pulmicort and Meconium-Aspiration-Syndrome

To study the clinical spectrum of Meconium aspiration syndrome babies and to find out the efficacy of early nebulized steroids (Budesonide) in the clinical course and outcome (morbidity and mortality) of neonates with meconium aspiration: randomized controlled trial.. A total of 78 neonates were included in the study. After randomization, intervention group received nebulization with Budesonide (0.5 mg dissolved in 2.5-ml sterile normal saline within 2 h of birth and second dose was given at 12 h of birth) whereas controls were nebulized with normal saline. All neonates were accessed for serial respiratory distress score (Downe's score), requirement (dependence) of oxygen (in days), duration of neonatal intensive-care unit (NICU) stay, any complication and their final outcome.. The mean days of oxygen requirement for the cases and controls were 1.79 and 3.46, respectively (p < 0.001). The mean respiratory rate in intervention group up to the age of 5 d was significantly less (p value < 0.01). There was significant difference in mean Downe's score and mean duration of NICU stay in intervention group.. Budesonide nebulization in meconium aspiration results in significant early improvement in general condition (early improvement in respiratory distress and early normalization of Downe's score) of the newborn with lesser oxygen requirement, thus early discharge from NICU but has no impact on final outcome.

Topics: Administration, Inhalation; Budesonide; Female; Glucocorticoids; Humans; Infant, Newborn; Male; Meconium Aspiration Syndrome; Respiratory Function Tests

Meconium Aspiration Syndrome (MAS) is an important cause of neonatal morbidity and mortality. The present study was undertaken to evaluate the role of steroids in the management of MAS. This was a double blinded randomized controlled trial and a prospective Interventional Study over one-year period in the neonatal unit of the Lady Hardinge Medical College and associated Kalawati Saran Children's hospital. Fifty-one babies of MAS which were randomly distributed into three groups, Control, systemic and nebulized steroids. Methyl prednisolone was given i.v. in dose of 0.5 mg/kg/day in two divided doses. Budecort was given by nebulization in dose of 50 microgram 12 hourly. Infants were assessed in terms of duration of stay, oxygen dependence, X-ray clearances and also assessed for short term adverse effects. There was a statistically significant difference in the duration of stay, duration of oxygen dependence and radiological clearance. The use of steroids was not associated with an increased incidence of sepsis. The conclusion is that steroids alter the course of Meconium Aspiration Syndrome and favorably affect the outcome.

Topics: Analysis of Variance; Budesonide; Double-Blind Method; Female; Glucocorticoids; Humans; India; Infant, Newborn; Injections, Intravenous; Male; Meconium Aspiration Syndrome; Methylprednisolone; Nebulizers and Vaporizers; Prospective Studies; Statistics, Nonparametric; Treatment Outcome

Meconium aspiration syndrome (MAS) is one of the major causes of severe respiratory distress in the newborn and there is no uniform protocol of management after the development of MAS.. The objective of the study was to determine whether systemic and inhalational steroid therapy can alter the clinical course of MAS and improve the outcome without causing any serious adverse effects.. A randomized controlled trial was conducted in three groups of MAS over a period of 1 year. Group A (n = 33) served as controls, Group B (n = 34) received systemic methyl prednisolone and Group C (n = 32) received nebulized budesonide both for a period of 7 days starting after 24 h of age. Details of clinical progress were noted during the hospital stay. Follow up for a minimum period of 3 months was done in all. Data were analysed by SPSS 10 software. Student's t and ANOVA were used to assess statistical significance.. Patient profile was similar in all the three groups. Period of oxygen dependency and duration of hospital stay was significantly less in the steroid treated groups. Similarly full enteral feeding and radiological clearance of chest could be achieved earlier in groups B and C. No difference between the steroid treated groups could be appreciated by Student's Newman Kuel (SNK) test. Development of sepsis was similar in all the groups and no serious adverse effects were noted in steroid treated groups.. Steroids are effective in the management of MAS and route of administration does not have a bearing on the efficacy.

Topics: Administration, Inhalation; Analysis of Variance; Anti-Inflammatory Agents; Budesonide; Female; Humans; Infant, Newborn; Male; Meconium Aspiration Syndrome; Methylprednisolone; Pneumonia, Aspiration; Respiratory Distress Syndrome, Newborn

Severe inflammation plays a vital role in the pathogenesis of meconium aspiration syndrome (MAS). Intratracheal (IT) instillation of corticosteroids may be beneficial for MAS in optimizing local effect and reducing systemic adverse effects, but the optimum dosing course remains open to question.. Thirty meconium-injured newborn piglets were enrolled into six study groups. The first four groups consisted of the IT instillation of 0.25/0.5 mg/kg using either one (IT-B251/IT-B501) or two (IT-B252/IT-B502) doses of budesonide, while the other two groups were the intravenous (IV) dexamethasone (0.5 mg/kg) (IV-Dex) group and the control group (Ctrl). Vital signs and cardiopulmonary functions were monitored throughout the experiments. Pulmonary histology was examined after completing the experiments.. Both the IV-Dex and IT-B501 groups got significant improvement in oxygenation (P < 0.05). Lung compliance became worse after one dose of 0.25 mg/kg of IT budesonide. Pulmonary histology revealed that there were significantly lower lung injury scores for all treatment groups compared to control group, especially at the non-dependent sites of both the IT-B501 and IT-B502 groups. There was no significant difference between double- and single-dose groups, no matter whether 0.25 or 0.5 mg/kg of budesonide was used.. IT instillation of one dose of 0.5 mg/kg budesonide is beneficial in treating meconium-injured piglet lungs during the first 8 h of injury, but a second dose at an interval of 4 h does not have a superior beneficial effect compared to one dose.

Topics: Administration, Inhalation; Adrenal Cortex Hormones; Animals; Animals, Newborn; Budesonide; Dexamethasone; Lung; Lung Compliance; Lung Injury; Male; Meconium Aspiration Syndrome; Swine

Meconium aspiration syndrome (MAS) is a serious condition, which can be treated with exogenous surfactant and mechanical ventilation. However, meconium-induced inflammation, lung edema and oxidative damage may inactivate delivered surfactant and thereby reduce effectiveness of the therapy. As we presumed that addition of anti-inflammatory agent into the surfactant may alleviate inflammation and enhance efficiency of the therapy, this study was performed to evaluate effects of surfactant therapy enriched with budesonide versus surfactant-only therapy on markers of oxidative stress in experimental model of MAS. Meconium suspension (25 mg/ml, 4 ml/kg) was instilled into the trachea of young rabbits, whereas one group of animals received saline instead of meconium (C group, n = 6). In meconium-instilled animals, respiratory failure developed within 30 min. Then, meconium-instilled animals were divided into 3 groups according to therapy (n = 6 each): with surfactant therapy (M + S group), with surfactant + budesonide therapy (M + S + B), and without therapy (M group). Surfactant therapy consisted of two bronchoalveolar lavages (BAL) with diluted surfactant (Curosurf, 5 mg phospholipids/ml, 10 ml/kg) followed by undiluted surfactant (100 mg phospholipids/kg), which was in M + S + B group enriched with budesonide (Pulmicort, 0.5 mg/ml). Animals were oxygen-ventilated for additional 5 hours. At the end of experiment, blood sample was taken for differential white blood cell (WBC) count. After euthanizing animals, left lung was saline-lavaged and cell differential in BAL was determined. Oxidative damage, i.e. oxidation of lipids (thiobarbituric acid reactive substance (TBARS) and conjugated dienes) and proteins (dityrosine and lysine-lipoperoxidation products) was estimated in lung homogenate and isolated mitochondria. Total antioxidant capacity was evaluated in lung homogenate and plasma. Meconium instillation increased transmigration of neutrophils and production of free radicals compared to controls (P < 0.05). Surfactant therapy, but particularly combined surfactant + budesonide therapy reduced markers of oxidative stress versus untreated animals (P < 0.05). In conclusion, budesonide added into surfactant enhanced effect of therapy on oxidative damage of the lung.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Bronchoalveolar Lavage Fluid; Budesonide; Disease Models, Animal; Female; Free Radicals; Inflammation; Lung; Lung Injury; Male; Meconium; Meconium Aspiration Syndrome; Neutrophils; Oxidative Stress; Pulmonary Edema; Pulmonary Surfactants; Rabbits; Trachea

To evaluate the combined effects of surfactant lavage and intratracheally instillation of budesonide on meconium-injured piglet lungs.. A prospective, randomized, animal model study.. An experimental laboratory.. Twenty-four anesthetized and mechanically ventilated newborn piglets.. Human meconium slurry was intratracheally instilled into piglet lungs to induce lung injury. The injured piglets were randomly assigned to either the sham treatment group (control) or one of the three therapeutic groups: the intratracheally instilled budesonide (Bud) group, the bronchoalveolar lavage with diluted surfactant (dsBAL) group, and the combination therapy of Bud and dsBAL (dsBAL + Bud) group.. Cardiopulmonary profiles were measured hourly. Proinflammatory cytokine (interleukin-1β, interleukin-6, and interleukin-8) levels in bronchoalveolar lavage fluid were measured. Finally, the pulmonary histology of the experimental subjects was examined at the end of experiments. Both of the lavaged groups (dsBAL and dsBAL + Bud) showed significantly better oxygenation than those that had not undergone lavage (control and Bud) (p < 0.05). The dsBAL + Bud group showed a significantly higher lung compliance and required a significantly lower peak inspiratory pressure during the experimental periods than the other three groups (p < 0.05). All treatment groups had significantly lower concentrations of interleukin-1β concentration in the bronchoalveolar lavage fluid than the control group (p < 0.05). The dsBAL + Bud group also had a significantly lower interleukin-6 concentration in the bronchoalveolar lavage fluid (p< 0.05), as well as a significantly lower lung injury score based on pulmonary histology than the control group (p < 0.05).. Therapeutic bronchoalveolar lavage with diluted surfactant followed by intratracheal instillation of budesonide has a synergistic and beneficial effect when treating severe meconium-injured newborn piglet lungs.

Topics: Animals; Anti-Inflammatory Agents; Biomarkers; Bronchoalveolar Lavage; Bronchoalveolar Lavage Fluid; Budesonide; Combined Modality Therapy; Cytokines; Humans; Instillation, Drug; Male; Meconium Aspiration Syndrome; Prospective Studies; Pulmonary Surfactants; Random Allocation; Respiration, Artificial; Swine; Treatment Outcome

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-alpha) 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.

Topics: Animals; Anti-Inflammatory Agents; Budesonide; Disease Models, Animal; Drug Therapy, Combination; Female; Inflammation Mediators; Lipid Peroxidation; Male; Meconium Aspiration Syndrome; Oxidative Stress; Pulmonary Surfactants; Rabbits

Severe meconium aspiration syndrome (MAS) in newborns is often treated by exogenous surfactant. Because its efficacy is reduced by meconium-induced inflammation, glucocorticoid budesonide was added into surfactant preparation Curosurf to enhance efficacy of the surfactant therapy in experimental model of MAS. Oxygen-ventilated rabbits were intratracheally given meconium (25 mg/ml, 4 ml/kg) to induce respiratory failure. Thirty minutes later, animals were treated by intratracheal budesonide (0.25 mg/kg) or surfactant lung lavage (10 ml/kg, 5 mg phospholipids/ml) repeated twice, followed by undiluted Curosurf (100 mg phospholipids/kg) or by the above mentioned surfactant treatment with the last surfactant dose fortified with budesonide (0.25 mg/kg) or were untreated. Animals were ventilated for additional 5 hours and respiratory parameters were measured regularly. After sacrificing animals, wet-dry lung weight ratio was evaluated and plasma levels of interleukins (IL)-1beta, -6, -8, and TNF-alpha were measured by ELISA method. Efficacy of the given therapies to enhance lung functions and to diminish lung edema formation and inflammation increased from budesonide-only and surfactant-only therapy to surfactant+budesonide therapy. Combined therapy improved gas exchange from 30 min of administration, and showed a longer-lasting effect than surfactant-only therapy. In conclusions, budesonide additionally improved the effects of exogenous surfactant in experimental MAS.

Topics: Animals; Anti-Inflammatory Agents; Biological Products; Bronchodilator Agents; Budesonide; Drug Combinations; Drug Synergism; Female; Immunologic Factors; Male; Meconium Aspiration Syndrome; Phospholipids; Pulmonary Surfactants; Rabbits; Respiratory Mechanics; Swine; Treatment Outcome

Inflammation, oxidation, lung edema, and other factors participate in surfactant dysfunction in meconium aspiration syndrome (MAS). Therefore, we hypothesized that anti-inflammatory treatment may reverse surfactant dysfunction in the MAS model. Oxygen-ventilated rabbits were given meconium intratracheally (25 mg/ml, 4 ml/kg; Mec) or saline (Sal). Thirty minutes later, meconium-instilled animals were treated by glucocorticoids budesonide (0.25 mg/kg, i.t.) and dexamethasone (0.5 mg/kg, i.v.), or phosphodiesterase inhibitors aminophylline (2 mg/kg, i.v.) and olprinone (0.2 mg/kg, i.v.), or the antioxidant N-acetylcysteine (10 mg/kg, i.v.). Healthy, non-ventilated animals served as controls (Con). At the end of experiments, left lung was lavaged and a differential leukocyte count in sediment was estimated. The supernatant of lavage fluid was adjusted to a concentration of 0.5 mg phospholipids/ml. Surfactant quality was evaluated by capillary surfactometer and expressed by initial pressure and the time of capillary patency. The right lung was used to determine lung edema by wet/dry (W/D) weight ratio. Total antioxidant status (TAS) in blood plasma was evaluated. W/D ratio increased and capillary patency time shortened significantly, whereas the initial pressure increased and TAS decreased insignificantly in Sal vs. Con groups. Meconium instillation potentiated edema formation and neutrophil influx into the lungs, reduced capillary patency and TAS, and decreased the surfactant quality compared with both Sal and Con groups (p > 0.05). Each of the anti-inflammatory agents reduced lung edema and neutrophil influx into the lung and partly reversed surfactant dysfunction in the MAS model, with a superior effect observed after glucocorticoids and the antioxidant N-acetylcysteine.

Topics: Acetylcysteine; Acute Lung Injury; Aminophylline; Animals; Anti-Inflammatory Agents; Antioxidants; Bronchoalveolar Lavage Fluid; Budesonide; Dexamethasone; Disease Models, Animal; Humans; Imidazoles; Infant, Newborn; Leukocyte Count; Lung; Meconium; Meconium Aspiration Syndrome; Neutrophils; Oxidative Stress; Phosphodiesterase Inhibitors; Pulmonary Edema; Pulmonary Surfactants; Pyridones; Rabbits

Combination of low-dose budesonide and low-dose aminophylline may improve lung function in reduced adverse effects compared with high-dose monotherapy. Adult rabbits intratracheally received 4 ml/kg of saline or meconium (25 mg/ml). Meconium-injured rabbits were treated at 0.5 and 2.5 h after meconium instillation by intravenous aminophylline (1.0 mg/kg), by intratracheal budesonide (0.125 mg/kg) followed by intravenous aminophylline (1.0 mg/kg), or were untreated. Although aminophylline improved some respiratory parameters, budesonide+aminophylline more effectively reduced intrapulmonary shunts and improved gas exchange, without significant cardiovascular effects. Combined treatment reduced lung edema and number of lung neutrophils to a higher extent than aminophylline alone. Both treatments reduced lung peroxidation and in vitro airway reactivity to histamine, with a better effect after aminophylline alone. Combination of budesonide and aminophylline enhanced respiratory parameters more effectively, having fewer side effects than aminophylline alone. However, no additive effect of budesonide was observed on lung peroxidation and in vitro airway reactivity.

Topics: Aminophylline; Animals; Animals, Newborn; Blood Pressure; Bronchodilator Agents; Budesonide; Humans; Immunoassay; Infant, Newborn; Injections, Intravenous; Leukocyte Count; Lipid Peroxidation; Lung Diseases; Meconium Aspiration Syndrome; Neutrophil Infiltration; Oxygen; Rabbits; Respiratory Function Tests; Thiobarbituric Acid Reactive Substances; Trachea

Local administration of corticosteroids may diminish acute lung injury associated with meconium aspiration. Budesonide was given intratracheally in 2 doses of 0.25 mg/kg each by means of inpulsion effect of high-frequency jet ventilation 0.5 and 2.5 hours after meconium instillation to oxygen-ventilated adult rabbits. Within 5 hours after the first dose, budesonide significantly improved gas exchange and decreased right-to-left pulmonary shunts, central venous pressure, and ventilatory pressures. In addition, budesonide reduced the meconium-induced lung edema formation, airway hyperreactivity to histamine, count of neutrophils in bronchoalveolar lavage fluid associated with higher total white blood cell and neutrophil counts in the blood, and diminished oxidative modifications of proteins and lipids in lung tissue compared to non-treated meconium-instilled group. The intratracheally administered corticosteroid budesonide effectively improved pulmonary functions and alleviated changes associated with inflammation in meconium-instilled rabbits.

Topics: Adrenal Cortex Hormones; Animals; Bronchial Provocation Tests; Bronchoconstriction; Bronchoconstrictor Agents; Budesonide; Central Venous Pressure; Disease Models, Animal; Histamine; Humans; Infant, Newborn; Intubation, Intratracheal; Lipid Peroxidation; Lung; Meconium Aspiration Syndrome; Neutrophil Infiltration; Oxidative Stress; Pneumonia, Aspiration; Protein Carbonylation; Pulmonary Circulation; Pulmonary Edema; Pulmonary Gas Exchange; Pulmonary Ventilation; Rabbits; Respiratory System Agents

Meconium aspiration causes intensive inflammatory reactions in the lungs, and may lead to neonatal respiratory disorder. Infiltrated inflammatory cells, particularly macrophages, play an important role in such an inflammation. A rat alveolar macrophage cell line (ATCC8383) was exposed to meconium alone or in combination with dexamethasone, budesonide, or interferon-gamma. Nitric oxide (NO) accumulation in the supernatant of the cell culture was detected by Griess reaction, and mRNA of inducible NO synthase (iNOS) expression was detected by reverse transcriptase-PCR. Nuclear factor-kappa B was analyzed by electrophoretic mobility shift assay, and iNOS location and nuclear factor-kappa B transactivation were determined by immunostaining. Our results showed that meconium was capable of inducing production of NO and expression of iNOS in alveolar macrophages in a dose- (1-25 mg/mL, p < 0.05) and time- (4-48 h, p < 0.05) dependent manner. This capability of meconium could be further enhanced in the presence of interferon-gamma (100 IU/mL, p < 0.05). Budesonide (10(-4)-10(-10) M) or dexamethasone (10(-4)-10(-6) M) effectively inhibited the meconium-induced NO production (p < 0.05). Using the protein synthesis inhibitor cycloheximide, we demonstrated that meconium directly induced iNOS in macrophages. Furthermore, meconium also triggered nuclear factor-kappa B activation, a mechanism possibly responsible for the iNOS expression. Our findings suggest that meconium is a potent inflammatory stimulus, resulting in iNOS expression, leading to overproduction of NO from the macrophages, which may be of pathogenic importance in meconium aspiration syndrome. In vitro steroids down-regulated the iNOS expression, thus suggesting a potential to down-regulate NO-mediated inflammation in neonates with meconium aspiration syndrome.

Topics: Animals; Anti-Inflammatory Agents; Base Sequence; Budesonide; Cell Line; Dexamethasone; DNA Primers; Gene Expression; Glucocorticoids; Humans; Infant, Newborn; Macrophages, Alveolar; Meconium; Meconium Aspiration Syndrome; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Rats; RNA, Messenger