings were then held constant (except fraction of inspired oxygen) before and after the administration of the drugs. The FRC was measured with a multiple-breath N2 washout technique by means of whole-body plethysmography to measure airway flow. The FRC and the ratio of arterial to alveolar oxygen tension decreased in seven of nine patients after treatment with morphine and pancuronium. The decrease in FRC for all patients was significant (2.4 +/- 2.9 ml/kg; p < 0.05), and a significant correlation was demonstrated between the change in the arterial/alveolar oxygen tension ratio and the change in FRC (r = 0.82; p < 0.01). Gestational age, birth weight, postnatal age, severity of lung disease, and time after the administration of morphine and pancuronium were not significantly correlated with the change in FRC. We believe that a decrease in oxygenation caused by alveolar derecruitment occurred even though the ventilator settings had been increased before the first set of measurements. The decrease in FRC in these infants, who are thought to have alveolar instability because of surfactant deficiency, may have resulted from the loss of expiratory braking mechanisms. We conclude that analgesia and paralysis should be used with caution under these circumstances.
Asunto(s)
Capacidad Residual Funcional/efectos de los fármacos , Enfermedad de la Membrana Hialina/fisiopatología , Recien Nacido Prematuro/fisiología , Morfina/farmacología , Oxígeno/sangre , Pancuronio/farmacología , Humanos , Enfermedad de la Membrana Hialina/terapia , Recién Nacido , Recien Nacido Prematuro/sangre , Respiración ArtificialRESUMEN
In a multicenter, double-blind, placebo-controlled rescue trial conducted at 21 American hospitals, two 5 ml/kg doses of a synthetic surfactant (Exosurf Neonatal) or air were administered to 419 infants weighing 700 to 1350 gm who had respiratory distress syndrome and an arterial/alveolar oxygen pressure ratio 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 those infants remaining on ventilatory support. Infants were stratified at entry by birth weight and gender. Among infants receiving synthetic surfactant, improvements in alveolar-arterial oxygen pressure gradient, arterial/alveolar oxygen pressure ratio, and oxygen and ventilator needs through 7 days of age were apparent. Death from respiratory distress syndrome was reduced by two thirds (21 vs 7; p = 0.007), and the overall neonatal mortality rate was reduced by half (50 vs 23; p = 0.001). Although there was no significant reduction in the incidence of bronchopulmonary dysplasia (39 vs 31; p = 0.107), the hypothesis that survival through 28 days without bronchopulmonary dysplasia would be enhanced by two rescue doses of synthetic surfactant was proved true (21% improvement, from 132 to 156 patients; p = 0.001). In addition, the incidence of pneumothorax was reduced by one third (62 vs 40; p = 0.022), and the incidence of pulmonary interstitial emphysema was reduced by half (102 vs 51; p = 0.001). The only side effect identified was an increase in the incidence of apnea (102 vs 134; p = 0.001). These findings indicate that rescue use of a synthetic surfactant can improve the morbidity and mortality rates for premature infants with respiratory distress syndrome.