RESUMEN
OBJECTIVE: To investigate whether a weekly 1500 IU/kg dose of recombinant human erythropoietin (rhEPO) is more effective than a dose of 750 IU/kg/week in preventing anemia and reducing the transfusion need in infants with birth weights less than 1000 gm. STUDY DESIGN: In a randomized, double-blind, multicenter trial, 184 infants with birth weights between 500 and 999 gm were treated with either rhEPO 750 (low-dose group) or 1500 IU/kg/week (high-dose group) from day 3 of life until 37 weeks' corrected age. RESULTS: Thirty-two percent of the infants in each group did not receive any transfusion during the treatment period. The total volume of erythrocytes received was similar in each group. The success rate, defined as no transfusion needed and hematocrit value 0.30 L/L or greater, was 27.6% in the low-dose and 29.5% in the high-dose group (p = 0.96). CONCLUSION: Doubling the rhEPO dose of 750 IU/kg/week is not indicated in infants with birth weights less than 1000 gm.
Asunto(s)
Anemia/prevención & control , Eritropoyetina/administración & dosificación , Recién Nacido de muy Bajo Peso , Transfusión Sanguínea/estadística & datos numéricos , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Edad Gestacional , Hematócrito , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/prevención & control , Recién Nacido de muy Bajo Peso/sangre , Hierro/uso terapéutico , Masculino , Proteínas RecombinantesAsunto(s)
Enfermedades del Prematuro/inmunología , Interleucina-8/fisiología , Enfermedades Pulmonares/inmunología , Dexametasona/uso terapéutico , Exudados y Transudados/efectos de los fármacos , Exudados y Transudados/inmunología , Humanos , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/tratamiento farmacológico , Enfermedades del Prematuro/fisiopatología , Enfermedades Pulmonares/tratamiento farmacológico , Enfermedades Pulmonares/fisiopatologíaRESUMEN
To evaluate the effects of dexamethasone on pulmonary inflammation and permeability in preterm infants at high risk for chronic lung disease (birth weight < 1200 gm), we assessed tracheobronchial aspirate fluid for chemotactic activity and concentrations of mediators of inflammation. In a prospective study, 21 infants still undergoing mechanical ventilation at day 10 of postnatal age who required a fraction of inspired oxygen > or = 0.3, a peak inspiratory pressure > or = 16 cm H2O, or both were randomly assigned to treatment with dexamethasone at day 10 (early treatment group, n = 10) or day 16 (late treatment group, n = 11). The groups were compared with respect to all measurements on day 15; the late treatment group served as a control group. Additionally, the effects of dexamethasone within both groups were evaluated. In the early treatment group, the chemotactic response of peripheral blood neutrophils exposed to tracheobronchial aspirate fluid was significantly reduced 5 days after initiation of dexamethasone treatment compared with pretreatment values of the late treatment group (median (25th to 75th percentile): migratory distance before dexamethasone, 149 microns (140 to 173 microns); after dexamethasone, 81 microns (68 to 114 microns); p < 0.01). In addition, the following values were decreased after dexamethasone therapy in the early treatment group: number of neutrophils in tracheobronchial aspirate fluid (p < 0.05), and concentrations of leukotriene B4 (p < 0.01), interleukin-1 (p < 0.01), elastase-alpha 1-proteinase inhibitor (p < 0.01), and albumin (p < 0.01). Free elastase activity was found in only two infants; detectable activity of protective alpha 1-proteinase inhibitor was present in the others. Analysis of dexamethasone effects within the groups showed that all measurements were significantly decreased after both the early and the late treatment regimens, with the exception of leukotriene B4 and interleukin-1, which declined only after early dexamethasone treatment. Our results indicate that the pulmonary inflammatory response and microvascular permeability are decreased by dexamethasone, which affects the release of inflammatory mediators and neutrophil influx into the airways of preterm infants who require mechanical ventilation.
Asunto(s)
Quimiotaxis de Leucocito , Dexametasona/farmacología , Enfermedades del Prematuro/fisiopatología , Inflamación/metabolismo , Enfermedades Pulmonares/fisiopatología , Pulmón/fisiopatología , Albúminas/análisis , Bronquios/metabolismo , Bronquios/patología , Enfermedad Crónica , Dexametasona/uso terapéutico , Humanos , Recién Nacido , Enfermedades del Prematuro/patología , Interleucina-1/análisis , Leucotrieno B4/análisis , Pulmón/patología , Enfermedades Pulmonares/prevención & control , Neutrófilos/fisiología , Elastasa Pancreática/análisis , Estudios Prospectivos , Factores de Riesgo , Succión , Tráquea/metabolismo , Tráquea/patología , alfa 1-Antitripsina/análisisRESUMEN
In 26 infants and children with septicemia or bacterial meningitis, significantly elevated plasma levels of elastase-alpha 1-proteinase inhibitor (E-alpha 1-PI) were present at time of recognition of infection, even in those patients with neutropenia (range of reference values: 25 to 190 micrograms/L, n = 142; patients: 444 to 2049 micrograms/L, n = 26). After initiation of therapy, normalization of E-alpha 1-PI levels was observed in all patients who recovered from infection. In addition, 18 of 19 children with bacterial meningitis had increased cerebrospinal fluid concentrations of E-alpha 1-PI above the range of normal (range of reference values: 0 to 39 micrograms/L, n = 62; patients: 30 to 3490 micrograms/L, n = 19); concentrations of E-alpha 1-PI in bacterial meningitis were significantly increased when compared with those in aseptic meningitis (range 25 to 194 micrograms/L; n = 15). In 30 patients with local bacterial infections (pneumonia, urinary tract infections, etc.), E-alpha 1-PI was also elevated. These data suggest that E-alpha 1-PI is a sensitive indicator of systemic and local bacterial infection in childhood.