Impact of Nebulized Dornase Alpha on Mechanically Ventilated Patients

Background: Lobar or segmental collapse of the lung in mechanically ventilated patients is a relatively common occurrence in the Intensive Care Unit. Available treatments are either labor or time intensive and not highly effective.

Methods: We conducted a randomized, placebo-controlled, double-blind pilot study to determine whether nebulized recombinant human dornase alpha (Pulmozyme, Genentech) improves radiologic and clinical outcomes in ventilated patients with lobar atelectasis. Outcomes of interest were chest radiograph score, oxygenation, lung compliance, and rate of extubation over the first 5 days. The groups consisted of 14 intervention patients and 16 control patients. They were similar with respect to basic demographics, age, gender, and use of therapeutic modalities relating to lung function. Baseline average chest x-ray scores, Pa02/FI02 ratios, and static compliance were not significantly different. Analysis was limited to the first 5 days.

Results: There was a significant improvement in oxygenation for the intervention group at day 5 (p=0.03). There were no significant differences in chest radiograph score, compliance, or rate of extubation. Two patients died in the intervention group, whereas none died in the control group (NS).

Conclusions: These pilot data suggest that inhaled dornase alpha appears to be safe and is associated with improved oxygenation 5 days after initiation of therapy in mechanically ventilated patients compared to placebo. Larger studies are needed to confirm these findings and determine if this intervention decreases ICU morbidity and mortality.

Inclusion criteria

• current ventilator use
• onset of lobar or whole lung collapse over the previous 12 hours
• age greater than 18

Exclusion criteria

• quadriplegia or debilitating neuromuscular condition
• chronic ventilator dependence
• pneumothorax
• frank hemoptysis
• elevated intracranial pressure
• intracranial bleed
• pregnancy or active nursing
• concurrent use of other investigational drugs
• history of allergy to Pulmozyme®, Chinese Hamster Ovary-derived biologics, or any of the components of the active or placebo formulations.