Does aminophylline benefit adults admitted to the hospital for an acute exacerbation of asthma? Emergency treatment of asthma. A comparison of two treatment regimens. Effect of adding aminophylline infusion to nebulised salbutamol in severe acute asthma. Aminophylline increases the toxicity but not the efficacy of an inhaled beta-adrenergic agonist in the treatment of acute exacerbations of asthma. Emergency room of treatment of asthma. Relationships among therapeutic combinations, severity of obstruction and time course of response. Ventricular arrhythmias during treatment for acute asthma. Inhaled albuterol and oral prednisone therapy in hospitalized adult asthmatics. Does aminophylline add any benefit? Aminophylline, salbutamol and combined intravenous infusions in acute severe asthma. Treatment of acute asthma. Is combination therapy with sympathomimetics and methylxanthines indicated? Comparative effect of epinephrine and aminophylline in the treatment of asthma. Aminophylline therapy for acute bronchospastic disease in the emergency room. A controlled trial of the use of single versus combined-drug therapy in the treatment of acute episodes of asthma. 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. Intravenous aminophylline confers no benefit in acute asthma treated with intravenous steroids and inhaled bronchodilators. Aminophylline in the treatment of acute asthma when beta 2-adrenergics and steroids are provided.
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. The effectiveness of epinephrine was compared to that of a combination of epinephrine and aminophylline in the initial treatment of acute asthma. Forty-four patients with 51 episodes of acute asthma were evaluated. Peak flow spirometry served as an objective measure of airway resistance, and theophylline levels were determined at fixed intervals throughout the study. Epinephrine and aminophylline were not found to be superior to epinephrine alone. There was no correlation between mean serum theophylline levels and the magnitude of improvement. Rapidity of emergency department discharge and frequency of admission was independent of treatment method. The failure of epinephrine-aminophylline to effect more rapid or profound improvement in pulmonary function might suggest that epinephrine alone, or an equivalent sympathomimetic is a rational choice in the initial treatment of acute asthma. The benefit of adding theophylline to beta 2 agonists in acute asthmatic attacks has been debated frequently.
                In an open randomised study 25 patients with severe acute asthma who presented to the emergency department were treated with either a combined nebulised salbutamol (5 mg/dose) and aminophylline infusion (0.6-0.9 mg/kg/hour), or nebulised salbutamol alone.
                The responses to treatment as measured by peak expiratory flow (PEF) and the time taken to achieve maximum PEF were similar in both groups. Side effects were observed more commonly in patients receiving the combined treatment.
                Nebulised salbutamol is equally efficacious in acute asthma when given alone or in combination with aminophylline. 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. In an effort to determine the optimal emergency therapy for acute episodes of asthma, we randomly, assigned 102 acute ill patients to 60 minutes of treatment with inhaled isoproterenol alone, isoproterenol plus intravenous aminophylline or isoproterenol plus a single oral dose of an elixir of theophylline. Patients requiring treatment beyond this time were given an injectable sympathomimetic agent in addition. The combination of isoproterenol and a methylxanthine was not found to be better than isoproterenol alone, and the route of administration of methylxanthine was not an important determinant of either the serum theophylline level or the therapeutic response. A major variable that influenced the duration of therapy needed to produce a remission was the severity of the obstruction at presentation. Persons whose initial 1-second forced expiratory volumes were less than 30 percent of predicted and who did not improve 35 percent or more to at least 40 percent of predicted at the end of 60 minutes of intense treatment were those who ultimately required prolonged emergency room therapy and/or hospital admission for control of their symptoms. Thus, simple objective assessment of the degree of impairment at presentation coupled with the response to initial treatment will serve to identify early a high-risk group of asthmatic patients in whom the usual emergency room therapeutic modalities will often prove ineffective. A double-blind, randomized study was performed to determine the occurrence of ventricular arrhythmias in acute asthma patients treated with epinephrine, aminophylline, or both in combination. Sixty patients were studied with Holter monitoring during the 90-minute study period. There was no statistical difference among the study groups in frequency or grade of ventricular arrhythmia. Combination treatment of acute asthma with these drugs is as safe as treatment with either alone. 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. 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. The role of bronchodilator regimens combining a sympathomimetic and a methylxanthine in the treatment of acute exacerbations of asthma remains controversial. This report describes the outcome of 157 emergency room visits for asthma in which patients were randomly assigned to single-drug therapy with intravenous aminophylline, subcutaneous epinephrine, or inhaled isoproterenol or to one of three regimens combining a sympathomimetic and a methylxanthine. The increase in one-second forced expiratory volume after one hour of treatment with the two-drug combinations (0.79 +/- 0.07 liter) was significantly greater than for epinephrine alone (0.57 +/- 0.08 liter; p less than 0.05) but did not differ significantly from that occurring with therapy with isoproterenol alone (0.72 +/- 0.09 liter; p = NS). This disparity reflects the greater bronchodilation effected by isoproterenol as a single agent than by epinephrine, in the dosing schedules and routes of administration chosen. Among patients presenting with severe airflow obstruction (one-second forced expiratory volume 35 percent or less of normal), the bronchodilator response to isoproterenol alone was 0.88 +/- 0.14 liter versus 0.51 +/- 0.11 for epinephrine alone (p less than 0.05). It is concluded that the observed benefit derived from use of combination therapy depends on the dosage and potency of the particular sympathomimetic to which a methylxanthine is added, and on the severity of the airflow obstruction at presentation. nan 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. Eighty-nine patients who presented to the hospital for treatment of acute episodes of asthma were randomly assigned to initial therapy with subcutaneously administered epinephrine or 1 of 2 combination regimens consisting of intravenously administered aminophylline and either subcutaneously administered of epinephrine or inhaled isoproterenol. During the first hour of treatment, as a group, the patients treated with the 2-drug regimens showed greater objective improvement than did patients who received epinephrine alone. This was particularly true for patients with either severe airway obstruction or a subtherapeutic theophylline concentration at the time of presentation. There were no differences in the heart rate and blood pressure responses to the 3 regimens, and symptoms consistent with drug side effects were not reported more frequently by patients treated with 2 drugs. Thus, the combination of sympathomimetics and aminophylline appear more effective, and no more toxic, than epinephrine alone for the initial treatment of acute episodes of asthma. 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. 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. 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 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.