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.

Seguridad del tratamiento con Surfacen® en recién nacidos pretérminos con síndrome de dificultad respiratoria / Safety of the treatment with Surfacen® in preterm newborns with syndrome of respiratory difficulty

Introducción: Varias han sido las publicaciones sobre Surfacen®, pero ninguna ha comparado la seguridad del producto entre su uso temprano y tardío. Objetivo: Comprobar las características de los eventos adversos en ambas formas de administración del producto. Métodos: Se realizó un estudio analítico observacional, no controlado, multicentro, nacional, desde 2007 al 2013. La muestra fue de 484 recién nacidos en los que se comprobaron los eventos adversos ocurridos por Surfacen® administrado de manera temprana y tardía. Las variables estudiadas fueron de caracterización general y de caracterización de los eventos adversos. Resultados: El grupo al que se le administró el surfactante de manera tardía tuvo mayor incidencia de eventos adversos que los tratados de manera temprana (277 vs 268). El porcentaje de pacientes con estos eventos fue mayor en los tratados de manera tardía (63,7 vs 41,3 por ciento). El rescate tardío tuvo 2,5 veces más riesgo de presentar la hemorragia peri- e intraventricular (10,4 vs 4,0 por ciento), mayor riesgo de presentar las diferentes formas de bloqueo aéreo, tres veces más riesgo de displasia broncopulmonar (8,8 vs 2,6 por ciento) y 6 veces más riesgo de presentar desaturación de oxígeno, que el rescate temprano. Conclusiones: El tratamiento con Surfacen®, tanto en su forma de rescate temprano como tardío presenta los mismos eventos adversos que otros surfactantes utilizados y el tratamiento de rescate temprano tiene menos riesgo de presentar eventos adversos como son la hemorragia intraventricular, el bloqueo aéreo, displasia broncopulmonar y desaturación de oxígeno, por lo que su administración es segura(AU)

Introduction: There have been several publications on SURFACEN®, but none has compared the safety of this product in the early and late uses of it. Objective: To check the characteristics of adverse events in both ways of administering the product. Methods: It was carried out an analytic, observational, non- controlled, national multicentric study from 2007 to 2013. The sample consisted of 484 newborns in whom were checked the adverse events occurred in the early and late ways by administered SURFACEN®. The studied variables were of general characterization and of characterization of the adverse events. Results: The group to which the surfactant was administered in a late way had more incidences of adverse events than the ones treated earlier (277 vs 268). The percentage of patients with these events was higher in the ones treated in a late way (63.7 vs 41.3 percent). The late rescue had 2.5 times more risk of presenting peri- and intra-ventricular hemorrhage (10.4 vs 4.0 percent), higher risk of presenting the different forms of air block, three times more risk of bronchopulmonary dysplasia (8.8 vs 2.6 percent), and six times more risk of presenting oxygen desaturation. Conclusions: As much in the way of early rescue as in the late one, the treatment with SURFACEN® presents the same adverse events that other used surfactants; and the early rescue's treatment has less risk of presenting adverse events or intraventricular hemorrhage, air block, bronchopulmonary dysplasia and oxygen desaturation, that is why its administration is safe(AU)

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.

A randomized controlled trial of the laryngeal mask airway for surfactant administration in neonates / Ensaio controlado randomizado de máscara laríngea para administração de surfactantes em neonatos

Abstract Objective: To compare the short-term efficacy of surfactant administration by laryngeal mask airway versus endotracheal tube. Methods: Preterm infants (28-35 weeks of gestational age), weighing 1 kg or more, with respiratory distress syndrome, requiring nasal continuous positive airway pressure, with increased respiratory effort and/or fraction of inspired oxygen (FiO2) ≥ 0.40 to maintain oxygen saturation 91-95%, were randomized to receive surfactant by LMA following nCPAP or by ETT following mechanical ventilation (MV). The primary outcome was a clinical response defined as FiO2 ≤ 0.30 three hours after surfactant. Secondary outcomes for LMA group were: need of surfactant retreatment during the first 24 h, MV requirement, and presence of surfactant in gastric content. Results: Forty-eight patients were randomized; 26 in the LMA group and 22 in the ETT group. Six of 26 patients (23%) in the LMA group and five of 22 patients (22.7%) in the ETT group did not meet the primary outcome (p = 0.977). Fourteen (53.8%) of the LMA patients were not intubated nor ventilated; 12 (46.1%) were ventilated: for surfactant failure (23%), for nCPAP failure (11.5%), and for late complications (11.5%). Groups were similar regarding prenatal status, birth conditions, and adverse events. No significant gastric content was found in 61.5% of the LMA patients. Oxygen and second dose surfactant requirements, arterial/alveolar ratio, and morbidities were similar among groups. Conclusions: Surfactant administration by LMA showed short-term efficacy, with similar supplementary oxygen need compared to surfactant by ETT, and lower MV requirement. Further studies with larger sample size are necessary to confirm these results.

Resumo Objetivo: Comparar a eficácia de curto prazo da administração de surfactante por máscara laríngea em comparação com o tubo endotraqueal. Métodos: Neonatos prematuros (28-35 semanas de idade gestacional), com 1 kg ou mais, com síndrome do desconforto respiratório, que necessitavam de pressão positiva nasal contínua nas vias aéreas, com aumento do esforço respiratório e/ou fração de oxigênio inspirado (FiO2) ≥ 0,40 para manter a saturação de oxigênio 91-95%, foram randomizados para receber surfactante por ML seguido por nCPAP ou por TE seguido por ventilação mecânica (VM). O resultado clínico primário foi definido como FiO2 ≤ 0,30 três horas após o surfactante. Os resultados secundários do grupo de ML foram: necessidade de segunda dose de surfactante nas primeiras 24 horas, necessidade de VM e presença de surfactante no conteúdo gástrico. Resultados: Foram randomizados 48 pacientes; 26 no grupo de ML e 22 no grupo de TE. Seis dentre os 26 pacientes (23%) do grupo de ML e cinco dentre 22 pacientes (22,7%) do grupo de TE não apresentaram o resultado primário (p = 0,977); 14 (53,8%) dos pacientes do grupo de ML não foram intubados nem ventilados; 12 (46,1%) foram submetidos a VM: por falha do surfactante (23%), por falha da nCPAP (11,5%) e por complicações tardias (11,5%). Os grupos foram semelhantes em relação às condições pré-natais e de nascimento e a ocorrência de eventos adversos. Não foi encontrado conteúdo gástrico significativo em 61,5% dos pacientes do grupo de ML. As necessidades de oxigênio e da segunda dose de surfactante, o índice arterial/alveolar e as morbidades foram semelhantes entre os grupos. Conclusões: A administração de surfactante por ML mostrou eficácia de curto prazo com necessidade complementar de oxigênio semelhante ao surfactante por TE e menor necessidade de VM. Serão necessários estudos adicionais com tamanho da amostra maior para confirmar esses resultados.

Déficit congénito de proteína de surfactante: caso clínico / Deficiency of surfactant protein: Case report

Introducción: El déficit congénito de surfactante es una entidad de diagnóstico inhabitual en recién nacidos. Se reporta un caso clínico de déficit de proteína B del surfactante, se revisa el estudio, tratamiento y diagnóstico diferencial de los déficit de proteínas del surfactante y enfermedad crónica intersticial de la infancia. Caso clínico: Recién nacido de término que cursa dificultad respiratoria, con velamiento pulmonar recurrente y respuesta transitoria a administración de surfactante. El estudio inmunohistoquímico y genético confirmaron diagnóstico de déficit de proteína B de surfactante. Conclusiones: La enfermedad pulmonar congénita requiere un alto índice de sospecha. El déficit de proteína B de surfactante genera un cuadro clínico progresivo y mortal en la mayoría de los casos, al igual que el déficit de transportador ATP binding cassette, sub-family A member 3 (ABCA3). El déficit de proteína C es insidioso y puede presentarse con un patrón radiológico pulmonar intersticial. Debido a la similitud en el patrón histológico, el estudio genético permite una mayor certeza en el pronóstico y la posibilidad de entregar un adecuado consejo genético.

Introduction: Congenital surfactant deficiency is a condition infrequently diagnosed in newborns. A clinical case is presented of surfactant protein B deficiency. A review is performed on the study, treatment and differential diagnosis of surfactant protein deficiencies and infant chronic interstitial lung disease. Case report: The case is presented of a term newborn that developed respiratory distress, recurrent pulmonary opacification, and a transient response to the administration of surfactant. Immunohistochemical and genetic studies confirmed the diagnosis of surfactant protein B deficiency. Conclusions: Pulmonary congenital anomalies require a high index of suspicion. Surfactant protein B deficiency is clinically progressive and fatal in the majority of the cases, similar to that of ATP binding cassette subfamily A member 3 (ABCA3) deficiency. Protein C deficiency is insidious and may present with a radiological pulmonary interstitial pattern. Due to the similarity in the histological pattern, genetic studies help to achieve greater certainty in the prognosis and the possibility of providing adequate genetic counselling.

Less invasive beractant administration in preterm infants: a pilot study

OBJECTIVES: The aims of this study were to assess the efficacy and feasibility of a new, less invasive surfactant administration technique for beractant replacement using a specifically designed cannula in preterm infants born at <32 weeks of gestation and to compare short- and long-term outcomes between this approach and standard treatment, consisting of intubation, administration of surfactant and early extubation to nasal continuous positive airway pressure. METHOD: This was a single-center, prospective, open-label, non-randomized, controlled pilot study with an experimental cohort of 30 patients treated with less invasive surfactant administration and a retrospective control group comprising the 30 patients most recently treated with the standard approach. Beractant (4 ml/kg) was administered as an exogenous surfactant in both groups if patients on nasal continuous positive airway pressure during the first three days of life were in need of more than 30% FiO2. Clinicaltrials.gov: NCT02611284. RESULTS: In the group with less invasive surfactant administration, beractant was successfully administered in all patients. Thirteen patients (43.3%) in the group with less invasive surfactant administration required invasive mechanical ventilation for more than 1 hour during the first 3 days of life, compared with 22 (73%) in the control group (p<0.036). The rate of requiring invasive mechanical ventilation for more than 48 hours was similar between the infants in the two groups (46% vs. 40%, respectively). There were no differences in other outcomes. CONCLUSION: The administration of beractant (4 ml/kg) using a less invasive surfactant administration technique with a specifically designed cannula for administration is feasible. Moreover, early invasive mechanical ventilation exposure is significantly reduced by this method compared with the strategy involving intubation, surfactant administration and early extubation.

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.

Early Prophylactic versus Late Selective Use of Surfactant for Respiratory Distress Syndrome in Very Preterm Infants: A Collaborative Study of 53 Multi-Center Trials in Korea

Pulmonary surfactant (PS) therapy was proven to be highly successful for the treatment of respiratory distress syndrome in premature infants. As a results, early prophylactic (EP) PS therapy has been introduced recently in Europe, the US and Korea. However, no multi-center study was compared EP and late selective (LS) PS therapies in Korea. We performed a retrospective multi-center study to compare the outcomes of EP and LS PS therapies in very preterm infants. We analyzed clinical morbidity and mortality for 1,291 infants in 2010 (LS group) and 1,249 infants in 2011 (EP group); the infants were born <30 weeks of gestation and had birth weight < or =1,250 g, and were chosen from 53 neonatal intensive care units in Korea. Compared to the LS group (22.5%), the overall mortality was better in the EP group (19.9%) and there was no increased need for retreatment.There were additional benefits in the EP group such as fewer associated complications. To the best of knowledge, our study is the first nationwide Korean study to compare the outcomes of EP and LS therapies, and it provides evidences that EP PS therapy is important in very preterm infants to improve for survival and reduce morbidities.

Early Prophylactic versus Late Selective Use of Surfactant for Respiratory Distress Syndrome in Very Preterm Infants: A Collaborative Study of 53 Multi-Center Trials in Korea

Pulmonary surfactant (PS) therapy was proven to be highly successful for the treatment of respiratory distress syndrome in premature infants. As a results, early prophylactic (EP) PS therapy has been introduced recently in Europe, the US and Korea. However, no multi-center study was compared EP and late selective (LS) PS therapies in Korea. We performed a retrospective multi-center study to compare the outcomes of EP and LS PS therapies in very preterm infants. We analyzed clinical morbidity and mortality for 1,291 infants in 2010 (LS group) and 1,249 infants in 2011 (EP group); the infants were born <30 weeks of gestation and had birth weight < or =1,250 g, and were chosen from 53 neonatal intensive care units in Korea. Compared to the LS group (22.5%), the overall mortality was better in the EP group (19.9%) and there was no increased need for retreatment.There were additional benefits in the EP group such as fewer associated complications. To the best of knowledge, our study is the first nationwide Korean study to compare the outcomes of EP and LS therapies, and it provides evidences that EP PS therapy is important in very preterm infants to improve for survival and reduce morbidities.

Lesao pulmonar induzida pela ventilacao em recem-nascidos prematuros / Ventilator-induced lung injury in preterm infants

A necessidade de intubação e do uso de ventilação mecânica na prematuridade está relacionada à chamada lesão pulmonar induzida pela ventilação e à consequente displasia broncopulmonar. Busca-se a melhor compreensão dos mecanismos de lesão envolvendo resposta inflamatória mediada pelas citocinas para o desenvolvimento de novas estratégias protetoras. Pesquisou-se na base de dados PubMed, incluindo artigos relevantes, os unitermos "ventilator induced lung injury preterm", "continuous positive airway pressure", "preterm" e "bronchopulmonary dysplasia". Dados e informações significativas foram compilados em tópicos, com o objetivo de formar uma visão crítica e plena acerca da lesão induzida pela ventilação e de suas consequências ao prematuro. Foi revisado o papel das citocinas pró-inflamatórias como mediadores da lesão, especialmente interleucinas 6 e 8, e fator de necrose tumoral alfa. Foram apresentadas evidências em estudos com animais e também em humanos, mostrando que breves períodos de ventilação mecânica são suficientes para a liberação dessas interleucinas inflamatórias. Também foram revisadas outras formas de ventilação mecânica e de ventilação não invasiva, como alternativas protetoras aos modos convencionais. Concluiu-se que o uso de ventilação não invasiva, a intubação com administração precoce de surfactante e a extubação rápida para CPAP nasal, além de estratégias que regulam o volume corrente evitando o volutrauma (como a ventilação com volume garantido), são medidas protetoras da lesão pulmonar induzida pela ventilação mecânica no prematuro.

In preterm infants, the need for intubation and mechanical ventilation is associated with ventilator-induced lung injuries and subsequent bronchopulmonary dysplasia. The aim of the present review was to improve the understanding of the mechanisms of injury that involve cytokine-mediated inflammation to contribute to the development of new preventive strategies. Relevant articles were retrieved from the PubMed database using the search terms "ventilator-induced lung injury preterm", "continuous positive airway pressure", "preterm", and "bronchopulmonary dysplasia". The resulting data and other relevant information were divided into several topics to ensure a thorough, critical view of ventilation-induced lung injury and its consequences in preterm infants. The role of pro-inflammatory cytokines (particularly interleukins 6 and 8 and tumor necrosis factor alpha) as mediators of lung injury was assessed. Evidence from studies conducted with animals and human newborns is described. This evidence shows that brief periods of mechanical ventilation is sufficient to induce the release of pro-inflammatory cytokines. Other forms of mechanical and non-invasive ventilation were also analyzed as protective alternatives to conventional mechanical ventilation. It was concluded that non-invasive ventilation, intubation followed by early surfactant administration and quick extubation for nasal continuous positive airway pressure, and strategies that regulate tidal volume and avoid volutrauma (such as volume guarantee ventilation) protect against ventilator-induced lung injury in preterm infants.

Eficacia de tres tipos de surfactante exógeno en prematuros con enfermedad de membrana hialina / Effectiveness of three types of exogenous surfactant in preterm infants with hyaline membrane disease

Introducción: La enfermedad de membrana hialina es causa importante de mortalidad neonatal. El objetivo de esta investigación fue evaluar la eficacia de tres tipos de surfactante exógeno en prematuros. Pacientes y Método: Estudio de cohorte retrospectiva, en 93 neonatos prematuros, > 24 semanas y > 500 g de peso al nacer, 31 para cada surfactante. La exposición fue la administración de 1ª dosis bovactant (Alveofact®) 50 mg/kg, beractant (Survanta®) 100 mg/kg inicial, y poractant alfa (Curosurf®) 200 mg/kg. Las variables en estudio incluyeron tiempo de ventilación mecánica, tiempo de oxigenoterapia, estancia hospitalaria, necesidad de segunda dosis de surfactante, eventos adversos por la administración del surfactante y complicaciones por prematuridad. Además, se evaluó mortalidad, displasia broncopulmonar (DBP) y mortalidad o DBP. Análisis estadístico mediante Stata® 11.0, empleando X² o Prueba Exacta de Fisher para variables cualitativas y Pruebas ANOVA o Kruskal-Wallis para cuantitativas y riesgo relativo para las asociaciones, todas con su intervalo de confianza de 95%. Resultados: No hubo diferencias para sexo, peso y edad gestacional al nacer entre los 3 grupos. No se hallaron diferencias estadísticamente significativas para tiempo de ventilación mecánica, tiempo de oxigenoterapia, administración de una segunda dosis de surfactante, estancia hospitalaria y complicaciones entre los 3 grupos. Los eventos adversos por administración de surfactante se presentaron para beractant y poractant alfa. Ocurrieron 30 (32,3 por ciento) muertes, 8 (25,8 por ciento) para bovactant, 10 (32,3 por ciento) beractant y 12 (38,7 por ciento) poractant alfa (p > 0,05). La mortalidad y/o DBP ocurrió en 10 (32,2 por ciento) neonatos con bovactant, 10 (32,2 por ciento) con beractant y 14 (45,2 por ciento) con poractant alfa (p > 0,05). Conclusiones: Los resultados primarios y secundarios entre los tres surfactantes evaluados fueron muy similares...

Introduction: Hyaline membrane disease is an important cause of neonatal mortality. The objective of this research is to evaluate the efficacy of three different exogenous surfactants in premature infants. Patients and Method: A retrospective cohort analysis in 93 preterm infants > 24 weeks and birth weight > 500 g was performed, 31 infants for each surfactant. Exposure consisted of the 1st dose of bovactant (Alveofact®) 50 mg/kg, beractant (Survanta®) 100 mg/kg initially, and poractant alfa (Curosurf®) 200 mg/kg. The variables included duration of mechanical ventilation, duration of oxygen therapy, hospital stay, need for second dose of surfactant, adverse events surfactant administration and prematurity complications. Mortality and bronchopulmonary dysplasia (BPD) were evaluated. Statistical analysis was performed using Stata® 11.0, X² or Fisher exact test for qualitative variables and ALNOVA or Kruskal-Wallis tests for quantitative and association relative risk, all with 95 percent confidence level. Results: There were no gender, weight and gestational age differences at birth among the three groups. No statistically significant differences were found regarding duration of mechanical ventilation, duration of oxygen therapy, administration of a second dose of surfactant, hospital stay and complications among the three groups. Adverse events related to surfactant administration occurred for beractant and poractant alpha. There were 30 (32.3 percent) deaths, 8 (25.8 percent) associated to bovactant, 10 (32.3%) to beractant and 12 (38.7 percent) to poractant alpha (p > 0.05). Mortality and/or BDP occurred in 10 (32.2 percent) infants who received bovactant, 10 (32.2 percent) beractant and 14 (45.2 percent) with poractant alpha (p > 0.05). Conclusions: The primary and secondary outcomes among the three surfactants tested were similar, taking into account the limitations of the work.

Eficacia y eficiencia de los surfactantes pulmonares en recién nacidos con síndrome de dificultad respiratoria en la unidad de cuidado intensivo neonatal de la Fundación Cardiovascular de Colombia, enero de 2009 - abril de 2011 / Effectiveness and Efficiency of Pulmonary Surfactants in Infants with Respiratory Distress Syndrome at the Neonatal Intensive Care Unit of the Colombian Cardiovascular Foundation, January 2009 - April 2011 / Eficácia e eficiência do surfactante pulmonar em recém-nascidos com síndrome de desconforto respiratório na UTI neonatal da Fundação Cardiovascular da Colômbia, janeiro de 2009 – abril de 2011

Para estimar la eficacia y eficiencia de los surfactantes pulmonares utilizados en los recién nacidos con síndrome de dificultad respiratoria en la Fundación Cardiovascular de Colombia sediseñó un estudio observacional, descriptivo. Se analizaron las historias clínicas de los recién nacidos hospitalizados allí entre enero de 2009 y abril de 2011 y se calcularon los indicadores de eficacia y eficiencia para cada surfactante. El medicamento más eficaz y eficiente para estos pacientes, cuando se analizaron datos globales, fue el survanta; su tratamiento requiere menos dosis, es más económico, genera menos días de estancia en unidad de cuidados intensivos y menos días de ventilación mecánica. Para algunos casos resultó ser más eficaz el infasurf que el survanta; causo menos extubaciones fallidas en recién nacidos con bajo peso y menos complicacionesdurante el tratamiento...

To estimate the effectiveness and efficiency of pulmonary surfactants used in infants with respiratory distress syndrome at the Colombian Cardiovascular Foundation, we designed an observational, descriptive study. We analyzed the medical records of newborns hospitalized in this institution between January 2009 and April 2011 and calculated the effectiveness and efficiency indicators for each surfactant. After analyzing aggregate data, we found that the most efficient and effective medication for these patients was Survanta. It requires fewer doses per treatment, is more economical, and generates fewer days in the intensive care unit and fewer days of mechanical ventilation. In some cases, however, Infasurf was more effective than Survanta, caused less extubation failure in infants with low birth weight and fewer complications during treatment...

Para estimar a eficácia e a eficiência dos surfactantes pulmonares utilizados nos recém- nascidos com síndrome de desconforto respiratório na Fundação Cardiovascular da Colômbia desenhouseum estudo observacional descritivo. Analisaram-se os protuários dos recém-nascidos internados entre janeiro de 2009 e abril de 2011 e foram calculados os indicadores de eficáciae eficiência de cada surfactante. O medicamento mais eficaz e eficiente para esses pacientes, quando analisados dados agregados, foi o survanta; seu tratamento requer doses menores, émais econômico, gera menos dias de estância na unidade de tratamento intensivo e menos dias de ventilação mecânica. Para alguns casos resultou mais eficaz o infasurf do que o survanta;causou menos extubações falhadas em recém-nascidos com baixo peso e menos complicações durante o tratamento...

Estrategias de prevención y tratamiento en displasia broncopulmonar / Strategies for prevention and treatment of broncopulmonary dysplasia

Bronchopulmonary Dysplasia (BPD) continues to be a highly frequent sequela of low birth weight infants. This, despite the many recent advances in perinatal medicine that include antenatal steroids, exogenous surfactant, new strategies for mechanical respiratory support, parenteral nutrition improvements and a more judicious use of supplemental oxygen. The purpose of this review is to analyze and describe the recent advances in the prevention and management of BPD. New preventive therapies have been developed, and vitamin A and caffeine administration have been shown to diminish the incidence of this disorder. Postnatal corticosteroids can also be useful, but due to their negative long-term neurological effects, these medications are not currently recommended. Corticosteroid administration in established BPD can decrease the need for mechanical ventilation and improve lung function. Other preventive interventions such as antioxidant administration and nitric oxide inhalation are currently being investigated. The persistence of the ductus arteriosus is associated with increased risk of BPD, therefore early pharmacologic closure can play a role in preventing this disorder. New modalities of mechanical ventilation, such as synchronized and high frequency ventilation, have not been shown to decrease the incidence of this disease. While a discussion regarding the best type of ventilation to be used still remains, the consensus is that that the lowest inspiratory pressure and lowest oxygen concentration necessary should be utilized to maintain adequate gas exchange. Optimal level of arterial oxygen saturation in premature infants is still controversial, but the current recommended range is between 88 percent and 95 percent. Summary: Vitamin A and caffeine are both effective drugs in the prevention of BPD. The role of early closure of the ductus arteriosus and the use of postnatal administration of corticosteroids in the prevention of BPD are...

La Displasia Broncopulmonar (DBP) es una de las secuelas más frecuentes que afecta al recién nacido de muy bajo peso. Esto es, a pesar de los avances de la medicina perinatal de los últimos años, como la administración de corticoides antenatales, surfactante exógeno, nuevos modos y estrategias de ventilación mecánica, mejoría de la nutrición parenteral y el uso más cuidadoso del oxígeno. El objetivo de la presente revisión es analizar y describir los recientes avances en la prevención y tratamiento de la DBP. Nuevas terapias preventivas han emergido, habiéndose demostrado que la administración de vitamina A y cafeína disminuyen la incidencia de esta afección. Los corticoides postnatales también disminuyen la incidencia de esta enfermedad, pero por sus efectos neurológicos a largo plazo, no se recomiendan actualmente. La administración de corticoides en la DBP establecida reduce el uso de ventilación mecánica y mejora la función pulmonar del recién nacido. Otras intervenciones preventivas como la administración de antioxidantes y óxido nítrico inhalado están siendo estudiadas. La persistencia del ductus arterioso se ha asociado a displasia, por lo cual, el cierre farmacológico precoz podría tener relevancia en la prevención de esta. Los nuevos modos de ventilación mecánica, como la ventilación sincronizada y la ventilación de alta frecuencia, no han disminuido la incidencia de esta enfermedad. Cualquiera sea el tipo de ventilación utilizada, debe aplicarse con la menor presión inspiratoria y concentración de oxígeno requeridas, para mantener un adecuado intercambio gaseoso. El rango de saturación arterial de oxígeno recomendado para el niño prematuro, aún es motivo de estudio, pero la recomendación actual más ampliamente aceptada es aquella que oscila entre 88 por ciento y 95 por ciento. Conclusión: La vitamina A y la cafeína son drogas efectivas en la prevención de la DBP. Faltan estudios para determinar con mayor exactitud el posible...

Chronic lung disease in newborns.

Chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) occurs in preterm infants who require respiratory support in the first few days of birth. Apart from prematurity, oxygen therapy and assisted ventilation, factors like intrauterine/postnatal infections, patent ductus arteriosus, and genetic polymorphisms also contribute to its pathogenesis. The severe form of BPD with extensive inflammatory changes is rarely seen nowadays; instead, a milder form characterized by decreased alveolar septation due to arrest in lung development is more common. A multitude of strategies, mainly pharmacological and ventilatory, have been employed for prevention and treatment of BPD. Unfortunately, most of them have not been proved to be beneficial. A comprehensive protocol for management of BPD based on the current evidence is discussed here.

Novas opções terapêuticas na síndrome de aspiração de mecônio / New therapeutic options in meconium aspiration syndrome

OBJETIVOS: revisar a literatura sobre a síndrome de aspiração de mecônio (SAM), enfocando aspectos clínicos, fisiopatológicos e abordagem terapêutica, com destaque ao uso do surfactante e lavado broncoalveolar. MÉTODOS: revisão baseada em artigos publicados na MEDLINE, SCIELO e resumos de congressos internacionais de 1988 a 2004, incluindo ensaios randomizados ou quasi-randomizados, estudos caso-controle e metanálises. RESULTADOS: devido à comprovação da inibição do surfactante na SAM, houve modificações em sua abordagem terapêutica. O manejo atual consiste na aspiração das vias aéreas na sala de parto, seguida de suporte ventilatório necessário para manter a oxigenação arterial adequada, e tratamento das complicações. Tendo em vista a obstrução mecânica do mecônio e seu efeito inibitório sobre o surfactante, a reposição e lavado broncoalveolar com surfactante estão sendo estudados atualmente. CONCLUSÕES: estudos em animais e em recém-nascidos apresentam resultados controversos quanto aos benefícios do uso de surfactante e lavado broncoalveolar na SAM. Torna-se importante a realização de mais estudos para avaliar novas estratégias ventilatórias e se existem vantagens no uso do surfactante e lavado broncoalveolar com surfactante na SAM.

OBJECTIVES: to review the literature on meconium aspiration syndrome (MAS) focusing on clinical aspects, pathophysiology, and treatment with emphasis on surfactant and bronchoalveolar lavage. METHODS: review including articles from MEDLINE, SCIELO and abstracts published in the national and international literature, from 1988 to 2004 using the keywords meconium aspiration syndrome, surfactant and bronchoalveolar lavage. Randomized and quasi-randomized trials, case control studies, meta-analyses and recently published reviews were selected. Other articles were included for their valuable contribution to the subject. RESULTS: the discovery of new pathophysiological mechanisms ensued new therapeutic options availability. MAS management is initiated with airway aspiration in the delivery room, followed by the ventilatory management required to maintain optimal arterial oxygenation, as well as complications treatment. Considering evidences showing that meconium mechanical airway obstruction and its inhibitory effect on the surfactant system, the use of surfactant replacement and bronchoalveolar lavage with surfactant suspension are under study. CONCLUSIONS: experimental studies and studies focused on newborn using different surfactant suspensions have demonstrated controversial results. Therefore, it is very important to identify new ventilatory strategies and evaluate whether there are advantages in using surfactant and bronchoalveolar lavage with surfactant suspension in MAS.

Influencia del reclutamiento alveolar sobre los efectos del surfactante exogeno / Influence of pulmonary recruitment on exogenous surfactant effects

Se investigaron los efectos producidos por una maniobra de insuflación sostenida previa a la administraciónde surfactante exógeno y los producidos por diferentes patrones ventilatorios sobre la respuesta al mismo. Se estudiaron 20 ratas albinas adultas a las que se les produjo una injuria pulmonar por repetidos lavados con solución fisiológica. Se evaluó el pH, PaO2, PaCO2, la presión arterial sistólica, la compliance toracopulmonar y la histología. Los animales se dividieron en 2 grupos según se les hubiera aplicado o no insuflación sostenida para evaluar el efecto inmediato de la misma. Posteriormente los grupos citados fueron subdivididos en función de la capacidad residual funcional (CRF) aplicada, quedando conformados 4 grupos experimentales. El grupo 1 recibió previo al surfactante una insuflación sostenida de 30 cm H2O durante 15 segundos y se ventiló posteriormente con presión al final de la espiración (PEEP) de10 cm H2O. El grupo 2, no recibió insuflación sostenida y se ventiló con PEEP 10 cm H2O. El grupo 3, recibió insuflación sostenida y se ventiló con PEEP 4 cm H2O y el grupo 4, sin insuflación sostenida se ventiló con PEEP 4 cm H2O. Los efectos inmediatos del surfactante no fueron modificados por la aplicación previa de insuflación sostenida. Se verificó durante el transcurso de la experiencia un aumento de la PaO2 asociada al aumento de la capacidad residual funcional (Grupo1 p=0.0001; Grupo2 p= 0.0001), e independiente de la insuflación sostenida. El uso de insuflación sostenida previo a la administración de surfactante sumado a la ventilación con capacidad residual funcional alta se asoció con infiltración de polimorfonucleares debajo del epitelio bronquiolar (p = 0.008). Nuestros resultados no avalan el uso de insuflación sostenida previo a la administración de surfactante exógeno.

Surfactante pulmonar / Pulmonary Surfactante

La terapia con surfactante ha constituido un importante avance en el manejo de recién nacidos prematuros con EMH. Tanto surfactantes naturales como sintéticos llevan a la mejoría clínica y disminución de la mortalidad. El uso profiláctico, después de la estabilización inicial del recién nacido, tiene beneficios sobre la terapia de rescate una vez establecida la EMH. En prematuros que no han sido tratados en forma profiláctica, la administración de rescate precoz (antes de las 2 horas) tiene beneficios sobre la terapia tardía. Los efectos adversos de esta terapia son infrecuentes y usualmente no serios. Futuras investigaciones demostrarán la utilidad de los nuevos surfactantes y la optimización del tratamiento junto con otras intervenciones respiratorias.

Different doses of exogenous surfactant for treatment of meconium aspiration syndrome in newborn rabbits

OBJETIVO: Avaliar os efeitos de duas diferentes doses de surfactante exógeno sobre a mecânica pulmonar e sobre a regularidade da expansão do parênquima pulmonar em coelhos recém-nascidos. MÉTODO: Coelhos recém-nascidos foram traqueostomizados e randomizados em quatro grupos de estudo: grupo-Controle, sem aspiração de mecônio; grupo MEC, com aspiração de mecônio e sem tratamento com surfactante exógeno; grupos S100 e S200, ambos com aspiração de mecônio e tratados respectivamente com 100 e 200 mg/kg de surfactante exógeno (produzido e fornecido pelo Instituto Butantan). Os animais dos 4 grupos foram ventilados por 25 minutos. A mecânica pulmonar foi avaliada a partir dos valores de complacência dinâmica, pressão ventilatória, volume-corrente e volume pulmonar máximo (curva P-V). A análise histológica foi feita calculando-se o diâmetro alveolar médio (Lm) e o índice de distorção através do desvio padrão do Lm. Utilizou-se ANOVA One Way com a = 0,05. RESULTADOS: Após 25 minutos de ventilação, os valores de complacência dinâmica (ml/cm H2O.kg) foram: 0,87± 0,07 (Controle); 0,49±0,04 (MEC*); 0,67±0,06 (S100) e 0,67±0,08 (S200) e de pressão ventilatória (cm H2O): 9,0± 0,9 (Controle); 16,5±1,7 (MEC*); 12,4±1,1 (S100) e 12,1±1,5 (S200). Ambos os grupos tratados tiveram padrão de expansão do parênquima mais homogêneo em relação aos animais não tratados: índice de distorção de 7,5± 1,9 (Controle); 11,3±2,5 (MEC*); 5,8±1,9 (S100) e 6,7±1,7 (S200) (*p < 0,05 vs outros grupos). CONCLUSÕES: Animais tratados com surfactante mostraram melhora significativa da mecânica pulmonar e maior homogeneidade do padrão de expansão pulmonar comparados ao grupo não tratado. Não houve influência das doses de surfactante utilizadas.