Addition of intravenous aminophylline to beta2-agonists in adults with acute asthma (Cochrane Review)

St. Joseph's Hospital-McMaster University, 50 Charlton Ave East, Hamilton, Ontario, Canada, L8N 4A6.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 10/2000; 3(4):CD002742. DOI: 10.1002/14651858.CD002742
Source: PubMed


Aminophylline has been used extensively in acute asthma, but its role is unclear especially with respect to any additional benefit when added to beta2-agonists.
To determine the magnitude of effect of the addition of intravenous aminophylline to beta2-agonists in adult patients with acute asthma treated in the emergency setting.
Studies were identified from the following sources: The Cochrane Airways Group register (derived from MEDLINE, EMBASE, CINAHL standardised searches), hand searched respiratory journals and meeting abstracts. Potentially relevant articles were obtained, and their bibliographic lists were hand searched for additional articles. The search included searches of the database up to 1999.
Randomised controlled trials comparing intravenous aminophylline versus placebo in adults with acute asthma and treated with beta-adrenergic agonists. Patients could be treated with or without corticosteroids or other bronchodilators.
A total of 210 abstracts were identified. Two independent reviewers selected a total of 27 eligible studies for possible inclusion, in which quality assessment was performed and a third reviewer was used to adjudicate disagreements. Peak expiratory flow (PEFR) and forced expiratory volume in the first second (FEV1) data were extracted and entered in Review Manager from these studies. Information not obtained from the authors was estimated from graphs. All data were entered and double checked by two reviewers. Results are reported as weighted mean differences (WMD) or odds ratio (OR), both with 95% confidential intervals (CI).
Fifteen trials were included. Overall, the quality of the studies was only moderate; concealment of allocation was assessed as clearly adequate in only seven (45%) of the trials. The doses of aminophylline and other medications and the severity of asthma varied between studies. There was no statistically significant effect of aminophylline on airflow outcomes at any time period. The aminophylline treated group had higher values of PEFR at 12 (PEFR 8 L/min or 2.3%) and 24 hours (PEFR 22 L/min or 6.4%), but these were not significant (p>0.05). Two subgroup analyses were performed by grouping studies according to mean baseline airflow limitation (n = 11 studies) and the use of any steroids (n = 9 studies). There was no relationship between baseline airflow limitation nor the use of steroids on the effect of aminophylline. Aminophylline treated patients reported more palpitations/arrhythmias (OR: 2.9; 95% CI: 1.5 to 5.7) and vomiting (OR: 4.2; 95% CI 2.4 to 7.4), but no difference was found in tremor or hospital admissions.
In acute asthma, the use of intravenous aminophylline did not result in any additional bronchodilation compared to standard care with beta-agonists. The frequency of adverse effects was higher with aminophylline. No subgroups in which aminophylline might be more effective could be identified. These results should be added to consensus statements and guidelines.

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    • "Intravenous theophylline is not recommended for routine management of severe asthma[21] as the clinical benefits of intravenous theophylline in intubated patients are unknown.[24] A review of fifteen trials of moderate quality found that adding intravenous theophylline to inhaled ß2-agonists in adult patients with asthma attacks treated in the emergency setting failed to show any evidence of benefit and was associated with a higher incidence of adverse effects compared with standard care.[26] For intubated patients with refractory asthma, intravenous theophylline can be used but with extreme caution especially in patients with significant comorbidities.[27] "
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    ABSTRACT: Near-fatal asthma (NFA) has not been well studied in Saudi Arabia. We evaluated NFA risk factors in asthmatics admitted to a tertiary-care hospital and described NFA management and outcomes. This was a retrospective study of NFA patients admitted to an ICU in Riyadh (2006-2010). NFA was defined as a severe asthma attack requiring intubation. To evaluate NFA risk factors, randomly selected patients admitted to the ward for asthma exacerbation were used as controls. Collected data included demographics, information on prior asthma control and various NFA treatments and outcomes. Thirty NFA cases were admitted to the ICU in the five-year period. Compared to controls (N = 120), NFA patients were younger (37.5 ± 19.9 vs. 50.3 ± 23.1 years, P = 0.004) and predominantly males (70.0% vs. 41.7%, P = 0.005) and used less inhaled steroids/long-acting ß2-agonists combination (13.6% vs. 38.7% P = 0.024. Most (73.3%) NFA cases presented in the cool months (October-March). On multivariate analysis, age (odds ratio [OR] 0.96; 95% confidence interval [CI], 0.92-0.99, P = 0.015) and the number of ED visits in the preceding year (OR, 1.25; 95% CI, 1.00-1.55) were associated with NFA. Rescue NFA management included ketamine (50%) and theophylline (19%) infusions. NFA outcomes included: neuromyopathy (23%), mechanical ventilation duration = 6.4 ± 4.7 days, tracheostomy (13%) and mortality (0%). Neuromuscular blockade duration was associated with neuromyopathy (OR, 3.16 per one day increment; 95% CI, 1.27-7.83). In our study, NFA risk factors were younger age and higher number of ED visits. NFA had significant morbidity. Reducing neuromuscular blockade duration during ventilator management may decrease neuromyopathy risk.
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    • "There is no support for routine use of intravenous magnesium sulfate for acute asthma, but there is evidence that it is effective for patients with no response to first line initial therapy and those with initial severe airflow obstruction (PEF< 30% predicted) [46]. Aminophylline is not recommended for acute asthma, as a systematic reviews have consistently concluded that it confer no additional benefit over B2 adrenergic bronchodilator, in addition this drug has a narrow therapeutic margin and can cause substantial toxic effects especially among toxic patients [47]. Both clinical and lung function are used in making the decision to admit patient to hospital. "
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    ABSTRACT: IntroductionAsthma is a continuous significant health problem. Strategies for treating exacerbations are best adapted and implemented at a local level. Severe exacerbations are potentially life threatening, and their treatment requires close supervision. The severity of the exacerbation determines the treatment administered. Indices of severity, particularly peak expiratory flow (PEF), pulse rate, respiratory rate, and pulse oximetry should be monitored during treatment.Aim of the workThe aim of this work was to assess the effect of the implementation of the Global Initiative for Asthma (GINA) guidelines in the prognosis and the outcome of asthma exacerbation in the emergency department.Subjects and methodsThe study was conducted on one hundred asthmatic patients. All patients were informed about the study and gave their consents. Patients were subjected to full history taking and clinical evaluation. Investigations were done in the form of peak flow rate (PFR) measurement, pulse oximetry assessment, ABG analysis (for only 17 patients), chest X-ray (it is not routinely recommended) and complete blood count (if needed). Then patients were classified according to their attacks. All patients were managed according to GINA guidelines.ResultsOlder patients were significantly suffering from severe to life threatening attacks than younger patients. We found that 12% of patients had occupational related asthma in relation to 88% of patients had non-occupational related asthma. There were no statistical significant differences between classification of severity of current attack and previous emergency department (ED) visits/year. There were no statistical significant differences between the studied groups regarding temperature. Systolic and diastolic blood pressure had statistically significant lower values in patients with severe to life threatening attacks than those with mild to moderate attacks. Severe to life threatening group had respiratory rate higher than mild to moderate group. Mild to moderate group had PEF and SaO2% higher than severe to life threatening group. PEF was statistically higher post treatment than pre treatment. Three patients of 17 had PaCo2 >45 mmHg with hypoxemia and respiratory acidosis and they admitted to the intensive care unit (ICU). All patients in ED were assisted to determine the severity of asthma concomitant with administration of initial treatment (plan A), which is oxygen to achieve O2 saturation ⩾92%, inhaled B2 adrenergic bronchodilator and an oral or intravenous dose of corticosteroids. Five patients met a good response so they enter in (plan C1). Seventy-five patients met with the criteria of moderate episode they go to plan B1, 68 patients of them (about 90%) had a good response within 2 h so go to plan C1 and the rest 7 patients (10%) had an incomplete response go to plan C2. Twenty patients met with criteria of severe episode, 17 of them (85%) with incomplete response move to plan C2, and the rest 3 patients (15%) had a poor response and moved to plan C3, no improvement noticed so they were admitted to the ICU. Hospitalization was done to 11 patients who met a poor response (plan C2), 86 patients were discharged from the ED (73 patients from plan C1 and 13 patients from plan C2). Severe to life threatening group stayed in ED longer than mild to moderate group.Conclusions and recommendationsAll patients presenting in the emergency department with asthma exacerbations should be evaluated and triaged immediately and must be treated according to their severity of classification using GINA guidelines. Measurements of airflow obstruction, using peak expiratory flow, can help to guide therapy for acute asthma. Continuous monitoring of oxyhaemoglobin saturation by pulse oximetry should be undertaken for all patients with acute exacerbation of asthma. We must; educate patients in ED about the nature of asthma and its therapy, educate patients how to use inhalers, encourage patients to use spirometer at home and discharge each patient with ED-asthma discharge plan.
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    • "Although methylxanthines were once a standard treatment for asthma in an emergency, it is now known that their use increases the risk of adverse events, without improving the outcomes. They were only recommended if inhaled SABA was not available.[112] In spite of these and other evidences that IV methylxanthines are less effective than inhaled SABA,[1314] IV methylxanthines are still commonly used in emergency treatment of asthma even in combination with SABA. "
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