Aminophylline in the hospital treatment of children with acute asthma

In 1971 Pierson and colleagues showed that in children with acute asthma, intravenous aminophylline provided additional benefit when added to a regimen of hydrocortisone and sympathomimetic drugs.1 As these drugs are pharmacologically different and each causes bronchodilatation it seemed reasonable that together their effect would be additive. For children with poor pulmonary function (peak flow <25% expected) or with hypercapnoea (arterial carbon dioxide pressure >5 kPa) this combination seemed to work2: less severely ill children recovered when given oral prednisolone and nebulisedsalbutamol and did not need inpatient care.

For nearly 20 years children with acute asthma have been managed along these lines. Recent practice, however, has seen the intravenous treatment of children with severe asthma replaced by the regimen now used to treat less severely ill children: oral prednisolone and nebulised β agonists. This combination seems to be efficacious and free of serious side effects and is now recommended for all but life threatening asthma.3 What then is the role of aminophylline in the management of acute asthma in children?

Several recent articles are relevant. Singh and Kumar reported that in a group of moderately ill inpatients a single dose of oral prednisolone 1.5 mg/kg together with salbutamol given continuously by nebuliser at a dose of 0.15 mg/kg/h resulted in more rapid improvement than intravenous aminophylline at 0.9 mg/kg/h given wit intravenous hydrocortisone and intermittent nebulised salbutamol. Unlike those receiving the aminophylline regimen, most children who received the continuous salbutamol regimen had peak expiratory flows of >75% expected at 24 hours and could be discharged from hospital.4 Other studies have shown that in children with moderately severe asthma no appreciable benefit resulted from adding intravenous aminophylline to nebulised salbutamol and intravenous steroids in terms of clinical improvement and the time for which supplemental oxygen was needed*RF 5 or the rate of improvement in pulmonary function.^6,7 No study has examined the value of aminophylline in children with very severe acute asthma who need or may need ventilatory support. The most likely explanation for the lack of added benefit from aminophylline in recent studies is the difference between the sympathomimetic drugs used now and those used in earlier work. Modern β agonists act for longer and are probably used in larger equivalent doses than their predecessors, such as isoprenaline.

Although some anxiety about cardiotoxicity always exists when aminophylline is used in adults, in children there is much less concern about this potentially serious side effect. In a group of clinically stable asthmatic children who underwent Holter monitoring and a maximal treadmill exercise test, neither theophylline alone nor theophylline combined with salbutamol was associated with any substantial adverse cardiovascular effect, including arrhythmias.8 Nausea, vomiting, headache, and abdominal pain were more common in children with acute asthma who received aminophylline as well as salbutamol.7

Aminophylline therefore seems to have nothing to add to corticosteroids (either oral prednisolone or intravenous hydrocortisone) and a nebulised β agonist in the hospital treatment of acute asthma for most children. But two groups need further consideration. As the value of aminophylline in life threatening asthma is unknown, withholding it seems unreasonable as a small benefit could make a large difference in outcome. For those children who do not improve when given a corticosteroid and β agonist consideration could be given to adding aminophylline as well as excluding alternative or coexisting diagnoses, such as an inhaled foreign body or pneumonia.

The second group the needs to be considered is children in developing countries and countries in eastern Europe and the former Soviet Union. In these countries aminophylline is cheaper and readily available more than β agonists. For as long as this is true aminophylline will remain a valuable drug for many children in the world who need treatment in hospital for acute asthma.