Efficacy and tolerance of high-dose inhaled ipratropium bromide vs. terbutaline in intubated premature human neonates

Neonatology. 2007;91(3):167-73. doi: 10.1159/000097448. Epub 2006 Nov 29.


Background: There is insufficient data to reliably assess the benefit of bronchodilators in ventilated premature neonates.

Objectives: To compare the efficacy/tolerance of inhaled ipratropium bromide (IB) vs. terbutaline (T) and to describe factors associated with their efficacy.

Methods: A cross-over randomized controlled double-blind trial including intubated neonates with respiratory distress syndrome. Two puffs of IB or T were administered at 0, 20, 40 min. Passive respiratory system resistance (Rrs) and compliance (Crs) were measured at 0, 20, 40, 60 min. A positive response was defined as a >2 individual coefficients of variation decrease in Rrs or increase in Crs.

Results: Twenty-one infants (gestational age (mean +/- SD): 27.3 +/- 1.6 weeks; birth weight: 947 +/- 250 g; postnatal age: 20 +/- 9 days) were included. At 60 min, no treatment effect for Rrs and Crs could be identified (cross-over analysis). Overall data (irrespective of order of administration) showed that after 6 puffs, the decrease in Rrs was greater in the IB vs. T group (-17.0 +/- 22.2% vs. -11.3 +/- 26.7%, respectively (NS)). Thirty-eight percent of infants responded to IB vs. 43% to T. However, in 19% of patients, decreased Crs was observed after 6 puffs of T. No marker of a positive or paradoxical response could be identified. Treatment was well-tolerated.

Conclusion: High doses of bronchodilators are required in ventilated neonates, but the positive response rate was <50%. Their long-term benefit remains to be proven.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Administration, Inhalation
  • Airway Resistance / drug effects
  • Airway Resistance / physiology
  • Birth Weight
  • Bronchodilator Agents / therapeutic use*
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gestational Age
  • Humans
  • Infant
  • Infant, Newborn
  • Infant, Premature*
  • Ipratropium / therapeutic use*
  • Lung Compliance / drug effects
  • Lung Compliance / physiology
  • Male
  • Respiration, Artificial
  • Respiratory Distress Syndrome, Newborn / drug therapy*
  • Respiratory Distress Syndrome, Newborn / physiopathology
  • Terbutaline / therapeutic use
  • Treatment Outcome


  • Bronchodilator Agents
  • Ipratropium
  • Terbutaline