To assess whether metered dose inhalers or nebulizers are better for delivering inhaled drugs to mechanically ventilated patients

Acute respiratory failure is common in patients with long term breathing problems who have been admitted to hospital for sudden worsening of their symptoms. A large number of these patients require admission to a critical care unit, where a machine can help them to breathe (mechanical ventilation). In addition, medicines are given to help ease breathing problems by opening up the airways of the lungs (bronchodilator drugs). Bronchodilator drugs relax the muscles in the lungs allowing the airways to widen so that more air passes through, making breathing easier. These drugs are mostly given through inhalation, with specially adapted nebulizers and metered dose inhalers (MDIs) being available for patients who are being mechanically ventilated. Which of these delivery methods is more effective is as yet unclear. We carried out a systematic review of the literature by searching five key databases and asking relevant manufacturers for high quality published or unpublished material which compared the effectiveness of these two delivery methods, nebulizers and MDIs.

This Cochrane systematic review included three trials with 46 patients in total (two trials with 18 patients, one trial with 10 patients), and showed that there is insufficient valid research evidence to recommend either delivery method. There is a clear need for more research into which delivery method is more effective.

Authors' conclusions: 

Existing randomized controlled trials, including randomized cross-over trials where the order of the intervention was randomized, comparing nebulizer and MDI for aerosol bronchodilation in mechanically ventilated adult patients do not provide sufficient evidence to support either delivery method at this time.

Read the full abstract...

Nebulizers and metered dose inhalers (MDI) have both been adapted for delivering aerosol bronchodilation to mechanically ventilated patients, but there is incomplete knowledge as to the most effective method of delivery.


To compare the effectiveness of nebulizers and MDIs for bronchodilator delivery in invasively ventilated, critically ill adults.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 5); Ovid MEDLINE (1950 to Week 19 2012); Ovid EMBASE (1980 to Week 19 2012); CINAHL via EBSCOhost (1982 to Week 19 2012) and reference lists of articles. We searched conference proceedings and reference lists of articles. We also contacted manufacturers and researchers in this field. There were no constraints based on language or publication status.

Selection criteria: 

Randomized controlled trials (RCTs), including randomized cross-over trials where the order of the intervention was randomized, comparing the nebulizer and MDI for aerosol bronchodilation in mechanically ventilated adult patients in critical care units.

Data collection and analysis: 

Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information where required. We collected information about adverse effects from the trials.

Main results: 

This review included three trials, two addressing the primary outcome measure of a reduction of airway resistance (measured as a reduction in interrupter and additional airway resistance) with a total of 28 patients (n =10, n =18) and two addressing adverse changes to haemodynamic observations with a total of 36 patients (n =18, n =18). Limitations in data availability and reporting in the included trials precluded meta-analysis and therefore the present review consisted of a descriptive analysis. Risk of bias in the included trials was judged as low or of unknown risk across the majority of items in the 'Risk of bias' tool.

Cautious interpretation of the included study results suggests that nebulizers could be a more effective method of bronchodilator administration than MDI in terms of a change in resistance. No apparent changes to haemodynamic observations (measured as an increase in heart rate) were associated with either mode of delivery. Due to missing data issues, meta analyses were not possible. Additionally, small sample sizes and variability between the studies with regards to patient diagnoses, bronchodilator agent and administration technique mean that it would be speculative to infer definitive recommendations based on these results at this time. This is insufficient evidence to determine which is the most effective delivery system between nebuliser and MDI for aerosol bronchodilation in adult patients receiving mechanical ventilation.