Acute and sustained effects of early administration of inhaled nitric oxide to children with acute respiratory distress syndrome

OBJECTIVE: To determine the acute and sustained effects of early inhaled nitric oxide on some oxygenation indexes and ventilator settings and to compare inhaled nitric oxide administration and conventional therapy on mortality rate, length of stay in intensive care, and duration of mechanical ventilation in children with acute respiratory distress syndrome. DESIGN: Observational study. SETTING: Pediatric intensive care unit at a university-affiliated hospital. PATIENTS: Children with acute respiratory distress syndrome, aged between 1 month and 12 yrs. INTERVENTIONS: Two groups were studied: an inhaled nitric oxide group (iNOG, n = 18) composed of patients prospectively enrolled from November 2000 to November 2002, and a conventional therapy group (CTG, n = 21) consisting of historical control patients admitted from August 1998 to August 2000. MEASUREMENTS AND MAIN RESULTS: Therapy with inhaled nitric oxide was introduced as early as 1.5 hrs after acute respiratory distress syndrome diagnosis with acute improvements in Pao(2)/Fio(2) ratio (83.7%) and oxygenation index (46.7%). Study groups were of similar ages, gender, primary diagnoses, pediatric risk of mortality score, and mean airway pressure. Pao(2)/Fio(2) ratio was lower (CTG, 116.9 +/- 34.5; iNOG, 62.5 +/- 12.8, p <.0001) and oxygenation index higher (CTG, 15.2 [range, 7.2-32.2]; iNOG, 24.3 [range, 16.3-70.4], p <.0001) in the iNOG. Prolonged treatment was associated with improved oxygenation, so that Fio(2) and peak inspiratory pressure could be quickly and significantly reduced. Mortality rate for inhaled nitric oxide-patients was lower (CTG, ten of 21, 47.6%; iNOG, three of 18, 16.6%, p <.001). There was no difference in intensive care stay (CTG, 10 days [range, 2-49]; iNOG, 12 [range, 6-26], p >.05) or duration of mechanical ventilation (TCG, 9 days [range, 2-47]; iNOG, 10 [range, 4-25], p >.05). CONCLUSIONS: Early treatment with inhaled nitric oxide causes acute and sustained improvement in oxygenation, with earlier reduction of ventilator settings, which might contribute to reduce the mortality rate in children with acute respiratory distress syndrome. Length of stay in intensive care and duration of mechanical ventilation are not changed. Prospective trials of inhaled nitric oxide early in the setting of acute lung injury in children are needed.

Positive end-expiratory pressure in acute respiratory distress syndrome: should the 'open lung strategy' be replaced by a 'protective lung strategy'?

In patients with acute respiratory distress syndrome, positive end-expiratory pressure is associated with alveolar recruitment and lung hyperinflation despite the administration of a low tidal volume. The best positive end-expiratory pressure should correspond to the best compromise between recruitment and distension, a condition that coincides with the best respiratory elastance.

Lung ultrasound in acute respiratory distress syndrome and acute lung injury

Purpose of reviewLung ultrasound at the bedside can provide accurate information on lung status in critically ill patients with acute respiratory distress syndrome.Recent findingsLung ultrasound can replace bedside chest radiography and lung computed tomography for assessment of pleural effusion, pneumothorax, alveolar- interstitial syndrome, lung consolidation, pulmonary abscess and lung recruitment/de-recruitment. It can also accurately determine the type of lung morphology at the bedside (focal or diffuse aeration loss), and therefore it is useful for optimizing positive end-expiratory pressure. The learning curve is brief, so most intensive care physicians will be able to use it after a few weeks of training.SummaryLung ultrasound is noninvasive, easily repeatable and allows assessment of changes in lung aeration induced by the various therapies. It is among the most promising bedside techniques for monitoring patients with acute respiratory distress syndrome.

Early administration of inhaled nitric oxide to children with acute respiratory distress syndrome and its effects on oxygenation and ventilator settings: prospective preliminary report of ten patients

Aim. To establish a protocol for the early introduction of inhaled nitric oxide (iNO) therapy in children with acute respiratory distress syndrome (ARDS) and to assess its acute and sustained effects on oxygenation and ventilator settings.Patients and Methods. Ten children with ARDS, aged 1 to 132 months (median, 11 months), with arterial saturation of oxygen <88% while receiving a fraction of inspired oxygen (FiO(2)) 0.6 and a positive end-expiratory pressure of greater than or equal to 10 cm H2O were included in the study. The acute response to iNO was assessed in a 4-hour dose-response test, and positive response was defined as an increase in the PaO2/FiO(2) ratio of 10 mmHg above baseline values. Conventional therapy was not changed during the test. In the following days, patients who had shown positive response continued to receive the lowest iNO dose. Hemodynamics, PaO2/FiO(2), oxygenation index, gas exchange, and methemoglobin levels were obtained when needed. Inhaled nitric oxide withdrawal followed predetermined rules.Results. At the end of the 4-hour test, all the children showed significant improvement in the PaO2/FiO(2) ratio (63.6%) and the oxygenation index (44.9%) compared with the baseline values. Prolonged treatment was associated with improvement in oxygenation, so that FiO(2) and peak inspiratory pressure could be quickly and significantly reduced., No toxicity from methemoglobin or nitrogen dioxide was observed.Conclusion. Administration of iNO to children is safe. iNO causes rapid and sustained improvement in oxygenation without adverse effects. Ventilator settings can safely be reduced during iNO treatment.

Ventilator-induced lung injury and acute respiratory distress syndrome: a basic science review

Acute respiratory distress syndrome is the most severe manifestation of acute lung injury and it is associated with high mortality rate. Despite better understanding of ARDS pathophysiology, its mechanism is still unclear. Mechanical ventilation is the main ARDS supportive treatment. However, mechanical ventilation is a non-physiologic process and complications are associated with its application. Mechanical ventilation may induce lung injury, referred to as ventilator-induced lung injury. Frequently, VILI is related to macroscopic injuries associated with alveolar rupture. The present article is a review of the literature on ventilator-induced lung injury in acute respiratory distress syndrome. Animal and human studies were reviewed. We mainly selected publications in the past 5 years, but did not exclude commonly referenced and highly regarded older publications.

Congenital diaphragmatic Bochdaleck hernia: Case report

Congenital diaphragmatic Bochdaleck hernia is an anatomical defect of the diaphragm, which allows protrusion of abdominal viscera into the chest, causing serious pulmonary and cardiac complications in the neonate. In this study we aimed to present a case of congenital Bochdaleck hernia. We investigated a 40 weeks old child, with a pregnancy carried out in a public hospital in Passo Fundo, Rio Grande do Sul, Brazil. We suggest that if diagnosis occurs in the prenatal period, the prognosis of this disease improves. As a consequence, it allows the parity of the fetus to occur in a higher complexity center, optimizing the chances of survival. © 2012 Lava et al.; licensee BioMed Central Ltd.

Perinatal factors associated with early deaths of preterm infants born in Brazilian Network on Neonatal Research centers

Objective: To evaluate perinatal factors associated with early neonatal death in preterm infants with birth weights (BW) of 400-1,500 g.Methods: A multicenter prospective cohort study of all infants with BW of 400-1,500 g and 23-33 weeks of gestational age (GA), without malformations, who were born alive at eight public university tertiary hospitals in Brazil between June of 2004 and May of 2005. Infants who died within their first 6 days of life were compared with those who did not regarding maternal and neonatal characteristics and morbidity during the first 72 hours of life. Variables associated with the early deaths were identified by stepwise logistic regression.Results: A total of 579 live births met the inclusion criteria. Early deaths occurred in 92 (16%) cases, varying between centers from 5 to 31%, and these differences persisted after controlling for newborn illness severity and mortality risk score (SNAPPE-II). According to the multivariate analysis, the following factors were associated with early intrahospital neonatal deaths: gestational age of 23-27 weeks (odds ratio - OR = 5.0; 95%CI 2.7-9.4), absence of maternal hypertension (OR = 1.9; 95%CI 1.0-3.7), 5th minute Apgar 0-6 (OR = 2.8; 95%CI 1.4-5.4), presence of respiratory distress syndrome (OR = 3.1; 95%CI 1.4-6.6), and network center of birth.Conclusion: Important perinatal factors that are associated with early neonatal deaths in very low birth weight preterm infants can be modified by interventions such as improving fetal vitality at birth and reducing the incidence and severity of respiratory distress syndrome. The heterogeneity of early neonatal rates across the different centers studied indicates that best clinical practices should be identified and disseminated throughout the country.

Preeclampsia: Early and late neonatal outcomes

Newborn infants exposed to preeclampsia (PE) present increased short-term morbidity, mainly respiratory diseases such as respiratory distress syndrome and bronchopulmonary dysplasia. Gastrointestinal problems are also frequent, although a higher risk of necrotizing enterocolitis has not been confirmed. These problems could be related not just to PE itself but also to prematurity or intrauterine growth restriction, which frequently occur in this maternal disease. Other findings, however, seem to be due to the direct effect of the maternal disease; these findings include an increased frequency of neutropenia and thrombocytopenia and a lower incidence of cerebral disorders, such as periventricularintraventricular hemorrhage and cerebral palsy. The evaluation of long-term outcome shows increasing evidence that PE has important implications for the future health of the mother and her child, suggesting that PE is not a simple gestational disorder but a clinical syndrome with an unclear etiology, a genetic component, and a complex pathophysiology. This syndrome involves important maternal and fetal vascular alterations that can persist and cause diseases in later life. The divergence in results on outcomes for children exposed to PE could, in part, be due to methodological differences in the studies, most of which are retrospective case-control studies. Better evidence on prognosis is obtained from cohort studies. Even in the cohort studies, differences in patient characteristics and severity of maternal disease, as well as sample size, follow-up time, and main outcome measures certainly contribute to the variability in results reported in the literature. © 2012 by the American Academy of Pediatrics. All rights reserved.

Effects of therapeutic approach on the neonatal evolution of very low birth weight infants with patent ductus arteriosus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos da fisioterapia respiratória convencional versus aumento do fluxo expiratório na saturação de O2, freqüência cardíaca e freqüência respiratória, em prematuros no período pós-extubação

INTRODUÇÃO: Recém-nascidos (RN) prematuros apresentam elevada morbidade respiratória e necessidade de ventilação mecânica, assim, a fisioterapia respiratória é parte integrante da assistência neonatal. Objetivo: Comparar os efeitos da fisioterapia respiratória convencional (FRC) versus aumento do fluxo expiratório (AFE), na saturação de O2 (SpO2), freqüência cardíaca (FC) e na freqüência respiratória (FR) em prematuros no período pós-extubação. Método: Ensaio clínico randomizado realizado na UTI Neonatal do Hospital das Clínicas de BotucatuUNESP, comparando duas técnicas fisioterapêuticas, aplicadas em recém-nascidos prematuros, nas primeiras 48 horas pós-extubação. Para a análise estatística foram utilizados o teste t Student, Mann-Whitney, Qui-quadrado e o teste exato de Fisher, com nível de significância em 5%. Resultados: Os dois grupos de estudo: Grupo FRC (n= 20) e grupo AFE (n= 20), não diferiram quanto à idade gestacional (média de 28 semanas) e peso de nascimento (média de 1100 gramas). em ambos os grupos a síndrome do desconforto respiratório (SDR) foi o principal diagnóstico. A mediana da idade no início da fisioterapia foi de sete dias no grupo AFE e 11 dias na FRC. Ambas as técnicas produziram aumento significativo da SpO2 aos 10 e 30 minutos, sem alterações na FR. A FC aumentou significativamente após a FRC e não se alterou após o AFE. Conclusão: Os resultados sugerem que o AFE é menos estressante que a FRC e pode ser aplicado em prematuros no período pós-extubação. Nestes recém-nascidos o AFE parece ser seguro e benéfico a curto prazo.

Sobrevida e morbidade em prematuros com menos de 32 semanas de gestação na região central do Brasil

OBJETIVO: Avaliar a sobrevida e complicações associadas à prematuridade em recém-nascidos com menos de 32 semanas. MÉTODOS: Estudo prospectivo do tipo coorte. Foram incluídos os nascidos vivos, com idade gestacional entre 25 semanas e 31 semanas e 6 dias, sem anomalias congênitas admitidos em UTI Neonatal, entre 1º de agosto de 2009 e 31 de outubro de 2010. Os recém-nascidos foram estratificados em três grupos: G25, 25 a 27 semanas e 6 dias; G28, 28 a 29 semanas e 6 dias; G30, 30 a 31 semanas e 6 dias, e acompanhados até 28 dias. Foram avaliadas a sobrevida aos 28 dias e a morbidade associadas à prematuridade. Para análise dos resultados, utilizou-se o teste do c², análise de variância, teste de Kruskal-Wallis, razão de risco com intervalo de confiança (IC) e regressão logística múltipla, com significância em 5%. RESULTADOS: A coorte compreendeu 198 prematuros, sendo G25=59, G28=43 e G30=96. O risco de óbito foi significativamente maior em G25 e G28, em relação ao G30 (RR=4,1; IC95% 2,2-7,6 e RR=2,8; IC95% 1,4-5,7). A sobrevida encontrada foi, respectivamente, 52,5, 67,4 e 88,5%. A partir da 26ª semana e peso >700 g, a sobrevida foi superior a 50%. A morbidade foi inversamente proporcional à idade gestacional, exceto para enterocolite necrosante e leucomalácia, que não diferiram entre os grupos. A análise de regressão logística mostrou que a hemorragia pulmonar (OR=3,3; IC95% 1,4-7,9) e a síndrome do desconforto respiratório (OR=2,5; IC95% 1,1-6,1) foram fatores independentes de risco para óbito. Houve predomínio das lesões cerebrais hemorrágicas graves em G25. CONCLUSÕES: Sobrevivência superior a 50% ocorreu a partir da 26ª semana de gravidez e peso >700 g. A hemorragia pulmonar e a síndrome do desconforto respiratório foram preditores independentes de óbito. Há necessidade de identificar e instituir práticas para melhorar a sobrevida de prematuros extremos.

Comparação entre ventilação mandatória intermitente e ventilação mandatória intermitente sincronizada compressão de suporte em crianças

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Doenças respiratórias neonatais em prematuros de mães hipertensas e normotensas

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)