Salbutamol and ipratropium by inhaler is superior to nebulizer in children with severe acute asthma exacerbation: Randomized clinical trial

Pediatr Pulmonol. 2019 Apr;54(4):372-377. doi: 10.1002/ppul.24244. Epub 2019 Jan 22.


Introduction: In moderate-severe asthma exacerbation, salbutamol by inhaler (MDI) is superior to salbutamol delivered by nebulizer (NEB); however, to our knowledge, no studies in children with exclusively severe exacerbations were performed.

Objective: To compare the efficacy of salbutamol and ipratropium bromide by MDI versus by NEB in severe asthma exacerbations.

Methods: We performed a clinical trial enrolling 103 children (2-14 years of age) with severe asthma exacerbations (defined by the Pulmonary Score ≥ 7) seen at the emergency room in Asuncion, Paraguay. One group received salbutamol and ipratropium (two puff every 10 min for 2 h and then every 30 min for 2 h more) by MDI with a valved-holding chamber and mask along with oxygen by a cannula separately (MDI-SIB); and the other received nebulization with oxygen (NEB-SIB) of salbutamol and ipratropium (1 every 20 min for 2 h and then every 30 min for 2 h more). Primary outcome was the rate of hospitalization (Pulmonary Score ≥ 7) after 4 h and secondary outcome was oxygen saturation.

Results: Fifty two children received MDI-SIB and 51 NEB-SIB. After the 4th hour, children on MDI-SIB had significantly (P = 0.003) lower rate of hospital admission than on NEB-SIB (5.8% vs 27.5%, RR: 0.21 [0.06-0.69], respectively). Similarly, a significant improved clinical score after 60 min and increase in oxygen saturation after 90 min of treatment was observed in MDI-SIB versus NEB-SIB group (4.46 ± 0.7 vs 5.76 ± 0.65, P < 0.00001; and 90.5 ± 1.7 vs 88.43 1 ± 1, P < 0.00001, respectively).

Conclusion: Even in severe asthma exacerbations administration of salbutamol and ipratropium by MDI with valved-holding chamber and mask along with oxygen by a cannula separately was more effective than by a nebulizer.

Keywords: MDI; children; ipratropium; nebulizer; salbutamol; severe acute asthma.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Albuterol / administration & dosage*
  • Asthma / drug therapy*
  • Bronchodilator Agents / administration & dosage*
  • Cannula
  • Child
  • Child, Preschool
  • Emergency Service, Hospital
  • Female
  • Hospitalization
  • Humans
  • Inhalation Spacers
  • Ipratropium / administration & dosage*
  • Male
  • Nebulizers and Vaporizers*
  • Oxygen / therapeutic use


  • Bronchodilator Agents
  • Ipratropium
  • Albuterol
  • Oxygen