scholarly journals N-Acetylcysteine Advancement of Surfactant Therapy in Experimental Meconium Aspiration Syndrome: Possible Mechanisms

2014 ◽  
pp. S629-S642 ◽  
Author(s):  
J. KOPINCOVÁ ◽  
D. MOKRÁ ◽  
P. MIKOLKA ◽  
M. KOLOMAZNÍK ◽  
A. ČALKOVSKÁ
Keyword(s):  
Oxidative Damage ◽  
Therapeutic Effect ◽  
Neutrophil Migration ◽  
Oxygenation Index ◽  
Meconium Aspiration Syndrome ◽  
Surfactant Therapy ◽  
Total Leukocyte Count ◽  
Exogenous Surfactant ◽  
Meconium Aspiration ◽  
Respiratory Parameters

Meconium aspiration syndrome (MAS) is meconium-induced respiratory failure of newborns associated with activation of inflammatory and oxidative pathways. For severe MAS, exogenous surfactant treatment is used which improves respiratory functions but does not treat the inflammation. Oxidative process can lead to later surfactant inactivation; hence, surfactant combination with antioxidative agent may enhance the therapeutic effect. Young New Zealand rabbits were instilled by meconium suspension and treated by surfactant alone, N-acetylcysteine (NAC) alone or by their combination and oxygen-ventilated for 5 h. Blood samples were taken before and 30 min after meconium application and 30 min, 1, 3 and 5 h after the treatment for evaluating of oxidative damage, total leukocyte count, leukocyte differential count and respiratory parameters. Leukocyte differential was assessed also in bronchoalveolar lavage fluid. NAC alone had only mild therapeutic effect on MAS. However, the combination of NAC and surfactant facilitated rapid onset of therapeutic effect in respiratory parameters (oxygenation index, PaO2/FiO2) compared to surfactant alone and was the only treatment which prevented neutrophil migration into the lungs, oxidative damage and lung edema. Moreover, NAC suppressed IL-8 and IL-β formation and thus seems to be favorable agent for improving surfactant therapy in MAS.

Surfactant Therapy in Full-term Neonates With Severe Respiratory Failure

PEDIATRICS ◽  
1993 ◽  
Vol 92 (1) ◽  
pp. 135-139
Author(s):  
Hatem Khammash ◽  
Max Perlman ◽  
Julian Wojtulewicz ◽  
Michael Dunn
Keyword(s):  
Respiratory Failure ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Distress Syndrome ◽  
Oxygenation Index ◽  
Meconium Aspiration Syndrome ◽  
Full Term ◽  
Surfactant Therapy ◽  
Term Infants ◽  
Meconium Aspiration

Objective. In light of the paucity of published data on the use of surfactant in full-term infants with respiratory failure due to meconium aspiration syndrome and respiratory distress syndrome, we report our experience with this therapy. Our goal was to explore possible justification for randomized controlled trials of surfactant treatment in similar patients at an earlier, less severe stage of the disease. Methods. Retrospective consecutive case series of 20 infants with severe meconium aspiration syndrome and 29 infants with severe respiratory distress syndrome who received bovine surfactant between March 1990 and December 1992 in three neonatal intensive care units in a regionalized setting. Outcome of treatment was assessed by comparing changes in several respiratory indices including the oxygenation index, between 4 and 6 hours and 1 and 3 hours before and after the first dose of surfactant. Differences were analyzed using analysis of variance for repeated measures, with treatment and time as co-variates. Results. In the meconium aspiration group the mean oxygenation index decreased from 36 ± 12 at 1 to 3 hours presurfactant to 24 ± 14 at 1 to 3 hours postsurfactant (P < .001). In the patients with respiratory distress syndrome the mean oxygenation index fell from 30 ± 17 at 1 to 3 hours presurfactant to 12 ± 6 at 1 to 3 hours postsurfactant (P = .0001). Three of 20 patients with meconium aspiration syndrome and 3 of 29 patients with respiratory distress syndrome received extracorporeal membrane oxygenation. Conclusions. Surfactant therapy in full-term infants with respiratory failure due to the meconium aspiration and respiratory distress syndromes is often effective in improving gas exchange. A randomized controlled trial of surfactant therapy at an earlier stage in the course of the illness should be performed.

scholarly journals Lung Inflammatory and Oxidative Alterations After Exogenous Surfactant Therapy Fortified With Budesonide in Rabbit Model of Meconium Aspiration Syndrome

2016 ◽  
pp. S653-S662 ◽  
Author(s):  
P. MIKOLKA ◽  
J. KOPINCOVÁ ◽  
P. KOŠÚTOVÁ ◽  
D. ČIERNY ◽  
A. ČALKOVSKÁ ◽  
...  
Keyword(s):  
Oxidative Damage ◽  
Expression Profiles ◽  
Rabbit Model ◽  
Weight Ratio ◽  
Meconium Aspiration Syndrome ◽  
Exogenous Surfactant ◽  
Lung Edema ◽  
Edema Formation ◽  
Meconium Aspiration ◽  
Cell Counts

Meconium aspiration syndrome (MAS) triggers inflammatory and oxidative pathways which can inactivate both pulmonary surfactant and therapeutically given exogenous surfactant. Glucocorticoid budesonide added to exogenous surfactant can inhibit inflammation and thereby enhance treatment efficacy. Neonatal meconium (25 mg/ml, 4 ml/kg) was administered intratracheally (i.t.) to rabbits. When the MAS model was prepared, animals were treated with budesonide i.t. (Pulmicort, 0.25 mg/kg, M+B); with surfactant lung lavage (Curosurf®, 10 ml/kg, 5 mg phospholipids/ml, M+S) followed by undiluted Curosurf® i.t. (100 mg phospholipids/kg); with combination of budesonide and surfactant (M+S+B); or were untreated (M); or served as controls with saline i.t. instead of meconium (C). Animals were oxygen-ventilated for additional 5 h. Cell counts in the blood and bronchoalveolar lavage fluid (BAL), lung edema formation (wet/dry weight ratio), oxidative damage of lipids/ proteins and inflammatory expression profiles (IL-2, IL-6, IL-13, TNF-α) in the lung homogenate and plasma were determined. Combined surfactant+budesonide therapy was the most effective in reduction of neutrophil counts in BAL, oxidative damage, levels and mRNA expression of cytokines in the lung, and lung edema formation compared to untreated animals. Curosurf fortified with budesonide mitigated lung inflammation and oxidative modifications what indicate the perspectives of this treatment combination for MAS therapy.

scholarly journals Recombinant Human Superoxide Dismutase and N-Acetylcysteine Addition to Exogenous Surfactant in the Treatment of Meconium Aspiration Syndrome

Molecules ◽  
2019 ◽  
Vol 24 (5) ◽  
pp. 905 ◽  
Author(s):  
Jana Kopincova ◽  
Maros Kolomaznik ◽  
Pavol Mikolka ◽  
Petra Kosutova ◽  
Juliana Topercerova ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Efficiency Index ◽  
Meconium Aspiration Syndrome ◽  
Mitogen Activated Protein Kinase ◽  
Exogenous Surfactant ◽  
Duration Of Treatment ◽  
Pulmonary Tissue ◽  
Meconium Aspiration ◽  
Oxidative Markers ◽  
Mitogen Activated Protein

This study aimed to evaluate the molecular background of N-acetylcysteine (NAC) and recombinant human superoxide dismutase (rhSOD) antioxidant action when combined with exogenous surfactant in the treatment of meconium aspiration syndrome (MAS), considering redox signalling a principal part of cell response to meconium. Young New Zealand rabbits were instilled with meconium suspension (Mec) and treated by surfactant alone (Surf) or surfactant in combination with i.v. NAC (Surf + NAC) or i.t. rhSOD (Surf + SOD), and oxygen-ventilated for 5 h. Dynamic lung-thorax compliance, mean airway pressure, PaO2/FiO2 and ventilation efficiency index were evaluated every hour; post mortem, inflammatory and oxidative markers (advanced oxidation protein products, total antioxidant capacity, hydroxynonenal (HNE), p38 mitogen activated protein kinase, caspase 3, thromboxane, endothelin-1 and secretory phospholipase A2) were assessed in pulmonary tissue homogenates. rhSOD addition to surfactant improved significantly, but transiently, gas exchange and reduced levels of inflammatory and oxidative molecules with higher impact; Surf + NAC had stronger effect only on HNE formation, and duration of treatment efficacy in respiratory parameters. In both antioxidants, it seems that targeting reactive oxygen species may be strong supporting factor in surfactant treatment of MAS due to redox sensitivity of many intracellular pathways triggered by meconium.

POLYETHYLENE GLYCOL ADDITION DOES NOT IMPROVE EXOGENOUS SURFACTANT FUNCTION IN AN EXPERIMENTAL MODEL OF MECONIUM ASPIRATION SYNDROME

2009 ◽  
Vol 35 (1) ◽  
pp. 76-88 ◽  
Author(s):  
Joao Cesar Lyra ◽  
Renata Suman Mascaretti ◽  
Alexander Roberto Precioso ◽  
Luciana Branco Haddad ◽  
Thais Mauad ◽  
...  
Keyword(s):  
Polyethylene Glycol ◽  
Experimental Model ◽  
Meconium Aspiration Syndrome ◽  
Exogenous Surfactant ◽  
Meconium Aspiration

Surfactant Therapy In Neonates With Respiratory Deterioration Due to Pulmonary Hemorrhage

PEDIATRICS ◽  
1995 ◽  
Vol 95 (1) ◽  
pp. 32-36
Author(s):  
Paresh B. Pandit ◽  
Michael S. Dunn ◽  
Enza A. Colucci
Keyword(s):  
Repeated Measures ◽  
Neonatal Intensive Care ◽  
Controlled Trial ◽  
Case Series ◽  
Pulmonary Hemorrhage ◽  
Oxygenation Index ◽  
Surfactant Therapy ◽  
Exogenous Surfactant ◽  
Retrospective Case ◽  
Clinically Significant

Objective. To study the effect of exogenous bovine surfactant on oxygen and ventilatory requirements in neonates with respiratory deterioration due to pulmonary hemorrhage. Design. Retrospective case series. Setting. Three regional neonatal intensive care units. Methods. Infants who received surfactant following a clinically significant pulmonary hemorrhage during the time period July 1991 to December 1993 were identified from a database. Infants were excluded if any other cause was found to explain their deterioration. The primary outcome was change in respiratory status following surfactant therapy, as reflected by oxygenation index (OI) and arterial/Alveolar oxygen ratio. Data points were taken as averages of 3 through 6 hours and 0 through 3 hours for the 6 hours before and after surfactant. Differences were analyzed using analysis of variance for repeated measures, with treatment and time as co-variates. Results. Fifteen patients fulfilled inclusion criteria. Median values (range): birth weight, 960 g (595 to 4045); age at pulmonary hemorrhage, 24.4 hours (0.3 to 62); and interval between pulmonary hemorrhage and surfactant therapy, 10 hours (3.7 to 46.5). Mean OI improved from 24.6, at 0 to 3 hours presurfactant, to 8.6 at 3 to 6 hours postsurfactant (P .001). No patient deteriorated following surfactant therapy. The primary respiratory diagnosis was respiratory distress syndrome (RDS) in 8, meconium aspiration syndrome in 3, and isolated pulmonary hemorrhage in 4. All those with RDS had also received surfactant before their pulmonary hemorrhage. Conclusions. Exogenous surfactant appears to be useful adjunctive therapy in neonates with a clinically significant pulmonary hemorrhage. Its use for this indication should be further investigated by a randomized controlled trial.

Modified Protocols for Surfactant Therapy in Experimental Meconium Aspiration Syndrome

Neonatology ◽  
2003 ◽  
Vol 83 (1) ◽  
pp. 49-56 ◽  
Author(s):  
Katsumi Tashiro ◽  
Xiao-Guang Cui ◽  
Tsutomu Kobayashi ◽  
Tore Curstedt ◽  
Bengt Robertson
Keyword(s):  
Meconium Aspiration Syndrome ◽  
Surfactant Therapy ◽  
Meconium Aspiration

Surfactant therapy for meconium aspiration syndrome in neonates: a systematic overview of systematic reviews and recent clinical trials

2020 ◽  
Vol 9 (8) ◽  
pp. 527-536
Author(s):  
Mohammed Ahmed Abdelaal ◽  
Dina Abushanab ◽  
Daoud Al-Badriyeh
Keyword(s):  
Clinical Trials ◽  
Systematic Reviews ◽  
Lung Lavage ◽  
Meconium Aspiration Syndrome ◽  
Risk Of Bias ◽  
Surfactant Therapy ◽  
High Quality ◽  
Meconium Aspiration ◽  
Systematic Overview ◽  
Overview Of Systematic Reviews

Aim: To conduct a systematic overview of systematic reviews (SRs) and randomized clinical trials (RCTs) on surfactant therapy in neonatal meconium aspiration syndrome. Methods: We searched EMBASE, PROQUEST and PubMed to summarize the different effects of surfactant lung lavage and bolus surfactant therapies in neonates with meconium aspiration syndrome. Results: With a total of 1377 patients, three SRs and two RCTs were included in analysis. Surfactant effectiveness was concluded by low-quality SRs, with high risk of bias, which was contradicted by high-quality SRs, with low risk of bias. In SRs, the surfactant lung lavage reduced mortality, need for extracorporeal membrane oxygenation and hospitalization, while the bolus surfactant did not. In recent high-quality RCTs, however, the two modalities did not significantly differ. Conclusion: The evidence on surfactant effectiveness and its method of administration is sparse and inconsistent.

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