Recombinant Human Deoxyribonuclease Shortens Ventilation Time in Young, Mechanically Ventilated Children

Abstract

Summary. Recombinant human deoxyribonuclease I (dornase alfa) is currently used as an inhaled mucoactive agent in the treatment of cystic fibrosis. In a randomized, placebo-controlled, double-blind clinical study in 100 infants, we investigated whether the therapeutic use of dornase alfa can be extended to ventilated, fluid-restricted children to reduce reintubation rate, ventilation duration, pediatric intensive care unit (PICU) stay, and ventilation complications. While reintubation rates were similar for dornase alfa 7% vs. placebo 9% (odds ratio, 0.77; confidence interval, 0.11-4.9), the incidence of atelectasis (6 vs. 17, respectively; P-value 0.051), median ventilation time (2.2 vs. 3.4 days, respectively; P-value 0.043), median length of PICU stay (7 vs. 8 days, respectively; P-value 0.051), and mean costs (s4,830 vs. s6,320, respectively) were lower in the dornase alfa group. No adverse effects were observed, even in critically ill patients. We found that dornase alfa was beneficial and safe. Our findings also indicate that dornase alfa is possibly of value from the first day of mechanical ventilation onward, particularly when longer ventilation (>3 days) is expected in fluid-restricted children after cardiac surgery.

Prophylactic Use of Nebulized Hypertonic Saline in Mechanically Ventilated Children: A Randomized Blinded Pilot Study

“…First, our sample size (N ϭ 18) was smaller than the prior prospective neonatal (N ϭ 40) or postoperative cohorts (N ϭ 100), and our study may not have been adequately powered to detect a statistically significant effect on mechanical ventilation duration. 8,9 However, there is no trend toward benefit observed in our data to suggest that this is the case. Second, our population probably represents a more heterogeneous cohort than either neonates or cardiac surgery patients.…”

“…This project was intended from the onset to be a pilot study and was approved by the institutional review board as such. Pilot studies are routinely not designed to be sufficiently powered, although our sample size (ϳ20) was selected a priori because it was powered to detect a 1.2-d difference in mechanical ventilation duration (as reported by Riethmueller et al) 8 if the SD value of our mechanical ventilation duration had been ϳ1 d. Despite our small sample size, no prior data regarding prophylactic nebulized hypertonic saline are available. Our sample size was insufficient to allow for meaningful subgroup analyses.…”

“…In the only available study of prophylactic mucolytic therapy in mechanically ventilated children, subjects Ͻ2 y old recovering from cardiac surgery randomized to dornase alfa therapy had a significantly decreased duration of mechanical ventilation versus those given saline placebo (52 h vs 82 h). 8 This suggests that all children undergoing mechanical ventilation may benefit from airway clearance therapy, probably related to their smaller airways, less developed musculature, and increased sedation requirements. Further study is needed to either confirm that such therapies should be provided in a prophylactic manner to all children undergoing mechanical ventilation or establish that only patients with evidence of significant secretion retention should be treated.…”

Intrapulmonary drug administration in neonatal and paediatric critical care: a comprehensive review

“…In the ICU setting, dornase-a was efficacious for resolving atelectasis in children without cystic fibrosis ventilated long-term [96]. Dornase-a also reduced ventilation days, while there was a trend towards shorter ICU stay and less atelectasis in congenital heart disease children [97].…”

Erken Neonatal Atelektazide Kurtarıcı rhDNase Tedavisi: Olgu Sunumu

“…Nebül formdaki ve inhalasyon yoluyla uygulanan rhDNase, kistik fibroziste kabul görmüş etkin bir tedavi yöntemidir (5). Birkaç olgu sunumunda, respiratuar sinsityal virüs (RSV) bronşioliti ve müküs tıkaçları gibi bazı solunum yolu hastalıklarında da etkili olduğu iddia edilmektedir (6)(7)(8)(9) …”