Relationship between inhaled β₂-agonists and ventilator-associated pneumonia: a cohort study

Crit Care Med. 2011 Apr;39(4):725-30. doi: 10.1097/CCM.0b013e318208ec61.


Objective: To determine the impact of aerosolized bronchodilators on ventilator-associated pneumonia.

Design: Prospective cohort study.

Setting: A 30-bed medical and surgical intensive care unit.

Methods: All intubated patients requiring mechanical ventilation for >48 hrs were eligible during a 13-month period. Nebulized β2-agonists were administered at the intensive care unit physician's discretion. Ventilator-associated pneumonia definition included clinical and quantitative microbiological criteria. Only first ventilator-associated pneumonia episodes were analyzed. Risk factors for ventilator-associated pneumonia were determined using univariate and multivariate analyses. The influence of inhaled β2-agonists on ventilator-associated pneumonia occurrence was also adjusted for confounding factors using Cox's proportional-hazards model.

Results: Ventilator-associated pneumonia was diagnosed in 137 (31%) of the 439 enrolled patients. Ventilator-associated pneumonia was early-onset in 14 (10%) patients. The incidence rate of ventilator-associated pneumonia was 20 per 1,000 ventilator days. Ventilator-associated pneumonia was polymicrobial in 16 (11%) patients, and related to multidrug-resistant bacteria in 42 (28%) patients. Most cases of ventilator-associated pneumonia were caused by Gram-negative bacteria. Inhaled β2-agonists were significantly more frequently used in patients with ventilator-associated pneumonia compared with those without ventilator-associated pneumonia (49% vs. 34%, odds ratio [95% confidence interval] = 1.9 [1.2-2.8], p = .003). Multivariate analysis identified aerosolized β2-agonists (odds ratio [95% confidence interval] = 1.7 [1.1-2.6], p = .012), Simplified Acute Physiology Score II at intensive care unit admission (odds ratio [95% confidence interval] = 1.01 [1.001-1.02] per point, p = .031), and red blood cell transfusion (odds ratio [95% confidence interval] = 2 [1.3-3.1], p = .001) as independent risk factors for ventilator-associated pneumonia. Cox's proportional-hazards model also identified inhaled β2-agonists as a risk factor for ventilator-associated pneumonia (odds ratio [95% confidence interval] = 1.52 [1.06-2.19], p = .021).

Conclusion: Use of aerosolized bronchodilators in intensive care unit mechanically ventilated patients is an independent risk factor for ventilator-associated pneumonia.

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / adverse effects*
  • Confidence Intervals
  • Female
  • Humans
  • Intensive Care Units / statistics & numerical data
  • Kaplan-Meier Estimate
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Odds Ratio
  • Pneumonia, Ventilator-Associated / chemically induced*
  • Pneumonia, Ventilator-Associated / etiology
  • Pneumonia, Ventilator-Associated / microbiology
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors


  • Adrenergic beta-2 Receptor Agonists