The efficacy of ketamine in pediatric emergency department patients who present with acute severe asthma. Ketotifen for asthma in children aged 5 to 15 years: a randomized placebo-controlled trial. [Intravenous infusion of reproterol (a beta-2-mimetic agent) in the therapy of severe asthma attacks in childhood]. A comparative study of inhaled ciclesonide 160 microg/day and fluticasone propionate 176 microg/day in children with asthma. Randomised trial of intravenous salbutamol in early management of acute severe asthma in children. Effect of ketotifen on childhood asthma: a double-blind study. Efficacy of aminophylline in the treatment of acute asthma exacerbation in children. Asthma and nifedipine. Comparison of nifedipine, ketotifen and placebo in the prophylaxis of childhood extrinsic asthma. Intravenous magnesium sulfate in acute severe asthma not responding to conventional therapy.
We determine whether a continuous infusion of ketamine can decrease the severity of a moderately severe acute asthma exacerbation by a clinically significant 2 points using a 15-point Pulmonary Index scoring scale.
                A double-blinded, randomized, placebo-controlled trial was performed to evaluate patients aged 2 to 18 years who presented to a pediatric emergency department with an acute asthma exacerbation. Exclusion criteria included temperature greater than 39 degrees C (102 degrees F), focal infiltrate on radiograph, or any glucocorticoid use in the last 72 hours. Eligible patients received 3 treatments with albuterol, ipratropium bromide, and a dose of oral or parenteral glucocorticoids. If the Pulmonary Index score remained 8 to 14, enrollment proceeded. All enrolled patients received continuous nebulized albuterol at 10 mg/hour and were randomized to receive an intravenous bolus of 0.2 mg/kg of ketamine, followed by a 2-hour ketamine infusion at 0.5 mg/kg per hour or an equal-volume regimen with normal-saline placebo. A Pulmonary Index score was performed on patients at 0, 30, 60, 90, and 120 minutes.
                Sixty-eight patients were enrolled, with 33 randomized to the ketamine infusion and 35 randomized to placebo. Mean ages of patients enrolled, chronic severity of asthma, and duration of symptoms before presentation were similar between groups. At enrollment, the mean Pulmonary Index score in the placebo group was 10.3+/-1.1 versus 10.5+/-1.5 for the ketamine group (difference of means 0.2; 95% confidence interval [CI] -0.5 to 0.8). Sixty-two patients completed the entire 2-hour infusion protocol. No significant difference between groups was seen in rate of improvement in the Pulmonary Index score at completion. The mean decrease in the Pulmonary Index scores at the end of the infusion was 3.6+/-1.3 in the placebo group versus 3.2+/-2.0 in the ketamine group (difference of means 0.4; 95% CI -0.4 to 1.3). No short-term adverse effects necessitating discontinuation of the infusion or adverse behavioral impacts at 48 hours after discharge were noted.
                We conclude that ketamine given at 0.2 mg/kg followed by an infusion of 0.5 mg/kg per hour for 2 hours provided no incremental benefit to standard therapy in this cohort of children with a moderately severe asthma exacerbation. The prophylactic agent ketotifen has been studied in mild-to-moderate asthma. Various trials showed benefit from 10 to 12 weeks of therapy, but no trial in children with followup beyond 12 weeks of the drug is available.
                We studied the efficacy of ketotifen, 1 mg twice a day, orally as a prophylactic drug in children with asthma.
                The double-blind, placebo-controlled trial studied 120 asthmatic children of either sex between the ages of 5 to 15 years at a tertiary care hospital. After an observation period of 4 weeks, children were randomly assigned to receive either ketotifen, 1 mg twice a day, or placebo for 6 months. Antiasthma drugs were continued as required. Main outcome measures included average duration for regular antiasthma drugs, average symptom scores, symptom free days, peak expiratory flow rate, FEV1, and need for emergency room visits.
                Of the 120 children enrolled, 13 could not complete the trial. Thus 58 children remained in the treatment group and 49 were in the placebo group. Both groups were comparable in their baseline characteristics. The average number of days that required antiasthma drugs were significantly less in the treatment group: salbutamol (27+/-4.7 versus 37+/-3.5 P < .05), theophylline (37+/-4.7 versus 51+/-4.8 P < .05), oral steroids (2+/-0.4 versus 5+/-1.6 P < .05), and inhalation steroids (18+/-2.7 versus 16+/-10.8 P < .05). The average symptom scores and symptom free days for cough, wheeze, and breathlessness also favored the ketotifen group. Emergency room visits were also significantly lower in the ketotifen group (20 versus 10 P < .05). Statistically significant improvement in all the above parameters were observed after 14 weeks of therapy. The mean PEFR, FEV1 and side effects of medications were comparable between the two groups.
                Ketotifen, 1 mg twice a day, is an effective prophylaxis for asthma in children between 5 to 15 years. Significant clinical improvement is evident after 14 weeks of therapy. 20 children (age range 0.8-14.7 years) with acute severe asthma were alternately randomized to receive one of two different treatment regimes. 10 children (control-group) received Salbutamol inhalation (75 micrograms/kg in 2 ml Saline every two hours). 10 children (reproterol-group) received reproterol infusion (0.2-2.0 micrograms/kg/min in Saline) and inhaled Saline only. Other therapy regimen were identical in both groups: Theophylline infusion, i.v. Prednisolone, adequate fluids intake and oxygen insufflation. Age, severity and maintenance therapy of asthma, and severity of the acute episode, were not significantly different in both groups. Treatment efficacy, assessed with a simple clinical score, the heart and respiratory rates, the peak expiratory flow (PEF) and the blood gases, was comparable in both groups. Side effects, i.e. tachycardia, blood pressure changes and tremor, were also similar and clinically not relevant in both groups. In two children, who previously needed repeated mechanical ventilation, severe respiratory failure could be successfully controlled only when the reproterol dose was raised 10 folds (2.0 micrograms/kg/min). Reproterol infusion can be recommended in children with acute severe asthma, who do not respond satisfactorily to current therapy regimen, particularly in children who previously experienced numerous intubations. Ciclesonide (CIC) is an inhaled corticosteroid (ICS) with high anti-inflammatory activity and low incidence of local and systemic adverse effects. The objective of this study was to compare the efficacy and safety of CIC with fluticasone propionate (FP) in children and adolescents with persistent asthma. This was a 12-week, randomized, double blind, parallel-group study. After a 2-to 4-week baseline period, a total of 556 children (ages 6-15 years) with asthma (forced expiratory volume in 1 sec [FEV(1)], 50% to 90% predicted) were treated twice daily with CIC 80 microg (ex-actuator, equivalent to 100 microg ex-valve) or FP 88 microg (ex-actuator, equivalent to 100 microg ex-valve) administered via a hydrofluoroalkane-propelled metered-dose inhaler. A statistically significant increase from baseline was observed in FEV(1) for both CIC (285 +/- 16 ml) and FP (285 +/- 15 ml) (P < 0.0001 for both) and in morning and evening peak expiratory flow (P < 0.0001 for both). Significant improvements were seen in asthma symptoms, use of rescue medication, and asthma symptom-free days in both treatment groups, without any differences between the treatment groups in changes from baseline. Two FP-treated patients experienced oral candidiasis and one patient experienced voice alteration. Creatinine-adjusted 24-hr urine cortisol levels increased from baseline levels by 10% in the CIC group (P < 0.05) and by 6% in the FP group (not significant). The efficacy and safety of CIC 160 microg/day were comparable to those of FP 176 microg/day in children with asthma.
                (c) 2006 Wiley-Liss, Inc. The mainstay of treatment for acute asthma in children is nebulised beta 2-adrenergic agents such as salbutamol, given with corticosteroids. However, penetration of the drug to the small airways is impeded by obstruction so intravenous salbutamol may be more effective. We assessed the use of intravenous salbutamol in the management of children with acute severe asthma in a double-blind randomised study.
                Children who presented to the Emergency Department of Westmead Hospital, Sydney, Australia with asthma were assessed with a clinical assessment scale, and those with severe acute asthma were given nebulised salbutamol at a dose of 2.5 mg (age < or = 2 years) or 5.0 mg (age > 2 years), made up to 4 mL with saline. Children who did not improve were eligible to enter phase one of the study. In this phase (0 h-2 h) treatment was by a standard protocol: nebulised salbutamol at the above dose: 4 L/min or 6 L/min continuous oxygen until oxygen saturation reached 93% in room air for at least 30 min; a bolus of intravenous hydrocortisone 5 mg/kg given over 3 min; and then 15 micrograms/kg intravenous salbutamol or saline, depending on randomised allocation. In phase two (2 h-24 h) the children were given nebulised salbutamol continuously then at 30 min, 1 h, 2 h, 3 h, and 4 h, according to need. All children were transferred to the ward once they were ready to start hourly nebulisation. All patients were followed up until discharge. The primary endpoints were recovery time (no longer requiring inhaled salbutamol) and persistent moderate to severe asthma 2 h after randomisation. Analyses were by intention-to-treat although no withdrawals occurred.
                The recovery time (time to cessation of nebulised salbutamol every 30 min) was 4 h in the 14 children allocated intravenous salbutamol compared with 11.5 h for the 15 children in the control group. 2 (14%) of the intravenous salbutamol group compared with 8 (53%) of the control group needed oxygen to maintain oxygen saturation at 93% room air. The intravenous salbutamol group were ready for discharge from the emergency department 9.7 h earlier than the control group. No clinically significant side-effects were found in either group.
                Addition of a 10 min infusion of salbutamol in the early treatment of children with acute severe asthma has the potential to curtail the clinical progression of asthma, reduce demand placed on hospital resources, and improve the quality of health care provided to the acutely sick child with asthma. Ketotifen was administered orally, for 3 months, to 40 children aged 3-14 years with chronic extrinsic asthma of moderate severity in a double-blind placebo-controlled study. A significant clinical improvement with concomitant reduction of antiasthmatic drugs was found in the group receiving the active drug compared with the placebo group (p less than 0.05). The continued administration of ketotifen in an open study to a group of 21 children comprised of patients belonging to both groups (active-placebo) for a period of 15-18 months resulted in disappearance of symptoms in 10 children (47.6%) and moderate improvement in 7 (33.3%). The role of aminophylline (ethylene diamine salt of theophylline) in the treatment of acute exacerbation of asthma has not been well established in children.
                The aim of the study was to determine the additional therapeutic benefit of intravenous aminophylline in the treatment of children hospitalized for acute asthmatic exacerbation and treated with inhaled bronchodilators and glucocorticoid therapy.
                Thirty-eight children aged from 2 to 16 years (mean age 5.64 +/- 3.31), admitted for acute exacerbation of asthma, participated in a prospective, randomized, double-blind, placebo-controlled study. All the subjects received methylprednisolone, administered intravenously, and nebulized salbutamol. The treatment group received intravenous aminophylline therapy and the placebo group received 0.9% saline solution for 24 hours.
                The number of salbutamol nebulizations needed and the clinical asthma scoring were recorded both at onset and at the end of 24 hours. There was no significant difference in either the mean number of nebulizations or the clinical asthma scores between the two groups (P = .7843, P = .8452).
                Intravenous aminophylline (ethylene diamine salt of theophylline) demonstrated no additional beneficial effect to the combination of beta adrenergic agonists and glucocorticoid treatment in acute asthma attack in children. These results were obtained on a double blinded study which compared the Nifedipine effects, a dihydropyrine calcium blocker of extensive cardiovascular function, the Ketotifen and a placebo orally administered, during 4 months, every 12 hours, on children with allergic asthma, older than 5 years old, who had a minimum of 2 years of evolution in their sickness. These people consulted the Allergic Service of the University Hospital of San Vicente de Paul in Medellín, Colombia, between July of 1984 and December 1986. Nifedipine diminished its intensity, frequency and the time the crisis lasted; it was seen at the end of the treatment. It also diminished bronchodilator consumption in more than 80% of the cases it 90% of the patients reported beneficial effects with Nifedipine and the improvement evaluated by the doctor showed 75%. These results were statistically similar to those obtained with Ketotifen but significantly superior to those obtained with the placebo. There wasn't any variation on the pulmonary function test, neither on the cardiovascular parameters evaluated. Side effects were mild and very few. We can assure that Nifedipine can be an alternative drug for the treatment of low or moderate child Extrinsic Asthma, given its similar behavior to Ketotifen, a drug of known effectiveness in this topic. The Calcium Blockers can become an elective treatment in the future for the asthmatic patient, if some molecules with higher affinity for respiratory tracts and better blocking effect, can be synthetized. To evaluate the effectiveness of early administration of intravenous Magnesium sulfate (i.v. MgSO4) in children with acute severe asthma not responding to conventional therapy.
                Randomized double-blind, placebo-controlled trial.
                Pediatric emergency service of a large teaching hospital.
                47 children aged between 1-12 years with acute severe asthma showing inadequate or poor response to 3 doses of nebulized salbutamol given at an interval of 20 min each.
                The MgSO4 group received 0.2 ml/kg of 50% MgSO4 as intravenous (i.v.) infusion over 35 minutes and the placebo group received normal saline infusion in the same dose and at the same rate. MgSO4 solution and normal saline were coded and dispensed in identical containers. Decoding was done at the completion of the study. All the patients received oxygen, nebulized salbutamol, i.v. aminophylline and corticosteroids.
                MgSO4 group showed early and significant improvement as compared to placebo group in PEFR and SaO2 at 30 min and 1, 2, 3 and 7 hours after stopping the infusion (p ranging from < 0.05 to < 0.01). The clinical asthma score also showed significant improvement in the MgSO4 group 1, 2, 3 and 11 hours after stopping the infusion (p < 0.01).
                Addition of MgSO4 to conventional therapy helps in achieving earlier improvement in clinical signs and symptoms of asthma and PEFR in patients not responding to conventional therapy alone.
The single study on non-intubated children with severe acute asthma did not show significant benefit and does not support the case studies and observational reports showing benefits of ketamine in both non-ventilated and ventilated children. There were no significant side effects of ketamine. We could not find any trials on ventilated children. To prove that ketamine is an effective treatment for acute asthma in children, there is need for sufficiently powered randomised trials of high methodological quality with objective outcome measures of clinical importance. Future trials should also explore different doses of ketamine and its role in children needing ventilation because of severe acute asthma.