Aminophylline Dosing in Acute Severe Asthma
For life-threatening asthma in adults, administer intravenous aminophylline 250 mg over 20 minutes as a loading dose, followed by a maintenance infusion; in children, use 5 mg/kg over 20 minutes followed by 1 mg/kg/hour maintenance infusion, but omit the loading dose entirely if the patient is already taking oral theophyllines. 1, 2
When to Use Aminophylline
Aminophylline is reserved specifically for life-threatening asthma features that have not responded to initial treatment with high-dose inhaled beta-agonists, systemic corticosteroids, and oxygen. 1, 3, 2
Life-threatening features requiring aminophylline include:
- Peak expiratory flow <33% of predicted or personal best 1, 2
- Silent chest, cyanosis, or feeble respiratory effort 1
- Bradycardia or hypotension 1
- Exhaustion, confusion, or coma 1
- Clinical deterioration despite initial bronchodilator therapy 2
Adult Dosing Protocol
Loading dose: 250 mg intravenous aminophylline administered over 20 minutes 1
Maintenance infusion: 0.5-0.7 mg/kg/hour, with specific adjustments based on patient size (750 mg/24 hours for small patients, 1500 mg/24 hours for large patients) 2, 4
Critical caveat: Do not give any bolus aminophylline to patients already taking oral theophyllines—proceed directly to maintenance infusion only. 1
Pediatric Dosing Protocol
Loading dose: 5 mg/kg intravenous aminophylline over 20 minutes 1, 2
Maintenance infusion: 1 mg/kg/hour 1, 2
Critical caveat: Omit the loading dose entirely if the child is already receiving oral theophyllines. 1, 2
Dosing Calculations and Monitoring
The FDA label provides the pharmacokinetic rationale: each mg/kg of theophylline (ideal body weight) administered as a loading dose over 30 minutes produces approximately a 2 mcg/mL increase in serum concentration, with a mean volume of distribution of 0.5 L/kg. 4
For patients already on theophyllines, if a loading dose becomes necessary, calculate as: D = (Desired C - Measured C) × V, where desired concentration should be conservative (approximately 10 mcg/mL). 4
Monitoring requirements:
- Measure serum theophylline concentrations if infusion continues beyond 24 hours 2
- Monitor vital signs, oximetry, and peak expiratory flow continuously during administration 2
- Obtain serum concentration 30 minutes after loading dose to guide subsequent therapy 4
- In patients with cor pulmonale, cardiac decompensation, or liver dysfunction, initial infusion rate should not exceed 17 mg/hour (21 mg/hour as aminophylline) 4
Important Evidence Considerations
The role of aminophylline is controversial and limited. Multiple high-quality randomized controlled trials from the 1980s-1990s demonstrated that aminophylline adds significant toxicity without improving efficacy when added to inhaled beta-agonists. 5, 6 One study showed patients treated with aminophylline had significantly more adverse effects (p<0.025) with no improvement in FEV1 compared to placebo when both groups received inhaled metaproterenol. 5 Another trial confirmed aminophylline increased toxicity (p<0.05) without benefit when added to high-dose inhaled salbutamol. 6
However, the British Thoracic Society guidelines maintain aminophylline as an option specifically for life-threatening features where initial therapy has failed, representing a consensus approach for the most severe cases. 1
A 2016 systematic review found poor correlation between aminophylline dosage and clinical outcomes in children, suggesting current dosing recommendations may not be optimal. 7
Common Pitfalls to Avoid
- Never administer a loading dose to patients on oral theophyllines without first checking serum levels—this can cause life-threatening toxicity. 1, 4
- Do not mix aminophylline with other drugs in the same syringe—add separately to IV solutions. 4
- Do not use aminophylline as first-line therapy—it is reserved only for life-threatening features after initial treatment with beta-agonists, steroids, and oxygen has been administered. 1, 3, 2
- Calculate doses based on ideal body weight, not total body weight—theophylline distributes poorly into body fat. 4, 8
- Recognize that aminophylline may increase adverse effects (tremor, tachycardia, nausea, arrhythmias) without necessarily improving bronchodilation in many patients. 5, 6