Gastric Aspirate Phosphatidylcholine Species in Preterm Neonates Receiving Aerosolized Surfactant.

OBJECTIVE: To characterize phosphatidylcholine (PC) molecular species in serial gastric aspirates as biomarkers for lung maturity, delivery of aerosolized surfactant (AS), and need for intubation. METHODS: In a phase II clinical trial of aerosolized surfactant in preterm neonates with respiratory distress syndrome receiving noninvasive ventilation, infants received a maximum of 2 doses of nebulized beractant. Gastric aspirates were collected before and after each dose and were analyzed for PCs using liquid chromatography mass spectrometry. RESULTS: Of 149 infants enrolled, gastric aspirates were obtained before (n = 91) and after (n = 94) dose 1, and before (n = 56) and after (n = 57) dose 2 of nebulized beractant. The mean ± SD values of birthweight, gestational age, and age at collection of baseline gastric aspirate were 1.7 ± 0.6 kg, 31.7 ± 2.8 weeks, and 5.5 ± 1.7 hours, respectively. The most abundant PC in beractant and gastric aspirates was PC(16:0/16:0). Advancing gestational age and number of antenatal corticosteroid doses predicted increased gastric aspirate PC(16:0/16:0), whereas maternal diabetes predicted a decrease. Several PCs increased significantly (P < .05) after nebulized beractant, consistent with effective aerosol delivery. Infants who received intubation within 72 hours of birth were more likely to have lower PC(16:0/16:0) levels in baseline gastric aspirates compared with those who did not (P = .024). CONCLUSIONS: PC molecular species in gastric aspirates of preterm neonates are potentially novel and precise biomarkers to assess lung maturity, aerosol delivery, and need for endotracheal intubation.

Who Needs a Second Dose of Exogenous Surfactant?

OBJECTIVE: To identify prenatal and postnatal risk factors associated with surfactant redosing. STUDY DESIGN: Retrospective, single-regional center study including all infants born from 24 + 0 to 31 + 6 weeks of gestation in the Marche Region, Italy, and admitted to a single level III regional NICU from January 1, 2004, to February 28, 2021. Clinical factors associated with surfactant redosing were identified through logistic regression analysis. RESULTS: Of 1615 consecutive admissions, 662 infants were treated with exogenous surfactant: 462 (70%) received a single dose and 200 (30%) received more than 1 dose (25.5% two doses and 4.5% three doses). Risk of redosing was higher for infants born to mothers with hypertension in pregnancy (OR 3.95, P < .001), for small for gestational age (SGA) infants (OR 3.93, P < .001) and when the first surfactant dose was 100 mg/kg instead of 200 mg/kg (OR 4.56/4.61, P < .001). Infants with greater GA, delayed first surfactant administration, and milder respiratory distress syndrome had reduced risk of redosing. Infants who required multiple surfactant doses had a higher rate of bronchopulmonary dysplasia and mortality, as well as longer duration of respiratory support than patients that received 1 dose. CONCLUSIONS: Hypertension in pregnancy and SGA status were found to be statistically and clinically significant predictors of surfactant redosing. Understanding the pathophysiology of these conditions requires further investigation.

[Prenatal rescue dose of betamethasone in the preterm infant with intrauterine growth restriction]. / Dosis prenatal de rescate de betametasona en el prematuro con restricción del crecimiento intrauterino.

Antenatal corticosteroids reduce mortality and respiratory distress syndrome (RDS) in preterm newborns. These benefits decrease after a week of administration, recommending a rescue therapy if there is a new threat of premature delivery. Repeated administration of antenatal corticosteroids may have deleterious effects and their benefits are controversial in intrauterine growth restriction (IUGR). OBJECTIVE: to verify the effects in the IUGR population of antenatal betamethasone rescue therapy on neonatal morbidity and mortality, RDS, and neurodevelopment at 2 years. PATIENTS AND METHOD: Retrospective study including ≤ 34 weeks and ≤ 1,500g preterm newborns divided according to antenatal betamethasone exposure: Single-cycle (2 doses) vs Rescue therapy (3 doses). Subgroups were created for those ≥ 30 weeks. Both cohorts were followed up to 24 months of corrected age. The Ages & Stages Questionnaires (ASQ)® was administered to assess neurodevelopment. RESULTS: 62 preterm infants with a diagnosis of IUGR were included. The rescue therapy group compared with the single-dose group showed no differences in morbidity and mortality and less intubation rate at birth (p = 0.02), with no differences in respiratory support at 7 days of life. Preterm newborns ≥ 30 weeks exposed to rescue therapy showed higher morbidity and mortality (p = 0.03) and bronchopulmonary dysplasia (BPD) (p = 0.02), showing no differences in RDS. The rescue therapy group showed worse mean scores on the ASQ-3 scale, with no significant differences in cerebral palsy or sensory deficits. CONCLUSIONS: Rescue therapy reduces intubation at birth but does not reduce morbidity and mortality. However, at > 30 weeks, this benefit is not observed and the IUGR population exposed to rescue therapy presented more BPD and lower scores on the ASQ-3 scale at 2 years. Future studies should be aimed at the individualization of antenatal corticosteroid therapy.

Randomized Trial of Surfactant Therapy via Laryngeal Mask Airway Versus Brief Tracheal Intubation in Neonates Born Preterm.

OBJECTIVE: To evaluate the possible noninferiority of surfactant administration via laryngeal mask airway (LMA) vs endotracheal tube (ETT) in avoiding the requirement for mechanical ventilation in preterm neonates with respiratory distress syndrome (RDS). STUDY DESIGN: This was a randomized controlled trial including infants born at 27 to 36 weeks of gestation, >800 g, diagnosed with RDS and receiving fraction of inspired oxygen 0.30-0.60 via noninvasive respiratory support. Infants were randomized to surfactant via LMA (with atropine premedication) or ETT (InSuRE approach with atropine and remifentanil premedication). Primary outcome was failure of surfactant treatment to prevent the need for mechanical ventilation. RESULTS: Patients were randomized, 51 to LMA and 42 to the ETT group. Both groups had similar baseline characteristics, with birth weights ranging from 810 to 3560 g. Failure rate was 29% in the ETT group and 20% in the LMA group (P = .311). This difference was due to early failures (within 1 hour), with 12.5% in the ETT group and 2% in the LMA group (P = .044). Surfactant therapy via LMA was non-inferior to administration via ETT; failure risk difference -9.0% (CI -∞ to 5.7%). Efficacy in decreasing fraction of inspired oxygen, number of surfactant doses administered, time to wean off all respiratory support, rates of adverse events, and outcomes including pneumothorax and BPD diagnosis did not differ between groups. CONCLUSIONS: Surfactant therapy via LMA was noninferior to administration via ETT and it decreased early failures, possibly by avoiding adverse effects of premedication, laryngoscopy, and intubation. These characteristics make LMA a desirable conduit for surfactant administration. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02164734.

Betamethasone for Preterm Birth: Auckland Steroid Trial Full Results and New Insights 50 Years on.

OBJECTIVES: The objective of this study was to use modern analysis and reporting methods to present the full results of the first randomized trial of antenatal corticosteroids, performed 50 years ago. STUDY DESIGN: In this single-center trial, women at risk of preterm birth at 24 to less than 37 weeks of gestation were randomized to receive 2 doses of betamethasone or placebo, 24 hours apart. Women and their caregivers were blinded to treatment allocation. The primary outcome was respiratory distress syndrome. Secondary outcomes included measures of neonatal mortality and morbidity, mode of birth, and maternal infection. RESULTS: Between 1969 and 1974, 1115 women (1142 pregnancies) were randomized, 560 pregnancies (601 infants) to betamethasone and 582 (617 infants) to placebo. The risk of respiratory distress syndrome was significantly reduced in the betamethasone group compared with placebo (8.8% vs 14.4%, adjusted relative risk 0.62, 95% CI 0.45-0.86, P = .004). Subgroup analyses indicated greater efficacy in male than female infants but no effect of tocolytic therapy or doubling of betamethasone dose. Fetal or neonatal death, neonatal or maternal infection, neonatal hypoglycaemia, cesarean delivery, and lactation status at discharge were not different between the groups. CONCLUSIONS: Antenatal betamethasone administered to women at risk of preterm birth between 24 and less than 37 weeks of gestation reduces the incidence of respiratory distress syndrome, with greater effect in male than in female infants. Doubling the dose of betamethasone does not provide additional benefit.

A Randomized, Controlled Trial to Investigate the Efficacy of Nebulized Poractant Alfa in Premature Babies with Respiratory Distress Syndrome.

OBJECTIVE: To investigate the efficacy and safety of nebulized poractant alfa (at 200 and 400 mg/kg doses) delivered in combination with nasal continuous positive airway pressure compared with nasal continuous positive airway pressure alone in premature infants with diagnosed respiratory distress syndrome. STUDY DESIGN: This randomized, controlled, multinational study was conducted in infants at 280/7 to 326/7 weeks of gestation. The primary outcome was the incidence of respiratory failure in the first 72 hours of life, defined as needing endotracheal surfactant and/or mechanical ventilation owing to prespecified criteria. Secondary outcomes included the time to respiratory failure in the first 72 hours, duration of ventilation, mortality, incidence of bronchopulmonary dysplasia, and major associated neonatal comorbidities. In addition, the safety and tolerability of the treatments were assessed reporting the number and percentage of infants with treatment-emergent adverse events and adverse drug reactions during nebulization. RESULTS: In total, 129 infants were randomized. No significant differences were observed for the primary outcome: 24 (57%), 20 (49%), and 25 (58%) infants received endotracheal surfactant and/or mechanical ventilation within 72 hours in the poractant alfa 200 mg/kg, poractant alfa 400 mg/kg, and nasal continuous positive airway pressure groups, respectively. Similarly, secondary respiratory outcomes did not differ among groups. Enrollment was halted early owing to a change in the benefit-risk balance of the intervention. Nebulized poractant alfa was well-tolerated and safe, and no serious adverse events were related to the study treatment. CONCLUSIONS: The intervention did not decrease the likelihood of respiratory failure within the first 72 hours of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03235986.

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.

RETREATMENT WITH SURFACTANT IN VERY LOW BIRTH WEIGHT PRETERM INFANTS: RISK PREDICTORS AND THEIR INFLUENCE ON NEONATAL OUTCOMES.

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.

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.

Synthetic Surfactant CHF5633 Compared with Poractant Alfa in the Treatment of Neonatal Respiratory Distress Syndrome: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial.

OBJECTIVE: To compare efficacy and safety of a new synthetic surfactant, CHF5633, enriched with surfactant proteins, SP-B and SP-C peptide analogues, with porcine surfactant, poractant alfa, for the treatment of respiratory distress syndrome in infants born preterm. STUDY DESIGN: Neonates born preterm on respiratory support requiring fraction of inspired oxygen (FiO2) ≥0.30 from 240/7 to 266/7 weeks and FiO2 ≥0.35 from 270/7 to 296/7 weeks of gestation to maintain 88%-95% oxygen saturation were randomized to receive 200 mg/kg of CHF5633 or poractant alfa. If necessary, redosing was given at 100 mg/kg. Efficacy end points were oxygen requirement (FiO2, respiratory severity score [FiO2 × mean airway pressure]) in the first 24 hours, 7 and 28 days, discharge home, and/or 36 weeks of postmenstrual age; mortality and bronchopulmonary dysplasia at 28 days and 36 weeks of PMA. Adverse events and immunogenicity were monitored for safety. RESULTS: Of the 123 randomized neonates, 113 were treated (56 and 57 in CHF5633 and poractant alfa groups, respectively). In both arms, FiO2 and respiratory severity score decreased from baseline at all time points (P < .001) with no statistically significant differences between groups. Rescue surfactant use (19 [33.9%] vs 17 [29.8%]), bronchopulmonary dysplasia (31 [55.4%] and 32 [56.1%]), and mortality at day 28 (4 [7.1%] and 3 [5.3%]) were similar in the CHF5633 and poractant alfa groups, respectively. In 2 (3.4%) and 1 (1.7%) neonates, adverse drug reactions were reported in CHF5633 and poractant alfa groups, respectively. No immunogenicity was detected. CONCLUSIONS: Treatment with CHF5633 showed similar efficacy and safety as poractant alfa in neonates born preterm with moderate-to-severe respiratory distress syndrome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02452476.

Randomized Trial of 42-Day Compared with 9-Day Courses of Dexamethasone for the Treatment of Evolving Bronchopulmonary Dysplasia in Extremely Preterm Infants.

OBJECTIVE: To compare pulmonary and neurodevelopmental outcomes in extremely preterm infants with evolving bronchopulmonary dysplasia treated with either a 42-day course of dexamethasone or 9-day course(s) of dexamethasone. STUDY DESIGN: This was a prospective, randomized study in 59 infants ≤27 weeks of gestation born between October 2006 and December 2010, who at day 10-21 of life had ventilatory support with mean airway pressure ≥8 cm H2O and FiO2 ≥60%. Infants received dexamethasone 0.5 mg/k/day × 3 days followed by a slow taper (42-day group, n = 30) or dexamethasone 0.5 mg/k/day followed by a rapid taper (9-day group, n = 29). Infants in the 9-day group received additional 9-day courses if they again required entry support. The primary outcome was intact survival (normal neurologic examination, IQ >70, and functioning in school without supplemental educational support) at 7 years of age. RESULTS: The 42-day and 9-day groups were similar for mean gestational age (25 weeks) and all baseline characteristics. Nineteen of 29 infants (66%) in the 9-day group received only 1 course of dexamethasone; therefore, the total steroid dose for the 42-day group (7.56 mg/kg) was significantly greater than that for the 9-day group (4.04 mg/kg), P < .001. Infants in the 42-day group had shorter duration of ventilation (25 vs 37 days), P < .005, received fewer transfusions (2 vs 3.5), P < .01, and reached full enteral feeds earlier (40 vs 46 days), P < .05. Intact survival at school age was significantly increased in the 42-day group (75%) compared with the 9-day group (34%), P < .005. CONCLUSION: A 42-day tapering course of dexamethasone in extremely preterm infants at high risk for bronchopulmonary dysplasia decreased hospital morbidities and increased rate of survival without handicap compared with a treatment protocol that attempted to minimize steroid exposure.

Síndrome da angústia respiratória aguda / Acute respiratory distress syndrome

A Síndrome da Angústia Respiratória Aguda (SARA) é uma resposta inflamatória pulmonar excessiva, devido a diferentes tipos de agressões, que leva ao aumento da permeabilidade capilar pulmonar e sistêmica e a instalação de uma insuficiência respiratória aguda. As causas mais frequentes incluem sepses, pneumonia grave, peritonite e politraumatismos e a SARA tem sido observada na prática clínica, em animais atropelados apresentando índice significativo de contusão pulmonar, que evolui agressivamente em períodos relativamente curtos e o tratamento prontamente empregado deve ser o de suporte. Objetiva-se, com esse trabalho, revisar os aspectos gerais relacionados a SARA, como a etiologia e fisiopatologia e, especialmente, auxiliar o veterinário na identificação dessa doença e posterior tratamento.

The acute respiratory distress syndrome (ARDS) is an excessive pulmonary inflammatory response, due to different kinds of aggressions, which leads to increase in systemic and pulmonary capillary permeability and installation of acute respiratory failure. The most common causes include sepsis, severe pneumonia, peritonitis and polytraumatized patient and SARA has been observed in clinical practice, to run over animals with significant rate of pulmonary contusion, which aggressively evolves in relatively short periods andtreatment promptly employee should be to support. This work aims to review the general aspects related to Acute Respiratory Distress Syndrome, such as etiology and pathophysiology, and especially to assist the veterinarian in identifying this disease and subsequent treatment.

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.

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.

Surfactant Components and Tracheal Aspirate Inflammatory Markers in Preterm Infants with Respiratory Distress Syndrome.

In 93 preterm infants ≤32 weeks of gestational age and 12 control infants, epithelial lining fluid disaturated-phosphatidylcholine, surfactant protein A and B, albumin, and myeloperoxidase activity were assessed after intubation and before exogenous surfactant administration. We found that disaturated-phosphatidylcholine, surfactant protein B, and myeloperoxidase were significantly higher in preterms with chorioamnionitis.

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.