Hydrocortisone therapy in meconium aspiration syndrome: a controlled study. The Collaborative Randomised Amnioinfusion for Meconium Project (CRAMP): 1. South Africa. Effect of steroid therapy on exercise performance in patients with irreversible chronic obstructive pulmonary disease. Treatment of severe meconium aspiration syndrome with porcine surfactant: a multicentre, randomized, controlled trial. The role of pulmonary inflammation in the development of pulmonary hypertension in newborn with meconium aspiration syndrome (MAS). Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. Efficacy of sequential early systemic and inhaled corticosteroid therapy in the prevention of chronic lung disease of prematurity. High-dose inhaled steroids in asthmatics: moderate efficacy gain and suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Research Council of the Norwegian Thoracic Society. Predictive value and utility of oral steroid testing for treatment of COPD in primary care: the COOPT study.
To evaluate the efficacy of glucocorticoids in the treatment of infants with meconium aspiration syndrome, a double-blind study using hydrocortisone or a lactose placebo was undertaken. Thirty-five infants were included in the study. No significant differences in arterial Po2, Pco2, pH, A-aDo2 gradients, in requirement for assisted ventilation, or in survival were domonstrated between the groups. In control infants, a significant decrease (p less than 0.01) in respiratory distress score was found at 48 to 72 hours of age; in treated infants, it was seen only after 72 hours. The infants in the treated group took a significantly longer (p less than 0.01) period of time to wean to room air than those in the control group (68.9 +/- 9.6 hours vs 36.6 +/- 6.9 hours). On the basis of these observations, hydrocortisone is not recommended for treatment of MAS. To evaluate transcervical amnioinfusion for meconium stained amniotic fluid during labout.
                Multicentre randomised controlled trial.
                Four urban academic hospitals in South Africa. Obstetric surveillance included the use of electronic fetal heart rate monitoring in most cases.
                Women in labour at term with moderate or thick meconium staining of the amniotic fluid.
                Transcervical amnioinfusion of 800 mL saline at 15 mL per minute, followed by a maintenance infusion at 3 mL per minute. The control group received routine care. Blinding of the intervention was not possible.
                Caesarean section, meconium aspiration syndrome and perinatal mortality.
                Caesarean section rates were similar (amnioinfusion group 70/167 vs control group 68/159; RR 0.98, 95% CI 0.76-1.26). The incidence of meconium aspiration syndrome was lower than expected on the basis of previous studies (4/162 vs 6/163; RR 0.67, 95% CI 0.19-2.33). There were no perinatal deaths. There were no significant differences between any of the subsidiary outcomes.
                This study concurred with three previous trials which found no effect of amnioinfusion for meconium-stained amniotic fluid on caesarean section rate, though the pooled data from all identified trials to date show a significant reduction. The findings with respect to meconium aspiration syndrome were inconclusive in this study alone because of the small number of babies affected, but the point estimate of the relative risk was consistent with the finding of a significant reduction in previous studies and with the Zimbabwe arm (CRAMP 2) of this study. Pooled data clearly support the use of amnioinfusion for meconium stained amniotic fluid to reduce the incidence of meconium aspiration syndrome. Many patients with irreversible chronic obstructive pulmonary disease (COPD) claim symptomatic improvement with steroid therapy, despite a lack of objective improvement in their spirometric data. To determine if steroids actually increase the exercise capacity of these individuals, 13 clinically stable patients (mean age, 63 +/- 4 years; 12 male patients) were given methylprednisolone (32 mg once daily) or placebo in a randomized double-blind crossover fashion. Spirometric data and minute ventilation, oxygen consumption (VO2), carbon dioxide production, and heart rate during incremental exercise were measured at each visit. Methylprednisolone did not produce a significant change in any of the measured parameters. Three patients had an increase in maximal VO2 of greater than 2 ml/kg/min during therapy with methylprednisolone, while two experienced a decline in maximal VO2 of similar magnitude. The change in exercise capacity was unrelated to the change in the forced expiratory volume in one second in individual patients (r = 0.08). We conclude that in the absence of any improvement in the usual tests of airway mechanics, steroid therapy does not improve exercise performance in patients with COPD. A randomized, controlled clinical trial was performed in 19 Chinese neonatal intensive care units to evaluate the safety and efficacy of exogenous surfactant replacement therapy for severe meconium aspiration syndrome (MAS) in term and near-term neonates.
                Sixty-one term infants with severe MAS were randomly assigned to either a surfactant or a control group within 36 h after birth. The infants in the surfactant group (n=31) received an initial dose of porcine lung-derived surfactant (Curosurf) at 200 mg/kg, and repeated doses of 200, 100 and 100 mg/kg were given at 6-12 h intervals to a maximum of four doses if oxygenation index (OI) deteriorated by >2 from baseline. The primary outcomes were a reduction of OI to less than 10 and an increase of the pre-treatment a/A PO(2) ratio of 100% over baseline 24 h after surfactant treatment. The secondary outcomes were duration of mechanical ventilation, incidence of complications and survival to discharge from hospital.
                The general demographic characteristics of the study subjects were similar. There was a trend for surfactant-treated infants to have an improvement in arterial oxygenation compared to the control group. In comparison with the control group at 24 h, the surfactant group had a lower mean OI (8.1 vs 10.9), more infants with a 100% increase of a/A PO(2) (83% vs 48%, p<0.01) over baseline, and a larger area under the curve for PaO(2)/FiO(2) over baseline (3762+/-1877 vs 2715+/-1644 mmHg(.)h, p<0.05). Repeated measures of these parameters were also in favour of the surfactant group during 24 h to 3 and 7 d compared to the baseline (p<0.05). No differences were found in mean duration of mechanical ventilation, incidence of major complications and number of survivors between the two groups.
                Surfactant replacement therapy improved oxygenation in the study subjects, suggesting that surfactant may have a role in the treatment of severe MAS in term and near-term infants. 1. There was no clear correlation between the tracheal aspirate cytokines and the elevation of pulmonary arterial pressure in newborn piglets with MAS. The use of dexamethasone significantly suppressed tracheal aspirate cytokines but did not significantly alter pulmonary arterial pressure. Dexamethasone significantly increased the cardiac stroke volume and blood pressure. 2. Early dexamethasone therapy (< 12 hrs) for one week in infants with MAS significantly improved pulmonary ventilation and facilitated weaning from mechanical ventilation. 3. The mechanisms for the improvement in cardiopulmonary status following early dexamethasone therapy in MAS remain unclear. An overall improvement in cardiac hemodynamics, along with a significant decrease in lung inflammation may be responsible for the improvement. To evaluate whether lung lavage with surfactant changes the duration of mechanical respiratory support or other outcomes in meconium aspiration syndrome (MAS).
                We conducted a randomized controlled trial that enrolled ventilated infants with MAS. Infants randomized to lavage received two 15-mL/kg aliquots of dilute bovine surfactant instilled into, and recovered from, the lung. Control subjects received standard care, which in both groups included high frequency ventilation, nitric oxide, and, where available, extracorporeal membrane oxygenation (ECMO).
                Sixty-six infants were randomized, with one ineligible infant excluded from analysis. Median duration of respiratory support was similar in infants who underwent lavage and control subjects (5.5 versus 6.0 days, P = .77). Requirement for high frequency ventilation and nitric oxide did not differ between the groups. Fewer infants who underwent lavage died or required ECMO: 10% (3/30) compared with 31% (11/35) in the control group (odds ratio, 0.24; 95% confidence interval, 0.060-0.97). Lavage transiently reduced oxygen saturation without substantial heart rate or blood pressure alterations. Mean airway pressure was more rapidly weaned in the lavage group after randomization.
                Lung lavage with dilute surfactant does not alter duration of respiratory support, but may reduce mortality, especially in units not offering ECMO.
                Copyright © 2011 Mosby, Inc. All rights reserved. In order to assess the efficacy of a combination of systemic and nebulized corticosteroids in reducing the incidence and severity of chronic lung disease (CLD) in very low birthweight (VLBW) infants, 60 ventilator-dependent infants < or = 1500 g were randomly assigned to receive either steroids or placebo as of 7 d. The steroid group (n = 30, GA = 25.8 +/- 1.6 weeks, BW = 731 +/- 147 g) received systemic dexamethasone for 3 d, followed by nebulized budesonide for 18 d. Control infants (n = 30, GA = 25.9 +/- 1.8 weeks, BW = 796 +/- 199 g) received systemic and inhaled saline. Steroid-treated infants required less ventilatory support between 9 and 17 d (p < 0.01), and had greater lung compliance at 10 d (p = 0.01), but not subsequently. CLD incidence at 36 weeks was 45.5% vs 56.0% in controls, and fewer steroid-treated infants required dexamethasone rescue (23.3% vs 56.7%, p = 0.017). Survival to discharge was similar (73.3% vs 83.3%), as were the durations of mechanical ventilation, supplemental oxygen use, and hospitalization. Tracheal effluent elastase/albumin ratios and serum cortisol values did not differ between groups, and no adverse effects were noted. We conclude that early dexamethasone administration was associated with improved pulmonary function, which was not sustained with nebulized budesonide. However, the steroid regimen studied reduced the need for dexamethasone rescue in infants with CLD. We wanted to evaluate the improvement in efficacy when increasing the daily dose of inhaled steroids and to compare the efficacy, safety, and tolerance of 1.6 mg beclomethasone dipropionate (BDP) with that of 2.0 mg fluticasone propionate (FP). The study was a randomized, double-blind, 3 month, multicentre study. One hundred and thirty four asthmatics currently using inhaled steroids (0.4-1.6 mg BDP or budesonide (BUD)) were stratified according to pretrial daily steroid use. Within each stratum they were randomized to either 1.6 mg BDP or 2.0 mg FP. A significant increase in the primary efficacy variables, i.e. mean morning and evening peak expiratory flow (PEF) (approximately 20 l.min-1) during the treatment period, was found for both treatments. No significant differences between the drugs were revealed for these primary or any other secondary efficacy variables (use of beta 2-agonists, symptom scores, and PEF, forced vital capacity (FVC), forced expiratory volume in one second (FEV1) recorded at the clinical visits). However, significant differences between treatments occurred regarding decrease of serum cortisol and adrenocorticotropic hormone. We conclude that, although both treatments gave statistically significant increases in efficacy parameters when compared with baseline, the increases were so small that they can be regarded as being clinically unimportant. Daily doses of BDP, 1.6 mg, and FP, 2.0 mg, had comparable effects on lung function. A suppression of the hypothalamic pituitary adrenal (HPA) axis was only found with a daily dose of 2 mg FP. The oral prednisolone test is widely used to distinguish chronic obstructive pulmonary disease (COPD) patients who might benefit from inhaled steroid treatment. Previous studies used selected patient groups that did not represent the large COPD population in primary care.
                The study included smokers and exsmokers with chronic bronchitis or COPD from primary care, who underwent prednisolone testing (30 mg for 14 days) before randomization in a three-year follow-up randomized controlled trial (COOPT Study). Spirometry was performed before and after the test. Responders and nonresponders were classified according to international criteria. Effectiveness of inhaled fluticasone relative to placebo was compared in terms of health status (Chronic Respiratory Disease Questionnaire), exacerbations, and postbronchodilator forced expiratory volume in one second (FEV(1)), using repeated measurement analysis.
                Two hundred eighty-six patients recruited from 44 primary care practices were randomized. Nine percent to 16% of the COPD population was classified as responder, depending on the international guideline criteria used. On average, responders did not reach the minimum clinically important difference in health status (0.29 points/year, P = 0.05), although a borderline significant effect of inhaled fluticasone was noted. Possible clinically relevant reductions in exacerbation rate (rate ratio 0.67) and FEV(1) decline (39 mL/year) occurred in responders, but did not reach statistical significance.
                Oral steroid testing identifies a limited proportion of COPD patients, but does not reveal any clinically relevant benefit from inhaled steroid treatment on health status. No significant effects on exacerbation rate and lung function decline occurred.
At present, there is insufficient evidence to assess the effects of steroid therapy in the management of meconium aspiration syndrome. A further large randomised controlled trial assessing potential benefits and harm would be required to determine its role.