RESUMO
OBJECTIVE: To test the hypothesis that infants born <30 weeks' gestation supported by Seattle-PAP will have lower rates of continuous positive airway pressure (CPAP) failure than infants supported with conventional, Fisher&Paykel-CPAP (FP-CPAP). STUDY DESIGN: Randomized trial (3/2017-01/2019) at 5 NICUs. The primary outcome was CPAP failure; subgroup analyses (gestational age, receipt antenatal corticosteroids) were performed. RESULTS: A total of 232 infants were randomized. Infants in the Seattle-PAP and FP-CPAP groups had mean gestational ages of 27.0 and 27.2 weeks, respectively. We observed no differences in rates of treatment failure between Seattle-PAP (40/112, 35.7%) and FP-CPAP (38/120, 31.7%; risk difference, 4.1%; 95% CI, -8.1-16.2; P = 0.51). Subgroup analysis indicated no differences in rates of CPAP failure. We observed no differences between the two groups in frequencies of adverse events or duration of respiratory support. CONCLUSIONS: Among infants born <30 weeks' gestation, rates of CPAP failure did not differ between Seattle-PAP and FP-CPAP.
Assuntos
Pressão Positiva Contínua nas Vias Aéreas , Síndrome do Desconforto Respiratório do Recém-Nascido , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/terapiaRESUMO
OBJECTIVE: We tested the hypothesis that Respiratory Severity Score (RSS) on day of life 30 is predictive of mortality and length of mechanical ventilation in premature infants on prolonged mechanical ventilation. METHODS: A retrospective chart review was performed using the Nationwide Children's Hospital medical record and Vermont-Oxford Network databases. The primary outcome variable was survival to hospital discharge and the secondary outcome was length of mechanical ventilation after day of life 30. RESULTS: We identified 199 neonates admitted to Nationwide Children's Hospital between 2004 and 2007 with birth weight less than 1,500 g that received prolonged mechanical ventilation in the first 30 days of their life. A total of 184 infants were included in the analysis, excluding 14 patients with congenital anomalies and one infant with incomplete data. RSS on day of life 30 was significantly greater in the group of infants that died compared to those that survived (P = 0.003, 95% CI = [0.08, 0.40]). Further analysis demonstrated that the maximum difference in mortality was obtained with a threshold RSS of 6. Of the 109 patients who had RSS less than 6 on day of life 30, mortality rate was 4.6% (5/109) while those greater than or equal to 6 had a mortality rate of 21.3% (16/75). Both Kaplan-Meier survival curves comparing mortality and length of mechanical ventilation in infants with RSS < 6 versus those with RSS ≥ 6 demonstrated strong associations between RSS on day of life 30 and survival (P = 0.002) and length of ventilation after day of life 30 (P < 0.001). CONCLUSION: RSS ≥ 6 on day of life 30 is associated with higher mortality and longer period of mechanical ventilation in premature infants requiring mechanical ventilation through 30 days of life.
Assuntos
Displasia Broncopulmonar/mortalidade , Respiração Artificial/estatística & dados numéricos , Índice de Gravidade de Doença , Displasia Broncopulmonar/terapia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido de muito Baixo Peso , Unidades de Terapia Intensiva Neonatal , Masculino , Ohio/epidemiologia , Estudos Retrospectivos , Fatores de TempoRESUMO
OBJECTIVE: To determine demographic and clinical variables associated with inhaled corticosteroid administration and to evaluate between-hospital variation in inhaled steroid use for infants with bronchopulmonary dysplasia (BPD). DESIGN: Retrospective Cohort Study. SETTING: Neonatal units of 35 US children's hospitals; as recorded in the Pediatric Health Information System (PHIS) database. PATIENTS: 1429 infants with evolving BPD at 28 days who were born at <29 weeks gestation with birth weight <1500 grams, admitted within the first 7 postnatal days, and discharged between January 2007-June 2011. RESULTS: Inhaled steroids were prescribed to 25% (nâ=â352) of the cohort with use steadily increasing during the first two months of hospitalization. The most frequently prescribed steroid was beclomethasone (nâ=â194, 14%), followed by budesonide (nâ=â125, 9%), and then fluticasone (nâ=â90, 6%). Birth gestation <24 weeks, birth weight 500-999 grams, and prolonged ventilation all increased the adjusted odds of ever receiving inhaled corticosteroids (p<0.05). Wide variations between hospitals in the frequency of infants ever receiving inhaled steroids (range: 0-60%) and the specific drug prescribed were noted. This variation persisted, even after controlling for observed confounders. CONCLUSIONS: Inhaled corticosteroid administration to infants with BPD is common in neonatal units within U.S. Children's hospitals. However, its utilization varies markedly between centers from no treatment at some institutions to the majority of infants with BPD being treated at others. This supports the need for further research to identify the benefits and potential risks of inhaled steroid usage in infants with BPD.
Assuntos
Beclometasona/administração & dosagem , Displasia Broncopulmonar/tratamento farmacológico , Budesonida/administração & dosagem , Fluticasona/administração & dosagem , Glucocorticoides/administração & dosagem , Administração por Inalação , Beclometasona/uso terapêutico , Budesonida/uso terapêutico , Fluticasona/uso terapêutico , Glucocorticoides/uso terapêutico , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Pacientes Internados , Estudos RetrospectivosRESUMO
OBJECTIVES: To determine (1) between-hospital variation in diuretic use for infants with bronchopulmonary dysplasia (BPD), including hospital-specific treatment frequency, treatment duration, and percentage of infants receiving short (≤5 consecutive days) versus longer (>5 days) courses, and to determine (2) demographic and clinical variables associated with diuretic administration. METHODS: A retrospective cohort study was conducted with the use of the Pediatric Health Information System to determine between-hospital variation in diuretic utilization patterns (primary outcome) and variables associated with diuretic use among <29-week-gestation infants with evolving BPD at age 28 days who were discharged between January 2007 and June 2011. RESULTS: During the 54-month study period, 1429 infants within 35 hospitals met the inclusion criteria for BPD at age 28 days, with 1222 (86%) receiving diuretic therapy for a median of 9 days (25th-75th percentile: 2-33 days). Short courses were administered to 1203 (83%) infants, and 570 (40%) infants received treatment for >5 consecutive days. Furosemide was the most widely prescribed diuretic (1218 infants; 85%), although chlorothiazide had the longest median duration of use (21 days; 25th-75th percentile: 8-46 days). The range of infants receiving a diuretic course of >5 days duration varied by hospital from 4% to 86%, with wide between-hospital variation even after adjustment for confounding variables. CONCLUSIONS: The frequency of diuretic administration to infants with BPD at US children's hospitals, as well as the specific diuretic regimen used, varies markedly by institution. Safety and effectiveness research of long-term diuretic therapy for BPD patients is needed to develop evidence-based recommendations.
Assuntos
Displasia Broncopulmonar/tratamento farmacológico , Diuréticos/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Hospitais Pediátricos/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Clorotiazida/uso terapêutico , Estudos de Coortes , Bases de Dados Factuais , Esquema de Medicação , Feminino , Furosemida/uso terapêutico , Humanos , Recém-Nascido , Modelos Logísticos , Masculino , Análise Multivariada , Estudos Retrospectivos , Estados UnidosRESUMO
OBJECTIVE: To determine the practice variance, prevalence, and economic burden of clinically diagnosed gastroesophageal reflux disease (GERD) in preterm infants. METHODS: Applying a retrospective cohort study design, we analyzed data from 18 567 preterm infants of 22 to 36 weeks' gestation and >400 g birth weight from the NICUs of 33 freestanding children's hospitals in the United States. GERD prevalence, comorbidities, and demographic factors were examined for their association with average length of stay (LOS) and hospitalization cost. RESULTS: Overall, 10.3% of infants received a diagnosis of GERD (95% confidence interval [CI]: 9.8-10.7). There was a 13-fold variation in GERD rates across hospitals (P < .001). GERD diagnosis was significantly (P < .05) associated with bronchopulmonary dysplasia and necrotizing enterocolitis, as well as congenital anomalies and decreased birth weight. GERD diagnosis was associated with $70 489 (95% CI: 62 184-78 794) additional costs per discharge and 29.9 additional days in LOS (95% CI: 27.3-32.5). CONCLUSIONS: One in 10 of these premature NICU infants were diagnosed with GERD, which is associated with substantially increased LOS and elevated costs. Better diagnostic and management strategies are needed to evaluate reflux-type symptoms in this vulnerable NICU population.
RESUMO
Inducible nitric oxide (NO) synthase (iNOS) is a stress response protein upregulated in inflammatory conditions, and NO may suppress cellular proliferation. We hypothesized that preventing L-arginine (L-arg) uptake in endothelial cells would prevent lipopolysaccharide/tumor necrosis factor-α (LPS/TNF)-induced, NO-mediated suppression of cellular proliferation. Bovine pulmonary arterial endothelial cells (bPAEC) were treated with LPS/TNF or vehicle (control), and either 10 mM L-leucine [L-leu; a competitive inhibitor of L-arg uptake by the cationic amino acid transporter (CAT)] or its vehicle. In parallel experiments, iNOS or arginase II were overexpressed in bPAEC using an adenoviral vector (AdiNOS or AdArgII, respectively). LPS/TNF treatment increased the expression of iNOS, arginase II, CAT-1, and CAT-2 mRNA in bPAEC, resulting in greater NO and urea production than in control bPAEC, which was prevented by L-leu. LPS/TNF treatment resulted in fewer viable cells than in controls, and LPS/TNF-stimulated bPAEC treated with L-leu had more viable cells than LPS/TNF treatment alone. LPS/TNF treatment resulted in cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase expression, which was attenuated by L-leu. AdiNOS reduced viable cell number, and treatment of AdiNOS transfected bPAEC with L-leu preserved cell number. AdArgII increased viable cell number, and treatment of AdArgII transfected bPAEC with L-leu prevented the increase in cell number. These data demonstrate that iNOS expression in pulmonary endothelial cells leads to decreased cellular proliferation, which can be attenuated by preventing cellular L-arg uptake. We speculate that CAT activity may represent a novel therapeutic target in inflammatory lung diseases characterized by NO overproduction.
Assuntos
Transportador 1 de Aminoácidos Catiônicos/metabolismo , Transportador 2 de Aminoácidos Catiônicos/metabolismo , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Pulmão/citologia , Óxido Nítrico/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Adenoviridae/genética , Animais , Arginase/metabolismo , Arginina/metabolismo , Transportador 1 de Aminoácidos Catiônicos/genética , Transportador 2 de Aminoácidos Catiônicos/genética , Bovinos , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/enzimologia , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Lipopolissacarídeos/farmacologia , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transfecção , Ureia/metabolismoRESUMO
Inhaled nitric oxide is being evaluated as a preventative therapy for patients at risk for bronchopulmonary dysplasia (BPD). Nitric oxide (NO), in the presence of superoxide, forms peroxynitrite, which reacts with tyrosine residues on proteins to form 3-nitrotyrosine (3-NT). However, NO can also act as an antioxidant and was recently found to improve the oxidative balance in preterm infants. Thus, we tested the hypothesis that the addition of a therapeutically relevant concentration (10 ppm) of NO to a hyperoxic exposure would lead to decreased 3-NT formation in the lung. FVB mouse pups were exposed to either room air (21% O(2)) or >95% O(2) with or without 10 ppm NO within 24 h of birth. In the first set of studies, body weights and survival were monitored for 7 days, and exposure to >95% O(2) resulted in impaired weight gain and near 100% mortality by 7 days. However, the mortality occurred earlier in pups exposed to >95% O(2) + NO than in pups exposed to >95% O(2) alone. In a second set of studies, lungs were harvested at 72 h. Immunohistochemistry of the lungs at 72 h revealed that the addition of NO decreased alveolar, bronchial, and vascular 3-NT staining in pups exposed to both room air and hyperoxia. The lung nitrite levels were higher in animals exposed to >95% oxygen + NO than in animals exposed to >95% oxygen alone. The protein levels of myeloperoxidase, monocyte chemotactic protein-1, and intracellular adhesion molecule-1 were assessed after 72 h of exposure and found to be greatest in the lungs of pups exposed to >95% O(2). This hyperoxia-induced protein expression was significantly attenuated by the addition of 10 ppm NO. We propose that in the presence of >95% O(2), peroxynitrite formation results in protein nitration; however, adding excess NO to the >95% O(2) exposure prevents 3-NT formation by NO reacting with peroxynitrite to produce nitrite and NO(2). We speculate that the decreased protein nitration observed with the addition of NO may be a potential mechanism limiting hyperoxic lung injury.
Assuntos
Lesão Pulmonar/prevenção & controle , Óxido Nítrico/administração & dosagem , Tirosina/análogos & derivados , Animais , Quimiocina CCL2/análise , Hiperóxia/metabolismo , Hiperóxia/patologia , Molécula 1 de Adesão Intercelular/análise , Pulmão/efeitos dos fármacos , Pulmão/patologia , Lesão Pulmonar/induzido quimicamente , Lesão Pulmonar/patologia , Camundongos , Oxigênio/efeitos adversos , Peroxidase/análise , Tirosina/antagonistas & inibidores , Tirosina/biossínteseRESUMO
Chronic lung injury in the neonate is termed bronchopulmonary dysplasia (BPD). These patients generally require supplemental oxygen therapy, and hyperoxia has been implicated in the pathogenesis of BPD. The concomitant use of oxygen and inhaled NO (iNO) may result in the generation of reactive nitrogen species or may have an anti-inflammatory effect in the neonatal lung. We tested the hypothesis that exposure to >95% O2 in neonatal mice would increase trafficking of leukocytes into the lung and that the addition of iNO to >95% O2 would decrease this leukocyte trafficking. Hyperoxia resulted in fewer alveoli, increased presence of neutrophils and macrophages, and decreased number of mast cells within the lung parenchyma. Adding iNO to hyperoxia prevented the hyperoxia-induced changes and resulted in the numbers of alveoli, neutrophils, macrophages, and mast cells approximating those found in controls (room air exposure). Intercellular adhesion molecule (ICAM) and monocyte chemotactic protein-1 (MCP-1), two factors responsible for leukocyte recruitment, were up-regulated by hyperoxic exposure, but the addition of iNO to the hyperoxic exposure prevented the hyperoxia-induced up-regulation of ICAM and MCP-1. These data demonstrate that iNO alters the hyperoxia-induced recruitment of leukocytes into the lung.