Asthma: acute exacerbation: multiple doses of anticholinergics reduce hospital admissions in children.

Clinical bottom line (level 1a)

  1. Children with acute moderate-to-severe asthma exacerbations who receive multiple doses of anticholinergics in addition to beta-agonists, compared with beta-agonists alone are less likely to be admitted to hospital (NNT = 10 at unknown) .
  2. There is no clear difference in side-effects or subsequent relapses.
  3. A single dose of anticholinergic has no clear effect on admission, side-effects or relapses, but does improve FEV1 for up to 2 hours.
Plotnick and Ducharme: The Cochrane Library, Issue 3, 1998. Oxford: Update Software 1998; 3: -
Expires November 2002

The study

Systematic review of randomised controlled trials of
  • Patients: children (aged 18 months to 17 years; typically school-aged) presenting to an emergency department with acute asthma exacerbations
  • Intervention: receiving inhaled anticholinergics in addition to beta2-agonists compared with placebo with beta2-agonists
  • Outcome: reporting of hospital admissions


    • Articles found in all using MEDLINE, EMBASE, CINAHL, 1966 to 1998 (search terms: detailed in text ) and Bibliographies were also searched, authors, pharmaceutical companies and experts contacted for unpublished studies or other relevant articles

    Selection criteria: as above
    Appraisal criteria: selected by two independent blinded reviewers using set criteria (detailed in text)
    Articles excluded if:

    Ten studies were included- all were double-blinded.
    Significant heterogeneity was noted.
  • Control group: Single or repeated doses of nebulised or inhaled placebo combined with a beta2-agonist.
  • Experimental group: Single or repeated doses of nebulised or inhaled short-acting anticholinergic (ipratropium bromide 250 to 500 mcg, or atropine) combined with a beta2-agonist.

    • The evidence

    Outcome Time to outcome CER OR
    (95% CI)    		 NNT
    (95% CI)
    single dose: admission to hospital unknown 43/183
    (23%)    		 0.89
    (0.53 to 1.5)     		50
    (NNT = 11 to infinity;
    NNH = 13 to infinity)
    nausea 60 minutes 21/119
    (18%)    		 0.49
    (0.24 to 1.03)     		12
    (NNT = 8 to infinity;
    NNH = 230 to infinity)
    tremor 60 minutes 18/53
    (34%)    		 1.30
    (0.59 to 2.86)     		-16
    (NNT = 9 to infinity;
    NNH = 4 to infinity)
    vomiting 60 minutes 12/138
    (8.7%)    		 0.60
    (0.24 to 1.47)     		30
    (NNT = 15 to infinity;
    NNH = 28 to infinity)
    relapse unknown 52/181
    (29%)    		 1.19
    (0.53 to 2.67)     		-27
    (NNT = 9 to infinity;
    NNH = 4 to infinity)
    multiple doses: admission to hospital unknown 61/181
    (34%)    		 0.62
    (0.39 to 0.98)     		10
    (6 to 220)
    nausea 60 minutes 19/167
    (11%)    		 0.52
    (0.23 to 1.16)     		20
    (NNT = 12 to infinity;
    NNH = 65 to infinity)
    tremor 60 minutes 23/150
    (15%)    		 1.02
    (0.50 to 2.08)     		-390
    (NNT = 15 to infinity;
    NNH = 8 to infinity)
    vomiting 60 minutes 7/139
    (5.0%)    		 1.03
    (0.35 to 3.02)     		-700
    (NNT = 31 to infinity;
    NNH = 11 to infinity)
    relapse unknown 56/179
    (31%)    		 0.66
    (0.29 to 1.5)     		12
    (NNT = 5 to infinity;
    NNH = 11 to infinity)

    • single dose: % change in FEV1 at 60 minutes: weighted mean difference (95% CI): 16 (2 to 30)
    • single dose: % change in FEV1 at 120 minutes: weighted mean difference (95% CI): 17 (4 to 15)
    • multiple doses: % change in FEV1 at 60 minutes: weighted mean difference (95% CI): 10 (4 to 15)
    • No significant differences were noted in other pulmonary function tests.

    Comments

    1. Half of the studies involved patients who had a moderate to severe exacerbation with baseline FEV1 in the range 50-55% of predicted normal. Others failed to provide information on baseline severity. The one study that assessed mild-to-moderate cases failed to show any benefit from adding ipratropium.
    2. Not all studies gave steroids to patients - this may affect the rate of admission, and consequently be a confounding factor.
    3. There were not enough studies to show clearly, any small increase in benefit following a single dose of anticholinergics.

    Citation

    1. Plotnick LH, and Ducharme FM: Efficacy and Safety of Combined Inhaled Anticholinergics and Beta-2-Agonists in the Initial Management of Acute Pediatric Asthma (Cochrane Review). The Cochrane Library, Issue 3, 1998. Oxford: Update Software 1998; 3: -
    Search Terms: acute asthma in Cochrane.
    Contributor: Chris Ball and Clare Wotton, November 2000
    Reviewer: Mona Nabulsi

    Clinical Question.
    Patient children with acute moderate to severe asthma
    Intervention or Exposure anticholinergics with beta-agonists
    Comparison beta-agonists alone
    Outcome admission, side effects