(877) Effect of Direct Endotracheal Administration of Dornase Alfa in Children on Mechanical Ventilation

Introduction: Dornase alfa (DA) is a recombinant human deoxyribonuclease I that cleaves extracellular long-chain DNA and has evidence of mucolytic properties. DA has been effective for treatment of patients with cystic fibrosis, but its role in non-cystic fibrosis patients with atelectasis is unknown. We hypothesized that direct endotracheal instillation of DA in mechanically ventilated non-cystic fibrosis children improves atelectasis.

Methods: After IRB approval, we retrospectively analyzed all mechanically-ventilated patients who received DA via direct endotracheal instillation for atelectasis at Nicklaus Children’s PICU from 2017 to 2022. Serial chest X-rays were reviewed for the presence and extent of atelectasis. Radiologic Atelectasis Score (RAS; max score:12) was used to assess the severity and comparison (from baseline [Day 0] to Day 1, Day 2, Day 3, and Day 7) of atelectasis. Data in neonates and non-neonates were compared. Cohen’s kappa for interrater reliability (IRR), Friedman test for repeated data analysis, Chi-square, and Mann Whitney U test for binary data analyses were used. Frequency (%) and median with IQR are used for descriptive statistics.

Results: A total of 37 children (17 neonates) were included in the study. DA was started on day 5 (4-11) in neonates and day 17 (5-35) in non-neonates (p=0.012) after admission. DA was given for a median of 1 (1-6) day at a frequency of 2 (1-2) times per day. 70% of patients received DA for 2 days or less. The dose of DA was 1.25 mg in neonates and 2.5 mg in non-neonates. NaCl 3% and acetylcysteine inhalations were given in 89% and 22% of patients, respectively. The mortality rate for the cohort was 27%. The baseline RAS was 8 (6-10). RAS improvement was seen by >1 point in 47% and by >2 points in 36% on Day 7. Neonates were more likely to show RAS improvement (p=0.047). Friedman test showed significant improvement in all patients (p=0.047) and in neonates (p=0.021) but not in the non-neonate subgroup (p=0.328). Other demographic and clinical variables were not associated with improvement in RAS. Kappa for IRR was 0.83.

Conclusions: In this observational study, direct endotracheal instillation of dornase alfa is associated with improvement in pulmonary atelectasis in neonates but not in non-neonates.