Xuebijing Injection Ameliorates H / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects and underlying mechanisms of Xuebijing Injection (XBJ) on the lung endothelial barrier in hydrogen sulfide (H@*METHODS@#Sprague-Dawley rats were exposed to H@*RESULTS@#The morphological investigation showed that XBJ attenuated H@*CONCLUSIONS@#XBJ ameliorated H

Retratamento com surfactante em prematuros de muito baixo peso: preditores de risco e sua influência nos resultados neonatais / Retreatment with surfactant in very low birth weight preterm infants: risk predictors and their influence on neonatal outcomes

ABSTRACT Objective: To assess clinical predictors and outcomes associated to the need for surfactant retreatment in preterm infants. Methods: Retrospective cohort study, including very low birth weight preterm infants from January 2006 to December 2015 who underwent surfactant replacement therapy. Beractant was used (100 mg/kg), repeated every six hours if FiO2 ≥0.40. The subjects were classified into two groups: single surfactant dose; and more than one dose (retreatment). We evaluated maternal and neonatal predictors for the need of retreatment and neonatal outcomes associated to retreatment. Results: A total of 605 patients (44.5%) received surfactant; 410 (67.8%) one dose, and 195 (32.2%) more than one dose: 163 (83.5%) two doses and 32 (16.4%) three doses. We could not find clinical predictors for surfactant retreatment. Retreatment was associated to a greater chance of BPD in infants >1000 g (RR 1.78; 95%CI 1.30‒2.45) and ≤1000 g (RR 1.33; 95%CI 1.04‒1.70), in infants with gestational age<28 weeks (RR 1.56; 95%CI 1.12‒2.18) and ≥28 weeks (RR 1.50; 95%CI 1.17‒1.92), in neonates with early sepsis (RR 1.48; 95%CI 1.20‒1.81), and in infants not exposed to antenatal corticosteroids (RR 1.62; 95%CI 1.20‒2.17) Conclusions: We could not find predictor factors associated to surfactant retreatment. The need for two or more doses of surfactant was significantly related to bronchopulmonary dysplasia.

RESUMO Objetivo: Avaliar preditores clínicos e resultados associados à necessidade de retratamento com surfactante. Métodos: Coorte retrospectiva com prematuros de muito baixo peso, no período de janeiro de 2006 a dezembro de 2015, em uso de terapia de reposição de surfactante. O surfactante utilizado foi beractante (100 mg/kg), repetido a cada seis horas se FiO2≥0.40. Foram analisados dois grupos: dose única de surfactante e mais de uma dose (retratamento). Foram avaliados preditores maternos e neonatais para retratamento e resultados neonatais. Resultados: 605 pacientes (44,5%) receberam surfactante; 410 (67,8%) uma dose e 195 (32,2%) mais de uma dose: 163 (83,5%) duas doses e 32 (16.4%) três doses. Não foram encontrados fatores associados ao retratamento com surfactante. A displasia broncopulmonar (DBP) foi associada ao retratamento (p<0.01). A presença de retratamento aumentou a chance de ocorrência de DBP em neonatos >1000 g (RR 1,78; IC95% 1,30‒2,45) e ≤1000 g (RR 1,33; IC95% 1,04‒1,70), em recém-nascidos com idade gestacional <28 semanas (RR 1,56; IC95% 1,12‒218) e ≥28 semanas (RR 1,50; IC95% 1,17‒1,92), naqueles com sepse precoce (RR 1,48; IC95% 1,20‒1,81), e nos que não foram expostos ao corticoide antenatal (RR 1,62; IC95% 1,20‒2,17). Conclusões: Não encontramos fatores preditores associados à necessidade de retratamento. A necessidade de duas ou mais doses de surfactante está associada à displasia broncopulmonar.

Síndrome do desconforto respiratório agudo associada à COVID-19 tratada com DEXametasona (CoDEX): delineamento e justificativa de um estudo randomizado / COVID-19-associated ARDS treated with DEXamethasone (CoDEX): study design and rationale for a randomized trial

RESUMO Objetivo: A infecção causada pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2) disseminou-se por todo o mundo e foi categorizada como pandemia. As manifestações mais comuns da infecção pelo SARS-CoV-2 (doença pelo coronavírus 2019 - COVID-19) se referem a uma pneumonia viral com graus variáveis de comprometimento respiratório e até 40% dos pacientes hospitalizados, que podem desenvolver uma síndrome do desconforto respiratório agudo. Diferentes ensaios clínicos avaliaram o papel dos corticosteroides na síndrome do desconforto respiratório agudo não relacionada com COVID-19, obtendo resultados conflitantes. Delineamos o presente estudo para avaliar a eficácia da administração endovenosa precoce de dexametasona no número de dias vivo e sem ventilação mecânica nos 28 dias após a randomização, em pacientes adultos com quadro moderado ou grave de síndrome do desconforto respiratório agudo causada por COVID-19 provável ou confirmada. Métodos: Este é um ensaio pragmático, prospectivo, randomizado, estratificado, multicêntrico, aberto e controlado que incluirá 350 pacientes com quadro inicial (menos de 48 horas antes da randomização) de síndrome do desconforto respiratório agudo moderada ou grave, definida segundo os critérios de Berlim, causada por COVID-19. Os pacientes elegíveis serão alocados de forma aleatória para tratamento padrão mais dexametasona (Grupo Intervenção) ou tratamento padrão sem dexametasona (Grupo Controle). Os pacientes no Grupo Intervenção receberão dexametasona 20mg por via endovenosa uma vez ao dia, por 5 dias, e, a seguir, dexametasona por via endovenosa 10mg ao dia por mais 5 dias, ou até receber alta da unidade de terapia intensiva, o que ocorrer antes. O desfecho primário será o número de dias livres de ventilação mecânica nos 28 dias após a randomização, definido como o número de dias vivo e livres de ventilação mecânica invasiva. Os desfechos secundários serão a taxa de mortalidade por todas as causas no dia 28, a condição clínica no dia 15 avaliada com utilização de uma escala ordinal de seis níveis, a duração da ventilação mecânica desde a randomização até o dia 28, a avaliação com o Sequential Organ Failure Assessment Score após 48 horas, 72 horas e 7 dias, e o número de dias fora da unidade de terapia intensiva nos 28 dias após a randomização.

Abstract Objective: The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV-2 infection (coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop acute respiratory distress syndrome. Several clinical trials evaluated the role of corticosteroids in non-COVID-19 acute respiratory distress syndrome with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe acute respiratory distress syndrome due to confirmed or probable COVID-19. Methods: This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48 hours before randomization) moderate or severe acute respiratory distress syndrome, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (Intervention Group) or standard treatment without dexamethasone (Control Group). Patients in the intervention group will receive dexamethasone 20mg intravenous once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until intensive care unit discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment Score evaluation at 48 hours, 72 hours and 7 days and intensive care unit -free days within 28.

p38MAPK plays a pivotal role in the development of acute respiratory distress syndrome

Acute respiratory distress syndrome (ARDS) is a life-threatening illness characterized by a complex pathophysiology, involving not only the respiratory system but also nonpulmonary distal organs. Although advances in the management of ARDS have led to a distinct improvement in ARDS-related mortality, ARDS is still a life-threatening respiratory condition with long-term consequences. A better understanding of the pathophysiology of this condition will allow us to create a personalized treatment strategy for improving clinical outcomes. In this article, we present a general overview p38 mitogen-activated protein kinase (p38MAPK) and recent advances in understanding its functions. We consider the potential of the pharmacological targeting of p38MAPK pathways to treat ARDS.

Prevalence and factors associated with surfactant use in Brazilian Neonatal Intensive Care Units: A multilevel analysis / Prevalência e fatores associados ao uso de surfactante em unidades de Terapia Intensiva Neonatais brasileiras: análise multinível

Abstract The treatment with exogenous surfactant reduces mortality and the risk of complications in preterm newborns with Respiratory Distress Syndrome. Higher usage levels have been associated with individual and institutional factors. The study aimed to identify these factors associated with use of this technology in 16 public Brazilian Neonatal Units using logistic multilevel analysis. In a sample of 630 newborns the use at some time was 82.6%. Only 24.7% made use of this technology up to two hours after birth. An intraclass correlation of 0.30 showed that 30% of the variance in the use of exogenous surfactant could be assigned to the contextual level. In the final model, a greater severity score (SNAPPE-II) was associated with increased surfactant use (OR = 2.64), whereas being small for gestational age (SGA) (OR = 0.59) was associated with lower use of this technology. At the contextual level the number of beds in the unit >15 (OR = 5.86), units with higher complexity (OR = 1.73) or units with implemented Kangaroo Mother Care (OR = 2.91), especially units in Rio de Janeiro state (OR = 16.17) were associated with greater surfactant use. Although individual clinical features explained most of the variation in the use of this technology, factors linked to the institution were also of utmost importance.

Resumo O tratamento com surfactante exógeno reduz a mortalidade e o risco de complicações em recém-nascidos com Síndrome de Angústia Respiratória. Maiores níveis de utilização dessa tecnologia têm sido associados tanto a fatores individuais como institucionais. O estudo teve como objetivo identificar esses fatores em 16 unidades neonatais públicas brasileiras usando análise multinível. De 630 recém-nascidos, 82,6% usaram a tecnologia em algum momento. Apenas 24,7% fizeram uso até duas horas após o nascimento. Uma correlação intraclasse de 0,30 mostrou que 30% da variação no uso podem ser atribuídos ao nível contextual. No modelo final, um escore de gravidade maior (SNAPPE-II) foi associado com aumento do uso de surfactante (OR = 2,64), enquanto que ser pequeno para a idade gestacional (PIG) (OR = 0,59) foi associado a um menor uso dessa tecnologia. No nível contextual o número de leitos na unidade > 15 (OR = 5,86), as unidades com mais alta complexidade (OR = 1,73) ou unidades com Método Canguru implementado (OR = 2,91), especialmente unidades no estado do Rio de Janeiro (OR = 16,17), foram associados com uma maior utilização de surfactante. Embora características individuais tenham explicado a maior parte da variação no uso desta tecnologia, fatores ligados à instituição também foram de extrema importância.

Development of a Synthetic Surfactant Using a Surfactant Protein-C Peptide Analog: In Vitro Studies of Surface Physical Properties

PURPOSE: Pulmonary surfactant (PS) replacement has been the gold standard therapy for neonatal respiratory distress syndrome; however, almost all commercial PSs contain animal proteins. We prepared a synthetic PS by using a human surfactant protein (SP) analog and evaluated its in vitro properties. MATERIALS AND METHODS: A peptide sequence (CPVHLKRLLLLLLLLLLLLLLLL) of human SP-C was chosen to develop the peptide analog (SPa-C). The new synthetic SP-C PS (sSP-C PS) was synthesized from SPa-C, dipalmitoyl phosphatidylcholine, phosphatidyl glycerol, and palmitic acid. Physical properties of the sSP-C PS were evaluated by measuring the maximum and minimum surface tensions (STs), surfactant spreading, and adsorption rate. In addition, we recorded an ST-area diagram. The data obtained on sSP-C PS were subsequently compared with those of purified natural bovine surfactant (PNBS), and the commercial product, Surfacten(R). RESULTS: The sSP-C PS and Surfacten(R) were found to have maximum ST values of 32-33 mN/m, whereas that of PNBS was much lower at 19 mN/m. The minimum ST values of all three products were less than 10 mN/m. The values that were measured for the equilibrium ST of rapidly spreading sSP-C PS, Surfacten(R), and PNBS were 27, 27, and 24 mN/m, respectively. The surface adsorptions were found to be the same for all three PSs (20 mN/m). ST-area diagrams of sSP-C PS and Surfacten(R) revealed similar properties. CONCLUSION: In an in vitro experiment, the physical properties exhibited by sSP-C PS were similar to those of Surfacten(R). Further study is required to evaluate the in vivo efficacy.

Efectividad del SURFACEN ® en neonatos prematuros con síndrome de dificultad respiratoria / Effectiveness of SURFACEN ® in preterm infant with respiratory distress syndrome

Introducción: el SURFACEN® es un surfactante natural cubano, de origen porcino, que desde su registro sanitario en 1995, se prescribe para tratar el Síndrome de Dificultad Respiratoria del pretérmino. Objetivo: ratificar la efectividad del SURFACEN® en recién nacidos pretérmino con síndrome de dificultad respiratoria. Método: se diseño un estudio descriptivo, longitudinal, prospectivo, de seguimiento poscomercialización, no controlado, multicéntrico nacional, durante el periodo comprendido del 2007 al 2009. El universo de estudio estuvo constituido por 259 recién nacidos con síndrome de dificultad respiratoria y menos de 37 semanas de edad gestacional, a los que se les administró SURFACEN®. La variable principal para evaluar la efectividad del surfactante fue la mortalidad neonatal. Resultados: predominó el sexo masculino en el 58,7 por ciento y los nacidos por cesárea en el 66,4 por ciento. Se aplicó como rescate tardío, el tiempo en ventilación mecánica fue de siete días y la mortalidad fue de un 19,7 por ciento, las complicaciones con mayor riego de morir fue la enterocolitis necrotizante. Conclusión: el SURFACEN® en la práctica clínica habitual demostró su efectividad(AU)

Introduction: SURFACEN® is a Cuban natural surfactant of swine origin, which since its sanitary registration in 1995, is prescribed to treat respiratory distress syndrome in preterm infants. Objective: to ratify the effectiveness of SURFACEN® in preterm infants with respiratory distress syndrome. Method: anational descriptive, longitudinal, prospective, post-market monitoring, uncontrolled and multicentered study was designed and conducted during the period from 2007 to 2009. The universe of study consisted of 259 infants with respiratory distress syndrome and less than 37 weeks old gestational age, who were administered SURFACEN®. The primary endpoint for evaluation of the surfactant effectiveness was neonatal mortality. Results: males prevailed in 58.7 percent and those born by Caesarean section in 66. 4 percent. It was applied as late rescue, length of time on mechanical ventilation was seven days and mortality was 19.7 percent, the complications with the highest risk of dying were necrotizing enterocolitis. Conclusions: SURFACEN® demonstrated its effectiveness in clinical practice(AU)

Descentralização das ações de vigilância epidemiológica em Pernambuco, Brasil / Decentralization of epidemiological surveillance in Pernambuco State, Brazil / Descentralización de la vigilancia epidemiológica en Pernambuco, Brasil

O objetivo do estudo foi analisar a relação entre o processo de descentralização da gestão do Sistema Único de Saúde (SUS) e o desenvolvimento das ações de vigilância epidemiológica em municípios de Pernambuco, Brasil. A estratégia de trabalho consistiu num estudo descritivo e exploratório qualitativo/quantitativo, com a realização de uma pesquisa de caráter documental e entrevistas semiestruturadas com informantes-chave, como também um estudo ecológico espacial e de série temporal, no qual foi traçada uma série histórica de dez anos (2001-2010), utilizando-se indicadores selecionados. O estudo evidenciou que o processo de descentralização em Pernambuco obteve adesão e evoluiu, porém com a existência de desigualdades e fragilidades no seu desenvolvimento, também apontadas pela oscilação nos resultados da série histórica dos indicadores selecionados. Assim, mesmo que o processo de descentralização das ações de vigilância epidemiológica ainda seja incipiente em alguns municípios, sabe-se que o papel de executor das ações promove o empoderamento do nível municipal, quando o mesmo passa a produzir as informações necessárias à tomada de decisão.

The study aimed to analyze the relationship between decentralization of the Brazilian Unified National Health System (SUS) and the development of epidemiological surveillance activities in municipalities (counties) in Pernambuco State, Brazil. This was an exploratory descriptive qualitative and quantitative study, including a document search, completion of semi-structured interviews by key informants, and an ecological spatial and time trend study of selected health indicators, covering a 10-year period (2001-2010). The study showed that municipalities adhered to the decentralization process, which was making progress in Pernambuco, but with inequalities and weaknesses in its development. There was also a fluctuation in the time series for the selected indicators. Thus, even though the decentralization of epidemiological surveillance is still incipient in some municipalities, their protagonist role in implementing the activities promotes empowerment at the local level by producing key information for decision-making.

El objetivo del estudio fue analizar la relación entre el proceso de descentralización del Sistema Único de Salud (SUS) y el desarrollo de acciones de vigilancia epidemiológica en los municipios de Pernambuco, Brasil. La estrategia de trabajo fue un estudio exploratorio descriptivo, cualitativo y cuantitativo, con la realización de una revisión documental, entrevistas semi-estructuradas con informantes clave, y un estudio ecológico espacial con una serie de tiempo de 10 años (2001-2010) de indicadores seleccionados. El estudio mostró que el proceso de descentralización en Pernambuco tiene adhesión y evolucionó, pero con la existencia de desigualdades y debilidades en su desarrollo, revelado también por la oscilación de la serie histórica de los indicadores. A pesar de que el proceso de descentralización de la vigilancia epidemiológica es aún incipiente en algunos municipios, se sabe que el papel de ejecutor de acciones promueve el empoderamiento del nivel municipal, cuando se comienza a producir información necesaria para la toma de decisiones.

Efficacy of Surfactant-TA, Calfactant and Poractant Alfa for Preterm Infants with Respiratory Distress Syndrome: A Retrospective Study

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.

Efficacy of Surfactant-TA, Calfactant and Poractant Alfa for Preterm Infants with Respiratory Distress Syndrome: A Retrospective Study

PURPOSE: To compare the efficacy of the new drug calfactant with the commonly used drugs surfactant-TA and poractant alfa. MATERIALS AND METHODS: A total of 332 preterm infants at 24-31 weeks' gestation with respiratory distress syndrome (RDS) were enrolled and allocated to three groups according to the surfactant instilled; Group 1 (n=146, surfactant-TA), Group 2 (n=96, calfactant), and Group 3 (n=90, poractant alfa). The diagnosis of RDS and the decision to replace the pulmonary surfactant were left to the attending physician and based on patient severity determined by chest radiography and blood gas analysis. Data were collected and reviewed retrospectively using patient medical records. RESULTS: Demographic factors including gestational age, birth weight, Apgar score, clinical risk index for babies II score, and maternal status before delivery were not different between the study groups. Instances of surfactant redosing and pulmonary air leaks, as well as duration of mechanical ventilation, were also not different. Rates of patent ductus arteriosus, intraventricular hemorrhage (> or =grade III), periventricular leukomalacia, high stage retinopathy of prematurity, necrotizing enterocolitis (> or =stage II), and mortality were also similar, as was duration of hospital stay. Cases of pulmonary hemorrhage and moderate to severe bronchopulmonary dysplasia were increased in Group 3. CONCLUSION: Calfactant is equally as effective as surfactant-TA and poractant alfa. This was the first study comparing the efficacy of surfactant-TA, calfactant, and poractant alfa in a large number of preterm infants in Korea. Further randomized prospective studies on these surfactants are needed.

Presión positiva continua en la vía aérea comparada con la respiración mecánica asistida en prematuros de 28 a 32 semanas de gestación con administración precoz de surfactante pulmonar / Nasal CPAP versus mechanical ventilation in 28 to 32-week preterm infants with early surfactant administration

Introducción. La presión positiva continua en la vía aérea ( Continuous Positive Airway Pressure , CPAP) es útil en prematuros de 28 a 32 semanas de gestación con síndrome de dificultad respiratoria, pero no se ha precisado si es mejor que la respiración mecánica asistida después de la administración precoz de surfactante pulmonar. Objetivo. Comparar la incidencia de eventos adversos en prematuros de 28 a 32 semanas de gestación con síndrome de dificultad respiratoria atendidos con surfactante y respiración mecánica asistida o CPAP de burbuja. Materiales y métodos. Se atendieron 147 neonatos con respiración mecánica asistida y 176 con CPAP, ninguno de los cuales presentaba asfixia perinatal o apnea. Resultados. La incidencia de fracaso de la CPAP fue de 6,5 % (IC 95% 11,3-22,8 %). Fallecieron 29 pacientes, 7 de los cuales habían recibido CPAP (4,0 %) y, 22, respiración mecánica asistida (15,0 %; p<0,001). El riesgo relativo (RR) de morir de quienes recibieron CPAP, comparado con el de quienes recibieron respiración mecánica asistida, fue de 0,27 (IC 95% 0,12-0,61), pero, al ajustar por los factores de confusión, el uso de CPAP no implicó mayor riesgo de morir (RR=0,60; IC 95% 0,29-1,24). La letalidad con respiración mecánica asistida fue de 5,70 (IC 95% 3,75-8,66) muertes por 1.000 días-paciente, mientras que con CPAP fue de 1,37 (IC 95% 0,65-2,88; p<0,001). La incidencia de neumopatía crónica fue menor con CPAP (RR=0,71, IC 95% 0,54-0,96), al igual que la de hemorragia cerebral (RR=0,28; IC 95% 0,09-0,84) y la de sepsis (RR=0,67; IC 95% 0,52-0,86), pero fue similar en cuanto a escapes de aire (RR=2,51; IC 95% 0,83-7,61) y enterocolitis necrosante (RR=1,68; IC 95% 0,59-4,81). Conclusión. La incidencia de neumopatía crónica, hemorragia ventricular y sepsis es menor con el uso de CPAP.

Introduction: Continuous positive airway pressure (CPAP) is useful in low birth weight infants with respiratory distress, but it is not known if it is a better alternative to mechanical ventilation after early pulmonary surfactant administration. Objective: To compare the incidence of adverse events in 28 to 32-week newborns with respiratory distress managed with mechanical ventilation or CPAP after early surfactant administration. Materials and methods: In total, 176 newborns were treated with CPAP and 147 with mechanical ventilation, all with Apgar scores >3 at five minutes and without apnea. Results: The incidence of CPAP failure was 6.5% (95% CI: 11.3-22.8%); 29 patients died: 7 with CPAP (4.0%) and 22 with mechanical ventilation (15.0%, p<0.001). The relative risk of dying with CPAP versus mechanical ventilation was 0.27 (95% CI: 0.12-0.61), but after adjusting for confounding factors, CPAP use did not imply a higher risk of dying (RR=0.60; 95% CI: 0.29-1.24). Mechanical ventilation fatality rate was 5.70 (95% CI: 3.75-8.66) deaths/1,000 days-patient, while with CPAP it was 1.37 (95% CI: 0.65-2.88, p<0.001). Chronic lung disease incidence was lower with CPAP than with mechanical ventilation (RR=0.71; 95% CI: 0.54-0.96), as were intracranial hemorrhage (RR=0.28, 95% CI: 0.09-0.84) and sepsis (RR=0.67; 95%CI: 0.52-0.86), and it was similar for air leaks (RR=2.51; 95% CI: 0.83-7.61) and necrotizing enterocolitis (RR=1.68, 95% CI: 0.59-4.81). Conclusion: CPAP exposure of premature infants with respiratory distress syndrome is protective against chronic lung disease, intraventricular hemorrhage and sepsis compared to mechanical ventilation. No differences were observed regarding air leak syndrome or death.

A multicenter, randomized, double-blind trial of a new porcine surfactant in premature infants with respiratory distress syndrome / Ensaio clínico multicêntrico duplo-cego randomizado com um novo surfactante de origem porcina em prematuros com síndrome do desconforto respiratório

Objective To compare the efficacy and safety of a new porcine-derived pulmonary surfactant developed by Instituto Butantan with those of animal-derived surfactants commercially available in Brazil, regarding neonatal mortality and the major complications of prematurity in preterm newborns with birth weight up to 1500g and diagnosed with respiratory distress syndrome. Methods Neonates diagnosed with respiratory distress syndrome were randomized to receive either Butantan surfactant (Butantan group) or one of the following surfactants: Survanta® or Curosurf®. Newborns receiving Survanta® or Curosurf® comprised the control group. The main outcome measures were mortality rates at 72 hours and at 28 days of life; the typical complications of prematurity as evaluated on the 28th day of life were defined as secundary outcomes. Results No differences were observed between the Butantan (n=154) and control (n=173) groups in relation to birth weight, gestational age, sex, and prenatal use of corticosteroids, or in mortality rates both at 72 hours (14.19% versus 14.12%; p=0.98) and at 28 days (39.86% versus 33.33%; p=0.24) of life. Higher 1- and 5-minute Apgar scores were observed among control group newborns. No differences were observed as regards the secondary outcomes, except for greater need for supplemental oxygen and a higher incidence of interstitial pulmonary emphysema in the Butantan group. Conclusion The mortality rates at 72 hours and 28 days of life and the incidence of major complications of prematurity were comparable to those found with the animal-derived surfactants commercially available in Brazil, showing the efficacy and safety of the new surfactant in the treatment of respiratory distress syndrome ...

Objetivo Comparar a eficácia e a segurança de um novo surfactante pulmonar de origem porcina, desenvolvido pelo Instituto Butantan, com os surfactantes de origem animal disponíveis no país, em relação à mortalidade neonatal e às principais complicações da prematuridade, em prematuros com peso de nascimento até 1500g e diagnóstico de síndrome do desconforto respiratório. Métodos Recém-nascidos com diagnóstico de síndrome do desconforto respiratório foram randomizados para receber surfactante Butantan (Grupo Butantan) ou um dos seguintes surfactantes: Survanta® ou Curosurf®. Os recém-nascidos que receberam Survanta® ou Curosurf® formaram o Grupo Controle. Foram definidas, como variáveis primárias, as mortalidades com 72 horas e 28 dias de vida e, como variáveis secundárias, as principais complicações típicas da prematuridade, avaliadas no 28O dia de vida. Resultados Não foram observadas diferenças em relação ao peso de nascimento, idade gestacional, sexo e corticoide pré-natal, assim como em relação à mortalidade dos recém-nascidos dos Grupos Butantan (n=154) e Controle (n=173), tanto com 72 horas (14,19% versus 14,12%; p=0,98) como em 28 dias de vida (39,86% versus 33,33%; p=0,24). Foram observados maiores valores do boletim de Apgar de 1 e de 5 minutos entre os recém-nascidos do Grupo Controle. Os grupos não diferiram em relação às variáveis secundárias, exceto por uma maior necessidade de uso de oxigênio e de enfisema pulmonar intersticial no Grupo Butantan. Conclusão As taxas de mortalidade com 72 horas ...

Economic evaluation of the use of exogenous pulmonary surfactants in preterm newborns in a Mexican population / Evaluación económica de la utilización de surfactantes pulmonares exógenos en recién nacidos pretérmino en población mexicana

OBJECTIVE: To estimate the cost-effectiveness ratio of surfactant rescue treatment of premature infants with respiratory distress syndrome (RDS) who are covered by the Medical Insurance for a New Generation. MATERIALS AND METHODS: A cost-effectiveness evaluation was conducted from the third-payer perspective. Comparisons were made between the use of bovine surfactant (BS) therapy and without BS therapy. A decision tree model with a lifetime horizon was used where the measurements of effectiveness were life years gained (LYG) and quality-adjusted life years (QALYs). A 5% discount rate was considered for costs and health outcomes. All costs are expressed in Mexican pesos 2009. RESULTS: Incremental cost-effectiveness ratios (ICER) were MXN$136670 per LYG and MXN$125250 per QALY. CONCLUSION: Surfactant therapy was confirmed as a cost-effective strategy in accordance with World Health Organization criteria of three per capita gross domestic product (GDP) per QALY in premature infants with RDS in Mexico.

OBJETIVO: Estimar la razón de costo efectividad incremental del tratamiento de surfactante de rescate en pacientes pretérmino con Síndrome de Dificultad Respiratoria (SDR) cubiertos por el Seguro Médico para una Nueva Generación. MATERIAL Y MÉTODOS: Evaluación de costo-efectividad desde la perspectiva del tercer pagador. Los comparadores fueron la terapia de surfactante bovino y la alternativa de no emplear ésta. Se utilizó un árbol de decisión que consideró la esperanza de vida como horizonte temporal y las medidas de efectividad fueron los años de vida ganados (AVG) y los años de vida ajustados por calidad de vida ( AVAC).Resultados en pesos mexicanos del 2009. RESULTADOS: Las RCEI por AVG y AVAC fueron de MXN$136670 y MXN$125250. CONCLUSIÓN: La razón de costo por AVG y AVAC para la terapia de surfactantes en pacientes prematuros con SDR en México fue menor a tres veces el PIB per cápita, por lo que es una estrategia costo-efectiva según los criterios de la OMS.

Complications among premature neonates treated with beractant and poractant alfa.

Objective. To compare the complications among preterm infants treated with two different natural surfactants. Methods. In a randomized clinical trial, 150 preterm infants with Respiratory distress syndrome (RDS) treated with exogenous surfactant, were enrolled in the study. Group A consisted of 79 neonates that received poractant (curosurf). Seventy one newborn infants in group B were treated with beractant (Survanta). Results. The mean gestational age for group A and B were 29.40±2.90 wk and 29.50±2.73 wk (P=0.82), respectively. The demographic and clinical variables were similar in both groups. The mean duration of intubation (as a primary outcome) was significantly shorter in infants treated with poractant (3.13±1.80 vs 4.06±2.7 days p=0.05). The mean duration of need for oxygen and hospitalization of patients in group A and B were 17.73±22.25 vs 19.14±17.85days (p=0.67) and 24.89±26.41 vs 29.14±23.54 days (p= 0.32), respectively. There was no significant difference between groups with respect to mortality and morbidity, including pulmonary hemorrhage, intraventricular hemorrhage (IVH), patent ductus arteriosus, sepsis, and bronchopulmonary dysplasia (secondary outcome). Conclusions. In this study, infants who received poractant had shorter duration of intubation than infants treated with beractant, without any difference in the duration of oxygen therapy or hospitalization. There was no significant superiority of poractant over beractant.

Surfactant and patent ductus arteriosus.

Objective. To investigate the relationship between surfactant replacement therapy and the development of a haemodynamically significant ductus arteriosus. Methods. All premature infants at 28-32 wk gestation with a clinical diagnosis of respiratory distress syndrome were retrospectively reviewed and subdivided into two groups; intubated, mechanically ventilated and received surfactant (Group 1); and received nasal continuous positive airway pressure alone (Group 2). The relationship between groups and characteristics of the hemodynamically significant ductus arteriosus was analyzed. Results. Seventy babies were identified of whom 35 (50%) received surfactant. Babies in group I and II were comparable for gestational age, birthweight, antenatal steroids, gender and fluid intake in first week of life. Babies treated with surfactant therapy were found to be more likely to have a haemodynamically significant ductus arteriosus (p< 0.01), larger transductal diameter (p=0.01) and increased rate of therapeutic interventions to close the ductus (p<0.01). Ventilation parameters (mean airway pressure and fractional inspired oxygen) were higher in group I. Conclusion. Neonates with respiratory distress syndrome (RDS) who were treated with surfactant replacement are at increased risk of a hemodynamically significant ductus arteriosus that requires therapeutic intervention. Whether the relationship reflects their underlying lung disease or is a direct effect of surfactant requires prospective evaluation.

Validación de puntos críticos de la producción de Surfacen / Validation of critical features of Surfacen production

El Surfacen® es un medicamento utilizado en el tratamiento del síndrome de dificultad respiratorio del recién nacido, causa importante de mortalidad y morbilidad neonatal. Este se fabrica en el Centro Nacional de Sanidad Agropecuaria (La Habana, Cuba) bajo un Sistema de Gestión de la Calidad y Buenas Prßcticas de Fabricación. El pulmón porcino constituye la materia prima fundamental, y es a partir de su calidad microbiológica y la del proceso productivo que se garantiza un producto final libre de contaminantes microbianos y de pirógenos. A partir del dise±o de protocolos específicos y de las regulaciones existentes se demostró que la crianza de cerdos, su proceso de sacrificio y los materiales utilizados en la obtención de los lavados pulmonares, permiten alcanzar una calidad microbiológica definida y bajo control. El proceso de producción fue capaz de eliminar la carga microbiana presente en los lavados pulmonares que junto al resto de las operaciones de preparación de materiales estériles, su traslado, uso, al igual que la limpieza y desinfección de las ßreas limpias, el llenado aséptico y el personal garantizaron la esterilidad del producto final. Todos estos resultados permiten concluir que los procesos críticos de la producción de Surfacen® estßn validados y garantizan que este sea estéril, libre de pirógenos y sin residuales tóxicos, lo que demuestra su seguridad, reproducibilidad y consistencia.

Surfacen® is a drug used in treatment of newborn respiratory distress syndrome, a significant cause of neonatal mortality and morbidity. This drug is manufactured by National Center of Farming and livestock Hygiene (La Habana, Cuba) under a Management System of Quality and Good Practices of Manufacture. Pig lung is the essential raw material, and it is from microbiologic quality and that of productive process, that a free of microbial contaminant and pyrogen end product is guaranteed. From design of specific protocols and of the available regulations, it was demonstrated that pig breeding, its sacrifice process, and materials used in achievement of lung lavages, allow us to obtain a defined microbiologic quality and under control. Production process was able to eliminate microbial charge present in lung lavages, which together with the remainder preparation tasks of sterile materials, its transfer, use, as well as cleaning and disinfection of clean areas, the aseptic filling, and staff guaranteed sterility of end product. All these results allow us to conclude that the critical processes of Surfacen® production are validated and guarantee that this one be sterile, pyrogen-free, and without toxic residuals, demonstrating its safety, reproducibility and consistence.

Corticosteróides na aceleração da maturidade fetal: evidências atuais / Corticosteroids in fetal maturity acceleration: update evidences

A síndrome da dificuldade respiratória neonatal é grave complicação da prematuridade. Em 1969, Liggins constatou que a maturação do pulmão fetal estava acelerada nos fetos de cordeiros infundidos com corticosteróides. Liggins, em 1972, realizou estudo controlado e randomizado que comprovou a eficácia da terapia antenatal com corticosteróide em reduzir a incidência da síndrome de dificuldade respiratória neonatal (SDR), em seres humanos. Liggins e outros autores demonstraram que esta redução estava presente nos recém-nascidos entre 48 horas e sete dias após o tratamento, o que poderia, conseqüentemente, traduzir benefício em repetir-se a dose do corticosteróide antenatal nas mulheres que permanecem em risco de parto pré-termo por mais de sete dias após o ciclo inicial. Desde a década de 80, os estudos em animais e em seres humanos levantam polêmicas sobre o uso de doses repetidas, em função dos potenciais efeitos adversos para a prole. Hoje, a avaliação da evidência na eficácia da terapia antenatal com corticosteróide permite concluir que todas as gestantes em risco de parto pré-termo, entre 24 e 34 semanas, são candidatas potenciais a receberem um único ciclo de corticosteróide. Não há prova suficiente para avaliar o uso de doses repetidas de corticosteróide nas mulheres que permanecem em risco de parto pré-termo por mais de sete dias após a primeira dose.

The neonatal respiratory distress syndrome is a serious complication of prematurity. In 1969, Liggins showed that fetal lung maturation was sped up in the embryos of lambs infused with corticosteroids. In 1972, Liggins carried out a controlled and radomized study that proved the effectiveness of the antenatal therapy with corticosteroid in reducing the incidence of the neonatal respiratory distress syndrome (NRDS), in human beings. Liggins and other authors had demonstrated that this reduction was present in newborns within 48 hours and seven days after the treatment which could, consequently, be translated into repeating the dose of corticosteroid antenatal in those women who remained at risk of preterm delivery for more than seven days after the initial cycle. Since the 1980's, the studies in animals and human beings have raised controversies on the use of repeated doses due to the potential adverse effect for the offspring. Today, the assessment of the evidence in the effectiveness of the antenatal therapy with corticosteroid has showed that all pregnant women at risk for preterm delivery , between 24 and 34 weeks, are potential cadidates to receive a single cycle of corticosteroid. There is not enough evidence to evaluate the use of repeated doses of corticosteroid in women who remain at risk for preterm delivery for more than seven days after the first dose.

Comparison of Clinical Efficacy of Newfactan(R) versus Surfacten(R) for the Treatment of Respiratory Distress Syndrome in the Newborn Infants

Newfactan(R) is a domestically developed, bovine lung-derived, semi-synthetic surfactant. The aim of this study was to compare the clinical efficacy of Newfactan(R) with that of Surfacten(R) in the treatment of respiratory distress syndrome (RDS). Newfactan(R) or Surfacten(R) was randomly allocated to 492 newborn infants who were diagnosed as RDS and required surfactant instillation in four participating hospitals. The comparisons were made individually in two subsets of infants by birth weight (or=1,500 g group [n=239]). Short-term responses to surfactant and acute complications, such as the total doses of surfactant instilled, response type, extubation rate, ventilator settings, changes in respiratory parameters, air leak, patent ductus arteriosus, pulmonary hemorrhage, and intraventricular hemorrhage, and mortality during the 96 hr after surfactant instillation were measured. Long-term outcome and complications, such as total duration of intubation, bronchopulmonary dysplasia and periventricular leukomalacia, and ultimate mortality were measured. There were no significant differences in demographic and perinatal variables, shortterm responses to surfactant and acute complications, and long-term outcome and complications between Newfactan(R) and Surfacten(R) in both birth weight groups. We concluded that Newfactan(R) was comparable to Surfacten(R) in the clinical efficacy in the treatment of RDS in both birth weight groups.