Aminophylline therapy for acute bronchospastic disease in the emergency room. Intravenous aminophylline confers no benefit in acute asthma treated with intravenous steroids and inhaled bronchodilators. Aminophylline increases the toxicity but not the efficacy of an inhaled beta-adrenergic agonist in the treatment of acute exacerbations of asthma. Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics. Does aminophylline add any benefit? Efficacy of aminophylline in the treatment of acute asthma exacerbation in children. Treatment of acute asthma. Lack of therapeutic benefit and increase of the toxicity from aminophylline given in addition to high doses of salbutamol delivered by metered-dose inhaler with a spacer. Aminophylline for acute exacerbations of chronic obstructive pulmonary disease. A controlled trial. Does aminophylline benefit adults admitted to the hospital for an acute exacerbation of asthma? Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma. Aminophylline therapy does not improve outcome and increases adverse effects in children hospitalized with acute asthmatic exacerbations. A controlled trial of intravenous salbutamol and aminophylline in acute asthma. Randomised controlled trial of aminophylline for severe acute asthma. Aminophylline in the treatment of acute asthma when beta 2-adrenergics and steroids are provided. Intravenous salbutamol bolus compared with an aminophylline infusion in children with severe asthma: a randomised controlled trial. Intravenous aminophylline in the treatment of acute bronchospastic exacerbations of chronic obstructive pulmonary disease.
To assess the role of aminophylline in the treatment of acute exacerbations of bronchospastic disease when used in addition to inhaled beta-agonists and intravenous corticosteroids.
                Randomized, double-blind, placebo-controlled intervention study.
                One hundred thirty-three adult patients with either asthma or chronic obstructive pulmonary disease who presented to the emergency department with asthma or wheezing.
                All patients received therapy with both aerosolized metaproterenol and intravenous methyl-prednisolone. Patients were randomly assigned to receive either a loading dose of aminophylline followed by a routine infusion (n = 65) or an equal volume of placebo as a loading dose and infusion (n = 68).
                At discharge from the emergency department, the median serum theophylline concentration for the aminophylline group was 54 mumol/L (9.7 mg/L). The two groups showed no differences (P greater than 0.2) in measurements of forced expiratory volume at 1 second (FEV1), forced vital capacity (FVC), or peak expiratory flow rate (PEFR) at baseline or at 60 or 120 minutes after aminophylline administration. Neither patient satisfaction nor physician assessment of response to therapy differed between the two groups. There was no difference (P greater than 0.2) in the frequency of side effects, except for a trend toward a higher frequency of nausea (P = 0.13) in the aminophylline group. There was, however, a threefold decrease in the hospital admission rate for patients treated with aminophylline (6%) compared with placebo recipients (21%) (P = 0.016).
                Aminophylline, in doses producing levels just below the commonly accepted therapeutic range, appears to decrease hospital admissions in patients with acute exacerbation of asthma or chronic obstructive pulmonary disease. This finding, if confirmed in larger studies, may represent a substantial cost savings. The role of intravenous aminophylline in acute asthma is unclear despite meta-analysis of many studies comparing aminophylline with other bronchodilator therapies.
                The aim of this study is to determine whether continuous aminophylline infusion confers any benefit in acute severe asthmatics treated with intravenous steroids and inhaled bronchodilators.
                The study was randomised, double-blind and placebo-controlled. All patients received nebulised salbutamol (1 mL of 0.5%) and ipratropium bromide (1 mL of 0.025%) with glycol diluent (1 mL) at 0, two, four, six, eight and 12 hours, and six-hourly thereafter. In addition all patients were given intravenous hydrocortisone 250 mg six-hourly and oxygen to maintain normoxia. Aminophylline infusions were adjusted to maintain therapeutic levels. Peak expiratory flow rate (PEFR) was measured before and after nebulised bronchodilator on a two-hourly basis in the Emergency Department (ED) and six-hourly on the inpatient wards.
                Thirty-one patients were clinically sufficiently improved within 12 hours to be discharged home from the ED. The remaining 28 patients were admitted to the inpatient ward for a total trial duration of 48 hours. No significant difference was found between the placebo and treatment groups for measurements of PEFR, or for the duration of stay of the patients in hospital. The power of the study was 80% for a 25% to 33% difference at a 5% level of significance. Presentation values of PEFR and arterial blood gases did not predict which patients would require inpatient admission and which could be safely discharged home from the ED. We studied 40 patients with acute exacerbations of asthma to determine the efficacy of a 3-h intravenous infusion of aminophylline in patients who were already being treated with an inhaled beta-adrenergic agonist (metaproterenol). Each patient was treated with inhaled metaproterenol at hourly intervals for 3 h. In addition, patients were randomly assigned to therapy with either intravenous aminophylline or placebo. Neither the patient nor the house officers and nurses caring for the patient knew whether aminophylline or placebo was given. The FEV1 improved continually throughout the study to a similar extent in both treatment groups, but the patients treated with aminophylline had significantly more adverse effects (p less than 0.025, Mann-Whitney). There was no apparent benefit from aminophylline even in patients who presented to the emergency room with severe airway obstruction (FEV1 less than 0.8L) or with plasma theophylline levels less than 10 mg/L. We conclude that intravenous aminophylline adds to the toxicity but not the efficacy of inhaled metaproterenol in the treatment of acute exacerbations of asthma. To determine the efficacy of intravenous aminophylline in the treatment of adult patients hospitalized for exacerbation of asthma.
                Randomized, double-blind, placebo-controlled trial throughout the study.
                University Hospital Clinical Research Center.
                Forty-four patients admitted from the emergency room with a primary diagnosis asthma; 39 patients completed the study.
                Patients received either intravenous aminophylline or placebo in addition to frequent nebulized albuterol; prednisone 0.5 mg/kg body weight every 6 h orally; and supplemental oxygen. Aminophylline infusion rates were adjusted to achieve serum theophylline concentrations of 10 to 20 micrograms/ml. Changes were made in placebo infusion rates to maintain the double blind design.
                Forced expiratory volume in 1 s (FEV1) and other spirometric measurements every 8 h by a blinded investigator or trained respiratory therapist. Subjective patient response and duration of hospitalization were compared. No difference in spirometric measurements was observed between the two groups at any time point. On admission to the study, FEV1 in the placebo group was 41.5 (+/- 2.9) percent predicted and in the aminophylline group 34.7 (+/- 2.3) percent predicted (p = 0.08). At discharge, FEV1 was 70.4 (+/- 2.9) percent predicted in the placebo group and 63.7 (+/- 2.8) percent predicted in the theophylline group (p = 0.10). There was no difference in subjective patient rating or duration of hospitalization between the two groups (placebo 1.95 days and aminophylline 1.78 days, p = 0.51).
                Our results suggest that aminophylline therapy does not add significant benefit to other standard therapies in hospitalized adult asthmatic patients. Because of the risks and cost of aminophylline treatment in the hospital setting, further research is needed to determine if there are subgroups of adult asthmatics who may benefit from the addition of aminophylline to other standard optimal therapies. 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. We conducted a randomized, double-blind, placebo-controlled study to determine if intravenous aminophylline adds any benefit to high doses of inhaled salbutamol in patients who presented for treatment of acute asthma. We studied 94 patients (mean age, 35.6 +/- 11.2 years) with moderate to severe acute asthma. All patients received therapy with salbutamol delivered with metered-dose inhaler (MDI) into a spacer device (Volumatic) in four puffs (400 micrograms) at 10-min interval, and intravenous hydrocortisone (500 mg). Patients were randomly assigned to receive either a loading dose of intravenous aminophylline followed by a routine infusion (n = 45) or an equal volume of placebo as a loading dose and infusion (n = 49). The two groups showed no differences in measurements of peak expiratory flow, FEV1, and FVC at baseline and at the end of treatment. However, the patients treated with aminophylline had significantly more adverse effects (p < 0.05). There were no differences in the final mean dose of salbutamol (6.3 +/- 44.5 mg for the placebo group and 5.8 +/- 4.2 mg for the aminophylline group), hospital admission rate (10.2 percent for the placebo group and 9.0 percent for the aminophylline group), and mean duration of Emergency Department treatment (2.5 +/- 1.83 h for the placebo group and 2.37 +/- 1.75 h for the aminophylline group). The results were similar when the patients were divided in accord with the degree of respiratory obstruction (baseline FEV1 < 30 percent of predicted) and theophylline level at 30 min of treatment (placebo group patients with theophylline level < 10 mg/L vs aminophylline group patients with theophylline level > or = 10 mg/L). We conclude that intravenous aminophylline adds to the toxicity but not the efficacy of inhaled salbutamol in the treatment of acute exacerbations of asthma. Study Objective: To determine the efficacy of intravenous aminophylline in the treatment of patients hospitalized for exacerbation of chronic obstructive pulmonary disease. Design: Randomized, double-blind, placebo-controlled trial during the first 72 hours of hospitalization. Patients: Thirty patients admitted from the emergency room or walk-in clinic with the primary diagnosis of an exacerbation of chronic obstructive pulmonary disease. Twenty-eight patients completed the study; 2 patients, 1 receiving placebo and 1 receiving aminophylline, were removed from the study because of respiratory failure requiring mechanical ventilation. Interventions: Patients received either intravenous aminophylline or placebo, in addition to nebulized, inhaled 0.3 mL of a 5% solution every 6 hours; methylprednisolone, 0.5 mg/kg body weight every 6 hours intravenously; ampicillin, 500 mg orally every 6 hours (tetracycline or trimethoprim-sulfamethoxazole were substituted in penicillin-allergic patients); and supplemental oxygen as needed. Aminophylline infusion rates were adjusted by an unblinded investigator to achieve theophylline levels of 72 to 83 mumol/L. Changes were also made in placebo infusion rates to maintain the double-blind design. Measurements and Main Results: The forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) before and after metaproterenol inhalation were measured twice daily by a blinded investigator, who also administered a verbal dyspnea index with a scale of 1 to 10 and questioned patients regarding possible side effects of treatment (tremor, palpitations, nausea, or vomiting). Arterial blood gas measurements at 72 hours were compared with those obtained on admission. Significant improvements in FEV1 and FVC measured before and after metaproterenol treatment and in dyspnea occurred over time in both treatment groups (p less than 0.05 for all measurements). However, there were no significant differences between the placebo and aminophylline groups in any of the spirometric measurements or the dyspnea indices (p greater than 0.5 in all five analyses). The mean increases (+/- SE) in Po2 of 1.9 (+/- 0.5) kPa with placebo and 1.7 (+/- 0.7) kPa with aminophylline and the mean decreases in PCO2 of 0.5 (+/- 0.4) kPa with placebo and 1.2 (+/- 0.4) kPa with aminophylline were not significantly different (p greater than 0.6 for PO2, p greater than 0.2 for PCO2).(ABSTRACT TRUNCATED AT 400 WORDS) To determine the effect of adding intravenous theophylline (administered as aminophylline) to nebulizations of albuterol and intravenous methylprednisolone in adults hospitalized for acute asthma.
                Randomized, placebo-controlled, double-blind study.
                Inpatient service of a tertiary-care, university teaching hospital.
                21 adults (22 to 48 years old)--10 in the aminophylline group and 11 in the placebo group.
                Nebulized albuterol, 2.5 or 5.0 mg every 0.5 to 4 hours; intravenous methylprednisolone, 60 mg every 6 hours; and either individualized doses of aminophylline or placebo for 48 hours.
                Forced expiratory volume in 1 second (FEV1), the number of "as needed" albuterol nebulizations and total dose, asthma symptom scores, and adverse effects.
                At admission from the emergency department, the mean +/- SD baseline FEV1 was 49% +/- 19% of the predicted value in the aminophylline group and 43% +/- 13% of the predicted value in the placebo group. The improvement in FEV1 at 3 hours was greater in the aminophylline group (29% +/- 23% compared with 10% +/- 10% in the placebo group; mean difference, 19 percentage points; 95% CI, 3 to 35 percentage points; P = 0.023). At 48 hours, FEV1 was 75% +/- 19% of the predicted value in the aminophylline group and 58% +/- 15% of the predicted value in the placebo group (mean difference, 17 percentage points; CI, 0.2 to 34.8 percentage points; P = 0.048). Aminophylline-treated patients required fewer nebulizations of albuterol (10.3 +/- 3.8 compared with 16.4 +/- 5.3; mean difference, -6.1; CI, -10.3 to -1.8) and less total dosage (34 +/- 16 mg compared with 70 +/- 34 mg; mean difference, -36 mg; CI, -60.6 to -11.3 mg P = 0.02). No statistical differences were observed in asthma symptom scores or frequency of adverse effects.
                Individualized doses of intravenous theophylline added to frequent nebulizations of albuterol and intravenous methylprednisolone appear to benefit adults admitted to the hospital with acute asthma and are well tolerated when serum concentrations are maintained in the therapeutic range. Twenty-one patients admitted to hospital with acute severe asthma were allocated in a random, single-blind manner to receive intravenous infusions for 24 hours or either aminophylline or salbutamol or a combination of the two drugs. Infusions were administered by a slow infusion pump with an initial loading dose given over 15 minutes, followed by a continuous lower dose of the drug 24 hours as follows: 1. Aminophylline 0.285 mg/kg/min for 15 min followed by 0.014 mg/kg/min (20 mg/min. followed by 1 mg/min for a 70 kg subject). 2. Salbutamol 0.285 microgram/kg/min for 15 min followed by 0.057 microgram/kg/min (20 microgram/min followed by 4 microgram/min for a 70 kg subject). 3. Combined regimen of the above infusions. In addition each patient received intravenous hydrocortisone (4 g) and potassium chloride (4 g) in 2 litres of 5% dextrose infused over 24 hours amd 35% oxygen given via a Ventimask. Peak expiratory flow rates showed a significant improvement after 15 minutes treatment with aminophylline and the combined infusion, but this was not seen until 60 minutes with the salbutamol infusion. No synergistic bronchodilator effect was seen with the combined infusion. The results show that intravenous aminophylline is superior to intravenous salbutamol in the doses given in the initial treatment of acute asthma and that the combination when given intravenously is not better than aminophylline alone. To evaluate the effects of aminophylline (Am) in children hospitalized with asthma.
                Prospective, randomized, double-blind, placebo-controlled trial. Subjects were children between the ages of 5 and 18 years admitted for asthma exacerbation to either a tertiary care children's hospital or an inner-city general hospital in New York. Exclusion criteria were admission to the intensive care unit, initial theophylline level > 5 micrograms/dL, or the presence of other systemic disorders. All patients received nebulized albuterol therapy and intravenous glucocorticosteroids in standardized doses. Thirty-one patients were randomized to receive either an Am bolus followed by continuous Am infusion or placebo (P) bolus and infusion. The outcome variables were: duration of hospitalization, percent of predicted peak expiratory flow rates recorded at 12-hour intervals, number of albuterol treatments required, and adverse effects.
                There were no significant differences at study entry in age, sex, race, number of previous hospital admissions, prior medications used, clinical symptom scores, or initial peak flow rates for the two groups. For 26 patients who completed this study, 15 patients in the P group were hospitalized for a mean duration of 2.33 +/- 1.3 days, whereas 11 patients in the Am group required 2.58 +/- 1.5 days. There were no significant differences between the two groups for hospital days, peak flow rates at any time interval, or amount of albuterol therapy required (P > .2). In the Am group, 6 of the 14 patients who entered the study experienced significant adverse effects consisting of nausea, emesis, headache, abdominal pain, and palpitations. Only 1 of 17 patients in the P group had an adverse effect (P < .05).
                There is no benefit and considerable risk of adverse effects associated with the use of Am in hospitalized asthmatic children. In a randomized double-blind trial an intravenous injection of salbutamol (100mug) was compared with an intravenous injection of aminophylline (250mg) in 23 patients with acute exacerbations of asthma. Salbutamol (11 cases) and aminophylline (12) produced a mean proportionate increase in FEV of 26% and 23% respectively. Blood gas pressures showed a trend to improvement with a mean rise in oxygen tension of 2mm Hg(0-2kPa) in the aminophylline group and of 6mm Hg (0-8kPa) in the salbutamol group. Electrocardiogram patterns also showed overall improvement, and mean decreases in pulse rate of 8 beats per minute and 2 beats per minute were noted in the aminophylline and salbutamol groups respectively. Differences in results did not reach conventional levels of significance and no serious side effects were noted. It was concluded that in the doses and routes of administration compared, salbutamol was as effective as aminophylline. To determine whether children with severe acute asthma treated with large doses of inhaled salbutamol, inhaled ipratropium, and intravenous steroids are conferred any further benefits by the addition of aminophylline given intravenously.
                Randomised, double blind, placebo controlled trial of 163 children admitted to hospital with asthma who were unresponsive to nebulised salbutamol.
                The placebo and treatment groups of children were similar at baseline. The 48 children in the aminophylline group had a greater improvement in spirometry at six hours and a higher oxygen saturation in the first 30 hours. Five subjects in the placebo group were intubated and ventilated after enrollment compared with none in the aminophylline group.
                Aminophylline continues to have a place in the management of severe acute asthma in children unresponsive to initial treatment. The purpose of this study was to test the contribution of aminophylline in improving peak expiratory flow rate (PEFR) during emergency department treatment of acute asthma when metaproterenol sulfate and steroid therapy are also provided.
                In a prospective, randomized, double-blind, and placebo-controlled trial at a municipal hospital emergency department, 44 patients with acute asthma, aged 18 to 45 years, with theophylline levels below 28 mumol/L, who had failed to achieve a PEFR of 40% predicted after one nebulized metaproterenol treatment, were recruited. An aminophylline or placebo loading dose and maintenance infusion were administered. All patients received hourly nebulized metaproterenol and initial methylprednisolone sodium succinate. The PEFR was measured hourly for 5 hours. Two-factor repeated-measures analysis of variance of improvement in PEFR ([final-initial PEFR]/predicted PEFR) was assessed.
                There was no difference in improvement of PEFR at any hour between the treatment and placebo groups. After 5 hours, the difference in improvement ratio was 0.40 (aminophylline) vs 0.36 (placebo) (P = .30; n = 22 in each group). The treatment group suffered more tremor, nausea or vomiting, and palpitations (P < .05).
                In the emergency department setting, aminophylline contributes no significant improvement in PEFR when beta 2-agonists and corticosteroids are being provided, while causing more side effects. The relative efficacies of aminophylline and salbutamol in severe acute childhood asthma are currently unclear. A single bolus of salbutamol was compared with a continuous aminophylline infusion in children with severe asthma in a randomised double blind study.
                Children aged 1-16 years with acute severe asthma were enrolled if they showed little improvement with three nebulisers (combined salbutamol and ipratropium) administered over an hour and systemic steroids. Subjects were randomised to receive either a short intravenous bolus of salbutamol (15 micro g/kg over 20 minutes) followed by a saline infusion or an aminophylline infusion (5 mg/kg over 20 minutes) followed by 0.9 mg/kg/h.
                Forty four subjects were enrolled, with 18 randomly allocated to receive salbutamol and 26 to receive aminophylline. The groups were well matched at baseline. An intention to treat analysis showed that there was no statistically significant difference in the asthma severity score (ASS) at 2 hours between the two groups (median (IQR) 6 (6, 8) and 6.5 (5, 8) for salbutamol and aminophylline respectively, p=0.93). A similar improvement in ASS to 2 hours was seen in the two groups (mean difference -0.08, 95% CI -0.97 to 0.80), there was a trend (p=0.07) towards a longer duration of oxygen therapy in the salbutamol group (17.8 hours (95% CI 8.5 to 37.5) v 7.0 hours (95% CI 3.4 to 14.2)), and a significantly (p=0.02) longer length of hospital stay in the salbutamol group (85.4 (95% CI 66.1 to 110.2) hours v 57.3 hours (95% CI 45.6 to 72.0)). There was no significant difference in adverse events between the two groups.
                This study suggests that, in severe childhood asthma, there is no significant difference in the effectiveness of a bolus of salbutamol and an aminophylline infusion in the first 2 hours of treatment. Overall, the aminophylline infusion was superior as it significantly reduced the length of stay in hospital. Often chronic obstructive pulmonary disease (COPD) patients treated for acute exacerbations receive intravenous (IV) aminophylline in addition to inhaled bronchodilators that may raise serum levels of theophylline into the toxic range. A double-blind, randomized study of 52 men with COPD who came to the emergency department for treatment of exacerbations was initiated to establish the efficacy and safety of this common practice. After history and physical examination, patients were treated with 28% oxygen by Venturi mask and 0.3 cc metaproterenol sulfate in 2.5 cc saline by nebulizer; an IV line was started and patients received either aminophylline or D5W. Measurements included baseline and two-hour serum theophylline levels, pulmonary function tests, and symptom questionnaires. Mean values from the entire group showed decreases in respiratory rate, cardiac rate, and pulsus paradoxus, and increases in forced expiratory volume in one second (FEV1) and vital capacity (VC) over a two-hour treatment period (P less than .01). Despite the increase in serum theophylline in the treatment group, the demographic, clinical, pulmonary function, and outcome data were found to have no statistically significant differences when compared to control patients. The data were then analyzed according to serum theophylline levels. Theophylline level greater than 20 micrograms/mL occurred in 15 patients with no untoward effects; premature ventricular contractions (PVCs) were no more frequent in this group than in those with lower serum theophylline levels. A theophylline level greater than 10 micrograms/mL after two hours of treatment resulted in the following differences, which were not statistically significant: mean FEV1 response less than or equal to 10 micrograms/mL vs greater than 10 micrograms/mL, 20% vs 28%; mean VC change, 17% vs 30%; or mean emergency department returns in one week, 0.1 vs 0.26. In our experience, oxygen and inhaled metaproterenol are effective treatment for exacerbations of COPD.
The use of intravenous aminophylline did not result in significant additional bronchodilation compared to standard care with inhaled beta2-agonists in patients experiencing an asthma exacerbation in the ED setting, or in a significant reduction in the risk of hospital admission. For every 100 people treated with aminophylline an additional 20 people had vomiting and 15 people arrhythmias or palpitations. No subgroups in which aminophylline might be more effective were identified. Our update in 2012 is consistent with the original conclusions that the risk-benefit balance of intravenous aminophylline is unfavourable.