RESUMEN
Intrauterine growth restriction (IUGR) increases the risk of bronchopulmonary dysplasia (BPD), one of the major complications of prematurity. Antenatal low-protein diet (LPD) exposure in rats induces IUGR and mimics BPD-related alveolarization disorders. Peroxisome proliferator-activated receptor-γ (PPARγ) plays a key role in normal lung development and was found deregulated following LPD exposure. The objective of this article was to investigate the effects of nebulized curcumin, a natural PPARγ agonist, to prevent IUGR-related abnormal lung development. We studied rat pups antenatally exposed to an LPD or control diet (CTL) and treated with nebulized curcumin (50 mg/kg) or vehicle from postnatal (P) days 1 to 5. The primary readouts were lung morphometric analyses at P21. Immunohistochemistry (P21) and microarrays (P6 and P11) were compared within animals exposed to LPD versus controls, with and without curcumin treatment. Quantitative morphometric analyses revealed that LPD induced abnormal alveolarization as evidenced by a significant increase in mean linear intercept (MLI) observed in P21 LPD-exposed animals. Early curcumin treatment prevented this effect, and two-way ANOVA analysis demonstrated significant interaction between diet and curcumin both for MLI [F(1,39) = 12.67, P = 0.001] and radial alveolar count at P21 [F(1,40) = 6.065, P = 0.0182]. Immunohistochemistry for fatty acid binding protein 4 (FABP4), a major regulator of PPARγ pathway, showed a decreased FABP4+ alveolar cell density in LPD-exposed animals treated by curcumin. Transcriptomic analysis showed that early curcumin significantly prevented the activation of profibrotic pathways observed at P11 in LPD-exposed animals. Nebulized curcumin appears to be a promising strategy to prevent alveolarization disorders in IUGR rat pups, targeting pathways involved in lung development.
Asunto(s)
Displasia Broncopulmonar/prevención & control , Curcumina/farmacología , Dieta con Restricción de Proteínas/efectos adversos , Alveolos Pulmonares/metabolismo , Animales , Animales Recién Nacidos , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/patología , Femenino , Retardo del Crecimiento Fetal/tratamiento farmacológico , Retardo del Crecimiento Fetal/etiología , Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/patología , Masculino , Nebulizadores y Vaporizadores , PPAR gamma/agonistas , PPAR gamma/metabolismo , Alveolos Pulmonares/patología , Ratas , Ratas Sprague-DawleyRESUMEN
Systematic culture of the tip of central lines is performed in many neonatal intensive care units (NICUs) to guide any subsequent antibiotic therapy. The clinical relevance of this procedure is debated, given the significant bacterial contamination during its removal. We aimed to describe infections related to catheters and assess the usefulness of central catheter systematic cultures for probabilistic antibiotic therapy in cases of suspicion of catheter-related infections in a NICU. A retrospective study in a NICU included all newborn patients hospitalized with a central catheter, between January 2018, and June 2019. The main outcome measures were bacterial catheter colonization, catheter-related infection rate, and simulation-based approach to antibiotic prescription. Three hundred and seventy-five newborns, with 634 central catheters were included. There were 273 (43%) catheters that were colonized by at least one microorganism. There were 183 cases of suspected sepsis, with 31 infections definitively related to the catheter. In our simulation antibiotic prescription approach, there was no significant difference in terms of the efficacy toward the microorganism(s) involved between the probabilistic antibiotic therapies proposed by the experts and those ultimately prescribed. Performing a catheter culture only if catheter-related infection is suspected could be an alternative to routine screening.
Asunto(s)
Infecciones Relacionadas con Catéteres , Cateterismo Venoso Central , Catéteres Venosos Centrales , Humanos , Recién Nacido , Unidades de Cuidado Intensivo Neonatal , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/epidemiología , Infecciones Relacionadas con Catéteres/prevención & control , Cateterismo Venoso Central/métodos , Estudios Retrospectivos , Catéteres Venosos Centrales/efectos adversos , Catéteres Venosos Centrales/microbiología , Antibacterianos/uso terapéuticoRESUMEN
Objective: To evaluate the efficacy and safety of remifentanil as a premedication in neonates undergoing elective intubation. Study Design: This retrospective study focused on neonates admitted to the Neonatal Intensive Care Unit of Port-Royal, Paris Centre University Hospitals, France, between June 2016 and November 2017, who received remifentanil before an elective intubation. First, atropine (10 µg/kg) was administered intravenously as a bolus, followed by remifentanil, which was administrated continuously. The dose of remifentanil was reduced twice during the study period in order to administer the minimum effective dose and thus reduce possible adverse events. Results: Fifty-four neonates were exposed to remifentanil and atropine. The intubating conditions were excellent or good for 46 procedures (85%) and the median Acute Pain in Newborn Infants score was 2 (IQ 25-75: 0-5) before the sedation, 1 (0-2) during the laryngoscopy, and 0 (0-0) after the intubation. The intubation was successful at the first attempt for 18 patients (33%). Chest wall rigidity occurred in 6 procedures (11%), other respiratory problems in 5 (9%), and laryngospasm in 1 (2%). Some of the procedures were complicated by bradycardia (23%) or desaturation (37%). Conclusions: Remifentanil and atropine prior to intubation provided satisfactory intubating conditions in neonates. Nevertheless, severe adverse effects (such as chest wall rigidity) are a potential risk, possibly related to the total dose received. These data do not support the safety of using remifentanil alone prior to intubation in neonates.