RESUMEN
OBJECTIVE: In a randomized, controlled, multicenter trial, we tested the hypothesis that high-frequency ventilation (HFV) with a high lung volume strategy results in fewer treatment failures than intermittent positive pressure ventilation (IPPV) with high rates and low peak inspiratory pressures. STUDY DESIGN: Infants with a gestational age between >/=24 weeks and <30 weeks, requiring mechanical ventilation within 6 hours of birth, were randomly assigned to receive either IPPV or HFV until 240 hours after randomization, extubation, or meeting treatment failure criteria. Treatment failure, the primary end point, was determined when air leaks, an oxygenation index >35 to 45 (depending on gestational age), death, or chronic lung disease occurred. Chronic lung disease was defined as persistent requirement of mechanical ventilation, continuous positive airway pressure, or supplemental oxygen at a postmenstrual age of 36 weeks. Secondary end points included the incidence of intracranial hemorrhage. RESULTS: The third scheduled interim analysis led to termination of the trial after recruitment of 284 infants. Treatment failure criteria were met by 46% of infants receiving IPPV and 54% of infants receiving HFV (1-tailed primary hypothesis, P =.92; 2-tailed chi2 test, P =.15). Air leaks occurred in 31% and 42% (P =.042), CLD in 23% and 25%, and grade 3-4 intracranial hemorrhage in 13% and 14% of IPPV-treated and HFV-treated patients, respectively. The mortality rate before discharge was 10% in both groups. CONCLUSION: HFV with a high lung volume strategy did not cause less lung injury in preterm infants than IPPV with a high rate and low peak inspiratory pressures.
Asunto(s)
Ventilación de Alta Frecuencia , Enfermedades del Prematuro/terapia , Ventilación con Presión Positiva Intermitente , Insuficiencia Respiratoria/terapia , Displasia Broncopulmonar/prevención & control , Femenino , Alemania/epidemiología , Humanos , Recién Nacido , Masculino , Análisis de Regresión , Insuficiencia Respiratoria/mortalidad , Mecánica Respiratoria , Tasa de SupervivenciaRESUMEN
The aim of the study was to determine if high-dose bovine surfactant (Alveofact, initially 100 mg/kg birth weight) would improve oxygenation compared with low-dose surfactant (50 mg/kg birth weight) administered intratracheally within 1 h after birth. Inclusion criteria included gestational age 24-29 weeks and birth weight 500-1500 g, intubation and mechanical ventilation, absence of congenital malformations and bacterial infections. Retreatment was considered if the fraction of inspired oxygen (FiO2) was > 0.4 (dose 50 mg/kg birth weight). The primary endpoint was level of oxygenation (PaO2/FiO2) 2 h after treatment. The study design was a sequential analysis using a triangular test with alpha = 0.05 and 95% power to detect a 25% improvement in the endpoint. Oxygenation was improved significantly with high-dose (n = 42) compared to low-dose treatment (n = 48): 30.9 +/- 15.0 kPa (231.5 +/- 112.7 mmHg) versus 24.1 +/- 15.7 kPa (180.6 +/- 118.0 mmHg) (mean +/- SD). The survival rate was 83% in both groups and the incidence of pulmonary interstitial emphysema was 33% versus 14% with the high-dose treatment. We conclude that high-dose surfactant significantly improved oxygenation and reduced lung barotrauma. An initial dose greater than 50 mg/kg birth weight of surfactant is required for optimal acute response.
Asunto(s)
Enfermedades del Prematuro/prevención & control , Lípidos/administración & dosificación , Fosfolípidos , Surfactantes Pulmonares/administración & dosificación , Síndrome de Dificultad Respiratoria del Recién Nacido/prevención & control , Relación Dosis-Respuesta a Droga , Femenino , Edad Gestacional , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Recien Nacido Prematuro , Enfermedades del Prematuro/sangre , Enfermedades del Prematuro/mortalidad , Masculino , Oxígeno/sangre , Enfisema Pulmonar/prevención & control , Síndrome de Dificultad Respiratoria del Recién Nacido/sangre , Síndrome de Dificultad Respiratoria del Recién Nacido/mortalidad , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To determine the effect of bovine surfactant (SF-RI 1, Alveofact) administered during the first hour following birth to very premature infants [gestational age (GA), 25-30 weeks] in a multicenter, controlled trial. HYPOTHESIS: Survival without bronchopulmonary dysplasia (BPD; definition: ventilator dependency or FiO2 greater than 0.3 during spontaneous respiration) at day 28 is increased in surfactant-treated infants (sequential analysis). PATIENTS AND METHODS: Thirty-four infants [GA 28.0 +/- 1.5 SD weeks, birth weight (BW), 1,048 +/- 299 g] received 50 mg/kg BW surfactant, whereas 35 infants (GA, 27.6 +/- 1.5 weeks, BW 969 +/- 269 g) served as controls. Retreatment with surfactant (up to three identical doses) 12-24 hours after the previous dose was permitted if FiO2 was greater than 0.5. RESULTS: Survival without BPD was significantly higher in surfactant treated infants (26/34) compared to controls (14/35; P = 0.003), but in the incidence of pulmonary air leaks, patent ductus arteriosus, intracranial hemorrhage, and nosocomial infections they were not different. CONCLUSION: Bovine surfactant treatment improves survival without BPD in very premature infants at risk for neonatal respiratory distress syndrome (RDS).