Effect of Direct Endotracheal Administration of Dornase alfa on Atelectasis in Children on Mechanical Ventilation

Abstract

Introduction and Objective. Dornase alfa (DA) is a recombinant human deoxyribonuclease I that cleaves extracellular long-chain DNA and shown to have 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 non-cystic fibrosis patients who received DA via direct endotracheal instillation for atelectasis at Nicklaus Children’s PICU from 2017 to 2022. We excluded those who required ECMO support. 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. 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 in neonates and day 17 in non-neonates (p=0.012) after admission. DA was given for a median of 1 (1-6) days at a frequency of 2 (1-2) per day. The baseline RAS was 8 (6-10). RAS improvement was seen by >1 point in 47% and 36% 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=328). Conclusions-Implications. In this observational study, direct endotracheal instillation of Dornase alfa is associated with improvement in pulmonary atelectasis in neonates but not in non-neonates. This demonstrates that there is utility for the use of DA in reducing the presence of persistent atelectasis in neonate non-cystic fibrosis patients.

Abstract Category

30. Other

Secondary Abstract Category

26. Pediatrics

Keywords

Dornase Alfa, Atelectasis, Pediatric, Mechanically Ventilated

Presentation Type

Poster Presentation

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Effect of Direct Endotracheal Administration of Dornase alfa on Atelectasis in Children on Mechanical Ventilation

Introduction and Objective. Dornase alfa (DA) is a recombinant human deoxyribonuclease I that cleaves extracellular long-chain DNA and shown to have 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 non-cystic fibrosis patients who received DA via direct endotracheal instillation for atelectasis at Nicklaus Children’s PICU from 2017 to 2022. We excluded those who required ECMO support. 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. 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 in neonates and day 17 in non-neonates (p=0.012) after admission. DA was given for a median of 1 (1-6) days at a frequency of 2 (1-2) per day. The baseline RAS was 8 (6-10). RAS improvement was seen by >1 point in 47% and 36% 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=328). Conclusions-Implications. In this observational study, direct endotracheal instillation of Dornase alfa is associated with improvement in pulmonary atelectasis in neonates but not in non-neonates. This demonstrates that there is utility for the use of DA in reducing the presence of persistent atelectasis in neonate non-cystic fibrosis patients.