RESUMEN
BACKGROUND: Though natural surfactants (SF) are clinically superior to protein-free synthetic preparations, CHF-5633, a synthetic SF containing SP-B and SP-C analog peptides is a potential alternative to natural SF for treating neonatal respiratory distress syndrome (RDS). Nevertheless, information is lacking regarding the safety of this new treatment for the neonatal brain. We sought to compare the cerebral and pulmonary effects of this new synthetic surfactant (CHF5633) with those of natural porcine surfactant (Cursosurf) in premature lambs with RDS. METHODS: Twenty-one preterm lambs were randomly assigned to receive CHF5633, Curosurf, or no treatment (control). Pulmonary (gas exchange, lung mechanics) and cerebral (carotid artery blood flow, cerebral oxygen metabolism) effects were measured every 30 min for 6 h. Pulmonary and cerebral histological analysis were also performed. RESULTS: After delivery, lambs developed severe RDS (FIO2 :1, pH < 7.15, PaCO2 > 70 mmHg, PaO2 < 40 mmHg, Cdyn < 0.1 mL/cmH2 O/kg). By 30 min after treatment, animals in both SF-treated groups had consistently better gas exchange and lung mechanics than controls. After CHF5633 administration, PaCO2 , carotid artery blood flow, and cerebral oxygen delivery tended to slowly decrease compared to other groups. By 2 h, SF-treated groups had similar values of all parameters studied, these remaining steady for the rest of the experiment. Lambs administered CHF5633 obtained better lung and brain injury scores than controls. CONCLUSION: Intratracheal administration of a bolus of CHF5633 improves pulmonary status in preterm lambs with severe RDS, obtaining better lung and brain injury scores than controls and favorable cerebral hemodynamics, comparable to those with gold standard Curosurf treatment.
Asunto(s)
Encéfalo/efectos de los fármacos , Pulmón/efectos de los fármacos , Fragmentos de Péptidos/uso terapéutico , Fosfatidilcolinas/uso terapéutico , Proteína B Asociada a Surfactante Pulmonar/uso terapéutico , Proteína C Asociada a Surfactante Pulmonar/uso terapéutico , Surfactantes Pulmonares/uso terapéutico , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Animales , Animales Recién Nacidos , Productos Biológicos/uso terapéutico , Análisis de los Gases de la Sangre , Encéfalo/patología , Encéfalo/fisiología , Circulación Cerebrovascular/efectos de los fármacos , Femenino , Hemodinámica , Pulmón/patología , Pulmón/fisiología , Masculino , Fosfolípidos/uso terapéutico , Intercambio Gaseoso Pulmonar/efectos de los fármacos , Síndrome de Dificultad Respiratoria del Recién Nacido/patología , Síndrome de Dificultad Respiratoria del Recién Nacido/fisiopatología , Ovinos , PorcinosRESUMEN
OBJECTIVE: Aerosolization has been proposed as a useful alternative to rapid intratracheal instillation for the delivery of exogenous surfactant in neonatal respiratory distress syndrome. However, there is a lack of information regarding the likely safety of this new therapeutic approach for the neonatal brain. We aimed to compare the cerebral effects of aerosolized versus bolus surfactant administration in premature lambs with respiratory distress syndrome. DESIGN: Prospective randomized study. SETTING: BioCruces Institute Animal Research Facility. SUBJECTS: Fourteen intensively monitored and mechanically ventilated preterm lambs. INTERVENTIONS: Preterm lambs were randomly assigned to receive intratracheal aerosolized surfactant or bolus surfactant. Brain hemodynamics (cerebral and regional cerebral blood flow) and cerebral oxygen metabolism (cerebral oxygen delivery, cerebral metabolic rate of oxygen, and oxygen extraction fraction) were measured every 30 minutes for 6 hours. We also performed cerebral biochemical and histological analysis. MEASUREMENTS AND MAIN RESULTS: In preterm lambs with respiratory distress syndrome, cerebral blood flow, regional cerebral blood flow, cerebral oxygen delivery, and cerebral metabolic rate of oxygen increased significantly in the bolus surfactant group during the first 5 minutes, without changes in cerebral oxygen extraction fraction. By 60 minutes, all parameters had decreased in both groups, cerebral blood flow and regional cerebral blood flow (in inner and cerebellum brainstem regions) remaining higher in the bolus surfactant than in the aerosolized surfactant group. Overall, the impact of aerosol surfactant was not significantly different to that of bolus surfactant in terms of cerebral necrosis, edema, inflammation, hemorrhage, infarct, apoptosis, or oxidative stress. CONCLUSIONS: In preterm lambs with severe respiratory distress syndrome, aerosol surfactant administration seems to be as safe as bolus administration, showing more stable cerebral hemodynamics and cerebral oxygen metabolism to the same dose of surfactant administered as a standard bolus.