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1.
Medicine (Baltimore) ; 99(9): e19216, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32118723

RESUMO

To explore the clinical effects of less invasive surfactant administration (LISA) via a gastric tube on the treatment of respiratory distress syndrome (RDS) in premature infants aged 32 to 36 weeks.A total of 97 premature infants with RDS admitted to the Children's Hospital of Shanxi from February 2017 to January 2018 were randomly divided into LISA (47 cases) and (intubation-surfactant-extubation,) INSURE groups (50 cases). In the LISA group, 6F gastric tubes were inserted into the trachea through direct laryngoscopy under nasal continuous positive airway pressure (NCPAP), and pulmonary surfactant (PS) was injected. In the INSURE group, PS was injected via tracheal intubation and NCPAP was performed after extubation. The incidence of technical-related adverse events and various complications in the two groups were observed.PS was successfully injected through gastric tube in the LISA group. There were no significant differences in reflux, asphyxia, bradycardia (<100 beats/min), apnea, FiO2, changes in PaO2 and PaCO2 at 1 hour post-treatment between the groups. During the course of administration, blood pressure and SpO2 in the LISA group were more stable, and significant differences between the 2 groups were observed. However, no significant differences in the complications and outcomes between the 2 groups occurred.The LISA technique can be used to treat premature infants with RDS aged 32 to 36 weeks with stronger spontaneous breathing ability. Further clinical studies are required to determine the optimal strategy of LISA administration and the most profitable patient population.


Assuntos
Recém-Nascido Prematuro , Intubação Intratraqueal/instrumentação , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Surfactantes Pulmonares/administração & dosagem , Resultado do Tratamento
2.
Science ; 367(6480)2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-32079747

RESUMO

Current influenza vaccines only confer protection against homologous viruses. We synthesized pulmonary surfactant (PS)-biomimetic liposomes encapsulating 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), an agonist of the interferon gene inducer STING (stimulator of interferon genes). The adjuvant (PS-GAMP) vigorously augmented influenza vaccine-induced humoral and CD8+ T cell immune responses in mice by simulating the early phase of viral infection without concomitant excess inflammation. Two days after intranasal immunization with PS-GAMP-adjuvanted H1N1 vaccine, strong cross-protection was elicited against distant H1N1 and heterosubtypic H3N2, H5N1, and H7N9 viruses for at least 6 months while maintaining lung-resident memory CD8+ T cells. Adjuvanticity was then validated in ferrets. When alveolar epithelial cells (AECs) lacked Sting or gap junctions were blocked, PS-GAMP-mediated adjuvanticity was substantially abrogated in vivo. Thus, AECs play a pivotal role in configuring heterosubtypic immunity.


Assuntos
Materiais Biomiméticos , Vacinas contra Influenza/imunologia , Nanopartículas , Nucleotídeos Cíclicos/administração & dosagem , Infecções por Orthomyxoviridae/prevenção & controle , Surfactantes Pulmonares/imunologia , Vacinação/métodos , Adjuvantes Imunológicos/administração & dosagem , Administração Intranasal , Animais , Materiais Biomiméticos/administração & dosagem , Linfócitos T CD8-Positivos/imunologia , Furões , Memória Imunológica , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Subtipo H7N9 do Vírus da Influenza A/imunologia , Vacinas contra Influenza/administração & dosagem , Lipossomos , Proteínas de Membrana/agonistas , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Nanopartículas/administração & dosagem , Nucleotídeos Cíclicos/farmacologia , Surfactantes Pulmonares/administração & dosagem
3.
Scand J Trauma Resusc Emerg Med ; 27(1): 95, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665094

RESUMO

The population of the Kingdom of Bhutan is scattered in small villages throughout the eastern Himalaya. Infants born prematurely in villages have no access to neonatal intensive care until they are transported to the national referral hospital, a process that once took hours, if not days. After the introduction of a helicopter critical-care retrieval team, we were able to send a trained team to a remote location that successfully administered surfactant and initiated critical care to a premature, extreme low birth weight infant in severe respiratory distress in the first hour of life. Although the infant was in shock and in a near-arrest state at the time the team arrived, he made an excellent recovery after resuscitation by the team.


Assuntos
Serviços Médicos de Emergência/métodos , Recém-Nascido de Baixo Peso , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Ressuscitação/métodos , Humanos , Recém-Nascido , Masculino
4.
PLoS Comput Biol ; 15(10): e1007408, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31622332

RESUMO

Surfactant Replacement Therapy (SRT), which involves instillation of a liquid-surfactant mixture directly into the lung airway tree, is a major therapeutic treatment in neonatal patients with respiratory distress syndrome (RDS). This procedure has proved to be remarkably effective in premature newborns, inducing a five-fold decrease of mortality in the past 35 years. Disappointingly, its use in adults for treating acute respiratory distress syndrome (ARDS) experienced initial success followed by failures. Our recently developed numerical model has demonstrated that transition from success to failure of SRT in adults could, in fact, have a fluid mechanical origin that is potentially reversible. Here, we present the first numerical simulations of surfactant delivery into a realistic asymmetric conducting airway tree of the rat lung and compare them with experimental results. The roles of dose volume (VD), flow rate, and multiple aliquot delivery are investigated. We find that our simulations of surfactant delivery in rat lungs are in good agreement with our experimental data. In particular, we show that the monopodial architecture of the rat airway tree plays a major role in surfactant delivery, contributing to the poor homogeneity of the end distribution of surfactant. In addition, we observe that increasing VD increases the amount of surfactant delivered to the acini after losing a portion to coating the involved airways, the coating cost volume, VCC. Finally, we quantitatively assess the improvement resulting from a multiple aliquot delivery, a method sometimes employed clinically, and find that a much larger fraction of surfactant reaches the alveolar regions in this case. This is the first direct qualitative and quantitative comparison of our numerical model with experimental studies, which enhances our previous predictions in adults and neonates while providing a tool for predicting, engineering, and optimizing patient-specific surfactant delivery in complex situations.


Assuntos
Surfactantes Pulmonares/administração & dosagem , Surfactantes Pulmonares/uso terapêutico , Animais , Simulação por Computador , Hidrodinâmica , Pulmão/fisiologia , Fluxo Expiratório Máximo/fisiologia , Modelos Anatômicos , Modelos Estatísticos , Ratos , Ratos Long-Evans , Ratos Sprague-Dawley , Ratos Wistar , Tensoativos
5.
Arch Dis Child Fetal Neonatal Ed ; 104(6): F587-F593, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31498776

RESUMO

BACKGROUND: The influence of pressure strategies to promote lung aeration at birth on the subsequent physiological response to exogenous surfactant therapy has not been investigated. OBJECTIVES: To compare the effect of sustained inflation (SI) and a dynamic positive end-expiratory pressure (PEEP) manoeuvre at birth on the subsequent physiological response to exogenous surfactant therapy in preterm lambs. METHODS: Steroid-exposed preterm lambs (124-127 days' gestation; n=71) were randomly assigned from birth to either (1) positive-pressure ventilation (PPV) with no recruitment manoeuvre; (2) SI until stable aeration; or (3) 3 min dynamic stepwise PEEP strategy (maximum 14-20 cmH2O; dynamic PEEP (DynPEEP)), followed by PPV for 60 min using a standardised protocol. Surfactant (200 mg/kg poractant alfa) was administered at 10 min. Dynamic compliance, gas exchange and regional ventilation and aeration characteristics (electrical impedance tomography) were measured throughout and compared between groups, and with a historical group (n=38) managed using the same strategies without surfactant. RESULTS: Compliance increased after surfactant only in the DynPEEP group (p<0.0001, repeated measures analysis of variance), being 0.17 (0.10, 0.23) mL/kg/cmH2O higher at 60 min than the SI group. An SI resulted in the least uniform aeration, and unlike the no-recruitment and DynPEEP groups, the distribution of aeration and tidal ventilation did not improve with surfactant. All groups had similar improvements in oxygenation post-surfactant compared with the corresponding groups not treated with surfactant. CONCLUSIONS: A DynPEEP strategy at birth may improve the response to early surfactant therapy, whereas rapid lung inflation with SI creates non-uniform aeration that appears to inhibit surfactant efficacy.


Assuntos
Surfactantes Pulmonares/farmacologia , Respiração Artificial/métodos , Animais , Animais Recém-Nascidos , Impedância Elétrica , Respiração com Pressão Positiva , Troca Gasosa Pulmonar , Surfactantes Pulmonares/administração & dosagem , Distribuição Aleatória , Mecânica Respiratória , Ovinos
7.
Arch Dis Child Fetal Neonatal Ed ; 104(6): F655-F659, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31296694

RESUMO

Non-invasive ventilation and especially the application of continuous positive airway pressure (CPAP) has become standard for the treatment of premature infants with respiratory problems. However, CPAP failure may occur due to respiratory distress syndrome, that is, surfactant deficiency. Less invasive surfactant administration (LISA) aims to provide an adequate dose of surfactant while the infant is breathing spontaneously, thus avoiding positive pressure ventilation support. Using a thin catheter for surfactant application allows infants to maintain function of the glottis and continue spontaneous breathing, whereas the INtubate-SURfactant-Extubate (INSURE) procedure is connected with sedation/analgesia, regular intubation and a (brief) period of positive pressure ventilation. Individual studies and meta-analyses summarised in this review point in the direction that LISA is more effective than standard treatment or INSURE both in terms of short-term (avoidance of mechanical ventilation) and long-term (intracerebral haemorrhage and bronchopulmonary dysplasia) outcomes. Open questions include exact treatment thresholds for different gestational ages, the usefulness of devices/catheters that have recently been purpose-built for the LISA technique and especially the question of analgesia/sedation during the procedure. The current technology still demands laryngoscopy with all its unpleasant effects for infants. Therefore, studies with pharyngeal surfactant deposition immediately after delivery, the use of laryngeal airways for surfactant administration and attempts to nebulise surfactant are under way. Finally, LISA is not simply an isolated technical procedure for surfactant delivery but rather part of a comprehensive non-invasive approach supporting the concept of a gentle transition to the extrauterine world enabling preterm infants to benefit from the advantages of spontaneous breathing.


Assuntos
Recém-Nascido Prematuro , Ventilação não Invasiva/métodos , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Idade Gestacional , Humanos , Recém-Nascido , Surfactantes Pulmonares/administração & dosagem
8.
Respir Res ; 20(1): 158, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319861

RESUMO

BACKGROUND: Respiratory Distress Syndrome (RDS) is a prematurity-related breathing disorder caused by a quantitative deficiency of pulmonary surfactant. Surfactant replacement therapy is effective for RDS newborns, although treatment failure has been reported. The aim of this study is to trace exogenous surfactant by 13C variation and estimate the amount reaching the lungs at different doses of the drug. METHODS: Forty-four surfactant-depleted rabbits were obtained by serial bronchoalveolar lavages (BALs), that were merged into a pool (BAL pool) for each animal. Rabbits were in nasal continuous positive airway pressure and treated with 0, 25, 50, 100 or 200 mg/kg of poractant alfa by InSurE. After 90 min, rabbits were depleted again and a new pool (BAL end experiment) was collected. Disaturated-phosphatidylcholine (DSPC) was measured by gas chromatography. DSPC-Palmitic acid (PA) 13C/12C was analyzed by isotope ratio mass spectrometry. One-way non-parametric ANOVA and post-hoc Dunn's multiple comparison were used to assess differences among experimental groups. RESULTS: Based on DSPC-PA 13C/12C in BAL pool and BAL end experiment, the estimated amount of exogenous surfactant ranged from 61 to 87% in dose-dependent way (p < 0.0001) in animals treated with 25 up to 200 mg/kg. Surfactant administration stimulated endogenous surfactant secretion. The percentage of drug recovered from lungs did not depend on the administered dose and accounted for 31% [24-40] of dose. CONCLUSIONS: We reported a risk-free method to trace exogenous surfactant in vivo. It could be a valuable tool for assessing, alongside the physiological response, the delivery efficiency of surfactant administration techniques.


Assuntos
Produtos Biológicos/metabolismo , Isótopos de Carbono/metabolismo , Pulmão/metabolismo , Fosfolipídeos/metabolismo , Surfactantes Pulmonares/metabolismo , Animais , Produtos Biológicos/administração & dosagem , Isótopos de Carbono/administração & dosagem , Relação Dose-Resposta a Droga , Pulmão/efeitos dos fármacos , Masculino , Fosfolipídeos/administração & dosagem , Surfactantes Pulmonares/administração & dosagem , Coelhos , Tensoativos/administração & dosagem , Tensoativos/metabolismo
9.
Respir Res ; 20(1): 134, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266508

RESUMO

BACKGROUND: Non-invasive delivery of nebulized surfactant has been a neonatology long-pursued goal. Nevertheless, the clinical efficacy of nebulized surfactant remains inconclusive, in part, due to the great technical challenges of depositing nebulized drugs in the lungs of preterm infants. The aim of this study was to investigate the feasibility of delivering nebulized surfactant (poractant alfa) in vitro and in vivo with an adapted, neonate-tailored aerosol delivery strategy. METHODS: Particle size distribution of undiluted poractant alfa aerosols generated by a customized eFlow-Neos nebulizer system was determined by laser diffraction. The theoretical nebulized surfactant lung dose was estimated in vitro in a clinical setting replica including a neonatal continuous positive airway pressure (CPAP) circuit, a cast of the upper airways of a preterm neonate, and a breath simulator programmed with the tidal breathing pattern of an infant with mild respiratory distress syndrome (RDS). A dose-response study with nebulized surfactant covering the 100-600 mg/kg nominal dose-range was conducted in RDS-modelling, lung-lavaged spontaneously-breathing rabbits managed with nasal CPAP. The effects of nebulized poractant alfa on arterial gas exchange and lung mechanics were assessed. Exogenous alveolar disaturated-phosphatidylcholine (DSPC) in the lungs was measured as a proxy of surfactant deposition efficacy. RESULTS: Laser diffraction studies demonstrated suitable aerosol characteristics for inhalation (mass median diameter, MMD = 3 µm). The mean surfactant lung dose determined in vitro was 13.7% ± 4.0 of the 200 mg/kg nominal dose. Nebulized surfactant delivered to spontaneously-breathing rabbits during nasal CPAP significantly improved arterial oxygenation compared to animals receiving CPAP only. Particularly, the groups of animals treated with 200 mg/kg and 400 mg/kg of nebulized poractant alfa achieved an equivalent pulmonary response in terms of oxygenation and lung mechanics as the group of animals treated with instilled surfactant (200 mg/kg). CONCLUSIONS: The customized eFlow-Neos vibrating-membrane nebulizer system efficiently generated respirable aerosols of undiluted poractant alfa. Nebulized surfactant delivered at doses of 200 mg/kg and 400 mg/kg elicited a pulmonary response equivalent to that observed after treatment with an intratracheal surfactant bolus of 200 mg/kg. This bench-characterized nebulized surfactant delivery strategy is now under evaluation in Phase II clinical trial (EUDRACT No.:2016-004547-36).


Assuntos
Produtos Biológicos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Modelos Biológicos , Nebulizadores e Vaporizadores , Fosfolipídeos/administração & dosagem , Surfactantes Pulmonares/administração & dosagem , Animais , Produtos Biológicos/metabolismo , Humanos , Recém-Nascido , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Tamanho da Partícula , Fosfolipídeos/metabolismo , Surfactantes Pulmonares/metabolismo , Coelhos
10.
Arch Dis Child Fetal Neonatal Ed ; 104(6): F643-F647, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31154421

RESUMO

OBJECTIVE: To report outcomes to 1 year, in infants born with congenital diaphragmatic hernia (CDH), explore factors associated with infant mortality and examine the relationship between surgical techniques and postoperative morbidity. DESIGN: Prospective national population cohort study. SETTING: Paediatric surgical centres in the UK and Ireland. METHOD: Data were collected to 1 year for infants with CDH live-born between 1 April 2009 to 30 September 2010. Factors associated with infant mortality are explored using logistic regression. Postoperative morbidity following patch versus primary closure, minimally invasive versus open surgery and biological versus synthetic patch material is described. Data are presented as n (%) and median (IQR). RESULTS: Overall known survival to 1 year was 75%, 95% CI 68% to 81% (138/184) and postoperative survival 93%, 95% CI 88% to 97% (138/148). Female sex, antenatal diagnosis, use of vasodilators or inotropes, being small for gestational age, patch repair and use of surfactant were all associated with infant death. Infants undergoing patch repair had a high incidence of postoperative chylothorax (11/54 vs 2/96 in infants undergoing primary closure) and a long length of hospital stay (41 days, IQR 24-68 vs 16 days, IQR 10-25 in primary closure group). Infants managed with synthetic patch material had a high incidence of chylothorax (11/34 vs 0/19 with biological patch). CONCLUSION: The majority of infant deaths in babies born with CDH occur before surgical correction. Female sex, being born small for gestational age, surfactant use, patch repair and receipt of cardiovascular support were associated with a higher risk of death. The optimum surgical approach, timing of operation and choice of patch material to achieve lowest morbidity warrants further evaluation.


Assuntos
Hérnias Diafragmáticas Congênitas/mortalidade , Hérnias Diafragmáticas Congênitas/cirurgia , Herniorrafia/métodos , Cardiotônicos/administração & dosagem , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Irlanda/epidemiologia , Tempo de Internação , Modelos Logísticos , Masculino , Procedimentos Cirúrgicos Minimamente Invasivos/mortalidade , Complicações Pós-Operatórias/epidemiologia , Diagnóstico Pré-Natal/estatística & dados numéricos , Estudos Prospectivos , Surfactantes Pulmonares/administração & dosagem , Fatores Sexuais , Reino Unido/epidemiologia
11.
Early Hum Dev ; 135: 32-36, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31229792

RESUMO

BACKGROUND: Surfactant administration traditionally involved endotracheal intubation and mechanical ventilation, which is associated with a risk of barotrauma and volutrauma. OBJECTIVE: To compare the morbidity and mortality rates between LISA-treated and INSURE-treated premature babies with respiratory distress syndrome (RDS). METHODS: We assessed retrospectively the medical records of preterm infants who were born at 250/7 to 296/7 weeks of gestation and were administered surfactant initially either with LISA or INSURE method over a five-year period. RESULTS: Analysis of the data of 205 LISA-treated and 178 INSURE-treated infants revealed the mean gestational age as 28.1 ±â€¯1.3 and 28 ±â€¯1.3 weeks and mean birth weight as 1041 ±â€¯205 and 1029 ±â€¯222 g in LISA and INSURE groups, respectively. The mechanical ventilation requirement in the first 72 h of life (%26.8-%42.1, p = 0.002) and the incidence of moderate-severe BPD (%12.2-%21.9, p = 0.01) were lower in LISA-treated infants. LISA method was found as an independent factor in reducing mechanical ventilation requirement in the first 72 h of life and incidence of moderate-severe BPD [RR: -0.49 (%95 CI -0.28 to -0.85), p = 0.01]. CONCLUSION: Data obtained from our five-year clinical experience are comparable with the recent literature. LISA is currently the most suitable method of surfactant administration and it should be the first choice in spontaneously breathing infants considering its favorable effects on respiratory morbidities in preterm infants with RDS.


Assuntos
Lactente Extremamente Prematuro , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Intubação Intratraqueal/efeitos adversos , Intubação Intratraqueal/métodos , Masculino , Surfactantes Pulmonares/efeitos adversos , Surfactantes Pulmonares/uso terapêutico , Respiração Artificial/efeitos adversos , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia
12.
Early Hum Dev ; 134: 19-25, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31121339

RESUMO

BACKGROUND: Treating respiratory distress syndrome (RDS) with intratracheal surfactant requires endotracheal intubation and mechanical ventilation, (MV) with their attendant risks. Use of non-invasive respiratory support in the delivery room averts the need for MV but delays surfactant administration. OBJECTIVE: We hypothesized that aerosolized surfactant is feasible and safe in infants 240/7-366/7 weeks gestational age (GA) with RDS, receiving non-invasive respiratory support. DESIGN/METHODS: In an unblinded Phase I study, sequentially enrolled infants with RDS stratified by GA received increasing doses (100 or 200 mg/kg of phospholipid) and dilutions (12.5 or 8.3 mg/ml) of surfactant using a jet nebulizer. Infants were monitored clinically and with cerebral oximetry. RESULTS: Seventeen infants were enrolled. Age at start of first dose and dose duration were 4.9 (3.4-10.1) and 2.1 (1.0-2.8) hours respectively. Two infants in the lowest GA stratum (240/7-286/7) required intubation within 2 h after the first dose. Fifteen infants completed the study; 13 received two doses. Infants tolerated the aerosol treatment well. No other significant adverse events were identified. Parental permission for cerebral oximetry was obtained in 16 infants. In the two infants who later exited the study, values prior to start of aerosolized surfactant were lower compared to 14 infants who completed the study (p = 0.0835), increased after start of study intervention (p = 0.0105) and decreased after intubation (p = 0.0003). CONCLUSIONS: We have demonstrated the feasibility and safety of aerosolized surfactant in preterm infants receiving non-invasive respiratory support. The treatment was well tolerated by infants and clinical caregivers.


Assuntos
Administração por Inalação , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Masculino , Nebulizadores e Vaporizadores , Surfactantes Pulmonares/efeitos adversos , Surfactantes Pulmonares/uso terapêutico
13.
Arch Dis Child Fetal Neonatal Ed ; 104(6): F636-F642, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31036700

RESUMO

OBJECTIVE: To evaluate incidence of minimally invasive surfactant therapy (MIST) failure, identify risk factors and assess the impact of MIST failure on neonatal outcome. DESIGN: Retrospective cohort study. MIST failure was defined as need for early mechanical ventilation (<72 hours of life). Multivariate logistic regression analysis was performed to identify risk factors for MIST failure and compare outcomes between groups. SETTING: Two tertiary neonatal intensive care centres in the Netherlands. PATIENTS: Infants born between 24 weeks' and 31 weeks' gestational age (GA) (n=185) with MIST for respiratory distress syndrome. INTERVENTIONS: MIST procedure with poractant alfa (100-200 mg/kg). MAIN OUTCOME MEASURES: Continuous positive airway pressure (CPAP) failure after MIST in the first 72 hours of life. RESULTS: 30% of the infants failed CPAP after MIST. In a multivariate logistic regression analysis, four risk factors were independently associated with failure: GA <28 weeks, C reactive protein ≥10 mg/L, absence of antenatal corticosteroids and lower surfactant dose. Infants receiving 200 mg/kg surfactant had a failure rate of 14% versus 35% with surfactant dose <200 mg/kg. Mean body temperature was 0.4°C lower at neonatal intensive care unit admission and before the procedure in infants with MIST failure.Furthermore, MIST failure was independently associated with an increased risk of severe intraventricular haemorrhage. CONCLUSION: We observed moderate MIST failure rates in concordance with the results of earlier studies. Absence of corticosteroids and lower surfactant dose are risk factors for MIST failure that may be modifiable in order to improve MIST success and patient outcome.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Recém-Nascido Prematuro , Surfactantes Pulmonares/uso terapêutico , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Corticosteroides/administração & dosagem , Temperatura Corporal , Proteína C-Reativa/análise , Relação Dose-Resposta a Droga , Feminino , Idade Gestacional , Humanos , Lactente Extremamente Prematuro , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Modelos Logísticos , Masculino , Países Baixos , Surfactantes Pulmonares/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo
14.
Ital J Pediatr ; 45(1): 44, 2019 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-30971298

RESUMO

BACKGROUND: We aimed to survey Delivery Room and Neonatal Intensive Care Unit (NICU) respiratory strategies dedicated to the extremely low gestational age newborn (ELGAN - GA < 28 wks) in Italy. METHODS: A questionnaire was sent to 113 Italian level III centres. A lead physician and a nurse with expertise in mechanical ventilation (MV) were identified in each unit to answer. Information about those aspects of ventilatory support considered by center's staff as needing improvement was also collected. RESULTS: A 100% response rate was obtained. In the Delivery Room, sustained lung inflation was performed in 74.8% of centres, and 89.2% used NCPAP. For ELGANs who need invasive MV, conventional MV was the most used strategy. Volume-targeted ventilation and High-frequency oscillatory ventilation (HFOV) were considered as primary mode in < 30% of centres. Among non-invasive strategies, NCPAP was the most utilized, followed by BiPAP, High-flow nasal cannula and nasal intermittent positive pressure ventilation. Nurses more commonly recorded in the nursing charts the ventilator's setting parameters rather than measured ones. HFOV and non-invasive ventilation were the most quoted aspects of neonatal ventilation felt as to be improved. CONCLUSION: The routine respiratory support practices in Italy showed marked variations among units. Focused interventions are largely required to improve clinical practice.


Assuntos
Recém-Nascido Prematuro , Padrões de Prática em Enfermagem/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Respiração Artificial/métodos , Respiração Artificial/estatística & dados numéricos , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Idade Gestacional , Humanos , Recém-Nascido , Itália , Medição da Dor/estatística & dados numéricos , Surfactantes Pulmonares/administração & dosagem , Inquéritos e Questionários
15.
Neonatology ; 115(4): 411-422, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30974437

RESUMO

Traditionally, surfactant has been administered to preterm infants with respiratory distress syndrome via an endotracheal tube and in conjunction with mechanical ventilation. However, negative consequences of mechanical ventilation such as pneumothorax and bronchopulmonary dysplasia are well known. In order to provide the benefits of surfactant administration without the negative effects of mechanical ventilation, several methods of less invasive surfactant administration have been developed. These methods include InSurE (intubate, surfactant, extubate), pharyngeal administration, laryngeal mask administration, aerosolized surfactant administration, and thin catheter administration (TCA). Of these, TCA has been studied most extensively and holds the most promise as a less invasive and effective mode of surfactant administration to preterm infants. Further studies will aid in determining which patients would benefit most from less invasive surfactant administration.


Assuntos
Pressão Positiva Contínua nas Vias Aéreas/métodos , Intubação Intratraqueal/métodos , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Displasia Broncopulmonar/prevenção & controle , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Pneumotórax/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Biochem Pharmacol ; 164: 64-73, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30928674

RESUMO

As an organ system, the lung has unique advantages and disadvantages for localized drug delivery. Its direct contact with the external environment allows for the upper airways to be easily accessible to intrapulmonary delivery. However, its complex branching structure makes direct delivery to the peripheral airways challenging. This review will discus the utility of exogenous surfactant, a lipoprotein complex currently used to treat neonatal respiratory distress syndrome, as a carrier for pulmonary therapeutics to enhance the delivery of these drugs to the deeper regions of the lung. The focus is to provide an update on the many tools available to develop new surfactant-based therapeutics using computer modeling, in vitro approaches, and in vivo testing, which may ultimately lead to clinical trials. Two clinical conditions, Acute Respiratory Distress Syndrome and Bacterial Pneumonia are utilized throughout as prototypical examples of pulmonary conditions in which surfactant drug combination may be beneficial. Consequently, the pharmaceuticals discussed are primarily those with antimicrobial or anti-inflammatory activities.


Assuntos
Anti-Inflamatórios/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Surfactantes Pulmonares/administração & dosagem , Tensoativos/administração & dosagem , Ensaios Clínicos como Assunto/métodos , Humanos , Síndrome do Desconforto Respiratório do Adulto/tratamento farmacológico , Síndrome do Desconforto Respiratório do Adulto/metabolismo
17.
J Neonatal Perinatal Med ; 12(3): 255-263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30932897

RESUMO

BACKGROUND: This study investigates trends in methods of surfactant administration and early respiratory management in neonatal intensive care units [NICU] in New South Wales [NSW] and the Australian Capital Territory [ACT] in 2015 and evaluate whether differences in practice translate to variances in short term outcomes. METHODS: Surveys were sent to NICUs in NSW and ACT to ascertain their practice of surfactant administration and respiratory management. A retrospective data analysis with data from the NICUS database from 01/01/2013-30/06/2015 was performed. Included were all patients that received Surfactant, were inborn, without major malformation, ≥24 weeks gestational age [GA] and birthweight ≥500 g. Major respiratory outcome measures were time ventilated, air leak, oxygen requirement at 36 weeks corrected gestational age [cGA], home oxygen therapy after discharge and retinopathy of prematurity [ROP]. Along with this data demographic and morbidity data was also obtained for comparison [mortality, necrotizing enterocolitis [NEC], persistent ductus arteriosus [PDA], intraventricular hemorrhage [IVH]. RESULTS: 1453 patients met inclusion criteria. Patient data comparing major respiratory outcomes showed patients receiving less invasive Surfactant therapy and respiratory management spent longer time on CPAP [559 vs. 407 hrs, p = 0.01] and in the older gestation subgroups less time on mechanical ventilation [18 vs. 50 hrs p = <0.001] and were discharged earlier [48 vs. 54 days, p = 0.03]. There was however, higher rates of oxygen requirement at 36 weeks cGA [33 vs. 26.3% p = 0.01] and a higher proportion of home oxygen in this patient group [11.3 vs. 7.1% p = 0.03]. Major morbidity outcome data showed no significant differences. CONCLUSIONS: Less invasive Surfactant therapy and gentle early respiratory management should be considered as a viable alternative to established methods of surfactant administration and ventilation.


Assuntos
Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/tratamento farmacológico , Índice de Apgar , Território da Capital Australiana , Peso ao Nascer/fisiologia , Vias de Administração de Medicamentos , Feminino , Idade Gestacional , Serviços de Assistência Domiciliar/estatística & dados numéricos , Humanos , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Terapia Intensiva Neonatal/métodos , Tempo de Internação/estatística & dados numéricos , Masculino , New South Wales , Prática Profissional , Respiração Artificial/métodos , Respiração Artificial/estatística & dados numéricos , Resultado do Tratamento
18.
J Coll Physicians Surg Pak ; 29(3): 226-330, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30823947

RESUMO

OBJECTIVE: To compare the need of mechanical ventilation between LISA (less invasive surfactant administration) method and conventional INSURE method (INtubation SURfactant administration and Extubation) in spontaneously breathing preterm infants with respiratory distress syndrome (RDS). STUDY DESIGN: An experimental study. PLACE AND DURATION OF STUDY: Department of Neonatology, PIMS, Islamabad, from April to December 2017. METHODOLOGY: A total of 100 preterm infants <34 weeks gestation, on nasal CPAP requiring fraction of inspire oxygen (FiO2) >0.4, with respiratory distress syndrome (RDS) were included in the study and divided randomly into two groups, 50 each. RESULTS: There were 28 (56%) males in LISA and 31 (62%) in the INSURE group. Median birth weight was 1300 grams (IQR 600) in LISA, while 1400 grams (IQR 400) in INSURE infants. C-section rate was 52% (n=26) and 48% (n=24) in LISA and INSURE, respectively. Pre-natal steroids were given to 38 patients (76%) in LISA and 30 patients (60%) in INSURE group. LISA patients had significantly less need of mechanical ventilation with p-value <0.05 {30% (n=15) vs. 60% (n=30)}. The median duration of mechanical ventilation was 40 hours (IQR 75) and 71 hours (IQR 62) in LISA and INSURE, respectively. Similarly, median FiO2 reduction was 30 (IQR 30) in LISA group and it was 25 (IQR 10) in INSURE group, with p-value <0.05. There was no significant difference in mortality, hospital stay and complications. CONCLUSION: LISA technique was safe, non-invasive approach of surfactant administration, with reduced need of mechanical ventilation rate and duration.


Assuntos
Recém-Nascido Prematuro , Respiração com Pressão Positiva/métodos , Surfactantes Pulmonares/administração & dosagem , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Tensoativos/administração & dosagem , Extubação , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Paquistão , Segurança do Paciente , Respiração Artificial/efeitos adversos , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Medição de Risco , Taxa de Sobrevida , Resultado do Tratamento
20.
Pediatr Pulmonol ; 54(5): 644-654, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30775857

RESUMO

BACKGROUND: Nasal continuous-positive airway pressure (nCPAP) with the INSURE (INtubation-SURfactant-Extubation) or LISA (Less-Invasive Surfactant Administration) procedures are increasingly being chosen as the initial treatment for neonates with surfactant deficiency. Our objective was to compare the effects on cerebral oxygenation of different methods for surfactant administration: INSURE and LISA, using a nasogastric tube (NT) or a LISAcath® catheter, in spontaneously breathing SF-deficient newborn piglets. METHODS: Eighteen newborn piglets with SF-deficient lung injury produced by repetitive bronchoalveolar lavages were randomly assigned to INSURE, LISA-NT, or LISAcath® groups. We assessed pulmonary (gas exchange, lung mechanics, lung histology) and hemodynamic (mean arterial blood pressure, heart rate) changes, cerebral oxygenation (cTOI) and cerebral fractional tissue extraction (cFTOE), with near-infrared spectroscopy, carotid blood flow and brain histology. RESULTS: SF-deficient piglets developed respiratory distress (FiO2 = 1, pH <7.2, PaCO2 >70 mmHg, PaO2 <70 mmHg, Cdyn <0.5 mL/cmH2 O/kg). Rapid improvements in pulmonary status were observed in all surfactant-treated groups without hemodynamic alterations. In the INSURE group, a transient decrease in cTOI occurred during and immediately after surfactant administration, while cTOI only decreased during surfactant administration in the LISA-NT group and did not change significantly in the LISAcath® group. Brain injury scores were low in all surfactant-treated groups. CONCLUSION: In spontaneously breathing SF-deficient newborn piglets, short-lasting decreases in cerebral oxygenation are associated with surfactant administration by the INSURE method or LISA using an NT, while no cerebral oxygenation changes occurred with LISA using a LISAcath®. Notably, none of treatments studied seems to have a negative impact on the neonatal brain.


Assuntos
Encéfalo/metabolismo , Circulação Cerebrovascular , Pressão Positiva Contínua nas Vias Aéreas/métodos , Oxigênio/metabolismo , Surfactantes Pulmonares/administração & dosagem , Síndrome do Desconforto Respiratório do Recém-Nascido/terapia , Extubação , Animais , Animais Recém-Nascidos , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Lavagem Broncoalveolar , Artéria Carótida Primitiva/diagnóstico por imagem , Artéria Carótida Primitiva/fisiologia , Hemodinâmica , Intubação Intratraqueal , Pulmão/metabolismo , Pulmão/fisiopatologia , Lesão Pulmonar , Troca Gasosa Pulmonar , Distribuição Aleatória , Síndrome do Desconforto Respiratório do Recém-Nascido/metabolismo , Espectroscopia de Luz Próxima ao Infravermelho , Suínos
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