You will be provided with the titles and abstracts of a collection of medical RCT reports studying a clinical question -- for instance, the efficacy of an intervention on some medical outcome. Please write a few sentences synthesizing the findings of these reports, which could serve as a conclusion section for a systematic review article. Your response should not include any other text. The RCT reports are below.



Title 1:
Metered dose inhalers for bronchodilator delivery in intubated, mechanically ventilated patients.
Abstract 1:
We determined the relative efficacy of two bronchodilator aerosol delivery methods in 18 intubated mechanically ventilated patients with airways obstruction. Two treatment arms, consisting of albuterol 270 micrograms (three puffs) from a metered dose inhaler and albuterol 2.5 mg from a saline solution nebulized with an updraft inhaler, were compared in a single blind, randomized crossover design. Pulmonary function was evaluated using an interrupter technique. Changes in passive expiratory flow at respiratory system recoil pressures between 6 and 10 cm H2O provided the therapeutic endpoints. Paired measurements were made before and 30 minutes after drug delivery. The MDI and NEB resulted in similar improvements in iso-recoil flow (mean increase for both groups = 0.1 L/s). Treatment sequence, severity of obstruction, and bronchodilator responsiveness had no effect on relative efficacy. Albuterol caused a small but significant increase in heart rate that was similar following both delivery methods. We conclude that bronchodilator aerosol delivery with metered dose inhalers provides a viable alternative to nebulizer therapy in intubated mechanically ventilated patients and may result in a cost savings to hospitals and patients.


Title 2:
Inhaled fenoterol-ipratropium bromide in mechanically ventilated patients with chronic obstructive pulmonary disease.
Abstract 2:
In 18 patients with chronic obstructive pulmonary disease intubated and mechanically ventilated, we prospectively randomized 200 micrograms fenoterol-80 micrograms ipratropium bromide (four puffs) from a metered-dose inhaler (MDI) versus 1.25 mg fenoterol-500 micrograms ipratropium bromide in 5 ml saline from a nebulizer (NEB). Respiratory mechanics were assessed before and 30 min after the end of each delivery by the rapid end-inspiratory airway occlusion technique. We did vary on single breaths the inflation flow (V) from 0.2 to 1.2 L. s-1, at constant inflation volume. The total respiratory resistance of the respiratory system (Rrs) was partitioned into airway (Rint,rs) and tissue (DeltaRrs) resistances. We found that Rrs was equivalently reduced, from 16.49 +/- 1.37 to 14.85 +/- 1.88 cm H2O. L-1. s with MDI (p < 0.05) and from 18.04 +/- 1.85 to 15.15 +/- 1.33 cm H2O. L-1. s with NEB (p < 0.01). Whereas the prevailing effect of MDI was to reduce Rint,rs, that of NEB was to decrease DeltaRrs. In addition, the V resistance of the respiratory system over the whole range of V was significantly affected by NEB but not by MDI.


Title 3:
Metered-dose inhaler versus nebulized albuterol in mechanically ventilated patients.
Abstract 3:
In nonintubated patients, beta 2-agonist bronchodilators are equally effective when delivered by metered-dose inhalers (MDI) or nebulizers (NEB). The delivery of these drugs by MDI to intubated, mechanically ventilated patients has become a widespread practice. To compare the efficacy of the two delivery systems and establish optimal dosing, we prospectively randomized 10 mechanically ventilated patients, with increased airways resistance, to receive albuterol by either MDI or nebulizer in incrementally higher doses. After a 4-hr washout, patients were crossed-over to receive the drug by the alternative route of administration. Albuterol delivered by NEB to a total dose of 2.5 mg reduced the inspiratory flow-resistive pressure (peak-pause airway pressures) from 21.5 +/- 5.7 to 17.6 +/- 5.4 cm H2O (p < 0.01). Nebulized albuterol at cumulative doses of 7.5 mg led to further reductions in 8 of 10 patients (p < 0.1), but led to toxic side effects in 4 of them; in the remaining 6 patients toxicity occurred at a cumulative dose of 15.0 mg. By contrast, albuterol in cumulative doses reaching 100 puffs (9 mg) from an MDI administered into an endotracheal tube adapter did not significantly reduce resistive pressures, and produced no toxicity. We conclude that nebulized albuterol provides objective physiologic improvement, while albuterol administered by MDI through an endotracheal tube adapter has no effect in mechanically ventilated patients with airflow obstruction. Nebulizer treatments can and should be titrated to higher-than-conventional doses, using toxic side-effects and physiologic response to guide therapy.
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.