Asthma exacerbation: children: iv aminophylline reduced intubations in severe cases.

Clinical bottom line (level 1b)

  1. Children with severe asthma who had iv aminophylline compared with placebo were less likely to require iv salbutamol (NNT = 8 at 48 hours) or require intubation (NNT = 16 at 48 hours) .
  2. Patients on aminophylline were more likely to stop therapy due to adverse effects (NNH = 4 at 48 hours) .
  3. There was no clear effect on admission to the intensive care unit.
Yung and South: Archives of Diseases in Children 1998; 79: 405-410
Expires November 2002

The study

Double-blinded concealed randomised trial with intention-to-treat
Setting: intensive care unit, children's hospital, Australia

163 patients (aged range 1 to 10 years; median 7, 55% male) children with acute severe asthma, unresponsive to three nebulised doses of 5 mg salbutamol (and asthma score >6, spirometry <50% predicted or 'obviously very sick')

Excluded if
  • <1 or >19 years old
  • pregnant
  • other chronic respiratory disease (eg. bronchopulmonary dysplasia, cystic fibrosis
  • significant disease of other organ systems
  • known adverse reaction to theophylline
  • administration of theophylline within previous 24 hours


    • Note:
  • Patients were stratified for age before randomisation.


    • Control Group: (n = 82, 82 analysed): placebo
    Experimental Group: (n = 81, 81 analysed): aminophylline iv 10 mg/kg over one hour, followed by a continuous infusion of 1.1 mg/kg/hr (0.7 mg/kg/hr if aged <10)
    All patients received frequent nebulised salbutamol delivered using 8 to 10 l oxygen.
    100% followed for 48 hours

    The evidence

    Outcome Time to outcome CEREERRRR
    (95% CI)    		ARR
    (95% CI)    		NNT
    (95% CI)
    admitted to intensive care 48 hours 41
    (50.0%)    		 30
    (37.0%)    		 26%
    (-6% to 48%)    		 13.0%
    (-2.13% to 28.1%)    		 8
    (NNT = 47 to infinity;
    NNH = 4 to infinity)
    iv salbutamol required 48 hours 26
    (31.7%)    		 15
    (18.5%)    		 42%
    (-2% to 67%)    		 13.2%
    (0.04% to 26.3%)    		 8
    (4 to 2800)
    intubation required 48 hours 5
    (6.10%)    		 0
    (0.00%)    		 100%
    (% to %)    		 6.10%
    (0.92% to 11.3%)    		 16
    (9 to 110)
    therapy stopped due to side-effects 48 hours 4
    (4.88%)    		 26
    (32.1%)    		 -558%
    (-1701% to -140%)    		 -27.2%
    (-38.4% to -16.0%)    		 -4
    (-6 to -3)

    Outcome Control Group
    (SD)    		 Experimental Group
    (SD)    		 Mean Difference
    (95% CI)
    time supplemental oxygen required (hours) 18
    ()     		6
    ()     		6 (p=0.015)
    ( to )

  • 48 patients were able to perform PEFR measurements. Aminophylline increased percentage predicted PEFR by 10% (95% CI: 0.3% to 20%) at 24 hours compared with placebo.
  • Patients given aminophylline had a higher oxygen saturation for up to 30 hours.

    • Comments

    1. Many studies on aminophylline in asthma have failed to find any benefit. This reflects the small numbers commonly used, and that most enrolled patients had only mild-to-moderate asthma.
    2. The study is too small to show any effect on ITU admissions or adverse effects.
    3. Whether the benefits of treatment justify the associated harms is a difficult question to answer, and must be judged on an individual patient basis.

    Citation

    1. Yung M, and South M: Randomised controlled trial of aminophylline for severe acute asthma. Archives of Diseases in Children 1998; 79: 405-410
    Search Terms: hand search
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: Mona Nabulsi

    Clinical Question.
    Patient children with acute severe asthma
    Intervention or Exposure aminophylline
    Comparison placebo
    Outcome admitted to intensive care